RESEARCH ARTICLE Open Access

Manual therapy for the pediatric population:a systematic reviewCarol Parnell Prevost1, Brian Gleberzon2, Beth Carleo1, Kristian Anderson3, Morgan Cark1 andKatherine A. Pohlman4*

Abstract

Background: This systematic review evaluates the use of manual therapy for clinical conditions in the pediatricpopulation, assesses the methodological quality of the studies found, and synthesizes findings based on healthcondition. We also assessed the reporting of adverse events within the included studies and compared ourconclusions to those of the UK Update report.

Methods: Six databases were searched using the following inclusion criteria: children under the age of 18 years old;treatment using manual therapy; any type of healthcare profession; published between 2001 and March 31, 2018;and English. Case reports were excluded from our study. Reference tracking was performed on six published relevantsystematic reviews to find any missed article. Each study that met the inclusion criteria was screened by two authorsto: (i) determine its suitability for inclusion, (ii) extract data, and (iii) assess quality of study.

Results: Of the 3563 articles identified, 165 full articles were screened, and 50 studies met the inclusion criteria.Twenty-six articles were included in prior reviews with 24 new studies identified. Eighteen studies were judged to beof high quality. Conditions evaluated were: attention deficit hyperactivity disorder (ADHD), autism, asthma, cerebralpalsy, clubfoot, constipation, cranial asymmetry, cuboid syndrome, headache, infantile colic, low back pain, obstructiveapnea, otitis media, pediatric dysfunctional voiding, pediatric nocturnal enuresis, postural asymmetry, preterm infants,pulled elbow, suboptimal infant breastfeeding, scoliosis, suboptimal infant breastfeeding, temporomandibulardysfunction, torticollis, and upper cervical dysfunction. Musculoskeletal conditions, including low back pain andheadache, were evaluated in seven studies. Twenty studies reported adverse events, which were transient andmild to moderate in severity.

Conclusions: Fifty studies investigated the clinical effects of manual therapies for a wide variety of pediatric conditions.Moderate-positive overall assessment was found for 3 conditions: low back pain, pulled elbow, and premature infants.Inconclusive unfavorable outcomes were found for 2 conditions: scoliosis (OMT) and torticollis (MT). All other condition’soverall assessments were either inconclusive favorable or unclear. Adverse events were uncommonly reported. Morerobust clinical trials in this area of healthcare are needed.

Trial registration: PROSPERA registration number: CRD42018091835

Keywords: Pediatric, Manual therapy, Chiropractic, Osteopathic, Systematic review

* Correspondence: kpohlman@parker.edu4Parker University, 2540 Walnut Hill Lane, Dallas, TX 75229, USAFull list of author information is available at the end of the article

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 https://doi.org/10.1186/s12906-019-2447-2

BackgroundParents consult complementary and alternative medicine(CAM) providers for a wide variety of pediatric conditions[1, 2]. In addition to botanical medicines and supplements,some seek manual therapy including soft tissue therapy,mobilization and high velocity low amplitude manipulationsdirected to the spine and peripheral joints. The UnitedStates (US) Department of Health and Human Servicesconducts a population-based survey and creates the Na-tional Health Interview Statistics (NHIS) reports on the useof CAM with children ages 4–17 every 5 years with resultspublished in 2007 and 2012. Overall, approximately 12% ofchildren used a CAM modality the previous year [1, 2].Manual therapy is a CAM therapy regulated for use

among many professions (e.g., doctor of osteopathy, med-ical doctors and physical therapists), but doctors of chiro-practic (DCs) are the most likely profession to use manualtherapy on a regular basis [3]. According to a recent jobanalysis of the overall DC profession, 17.1% of chiropracticpatients are 17 years of age or less; this increases to 38.7%among DCs who have specialized in pediatrics [3, 4]. Nde-tan et al. conducted a sub-analysis of the 2007 NHIS datafor chiropractic and/or osteopathic manipulation use andfound that 3.3% of US children had received chiropracticor osteopathic manipulation the previous year [5]. Mostcommonly, children were between 12 and 18 years of ageand received care for back or neck pain.Concerns regarding manual therapy, specifically ma-

nipulation [6], have led to complications identified in theliterature. However, no prospective population-based ac-tive surveillance have been conducted [7]. Serious eventsare rare, but may be related to high-velocity extension androtational spinal manipulation [8]. The serious eventsidentified in mostly retrospective studies commonly oc-curred with patients that had preexisting underlying path-ology, which emphasizes the need for a thorough historyand physical examination so that abnormal findings areidentified prior to manual therapy in a child [7–9].Six systematic reviews have previously been conducted

to evaluate the use of manual therapy for pediatric healthconditions [9–14]. These reviews ranged in manual ther-apy definitions from high-velocity variable amplitude toprofession-specific manipulative therapy. Nonetheless, allreviews concluded that this is a paucity of evidence for theeffectiveness of manual therapy for conditions within thepediatric population, especially for musculoskeletal condi-tions. The purpose of this systematic review was to evalu-ate the use of manual therapy for clinical conditions in thepediatric population, assess the methodological quality ofthe studies found, and synthesize findings based on healthcondition. We also assessed the reporting and incidenceof adverse events within the included studies. Additionally,we compared conclusions to Clar et al.’s UK Updatemanuscript [10].

MethodsThis study was registered at the PROSPERA - Center forReviews and Dissemination, University of York, York,U.K. on March 28, 2018. Details of the protocol for thissystematic review were registered on PROSPERO andcan be accessed at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=91835.

Search strategyA comprehensive search of the literature was performedby three independent librarians at three different educa-tional institutions. The databases stated in Table 1 weresearched for English manuscripts published between2001 through March 31, 2018. Data mining and refer-ence tracking of the six previously published systematicreviews were performed for relevant papers. No condi-tion terms were included to keep the search as broad aspossible. The list of search terms and keywords used inthe search are included in Table 1.

Eligibility criteriaStudies were eligible for inclusion if they were full textreports of RCTs (no abstracts). Feasibility studies with-out outcome measures were not included in this review.For observational studies, the Agency for Healthcare Re-search and Quality’s (AHRQ) Assessing Risk of Bias andConfounding in Observational Studies of Interventions orExposures was utilized to determine study type withnon-comparative (case report or case series without preand post measurements) and cross-sectional studies ex-cluded [15]. Additional eligibility criteria were that a study

Table 1 Databases searched: PubMed, Cochrane Library, Medlinecomplete, CINAHL complete, ScienceDirect, McCoy Press, Index toChiropractic Literature, and National Guideline Clearinghouse

Chiropractic AND pediatric*

Chiropractic AND child*

Chiropractic AND adolescent*

Manipulation, chiropractic(MeSH heading)

AND (pediatric*, child*, adolescent*)

Manipulation, orthopedic(MeSH heading)

AND (pediatric*, child*, adolescent*)

Manipulation, osteopathic(MeSH heading)

AND (pediatric*, child*, adolescent*)

Osteopath* AND (pediatric*, child*, adolescent*)

Orthopedic manipulation AND (pediatric*, child*, adolescent*)

Orthoped* AND (pediatric*, child*, adolescent*)

Pediatric manual therapy AND (pediatric*, child*, adolescent*)

Ped MT AND (pediatric*, child*, adolescent*)

Spinal manipulative therapy AND (pediatric*, child*, adolescent*)

SMT AND (pediatric*, child*, adolescent*)

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 2 of 38

had to include children under the age of 18 who weretreated with manual therapy (definitions and abbreviationsshown in Table 2) of any type from any health care profes-sional for any condition.

Study selection, data extraction, & summary assessmentTwo independent reviewers evaluated the studies identi-fied by the searches for potential inclusion in our study.They applied the inclusion/exclusion criteria to the studiesidentified by first screening the abstracts and then the fulltext of any studies appearing to fulfill the inclusion cri-teria. Any discrepancies as to whether or not to include astudy was resolved by a third independent evaluator. Dataextraction was conducted by an independent reviewerusing an a priori designed data extraction form with a sec-ond reviewer validating the findings.An overall result summary assessment was determined

for each study based on their results as either: “improve-ment” (manual therapy appeared to be effective in theintervention group), “no improvement” (manual therapydid not appear to be effective in the intervention group),or “no difference” (results appeared to be the same in theintervention group as compared to a different interven-tion, sham intervention or control group).

Quality assessment-individual studiesThe quality assessment process was conducted by an in-dependent reviewer and validated by a second randomlyassigned reviewer. Disagreements for each criterion weresettled through discussion with a third reviewer. Two

different assessment tools were utilized to assess thequality of the RCTs and observational studies includedin this review. The Cochrane Risk of Bias tool, consistingof 7 domains, was used to assess the risk of bias of theRCTs [16]. The domains were:

� adequate sequence generation,� allocation concealment,� patient blinding,� assessor blinding,� addressing of incomplete data,� selective outcome reporting, and� other sources of bias.

The tool used to assess observational studies was thesame used to evaluate the observational study design [15].This AHRQ tool consists of 9 domains:

� inclusion/exclusion criteria variances across groups(cohort studies only),

� recruitment strategies for groups (cohort studiesonly),

� appropriate, selection of comparison groups (cohortstudies only),

� blinding outcome assessor to intervention,� use of valid and reliable outcome tools,� length of follow-up variances across study groups,� missing important primary outcomes,� missing harms or adverse events, and� account of any confounding variables.

Table 2 Abbreviations and definitions used for this study

SMT (Spinal ManipulativeTherapy)

A procedure involving an high velocity, low amplitude (HVLA) thrust beyond the passive range of motion into thepara-physiological space, but within the limits of anatomic integrity [71]p10, [72]p142–143, [73]. It is a bimanual motorskill involving various levels of interlimb coordination and postural control combined with a timely weight transfer andis characterized by a HVLA thrust that typically results in joint cavitation [74]. SMT is highly adaptive and context-dependent,meaning the amount of force delivered to the patient must take into account clinically relevant pathologies as well asanthropomorphic differences between the doctor and patient [73].The safe delivery of SMT requires consideration withrespect to preload, speed of force production, peak amplitude of force delivered, duration of impulse/thrust delivered,doctor position, patient positioning, and line of drive (direction of thrust) [71, 74].

Mobilization A low velocity, low amplitude (LVLA) oscillation procedure, within the active or passive ranges of motion [71]p18,[72]p142.

OMT (OsteopathicManipulative Therapy)

Involves physical manipulation of various tissues and parts of the body that includes soft tissue massage and stretch,strain-counter-strain, articulation, high velocity thrust, gentle low amplitude mobilizations and neuromusculartechniques [49]p1–2. In some instances OMT is better classified as a mobilization [71]p18 .

CST (Cranial-Sacral Therapy) A group of manual procedures directed to the sutures of the skull designed to enhance the functioning ofthe membranes, tissues, fluids, and bones surrounding or associated with the brain and spinal cord. It is postulated thatlow-force pressure can influence the vitality of the Cranial Rhythmic Impulse created by the flow of cerebrospinal fluidas it moves from the ventricles of the skull to the sacrum within the spinal cord [71]p123–136.

CMT (ChiropracticManipulative Therapy)

Synonymous with SMT, but performed by a doctor of chiropractic.

VOMT (Visceral OsteopathicManipulation)

A manual therapy directed to various organs of the body to aid in smooth muscle function,influence somatic biomechanics and body fluid mechanics [49]p251–252.

Instrument-assistedmanipulation

The use of any number of different types of hand held instruments used to provide a manipulation-type force.

MT (Manual Therapy) Any of the above.

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 3 of 38

We omitted the following questions from the AHRQassessment for the following reasons. Questions 4(Does the study fail to account for important variationsin the execution of the study from the proposed proto-col?) and 12 (Any attempt to balance the allocation be-tween the groups or match groups (e.g., throughstratification, matching, propensity scores)?) as thesewere not relevant for our body of literature. Question 8(In cases of high loss to follow-up (or differential lossto follow-up), was the impact assessed (e.g., throughsensitivity analysis or other adjustment method)?) asour included studies did not have this level of statisticalanalysis involved. And question 11 (Are results believ-able taking study limitations into consideration?) as wefelt this question was too subjective [15, 17].The study’s overall quality score was then determined to

be: low quality study if the score was between 0 and33.3%, medium quality, if the score was between 33.4 and66.6%, and high quality if the score was above 66.6%.

Quality assessment-overall conditionsWe employed the same criteria to summarize the overallstrength of evidence for the studies by conditions to beconsistent with the UK Update/Clar et al. report [10],which used an adapted version from the US PreventiveServices Task Force. This report, along with Clar et al.reports, summarized the overall strength/quality of evi-dence as: “high-quality positive/negative”, “medium-qual-ity positive/negative”, or “inconclusive evidence favorable/non-favorable/unclear” [10]. The overall evidence gradingsystem used allows the evidence to be grouped into threecategories based upon its strength: high quality evidence,moderate quality evidence, or inconclusive evidence. Thedefinitions of these three categories are listed below:

High quality evidenceThe evidence comes from at least 2 RCTs and is consid-ered high quality due to low risk of bias. As a result, theconclusion is unlikely to be affected by future studies.

Moderate quality evidenceThe evidence comes from at least 1 high-quality RCT(with sufficient statistical validity) OR at least 2higher-quality RCTs (with some inconsistency) OR atleast 2 consistent lower-quality RCTs.

Low quality (inconclusive) evidenceThe available evidence is insufficient to determine effect-iveness. If all papers showed improvement they are clas-sified as “Favorable”. If all papers failed to showimprovement they are classified as “Unfavorable”. If allpapers showed a mix of improvement, lack of improve-ment, or no difference they are classified as “Unclear”.Note that observational studies cannot be rated higherthan “Inconclusive (unclear)”, as observational studiesare not designed to show effectiveness.

ResultsSearch resultsAs shown in Fig. 1, the initial database searches gener-ated a total of 3563 records (2440 after deduplication).Of which, 166 full articles were assessed in detail. Onehundred sixteen of the articles were excluded. Of the 50included articles, 32 were RCTs and 18 were observa-tional studies. Table 3 provides a summary of the studiesalong with the details, sample sizes, quality, results ofthe study and an overall summary. This table also com-pares the overall summary from Clar et al.’s UK Updatestudy [10]. These studies are then summarized by studydesign (RCT and observational) in Table 4 and 5, re-spectively, with the individual quality assessment criteriaoutlined.Overall, we found 23 studies that used OMT (7 of

which specifically used cranial therapies and 1 VOMT);17 studies used CMT/SMT (including one using Toft-ness technique, one using an upper cervical technique,one using a neuroimpulse instrument, and one usingcranial therapy with CMT), 10 studies used mobiliza-tions (1 also using CST).

Fig. 1 Study selection flow diagram (PRISMA style)

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 4 of 38

Table

3Overallsummaryin

comparison

with

theUKUpd

aterepo

rt

Clinicalcond

ition

UKup

date

(1)summary

Stud

iesin

curren

treview

Interven

tion

Citatio

nsQuality

Sample

size

Results

ofstud

yCurrent

stud

yoverall

summary

Gastrointestin

alCon

ditio

ns

Con

stipation

Not

evaluated

1OBS

OMT

Tarsuslu,2009[18]

Med

ium

13Nodifference

Inconclusive

(unclear)

Infantile

Colic

Inconclusive/favorable

3RC

T1OBS

CMT

Miller,2012[19]

Wiberg,

2010

[20]

Brow

ning

,2008[21]

Olafsdo

ttir,2001

[22]

High

Low

High

High

104

749

43 86

Improvem

ent

Noim

provem

ent

Nodifference

Nodifference

Inconclusive

(unclear)

Infantile

Colic

Inconclusive/favorable

1RC

TOMT/CST

Hayde

n,2006

[23]

Med

ium

28Im

provem

ent

Inconclusive

(favorable)

Pediatric

dysfun

ctionalvoiding

Inconclusive/favorable

1RC

TOMT

Nem

ett,2008

[24]

Med

ium

21Im

provem

ent

Inconclusive

(favorable)

Pediatric

nocturnalenu

resis

Inconclusive/favorable

1OBS

CMT

vanPoecke,2009[25]

Med

ium

33Im

provem

ent

Inconclusive

(unclear)

Subo

ptim

alinfant

breastfeed

ing

Not

evaluated

2OBS

CMT/CST

Miller,2009[26]

Vallone

,2004[27]

Med

ium

Low

114

25Im

provem

ent

Improvem

ent

Inconclusive

(favorable)

MusculoskeletalCon

ditio

ns

Clubfoo

tNot

evaluated

1RC

TMT

Nilgun

,2011[28]

Low

29Im

provem

ent

Inconclusive

(favorable)

Cub

oidSynd

rome

Not

evaluated

1OBS

MT

Jenn

ings,2005[29]

Med

ium

2Im

provem

ent

Inconclusive

(unclear)

Headache

Not

evaluatedforp

ediatrics

1OBS

OMT

Przekop,

2016

[30]

Med

ium

83Im

provem

ent

Inconclusive

(unclear)

Headache

Not

evaluatedfor

pediatrics

1RC

TMT

Borusiak,2010[31]

Med

ium

52Nodifference

Inconclusive

(unclear)

Headache

Not

evaluatedfor

pediatrics

1OBS

CMT

Marchand,

2009

[32]

Low

13Im

provem

ent

Inconclusive

(unclear)

Low

Back

Pain

Not

evaluated

1RC

T1OBS

CMT

Evans,2018

[33]

Hayde

nJ,2003

[36]

High

Med

ium

185

54Im

provem

ent

Improvem

ent

Mod

erate(favorable)

Low

back

pain

Not

evaluated

1OBS

1RC

TMT

Walston

,2016[34]

Selhorst,2015[35]

Med

ium

Med

ium

3 35Im

provem

ent

Nodifference

Inconclusive

(unclear)

Pulled(Nursemaid’s)Elbo

wNot

evaluated

2RC

TMT

Garcia-Mata,2014

[37]

Bek,2009

[38]

Med

ium

Med

ium

115

66Im

provem

ent

Improvem

ent

Mod

erate(favorable)

Tempo

romandibu

larJoint

Dysfunctio

nNot

evaluatedforp

ediatrics

1RC

TOMT

Mon

aco,2008

[39]

Low

28Im

provem

ent

Inconclusive

(favorable)

Respiratory

Con

ditio

ns

Asthm

aNot

evaluatedforp

ediatrics

1RC

TOMT

Guine

y,2005

[40]

Med

ium

140

Improvem

ent

Inconclusive

(favorable)

Asthm

aNot

evaluatedforp

ediatrics

1RC

TCMT

Bron

fort,2001[41]

High

34Noim

provem

ent

Inconclusive

(unclear)

Obstructiveapne

aNot

evaluated

1RC

TOMT

Vand

enplas,2008[42]

Med

ium

34Im

provem

ent

Inconclusive

(favorable)

OtitisMed

iaInconclusive/un

clear

3RC

T1OBS

OMT

Steele,2014[43]

Wahl,2008

[44]

Degenhardt,2006

[45]

Mills,2003

[47]

Med

ium

High

Med

ium

High

34 90 8 57

Improvem

ent

Nodifference

Improvem

ent

Improvem

ent

Inconclusive

(favorable)

OtitisMed

iaNot

evaluated

1OBS

CMT

Zhang,

2004

[46]

Med

ium

22Im

provem

ent

Inconclusive

(unclear)

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 5 of 38

Table

3Overallsummaryin

comparison

with

theUKUpd

aterepo

rt(Con

tinued)

Clinicalcond

ition

UKup

date

(1)summary

Stud

iesin

curren

treview

Interven

tion

Citatio

nsQuality

Sample

size

Results

ofstud

yCurrent

stud

yoverall

summary

SpecialN

eeds

ADHD

Inconclusive/un

clear

1RC

TOMT

Accorsi,2014[48]

High

28Im

provem

ent

Inconclusive

(favorable)

Autism

Not

evaluated

1OBS

VOMT

Bram

ati-Castellarian,

2016

[49]

Med

ium

49Im

provem

ent

Inconclusive

(unclear)

Not

evaluated

1RC

TCMT

Khorshid,2006[50]

Low

14Im

provem

ent

Inconclusive

(favorable)

Cereb

ralP

alsy

Inconclusive/un

clear

3RC

TOMT

Wyatt,2011[51]

Dun

can,2008

[53]

Dun

can,2004

[52]

High

High

Low

142

55 50

Noim

provem

ent

Improvem

ent

Improvem

ent

Inconclusive

(unclear)

Preterm

infants

Inconclusive/un

clear

4RC

TOMT/CST

Raith

,2015[54]

Cerretelli,2015[55]

Pizzolorusso,2014[56]

Cerretelli,2013[57]

High

High

High

High

30 695

110

110

Nodifference

Improvem

ent

Improvem

ent

Improvem

ent

Inconclusive/unclear

for

gene

ralm

ovem

ent

Mod

erate(favorable)

leng

thof

stay

and

hospitalcosts

StructuralCon

ditio

ns

Cranialasym

metry

Not

evaluated

1RC

TMT/CS

TCabrera-Martos,2016

[58]

High

46Im

provem

ent

Inconclusive

(favorable)

Not

evaluated

1OBS

OMT

Lessard,

2011

[59]

Med

ium

12Im

provem

ent

Inconclusive

(unclear)

PosturalAsymmetry

Not

evaluated

1RC

TOMT/CST

Phillippi,2006[60]

High

32Im

provem

ent

Inconclusive

(favorable)

Scoliosis

Not

evaluated

1RC

T3OBS

CMT

Byun

,2016[61]

Rowe,2006

[62]

Morning

star,2004[63]

Lantz,2001

[64]

Med

ium

High

Low

Med

ium

5 6 6 42

Improvem

ent

Nodifference

Improvem

ent

Noim

provem

ent

Inconclusive

(unclear)

Scoliosis

Not

evaluated

1RC

TOMT

Hasler,2010

[65]

High

20Noim

provem

ent

Inconclusive

(unfavorable)

Torticollis

Not

evaluated

1RC

TMT

Hauge

n,2011

[66]

Med

ium

32Nodifference

Inconclusive

(unfavorable)

Upp

ercervicaldysfun

ction

Not

evaluated

1OBS

MT

Saed

t,2017

[67]

High

307

Improvem

ent

Inconclusive

(unclear)

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 6 of 38

Pediatric clinical conditions

1. Gastrointestinal/urinary conditions

Table 6 provides a summary of the 10 studies that inves-tigated the clinical effects of manual therapy for condi-tions categorized as “gastrointestinal/urinary conditions”.One of the studies investigated the use of manual therapyfor constipation [18], five for infantile colic [19–23], onefor children with dysfunctional voiding [24], one forpediatric nocturnal enuresis [25], and two studies forsuboptimal infant breastfeeding [26, 27].

1.1.Constipation

One study was found that investigated the use ofOMT for constipation [18].Tarsuslu et al. conducted a medium quality, inter-

rupted time-series with a comparison group that investi-gated the potential effects of OMT on constipation in 13children ages 2–16 with cerebral palsy. The childrenwere put into one of two groups with no description ofhow this allocation happened. The first group receivedOMT alone and the second group received OMT inaddition to medical treatment. Both groups showed sig-nificant changes from all baseline measures at 3 months.The baseline measures included defecation frequency,gross motor function, and functional independencemeasure. Group 1 showed significantly favorable changesin defecation frequency and constipation scale at 6months. Group 2 showed significantly favorable changesfrom baseline measures at 6 months. The researcherssuggest advanced additional studies should be con-ducted. There was no mention of adverse events madein this study [18].Overall Summary:Inconclusive (unclear) for use of OMT in treating

constipation.

1.2.Infantile colic

Four of the five studies investigated the use of CMT intreating infantile colic; three of these studies were highquality RCTs [19, 21, 22] and one low quality retrospect-ive investigation of the clinical records [20]. Onemedium quality prospective RCT investigated the use ofOMT cranial therapy [23].A high quality parent-blinded RCT, authored by Miller

et al., showed favorable results in treating 104 colicky in-fants less than 8 weeks of age with CMT. This study hadtwo objectives; the first was to determine the efficacy intreating colic with CMT and the second was to determineif parental reporting bias contributes to the success of thetreatment. The infants were randomized into 3 groups:

infant treated-parent aware; infant treated-parent un-aware; and infant not treated-parent unaware. The out-comes were determined by a decrease in crying time, asassessed by a parent questionnaire and a 24 h crying diary.The study found there was a greater decrease in cryingtime in the infants treated with CMT, either parent awareor unaware, compared to infants who were not treated,concluding that parents did not appear to contribute tothe observed treatment effects in the study. Adverse eventwas reported in one patient in the control (non-treatment)group that reported increased crying [19].Wiberg et al. conducted a low quality interrupted time

series without a comparison group observational studythat looked at 749 clinical records of infants 0–3 years ofage who fulfilled the study’s definition of excessive cry-ing. This study investigated if the outcome of excessivelycrying infants treated with CMT was associated with orpartially associated with age in the natural decline incrying with age in infants. The outcomes were deter-mined by the parents recording crying in the infants as“improved”, “uncertain”, or “non-recovery”. These re-searchers concluded that there was no apparent link be-tween the clinical effect of chiropractic treatment andimprovement in the crying patterns. Limitation of thestudy was that it was pragmatic, thus not standardizedon management or CMT technique. There was no men-tion of adverse events in this study [20].Browning and Miller conducted a high quality

parent-blind RCT involving 43 infants less than 8 weeksof age that presented with infantile colic. The study ob-jective was to compare two intervention groups in thetreatment of infantile colic. One intervention group re-ceived CMT and the other occipital-sacral decompres-sion. The outcomes were determined by the change inmean daily hours of crying as recorded in a crying diaryby a parent. Although the mean hours of daily cryingwere statistically significantly reduced in both studygroups, there were no statistically significant differencesbetween them. The researchers noted that although allparticipants’ symptoms improved prior to the normal re-mission age of colic, the natural course of remissioncould not be ruled out. There was no mention of adverseevents made in this study [21].Olafsdottir et al. conducted the third high quality RCT

that set out to evaluate the effect of CMT on infantilecolic. This study included 86 colicky infants (46 receivingCMT, 40 in control group) at 3–9 weeks of age. The out-come was determined by the parents recording the hoursof infant crying per 24 h period in a crying diary. The re-sults showed no statistically significant improvement inthe infants in either group. There was no mention of ad-verse events made in this study [22].Another medium quality prospective, open-controlled

RCT that investigated the impact of cranial osteopathy

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 7 of 38

Table

4Qualityratin

gof

rand

omized

controlledtrials

Autho

r/year

Con

ditio

nsample

size

(n)

Results

summary

Interven

tion

Selectionbias:

rand

omSelectionbias:

allocatio

nPerfo

rmance

bias:b

linding

ofpe

rson

nel

andparticipants

Detectio

nbias:

blinding

ofou

tcom

eassessmen

t

Attritionbias:

incomplete

outcom

edata

Repo

rtingbias:

selective

repo

rting

Other

bias:

anything

else,

ideally

pre-

specified

Overall

quality

ratin

g

Gastrointestin

al/Urin

ary

Mille

rJ,etal.2012

[19]

Infantile

Colic

(n=104)

Improvem

ent

CMT

Lcompu

ter

gene

rated

perm

utated

blocks

Lsealed

insequ

entially

numbe

red

opaque

envelope

s

Len

velope

srevealed

totreatin

gprovider

before

treatm

ent,1of

3grou

psparents

knew

infants

werebe

ing

treated

U-PYtw

oof

threegrou

psof

parents

blinde

dto

treatm

ent,data

extractor

blinde

dto

teratm

ent

Hpe

rprotocol

analysis

cond

ucted

Lallo

utcomes

repo

rted

U-PN“paren

tdiagno

sis”,

selective

nature

ofdiary

High

Brow

ning

M&Miller

J,2008

[21]

Infantile

Colic

(n=43)

Nodifference

CMT

Lcompu

ter

gene

rated

Hno

tstated

Lblinding

ofbo

thparents

andpatients

Linde

pend

ent

observer

bind

edto

treatm

ent

Lallo

utcomes

repo

rted

Lallo

utcomes

repo

rted

Hstrict

inclusion

criteria,small

stud

ysize,

inexpe

rienced

iterns

High

Hayde

nC&Mullinge

rB,

2006

[23]

Infantile

Colic

(n=28)

Improvem

ent

OMT/CST

Lrand

omnu

mbe

rtable

U-PYrand

omtablenu

mbe

rutilizedbu

tno

tdiscussed

Hpatientsand

providersno

tblinde

d

Hou

tcom

eassessors

unblinde

d

H2with

drew

andno

tinclud

edin

analysis

Lallo

utcomes

repo

rted

U-PNsm

all

stud

ysize,

lack

ofstandardized

treatm

ent

Med

ium

Olafsd

ottirE,etal.2001[22]

Infantile

Colic

(n=86)

Nodifference

CMT

H“rando

mized

”no

tde

scrib

edU-PY“sealed”

envelope

sLparentsand

providers

blinde

d

Lou

tcom

eassessor

blinde

d

Lintentionto

treatanalysis

Lallo

utcomes

repo

rted

U-PYsm

all

samplesize

High

Musculoskeletal

Nem

ettD,etal.2008[24]

Pediatric

Dysfunctio

nal

Voiding(n

=21)

Improvem

ent

OMT

U-PYstated

“rando

mized

assign

ed”with

nofurthe

rde

scrip

tion

Hno

thing

stated

Hno

thing

stated

Hon

lyprim

ary

outcom

eassessor

blinde

d

Hpe

rprotocol

analysis

cond

ucted

Lallexpected

outcom

esrepo

rted

,second

ary

outcom

eno

tinitially

evaluated

incontrol

grou

ppe

rprotocol

Lstud

yappe

arsfre

eof

othe

rsourcesof

bias

Med

ium

Nilgun

B,et

al.2011[28]

Idiopathic

Clubfoo

t(n

=29)

Improvem

ent

MT

Hrand

omized

bytraveland

physicalabilities

Hno

tconcealed

Hparents,

patients,

therapistsno

tblinde

d

Hou

tcom

eassessor

not

blinde

d

Lallo

utcomes

repo

rted

Lallo

utcomes

repo

rted

Hpilotstud

yon

lyLow

BorusiakP,et

al.2010[31]

Cervicoge

nicHA(n

=52)

Nodifference

MT

Lcompu

ter

gene

rated

Lsequ

entially

numbe

red

iden

tical

opaque

envelope

s

Lparents,

patientsand

pediatrician

blinde

d

U-PYpre-

establishe

danalysisplan

notde

scrib

ed

Hpe

rprotocol

analysis

cond

ucted

Lallo

utcomes

repo

rted

Hsm

all

samplesize,

clinicaleffect

ofsham

,ob

servational

bias

Med

ium

EvansR,et

al.2018[33]

Subacute

and

Chron

icLBP

(n=185)

Improvem

ent

CMT

Lcompu

terized

dynamic

allocatio

n

Lsealed

insequ

entially

numbe

red

Hpatientsand

providersno

tblinde

d

Lou

tcom

eassessor

blinde

d

Lallo

utcomes

repo

rted

Lallo

utcomes

repo

rted

Lstud

yappe

ars

freeof

othe

rsourcesof

bias

High

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 8 of 38

Table

4Qualityratin

gof

rand

omized

controlledtrials(Con

tinued)

Autho

r/year

Con

ditio

nsample

size

(n)

Results

summary

Interven

tion

Selectionbias:

rand

omSelectionbias:

allocatio

nPerfo

rmance

bias:b

linding

ofpe

rson

nel

andparticipants

Detectio

nbias:

blinding

ofou

tcom

eassessmen

t

Attritionbias:

incomplete

outcom

edata

Repo

rtingbias:

selective

repo

rting

Other

bias:

anything

else,

ideally

pre-

specified

Overall

quality

ratin

g

(rank-order

minization)

system

opaque

envelope

s

SelhorstM

&SelhorstB,

2015

[35]

MechanicalLBP

(n=35)

Nodifference

MT

Hno

tde

scrib

edHno

tde

scrib

edU-PYblinding

ofpatients,exercise

therapist,no

blinding

ofmanual

therapist

Lallo

utcomes

patient

self-

repo

rtblinde

d

Hpe

rprotocol

anaylsis

cond

ucted

Lallo

utcomes

repo

rted

Lstud

yappe

arto

befre

eof

othe

rsourcesof

bias

Med

ium

Garcia-MataS&

Hidalgo

-Ovejero

A,2014[37]

PulledElbo

w(n

=115)

Improvem

ent

MT

Hno

tde

scrib

edHno

tde

scrib

edHparents,

patients,

therapistsno

tblinde

d

Hou

tcom

eassessorsno

tblinde

d

Lallexpected

outcom

esrepo

rted

Lallo

utcomes

repo

rted

Lstud

yappe

arto

befre

eof

othe

rsourceso

bias

Med

ium

BekB,et

al.2009[38]

PulledElbo

w(n

=66)

Improvem

ent

MT

Hno

tde

scrib

edHno

tde

scrib

edHno

blinding

Hou

tcom

eassessorsno

tblinde

d

Lintentionto

treatanalysis

Lallo

utcomes

repo

rted

Lstud

yappe

ars

freeof

othe

rsource

ofbias

Med

ium

Mon

acoA,etal.2008[39]

Non

-Spe

cific

Tempo

romandibu

lar

Disorde

r(n

=28)

Improvem

ent

OMT

Hno

tde

scrib

edHno

tde

scrib

edHpatientsand

providersno

tblinde

d

Hou

tcom

eassessor

not

blinde

d

Hfollow

upof

participants

wereno

tdiscussed

U-PNsample

respon

sefor

each

outcom

eno

tprovided

U-PNsm

all

stud

ysize

Low

Respiratory

Guine

yP,et

al.2005[40]

Asthm

a(n

=140)

Improvem

ent

OMT

U-PYno

twell

describ

ed“rando

mization

basedon

a2:1

ratio

”

Hno

tde

scrib

edHprovider

not

blinde

dHou

tcom

eassessor

not

blinde

d

Lallp

atients

accoun

tedfor

Lallo

utcomes

repo

rted

Lstud

yappe

ars

freeof

othe

rsourcesof

bias

Med

ium

Bron

fortGet

al.2001[41]

Asthm

a(n

=34)

No

improvem

ent

CMT

Lcompu

ter

gene

rated

Lsealed

inop

aque

envelope

s

Lblinding

ofbo

thparentsand

patients

Lou

tcom

eassessor

blinde

d

Lallp

atients

accoun

tedfor

Lallo

utcomes

repo

rted

Lstud

yappe

ars

freeof

othe

rsourcesof

bias

High

Vand

enplas

YDE,et

al.

2008

[42]

ObstructiveApn

ea(n

=34)

Improvem

ent

OMT

Hno

tde

scrib

edHno

tde

scrib

edLpatientsblinde

dLou

tcom

eassessors

blinde

d

Hpe

rprotocol

analysis,6

participants

drop

pedou

tandno

tinclud

edin

analysis

Lallo

utcomes

repo

rted

U-PNsm

allstudy

size,imbalance

insizesof

controltostud

y

Med

ium

SteeleD,etal.2014[43]

OtitisMed

ia(n

=34)

Improvem

ent

OMT

Lstud

yused

“Research

Rand

omizer”

U-PY

rand

omized

tables

gene

rated

with

unique

numbe

rassign

men

t

Hprovidersno

tblinde

d,parents

blinde

dbu

tin

treatm

entroom

Lou

tcom

eassessors

blinde

d

Lallp

atients

accoun

tedfor

Lallo

utcomes

repo

rted

Hsm

allsam

ple

size,p

ilotstud

yMed

ium

WahlR

,etal.2008[44]

OtitisMed

ia(n

=90)

Nodifference

OMT

Lrandom

ization

inblockesof8

usingrandom

numbertable

L2by2

factorial

design

Lpatients,parents,

providersblinde

dLou

tcom

eassessor

blinde

d

Lallp

atients

accoun

tedfor

Lallo

utcomes

repo

rted

U-PNun

equal

distrib

utionof

riskfactorsin

treatm

entgrou

p

High

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 9 of 38

Table

4Qualityratin

gof

rand

omized

controlledtrials(Con

tinued)

Autho

r/year

Con

ditio

nsample

size

(n)

Results

summary

Interven

tion

Selectionbias:

rand

omSelectionbias:

allocatio

nPerfo

rmance

bias:b

linding

ofpe

rson

nel

andparticipants

Detectio

nbias:

blinding

ofou

tcom

eassessmen

t

Attritionbias:

incomplete

outcom

edata

Repo

rtingbias:

selective

repo

rting

Other

bias:

anything

else,

ideally

pre-

specified

Overall

quality

ratin

g

MillsM,etal.2003[47]

Acute

OtitisMed

ia(n

=57)

Improvem

ent

OMT

Lcompu

ter

gene

rated

Linde

pend

ent

nurse

mon

itored

anddisclosed

byph

one

Hparentsand

provider

not

blinde

d

Lou

tcom

eassessor

blinde

d

Hpe

rprotocol

analysis,19

drop

pedou

tandno

tinclud

edin

analysis

Lallo

utcomes

repo

rted

Lstud

yappe

ars

freeof

othe

rsourcesof

bias

High

SpecialN

eeds

AccorsiA,etal.2014[48]

Atten

tion-Deficit/

Hyperactivity

Disorde

r(n

=28)

Improvem

ent

OMT

Lpermuted-

blockratio

1:1usingRstatistical

program

U-PN

allocatio

nwas

concealed

butno

tde

scrib

ed

U-PYpatients/

parents/providers

notblinde

dbu

twereblinde

das

toou

tcom

es

Lou

tcom

eassessors

blinde

d

Lallp

atients

accoun

tedfor

U-PNadverse

even

tswere

beingcollected

butno

trepo

rted

U-PNsample

size

not

justified

High

KhorshidKA,etal.2006

[50]

Autism

(n=14)

Improvem

ent

CMT

Hnotd

escribed

Hno

tde

scrib

edHpatientsand

providersno

tblinde

d

Hou

tcom

eassessorsno

tblinde

d

U-PN

enrollm

ent

numbe

rno

tdiscussed

Lallo

utcomes

repo

rted

U-PNsample

size

not

justified

Low

WyattK,et

al.2011[51]

Cereb

ralP

alsy

(n=142)

No

improvem

ent

OMT

Lteleph

one

based

rand

omization

byindepend

ent

statisticianat

remotesite

Lallocatio

nprovided

byinde

pend

ent

statisticianat

remotesite

Hparentsand

patientsno

tblinde

d

Lou

tcom

eassessors

blinde

d

Lallp

atients

accoun

tedfor

Lallo

utcomes

repo

rted

U-PNsample

size

not

justified

High

Dun

canB,et

al.2008[53]

Cereb

ralP

alsy

(n=55)

Improvem

ent

OMT

Ldraw

techniqu

eusing

stratification

Lblinding

ofconcealm

ent

Hparents,patients,

providersno

tblinde

d

Lou

tcom

eassessor

blinde

d

Hpe

rprotocol

analysis

cond

ucted

Lallo

utcomes

repo

rted

Lstud

yappe

ars

freeof

othe

rsourcesof

bias

High

Dun

canB,et

al.2004[52]

CerebralPalsy

(n=50)

Improvem

ent

OMT

Hno

tde

scrib

edHno

tde

scrib

edHno

tde

scrib

edHou

tcom

eassessorsno

tdiscussed

Hpe

rprotocol

analysis

cond

ucted

Lallo

utcomes

repo

rted

Lstud

yappe

ars

freeof

othe

rsourcesof

bias

Low

Raith

W,etal.2016[54]

Prem

aturity

(n=30)

Nodifference

OMT/CST

Lrand

omized

usingblock

design

with

blocksize

6

Lsequ

entially

sealed

opaque

envelope

s

Lparentsand

providersblinde

dLou

tcom

eassessors

blinde

d

Lallp

atients

accoun

tedfor

Lallo

utcomes

repo

rted

Lstud

yappe

ars

freeof

othe

rsourcesof

bias

HIgh

CerritelliF,et

al.2015[55]

Prem

aturity

(n=695)

Improvem

ent

OMT/CST

Lrand

omized

usingblock

design

with

blocksize

10

Lpe

rform

edin

coordinatin

gcenter

U-PNproviders

notblinde

dLNICUstaff

blinde

dHpe

rprotocol

analysis

perfo

rmed

Lallo

utcomes

repo

rted

Lstud

yappe

ars

freeof

othe

rsourcesof

bias

High

Pizzolorusso

G,etal.

2014

[56]

Prem

aturity

(n=110)

Improvem

ent

OMT/CST

Lcompu

ter

gene

rated

perm

uted

block

Lrand

omized

byIT

consultant

U-PNproviders

notblinde

dLou

tcom

eassessors

blinde

d

Lallp

atients

accoun

tedfor

Lallo

utcomes

repo

rted

Lstud

yappe

ars

freeof

othe

rsourcesof

bias

High

CerritelliF,et

al.2013[57]

Prem

aturity

(n=110)

Improvem

ent

OMT/CST

Lcompu

ter

gene

rated

perm

uted

block

Lrand

omallocatio

nby

inde

pend

ent

consultant

Hparents,patients,

providersno

tblinde

d

Lou

tcom

eassessor

blinde

d

Hpe

rprotocol

analysis

cond

ucted

Lallo

utcomes

repo

rted

Lstud

yappe

ars

freeof

othe

rsourcesof

bias

High

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 10 of 38

Table

4Qualityratin

gof

rand

omized

controlledtrials(Con

tinued)

Autho

r/year

Con

ditio

nsample

size

(n)

Results

summary

Interven

tion

Selectionbias:

rand

omSelectionbias:

allocatio

nPerfo

rmance

bias:b

linding

ofpe

rson

nel

andparticipants

Detectio

nbias:

blinding

ofou

tcom

eassessmen

t

Attritionbias:

incomplete

outcom

edata

Repo

rtingbias:

selective

repo

rting

Other

bias:

anything

else,

ideally

pre-

specified

Overall

quality

ratin

g

Structural

Cabrera-M

artosI,et

al.

2016

[58]

CranialAsymmetry

(non

syno

stotic

plagioceph

aly)

(n=46)

Improvem

ent

MT/CST

Lrand

omized

numbe

rge

neratorin

blocks

of4

Lsealed

envelope

Hpatientsand

providersno

tblinde

d

Lou

tcom

eassessors

blinde

d

Lallo

utcomes

accoun

tedfor

Lallo

utcomes

repo

rted

Lstud

yappe

ars

freeof

othe

rsourcesof

bias

High

Philipp

iH,etal.2006[60]

PosturalAsymmetry

(n=32)

Improvem

ent

OMT/CST

Lblock

rand

omization

Lsealed

insequ

entially

numbe

red

envelope

s

Lparents,patients,

provider

blinde

dLou

tcom

eassessor

blinde

d

Lallo

utcomes

accoun

tedfor

Lallo

utcomes

repo

rted

Lstud

yappe

ars

freeof

othe

rsourcesof

bias

High

HaslerC,etal.2010[65]

Scoliosis(n

=20)

No

improvem

ent

OMT

Lblock

rand

omization

U-PY

consealed

envelope

s

Hpatientsand

provider

not

blinde

d

Lou

tcom

eassessor

blinde

d

Lallo

utcomes

accoun

tedfor

Lallo

utcomes

repo

rted

U-PNsm

all

samplesize

High

RoweDE,et

al.2006[62]

Scoliosis(n

=6)

Nodifference

CMT

Lcompu

ter

gene

rated

Lindepend

ent

person

nel

provided

allocation

assig

nent

viae-mail

Lpatientsand

provider

blinde

dLou

tcom

eassessors

blinde

d

Lallo

utcomes

accoun

tedfor

Lallo

utcomes

repo

rted

U-PNsm

all

samplesize

High

Hauge

nE,et

al.2011[66]

Torticollis

(n=32)

Nodifference

MT

Hno

tde

scrib

edU-PYselaed

envelope

U-PNpatients

blinde

d,providers

notblinde

d

Lou

tcom

eassessor

blinde

d

U-PNpatient

descrip

tionand

enrollm

ent

notdiscussed

Hno

tall

outcom

esrepo

rted

U-PNsample

size

not

justified

Med

ium

Lege

nd:H

-Highriskof

bias;L-Low

riskof

bias;N

A-Not

applicab

le;U

-Unclear;P

N-Proba

blyNo(highriskof

bias);PY

-Proba

blyYe

s(lo

wriskof

bias).

Interven

tions:C

MTChiropractic

Man

ipulativeTh

erap

y,CS

TCraniosacralT

herapy

,MTMan

ualT

herapy

,OMTOsteo

pathicMan

ipulativeTh

erap

y.

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 11 of 38

Table

5Qualityratin

gof

observationalstudies

Autho

r/year

Stud

yde

sign

type

Con

ditio

nsample

size

(n)

Result

summary

Interven

tion

Includ

e/exclud

eRecruitm

ent

strategy

Com

parison

selection

Blinde

dou

tcom

eassessor(s)

Valid,reliable

measures

Leng

thof

follow-up

Missing

outcom

esMissing

harm

s/adverse

even

ts

Missingconfound

ing

variables

Overall

quality

ratin

g

Gastrointestin

al/Urin

ary

Tarsuslu

T,et

al.2009[18]

Interrup

ted

timeseries

(with

comparison

grou

p)

Con

stipation

andCereb

ral

Palsy(n

=13)

Nodifference

OMT

Ldo

esno

tvary

Hno

tde

scrib

edHno

tde

scrib

edHno

tblinde

dU-PNprop

erty

measuremen

tsno

tfully

evaluatedfor

children

Lconsistent

Lall

outcom

esdiscussed

H adverse

even

tsno

trepo

rted

U-PNdietary

Medium

WibergK&

WibergJ,

2010

[20]

Interrup

ted

timeseries

(with

outa

comparison

grou

p)

Infantile

colic

(n=749)

No

improvem

ent

CMT

NA

NA

NA

Hno

tblinde

dU-PNprop

erty

measuremen

tsno

tfully

evaluatedfor

children

Hno

tdiscussed

Lall

outcom

esdiscussed

H adverse

even

tsno

trepo

rted

U-PN

co-interventions

missing

Low

vanPo

ecke

A&Cun

liffe

C,

2009

[25]

Before-after

Nocturnal

Enuresis

(n=33)

Improvem

ent

CMT

NA

NA

NA

Hno

tblinde

dU-PNprop

erty

measuremen

tsno

tfully

evaluatedfor

children

Lconsistent

Lall

outcom

esdiscussed

H adverse

even

tsno

trepo

rted

U-PN

dietary

Medium

Miller

J,et

al.

2009

[26]

Before-after

Subo

ptim

alInfant

Breastfeed

ing

(n=114)

Improvem

ent

CMT

NA

NA

NA

Hno

tblinde

dU-PNprop

erty

measuremen

tsno

tfully

evaluatedfor

children

Hno

tdiscussed

Lall

outcom

esdiscussed

Ladverse

even

tsrepo

rted

Lconfou

nding

variables

accoun

tedfor

Medium

Vallone

S,2004

[27]

Before-after

Subo

ptim

alInfant

Breastfeed

ing

(n=25)

Improvem

ent

CMT/CST

NA

NA

NA

Hno

tblinde

dU-PNprop

erty

measuremen

tsno

tfully

evaluatedfor

children

Hno

tdiscussed

U-PN

different

outcom

esfor

participants

H adverse

even

tsno

trepo

rted

Hno

confou

nding

variables

includ

edLow

Musculoskeletal

Jenn

ings

J&

DaviesG,2005

[29]

Interrup

ted

timeseries

(with

out

comparison

grou

p)

Cub

oid

Synd

rome

(n=2)

Improvem

ent

MT

NA

NA

NA

Hno

tblinde

dU-PNprop

erty

measuremen

tsno

tfully

evaluatedfor

children

U-PYno

tdifferent

but

notspecified

Lall

outcom

esdiscussed

H adverse

even

tsno

trepo

rted

U-PNvariables

that

may

influence

outcom

ediscussed

butn

oadjustment

tooutcom

etaken

into

accoun

t

Medium

PrzekopP,et

al.2016[30]

Before-after

Chron

ictension-type

headache

(n=83)

Improvem

ent

OMT

NA

NA

NA

Hno

tblinde

dU-PNprop

erty

measuremen

tsno

tfully

evaluatedfor

children

Lconsistent

Lall

outcom

esdiscussed

H adverse

even

tsno

trepo

rted

Lconfou

nding

variables

accoun

tedfor

Medium

MarchandA,

etal.2009[32]

Before-after

Benign

infant

headache

(n=13)

Improvem

ent

CMT

NA

NA

NA

Hno

tblinde

dU-PNprop

erty

measuremen

tsno

tfully

evaluatedfor

children

Hno

tdiscussed

Lall

outcom

esdiscussed

H adverse

even

tsno

trepo

rted

Hmed

ication

notaccoun

ted

for

Low

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 12 of 38

Table

5Qualityratin

gof

observationalstudies

(Con

tinued)

Autho

r/year

Stud

yde

sign

type

Con

ditio

nsample

size

(n)

Result

summary

Interven

tion

Includ

e/exclud

eRecruitm

ent

strategy

Com

parison

selection

Blinde

dou

tcom

eassessor(s)

Valid,reliable

measures

Leng

thof

follow-up

Missing

outcom

esMissing

harm

s/adverse

even

ts

Missingconfound

ing

variables

Overall

quality

ratin

g

Walston

Z&

Yake

D,2016

[34]

Interrup

ted

timeseries

(with

out

comparison

)

Mechanical

Low

Back

Pain

(n=3)

Improvem

ent

MT

NA

NA

NA

Hno

tblinde

dU-PNprop

erty

measuremen

tsno

tfully

evaluatedfor

children

Hno

tconsistent

Lall

outcom

esdiscussed

Ladverse

even

tsrepo

rted

U-PNinform

ation

notconsistently

collected

Medium

Hayde

nJ,

etal.2003[36]

Before-after

MechanicalLow

Back

Pain

(n=54)

Improvem

ent

CMT

NA

NA

NA

Hno

tblinde

dU-PNprop

erty

measuremen

tsno

tfully

evaluatedfor

children

Lconsistent

U-PNno

tallcases

collected

H adverse

even

tsno

trepo

rted

U-PYretrospe

ctive

data,information

notconsistently

collected

Medium

Respiratory

DegenhardtB

&KucheraM,

2006

[45]

Before-after

Otitismed

ia(n

=8)

Improvem

ent

OMT/CST

NA

NA

NA

Hno

tblinde

dU-PNprop

erty

measuremen

tsno

tfully

evaluatedfor

children

Lconsistent

Lall

outcom

esdiscussed

H adverse

even

tsno

trepo

rted

U-PNnaturalcou

rse

ofOM

diagno

sis,

differences

inAOM

andOM,d

ietary

considerations

Medium

ZhangJQ

&Snyder

BJ,

2004

[46]

Before-after

Otitismed

ia(n

=22)

Improvem

ent

CMT

NA

NA

NA

Hno

tblinde

dU-PNprop

erty

measuremen

tsno

tfully

evaluatedfor

children

Hno

tdiscussed

Lall

outcom

esdiscussed

Ladverse

even

tsrepo

rted

Hseveralconfounding

varaiblesmissing

Medium

SpecialN

eeds

Bram

ati-

Castellarin

I,etal.2016

[49]

Interrup

ted

timeseries

(with

out

comparison

)

Autism

(n=49)

Improvem

ent

VOMT

NA

NA

NA

Hno

tblinde

dU-PNprop

erty

measuremen

tsno

tfully

evaluatedfor

children

Lfollow

upconsistent

Lall

outcom

esdiscussed

H adverse

even

tsno

trepo

rted

U-PYno

tall

confou

ndingvariables

know

n

Medium

Structural

LessardS,

etal.2011

[59]

Before-after

Cranialasym

metry

(non

syno

stotic

plagioceph

aly)

(n=12)

Improvem

ent

OMT

NA

NA

NA

Lblinde

dU-PNprop

erty

measuremen

tsno

tfully

evaluatedfor

children

Lfollow-up

consistent

Lall

outcom

esdiscussed

H adverse

even

tsno

trepo

rted

U-PNnaturalcou

rse

Medium

Byun

S&

Han

D,

2016

[61]

Before-after

Scoliosis(n

=5)

Improvem

ent

CMT

NA

NA

NA

Hno

tblinde

dLCob

bangle

Lfollow-up

consistent

Lall

outcom

esdiscussed

H adverse

even

tsno

tdiscussed

Hconfou

nding

variables

not

accoun

tedfor,no

men

tionof

natural

course

Medium

MorningstarM

,etal.2004

[63]

Before-after

Scoliosis(n

=6)

Improvem

ent

CMT

NA

NA

NA

Hno

tblinde

dLCob

bangle

Hleng

thof

follow-upsim

ilar

butsom

epatientshad

received

prior

Lall

outcom

esdiscussed

H adverse

even

tsno

trepo

rted

Hconfou

nding

variables

not

accoun

tedfor,no

men

tionof

natural

course

Low

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 13 of 38

Table

5Qualityratin

gof

observationalstudies

(Con

tinued)

Autho

r/year

Stud

yde

sign

type

Con

ditio

nsample

size

(n)

Result

summary

Interven

tion

Includ

e/exclud

eRecruitm

ent

strategy

Com

parison

selection

Blinde

dou

tcom

eassessor(s)

Valid,reliable

measures

Leng

thof

follow-up

Missing

outcom

esMissing

harm

s/adverse

even

ts

Missingconfound

ing

variables

Overall

quality

ratin

g

treatment

LantzC&

Che

nJ,

2001

[64]

Before-after

Scoliosis(n

=42)

No

improvem

ent

CMT

NA

NA

NA

Lblinde

dLCob

bangle

Hfollow-upno

tconsistent

Lall

outcom

esdiscussed

H adverse

even

tsno

trepo

rted

Hconfou

nding

variables

missing

,no

men

tionof

natural

course

Medium

Saed

tE,

etal.2018

[67]

Before-after

Upp

ercervical

dysfun

ction

(n=307)

Improvem

ent

MT

NA

NA

NA

Lblinde

dU-PNprop

erty

measuremen

tsno

tfully

evaluatedfor

children

Lfollow-up

consistent

Lall

outcom

esdiscussed

Ladverse

even

tsdiscussed

U-PYno

tall

confou

ndingvariables

know

n

High

Lege

nd:H

-Highriskof

bias;L-Low

riskof

bias;N

A-Not

applicab

le;U

-Unclear;P

N-Proba

blyNo(highriskof

bias);PY

-Proba

blyYe

s(lo

wriskof

bias)

Interven

tions:C

MTChiropractic

Man

ipulativeTh

erap

y,CS

TCraniosacralT

herapy

,MTMan

ualT

herapy

,OMTOsteo

pathicMan

ipulativeTh

erap

y

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 14 of 38

Table

6Dataextractio

nforthegastrointestinal/urin

arystud

ies

Con

ditio

nAutho

r/year

Stud

yob

jective

Stud

yde

sign

Samplesize

Interven

tion

Patient

descrip

tion/

cond

ition

Prim

ary/

mainou

tcom

e(s)

Mainresults/conclusion

sAdverse

even

ts

Con

stipation

Tarsuslu

T,et

al.

2009

[18]

Investigatepo

tentialeffects

ofosteop

athictreatm

enton

constip

ationin

childrenwith

cerebralpalsy.

Interrup

tedTime

Series(with

comparison

grou

p)n=13

OMT

Childrenwith

CP,ages

2–16,w

ithconstip

ation

Defecationfre

quen

cy,g

ross

motor

functio

nclassification

system

,Mod

ified

Ashworth

scale,functio

nalind

epen

dence

measure

forchildren,

constip

ationassessmen

tscale,visualanalog

scale

Both

grou

psshow

edsign

ificant

change

sfro

mallb

aseline

measuresat

3mos.

Therewas

nomen

tionof

adverse

even

tsmadein

this

stud

y.

Infantile

Colic

Miller

JE,

etal.2012[19]

Two-fold:1.D

etermineefficacy

ofchiro

practic

manipulation

therapyforinfantswith

colic;

and

2.Parentalrepo

rtingbias.

RCT

n=104

CMT

Infants<8weeks,

diagno

sedwith

colic

Decreased

crying

(asassessed

byparent

questio

nnaire

and

24hcrying

diary)

1.Greater

decrease

incrying

incolicky

infants

treatedwith

CMT

comparedto

infants

who

wereno

ttreated.

2.Unlikelythat

observed

treatm

enteffect

isdu

eto

bias

onpartof

repo

rtingparent.

One

patient

inthe

controlg

roup

noted

increasedcrying

.

WibergK&

WibergJ,2010

[20]

Investigateiftheou

tcom

eof

excessivelycrying

infants

treatedwith

chiro

practic

manipulationisassociated

with

age.

Interrup

tedTime

Series(with

out

comparison

grou

p)n=749

CMT

Health

y,thrivinginfants,

ages

0–3mon

ths,who

fitdiagno

sticcriteria

ofinfantile

colic

Parent

repo

rtof

crying

:classifiedas

“improved

”,“uncertain

recovery”,“non

recovered”

Noapparent

link

betw

eenclinicaleffect

ofchiro

practic

treatm

ent

andanaturalcrying

patternwas

foun

d,Slightlyolde

ragewas

foun

dto

belinkedto

crying

infantswith

clinicalim

provem

ent

Therewas

nomen

tionof

adverse

even

tsmadein

this

stud

y.

Brow

ning

M&

Miller

J,2008

[21]

Tocompare

chiro

practic

manualthe

rapy

and

occipital-sacrald

ecom

pression

inthetreatm

entof

infant

colic.

RCT

n=43

CMT

Infants<8weeks,w

hocriedmorethan

3ha

dayforat

least4of

theprevious

7days

Chang

ein

grou

pmean

daily

hoursof

crying

(recorded

incrying

diary)

Meanho

ursof

crying

weresign

ificantly

redu

cedin

both

groups.Bothtreatments

appearto

offerb

enefits

toinfantswith

colic.

Therewas

nodifference

betweentwotreatment

approaches.

Therewas

nomen

tionof

adverse

even

tsmadein

this

stud

y.

Olafsdo

ttirE,

etal.2001[22]

Toevaluate

chiro

practic

spinalmanipulation

managem

enton

infantile

colic.

RCT

n=86

CMT

Infantsages

3–9weeks,

diagno

sedwith

infantile

colic

24hdiaryof

infant’s

crying

(cryingdiary)

completed

byparent;

Parent

repo

rtof

effect

afterlastvisit(8–14days

later)

Nodifferencebe

tween

grou

pswith

either

outcom

e.

Therewas

nomen

tionof

adverse

even

tsmadein

this

stud

y.

Hayde

nC&

Mullinge

rB,

2006

[23]

Tode

term

inetheim

pact

ofcranialo

steo

pathyon

infantile

colic.

RCT

n=28

OMT/CST

Infants1–12

weeks,w

ithsign

sof

infantile

colic

that

includ

ed;90min/

24h.of

inconsolable

crying

on5ou

tof

7days

andadditio

nal

Parentsrecord

oftim

espen

tcrying

and

sleeping

ina24-h

diary

Nobe

tweengrou

pcomparison

sdo

ne.

Whilebo

thgrou

ps,

demon

strated

decreases,

onlytheOMT/CST

Therewas

nomen

tionof

adverse

even

tsmadein

this

stud

y.

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 15 of 38

Table

6Dataextractio

nforthegastrointestinal/urin

arystud

ies(Con

tinued)

Con

ditio

nAutho

r/year

Stud

yob

jective

Stud

yde

sign

Samplesize

Interven

tion

Patient

descrip

tion/

cond

ition

Prim

ary/

mainou

tcom

e(s)

Mainresults/conclusion

sAdverse

even

ts

clinicalsign

ssuch

asbo

rborygmi,knees

draw

nup

tochest,fists

clen

ched

,backw

ard

bend

ingof

head

ortrun

k

grou

phadsign

ificant

redu

ctionfortim

espen

tcrying

and

sleeping

.

Pediatric

dysfun

ctional

voiding

Nem

ettD,etal.

2008

[24]

Tode

term

inewhe

ther

manualp

hysicalthe

rapy-

osteop

athicapproach

adde

dto

standard

treatm

ent

improves

dysfun

ctional

voidingmoreeffectively

than

standard

treatm

ent

alon

e.

RCT

n=21

OMT

Childrenages

4–11,

diagno

sedwith

dysfun

ctionalvoiding

andsymptom

sof

daytim

eincontinen

ceandor

vesicoureteral

reflux

Improved

dysfun

ctional

voidingsymptom

s;1.im

proved

orresolved

vesicoureteralreflux

2.elim

inationof

post-void

urineresidu

als

Results

sugg

estthat

manualp

hysical

therapy-osteop

athic

approach

treatm

ent

canim

proveshort-term

outcom

esin

children

with

dysfun

ctional

voiding,

beyond

improvem

entsob

served

with

standard

treatm

ents.

Therewas

nomen

tionof

adverse

even

tsmadein

this

stud

y.

Nocturnal

Enuresis

vanPo

ecke

A&

Cun

liffe

C,2009[25]

Toevaluate

theeffect

ofchiro

practic

treatm

enton

thewet

nigh

tfre

quen

cyof

patientswith

nocturnal

enuresis.

Before-After

n=33

CMT

Childrenages

3–18,

diagno

sisof

nocturnalenu

resis

Diary

ofwet

nigh

tfre

quen

cy,d

iurnal

urinaryou

tput

66.6%

resolutio

nrate

with

in1year,ind

ication

forpo

ssibleeffectiven

ess

ofchiro

practic

treatm

ent

(Neuroim

pulseinstrumen

t)in

patientswith

prim

ary

nocturnalenu

resis.

Therewas

nomen

tionof

adverse

even

tsmadein

this

stud

y.

Subo

ptim

alinfant

breastfeed

ing

Miller

J,et

al.

2009

[26]

Tode

term

inetheeffect

ofchiro

practic

manipulative

therapyon

infantswho

had

difficulty

breastfeed

ing.

Before-After

n=114

CMT

Infantsages

2days

-12

weeks

diagno

sed

bymed

icalprovider

with

feed

ingdifficulties

Mothe

r’srepo

rtof

exclusivity

ofbreastfeed

ing,

ratin

gof

improvingand

infant

weigh

tgain

Exclusivelyof

breastfeed

ing

was

accomplishe

din

78%.

None

gativeside

effectswere

repo

rted

.

Vallone

S,2004

[27]

Toinvestigateprob

lems

interfe

ringwith

successful

breastfeed

ingandto

seeif

prop

erlactation

managem

entcanincrease

thebo

ndingexpe

rience.

Before-After

n=25

CMT/CST

Infantsages

5days

-12

weeks,referredby

othe

rhe

althcare

providersas

having

difficulty

breastfeed

ing

Improvem

entin

ability

tolatchand

ability

tobreastfeed

>80%ofinfantsexperienced

improvem

entinlatchand

abilityto

breastfeed.

Therewas

nomen

tionof

adverse

even

tsmadein

this

stud

y.

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 16 of 38

on infantile colic in 28 infants was conducted by Haydenet al. These researchers found a reduction in cryingtimes (63%), improved sleeping (11%), and a need forless parental attention. Due to the favorable findings ofthis study, the researchers suggested that a larger scalestudy is warranted. There was no mention of adverseevents made in this study [23].Overall Summary:Inconclusive (unclear) for CMT in treating infantile

colic.Inconclusive (favorable) for OMT/CST in treating

infantile colic.

1.3.Pediatric dysfunctional voiding

A medium quality RCT sought to determine whetherOMT in addition to standard treatment improved dysfunc-tional voiding in 21 children diagnosed with pediatric dys-functional voiding. Improvements in short-term outcomesin children with dysfunctional voiding were reported be-yond improvements observed with standard treatment. Nomention of adverse events were reported in this study [24].Overall Summary:Inconclusive (favorable) evidence for use of OMT plus

standard treatment to improve dysfunctional voiding.

1.4.Pediatric nocturnal enuresis

A medium quality before-after retrospective recordreview of 33 consecutive patients over a three-yearperiod found somewhat favorable results using CMT,specifically utilizing the Neuroimpulse protocol. Thechildren were between the ages 3–18 with primarynocturnal enuresis. The frequency of wet nights wasabstracted from the records at 3, 6, 9 and 12 monthsafter the commencement of treatment. The recordsfound 22 patients showed complete resolution of pri-mary nocturnal enuresis during the 12 months aftercommencement of chiropractic care. The resolutionrate was 66.6% within 1 year with the mean numberof treatments in the responder’s group being 2.05 ±1.33. There was no mention of adverse events madein this study [25].Overall Summary:Inconclusive (unclear) evidence for use of CMT to im-

prove nocturnal enuresis.

1.5.Suboptimal infant breastfeeding (SIB)

Two case series with pre and post measurements in-vestigated the use of CMT on infants with SIB [26, 27].A medium quality before-after case series investigated

the effect of CMT on 114 infants with SIB, 112 classifiedwith an ineffective suck (grades 0–2) and 2 having

excessive suck (grade 4) as objectively determined with asuck grading chart. The results of this study showed fa-vorable improvement in all the infants after four treat-ments (78% were able to exclusively breastfeed).Outcomes included the mother’s report of improvedweight gain and a specific list of historical data and clin-ical examination findings including improvements insuck reflex grading. No negative side effects were re-ported [26].A low quality before-after case series of 25 infants with

SIB set out to determine if proper lactation might increasethe bonding experience between mother and infant follow-ing CMT/CST. This study reported improvement in theability to latch after the infants received CMT (which in-cluded craniosacral treatment). The study’s authors positedCMT/CST in the early stages of neurological imprintingappear to safely and effectively address the craniocervicaldysfunction and help restore natural efficient sucking pat-terns for infants who are unable to latch. There was nomention of adverse events made in this study [27].Overall Summary:Inconclusive (favorable) evidence for use of CMT/CST

for children with SIB.

2. Musculoskeletal conditions

Table 7 summaries the 12 studies that investigated theclinical effects of manual therapy for conditions catego-rized as “musculoskeletal conditions”. One of these in-vestigated the use of manual therapy on clubfoot [28]and one on cuboid syndrome [29]. Three of these studiesinvestigated the use of manual therapy for headaches[30–32], four for low back pain [33–36], two investigatedpulled elbow [37, 38], and one study for temporoman-dibular (TMD) dysfunction [39].

2.1.Clubfoot

One study was found that investigated the use of MTon patients with clubfoot [28].A low quality RCT conducted by Nilgun et al. investi-

gated the effectiveness of intensive physical therapy (in-cluding mobilization technique) as an adjunct to Ponsetitechnique in 29 children (average age 15–12months) withidiopathic clubfoot. Using the Dimeglio classification sys-tem they reported a statistically significant improvementin the group that received both MT and the Ponseti tech-nique combined. The study group received the interven-tion once per day, 5 days a week for 1month. There is nomention of adverse events made in this study [28].Overall Summary:Inconclusive (favorable) evidence for the use of MT

combined with Ponseti technique in children withclubfoot.

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 17 of 38

Table

7Dataextractio

nforthemusculoskeletalstud

ies

Con

ditio

nAutho

r/year

Stud

yob

jective

Stud

yde

sign

samplesize

interven

tion

Patient

descrip

tion/

cond

ition

Prim

ary/mainou

tcom

e(s)

Mainresults/con

clusions

Adverse

even

ts

Clubfoo

tNilgun

B,et

al.2011[28]

Tode

term

ineefficacyof

physicaltherapy,includ

ing

manualm

obilizatio

n,as

adjunctto

Ponsetitechn

ique

inidiopathicclub

foot.

RCT

n=29

MT

Childrenages

3and

unde

r,Dim

eglio

Score

of17

orun

derwith

idiopathicclub

foot

Improvem

entsin

passive

rang

esof

motionfor

plantarflexion

,inversion

,eversion

,rearfoot

varus

angleandforefoot

addu

ctionangleand

decrease

inDim

eglio

Score

Treatm

entprocured

astatisticallysign

ificant

improvem

entsin

rang

esof

motion,

Dim

eglio

Scoreand

decrease

ofrear

foot

varusanglein

the

stud

ygrou

p.

Thereisno

men

tion

ofadverseeven

tsmadein

thisstud

y.

Cub

oidSynd

rome

Jenn

ings

J&DaviesD,

2005

[29]

Describetheexam

ination

andtreatm

entof

the

cubo

idsynd

romefollowing

lateralanklesprain.

Interrup

ted

TimeSeries

(with

comparison

grou

p)n=2

MT

7patientsagerang

e15–36(2

pediatric

patientscanbe

isolated

),with

cubo

idsynd

rome

VisualAnalogScale:

Pre-

andpo

st-treatmen

tAllpatientshad

substantialresolution

ofsymptom

sfollowing

cubo

idmanipulation.

Thereisno

men

tion

ofadverseeven

tsmadein

thisstud

y.

Headache

PrzekopP,

etal.2016

[30]

Evaluate

andcompare

amultim

odalwith

pharmacolog

ictreatm

entforthe

preven

tionof

chronic

tensiontype

headache

s(CTTH)inadolescents.

Before-Afte

rn=83

OMT

Childrenages

13–18,

diagno

sedwith

CTTH

5maineffects:he

adache

frequ

ency,p

ainintensity,

gene

ralh

ealth

,pain

restrictio

nandnu

mbe

rof

tend

erpo

ints

Both

approaches

show

edsign

ificant

improvem

entsacross

all5

maineffects

outcom

es,b

utmultim

odal

treatm

ents

prod

uced

more

favorableresults

inhe

adache

frequ

ency,

gene

ralh

ealth

,and

numbe

rof

tend

erpo

ints.

Thereisno

men

tion

ofadverseeven

tsmadein

thisstud

y.

Borusiak

P,et

al.2010[31]

Toinvestigatethe

efficacyof

spinal

manipulativetherapy

inadolescentswith

recurren

the

adache

.

RCT

n=52

MT

Ado

lescen

tsages

7–15,w

ithcervicog

enic

headache

Assessm

entof;p

ercentage

ofdays

with

headache

,total

duratio

nof

headache

,days

with

scho

olabsencedu

eto

headache

,con

sumption

ofanalge

sics,and

intensity

ofhe

adache

Nodifferencein

any

outcom

emeasure

betw

eenplaceb

oandcervicalspine

manipulation.

Noserious

ormod

erate

adverseeventswere

noted.Minor

adverse

eventsoccurredinbo

thgrou

psthatinclud

ed;

hotskinin15

patients

(treatm

entg

roup

6,placebo9),dizziness

in11

patients(treatm

ent

grou

p7,placebo4).

Therewas

repo

rted

transitoryincrease

inheadache

intensity

and

frequ

ency

being

repo

rtedforu

pto

4days

(treatm

ent

grou

p8,placebo6).

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 18 of 38

Table

7Dataextractio

nforthemusculoskeletalstud

ies(Con

tinued)

Con

ditio

nAutho

r/year

Stud

yob

jective

Stud

yde

sign

samplesize

interven

tion

Patient

descrip

tion/

cond

ition

Prim

ary/mainou

tcom

e(s)

Mainresults/con

clusions

Adverse

even

ts

MarchandA,

etal.2009[32]

Toconducta

retro

spective

filesearch

ofinfants

presentingwith

probable

benign

infantile

headache

atachiropractic

teaching

clinic.

Before-Afte

rn=13

CMT

Childrenages

2days

-8.5mon

ths,with

benign

infant

headache

Redu

ctionin

behavioral

finding

srecorded

verbatim

byparentssuch

as;g

rabb

ing

holdingface,ine

ffective

latching

,grim

acingand

positio

nald

iscomfort,rapping

head

againstfloor,p

hotoph

obia,

andanorexia.

All13

consecutive

caseshadfavorable

results

basedon

parent

repo

rtof

outcom

es.

Thereisno

men

tion

ofadverseeven

tsmadein

thisstud

y.

Low

Back

Pain

EvansR,et

al.

2018

[33]

Tocompare

12weeks

ofchiro

practic

manipulativetherapy

combine

dwith

exercise

therapyto

exercise

therapyalon

ein

the

treatm

entof

chronic

lower

back

pain

inchildren.

RCT

n=185

CMT

Childrenages

12–18,

with

chroniclower

back

pain

Prim

aryou

tcom

e-self-repo

rted

levelo

flow

back

pain

(11bo

xnu

mericalratin

gscale),Secon

dary

outcom

es-patient-rated

disability

(18item

Roland

-Morris

Disability

questio

nnaire),qu

ality

oflife(23

item

PedsQL),improvem

ent

(9-point

scale),frequ

ency

ofmed

icationuseforlow

back

pain

(days/week),p

atient

satisfactionwith

care

(7-point

scale)

Chiropractic

manipulative

therapyplus

exercise

resultedinlarger

reductioninprimary

outcom

eofpainseverity

overthecourse

of1year.

Side

effectswere

similarin

both

grou

ps,

mild

andself-lim

iting

andoccurred

ata

frequ

ency

comparable

toadultpo

pulatio

n.

Walston

Z&

Yake

D,2016

[34]

Toillustratethefeasibility

andsafety

oflumbar

manipulationas

anadjunctto

exercise

for

treatm

entof

adolescent

popu

latio

nwith

mechanicallow

back

pain.

Interrup

ted

TimeSeries

(with

out

comparison

grou

p)n=3

MT

Ado

lescen

tsages

13–15,with

mechanicallow

back

pain

Pain

measuredon

numerical

pain

ratin

gscaleanddisability

(Osw

estry)foreach

patient

Allou

tcom

eshow

edim

provem

ents(0/10

onnu

mericscaleand

0%in

theOsw

estry

disabilityinde

x)for

each

patient.

Noadversereactio

nswererepo

rted

orob

served

with

any

episod

eof

manipulation.

SelhorstM

&SelhorstB,

2015

[35]

Toassess

efficacyof

lumbarmanipulation

inadditio

nto

a4-week

physicaltherapyexercise

prog

ram.

RCT

n=35

MT

Ado

lescen

tsages

13–17,with

mechanicallow

back

pain

of<90

days

Patient

SpecificFunctio

nalScale,

pain

(11-po

intNum

ericalPain

Ratin

gScale),and

Global

Ratin

gof

Chancescales

Nodifferencebe

tween

grou

psforPatient

SpecificFunctio

nal

Scale,pain,orGlobal

Ratin

gof

Chance

scales.A

llpatients

improved

.

Twopatientsin

both

thesham

and

manipulationgrou

phadan

adverse

reactio

nat

1week.

Nopatientsin

either

grou

psrepo

rted

adversereactio

nsat

either

4weeks

or6mon

ths.They

conclude

dthat

noadditio

nalriskof

having

anadverse

reactio

nwereno

ted

inthisstud

y.

Hayde

nJ,

etal.2003[36]

Tode

scrib

echiro

practic

managem

ent,ou

tcom

es,

andfactorsassociated

Before-Afte

rn=54

CMT

Childrenages

4–18,w

ithacute

mechanicallow

Subjectiveassessmen

tof

improvem

enton

a5-po

int

ratin

gscale(Ped

iatricVisual

Overacourse

of4–6weeksofchiropractic

managem

ent,55–62%

Com

plications

from

chiro

practic

patient

managem

entwere

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 19 of 38

Table

7Dataextractio

nforthemusculoskeletalstud

ies(Con

tinued)

Con

ditio

nAutho

r/year

Stud

yob

jective

Stud

yde

sign

samplesize

interven

tion

Patient

descrip

tion/

cond

ition

Prim

ary/mainou

tcom

e(s)

Mainresults/con

clusions

Adverse

even

ts

with

outcom

esforlow

back

pain

inchildho

od.

back

pain

AnalogScale)

ofpatientshad

improvem

entthatm

etthestudy’s

stringent

criteria

and82–87%

had

muchimprovem

ent.

collected

with

none

notedthroug

hout

thestud

ydata

collectionpe

riod.

PulledElbo

wGarcía-MataS

&Hidalgo

-Ovejero

A,

2014

[37]

Tode

term

inethe

relativeefficacyof

two

pulledelbo

wredu

ction

maneuvers,hyper

pron

ationandsupinatio

n-flexion

.

RCT

n=115

MT

Childrenages

1–5,with

pulled

elbo

w

Redu

ctionof

pulledelbo

wverifiedby

observingactive

flexion

andextension

Both

maneuverswere

effectivewith

ahigh

erfirst-attem

ptsuccess

rate

with

hype

rpron

ation.

Thereisno

men

tion

ofadverseeven

tscollected

inthis

stud

y.

BekD,etal.

2009

[38]

Tocompare

theredu

ction

efficiencyof

hype

rpron

ationto

supinatio

n-flexion

maneuversfora

pulledelbo

w.

RCT

n=66

MT

Childrenages

1–5,with

pulled

elbo

w

Redu

ctionof

pulledelbo

windicatedby

child

using

thearm

Finalred

uctio

nrates

similar.Hyper

pron

ation

maneuverwas

more

successful

onthefirst

attempt.

Thereisno

men

tion

ofadverseeven

tscollected

inthis

stud

y.

Tempo

romandibu

lar

Disorde

rMon

acoA

etal.2008[39]

Toevaluate

theeffects

ofosteopathicmanipulative

therapyon

mandibular

kinem

aticsinpatientswith

temporomandibular

dysfu

nction.

RCT

n=28

OMT

Childrenaverage

age12,d

iagn

osed

with

TMD

Objectivemeasurespre-

andpo

st-treatmen

tusing

kine

siog

raph

ictracings

toassess

mandibu

larmovem

ent

Osteo

pathicmanipulation

madesign

ificant

improvem

entsin

maxim

almou

thop

eningandin

maxim

almou

thop

ening

velocity.

Thereisno

men

tion

ofadverseeven

tsmadein

thisstud

y.

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 20 of 38

2.2.Cuboid syndrome

One study was found that investigated the use of MTon patients with cuboid syndrome [29].A medium quality interrupted time-series without a

comparison group described the proper examination,evaluation, and treatment of cuboid syndrome withmanual manipulation following lateral ankle sprains in 7patients aged 15–36 of which 2 children met our inclu-sion (ages 15 and 16). Using visual analog scales pre andpost treatment Jennings et al. reported patients’ subject-ive pain at rest, during palpation, during midtarsal mo-bility testing, with gait, and with single-leg hop. Bothchildren were diagnosed with this condition and re-ceived a cuboid manipulation. They each required onlyone treatment and were able to return to competitive ac-tivity with one treatment without injury recurrence.There is no mention of adverse events made in thisstudy [29].Overall Summary:Inconclusive (unclear) evidence for MT in patients

with cuboid syndrome.

2.3.Headache

Three studies investigated the use of manual therapy onpediatric headaches. One medium quality before-afterstudy investigated the use of OMT on chronic ten-sion-type headaches in adolescents [30]. One mediumquality RCT that was stopped early (before recruit-ment goal based on interim analysis) evaluated theclinical effectiveness of MT [31]. One low qualityretrospective case series with pre and post measure-ments looked at the CMT [32].Przekop et al. conducted a medium quality before-after

observational study that compared multimodal (OMT)and pharmacologic effects on chronic tension-type head-aches (CTTH). This study included 83 patients, (67 fe-males and 16 males), between the ages of 13 and 18.Outcome measures included: headache frequency, painintensity, general health, pain restriction and the numberof tender points as found by the provider. They reportedthat both multimodal and pharmacologic treatments wereeffective for CTTH; however, results from multimodaltreatment produced more favorable results in headachefrequency, general health and in the number of tenderpoints elicited. There was no mention of adverse events inthis study [30].Borusiak et al. conducted a medium quality RCT com-

paring the use of cervical MT to a sham MT in 56 chil-dren with cervicogenic headaches. Of these, data sets of52 children were analyzed (mean age 11.6 years). Out-comes included: percentage of days with a headache,total duration of headache in hours, percentage of days

missing school, percentage of days with necessity of an-algesic medication, and intensity of headache based on a10-point numerical analog scale. No significant differ-ence was reported for any outcome measure. They didnote that baseline and follow-up frequency of days withheadache was reduced in both groups however, the dif-ferences were not significant. Minor adverse events oc-curred in both groups with no serious or moderateadverse events reported [31].Marchand et al. conducted a low quality before-

after case series that investigated the effects CMT for13 infants (aged 2 days to 8.5 months) with probablebenign infant headache. Outcome measures werechanges noted in behavioral findings as reportedverbatim by parents including: less grabbing orholding of the face, improved latching, less grimacingand positional discomfort, less rapping of the headagainst the floor and less photophobia and anorexia.They reported that all of the patients responded fa-vorably to CMT and that a therapeutic trial is war-ranted. There is no mention of any adverse events inthis article [32].Overall Summary:Inconclusive (unclear) for the use of OMT for chronic

tension-type headaches in adolescents, for the use of MTfor cervicogenic HA, and for the use of CMT for benigninfant headache.

2.4.Low back pain (LBP)

Four studies investigated the use of manual therapy forLBP in the pediatric population. Two studies looked at theuse of CMT; one high quality RCT, the other a mediumquality before-after study [33, 36]. The other two lookedat the use of MT; a medium quality interruptedtime-series, the other a medium quality RCT [34, 35].Evans et al. presented a high quality RCT with a compari-

son group between CMT with exercise against solely focus-ing on exercise therapy. The patients included a rangeof ages between 12 and 18 years, concluding with 185total patients. They concluded that adolescentsshowed that by adding CMT with exercise therapy,resulted in a larger reduction in the primary outcome(visual analog scale) of pain severity over the courseof 1 year. The study reported minor self-limiting ad-verse events that were about equal frequency in bothgroups [33].Walston and Yake conducted a medium quality

interrupted time- series without a comparison groupof 3 patients (age range 13 through 15). They showedfeasibility and safety of lumbar manipulation with ex-ercise in the adolescent population with LBP. Patientcentered outcomes used included: subjective painmeasured on a numeric pain rating scale and the use

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 21 of 38

of Oswestry disability index. All outcomes showedimprovement for all patients with no adverse reac-tions to manipulation [34].The medium quality RCT of 35 patients (age range

13–17, mean 14.9 years) with mechanical LBP of lessthan 90 days, was conducted to evaluate the clinical ef-fects of MT in addition to an exercise program. Eighteenchildren received MT and 17 received a sham manipula-tion, which consisted of the child lying on their side anda therapist passively flexing both hips until slight lumbarflexion. Patient centered outcomes utilized included, Pa-tient Specific Functional Scale and Numerical Pain Rat-ing Scale. Global Rating of Change scales was used toevaluate perceived improvement. Both groups of patientsreported improvements in LBP. The authors reportedthat there was no additional risk for lumbar manipula-tion, as both groups reported the same number of ad-verse events [35].Hayden et al. conducted a medium quality before-

after cohort study without a control group that investi-gated the effectiveness of CMT for LBP for 54 patientsranging in age between 4 and 18 years. They reportedthat the majority of the patients responded favorablyand there were no reported adverse events. The re-searchers were quick to point out that a causal relation-ship between CMT and improvements in pediatric LBPcould not be established due to both the small study sizeand the observational design of the study itself. Compli-cations from chiropractic patient management were col-lected with none noted throughout the study datacollection period [36].Overall Summary:Moderate (positive) evidence for the use of CMT for

adolescent LBP.Inconclusive (unclear) evidence for the use of MT for

pediatric mechanical LBP.

2.5.Pulled (nurse’s) elbow

Two RCTs met our inclusion criteria and investi-gated the effectiveness of two MT maneuvers for thereduction of pulled elbow. It is important to pointout that both of these studies compared two differenttypes of manipulation and both show favorable resultson pulled elbow [37, 38].A medium quality RCT of 115 patients (mean age 2.3

years old) was conducted by Garcia-Mata et al. andsought to determine which procedure was the most ef-fective to reduce a pulled elbow. There were 65 patientsallocated to the hyper pronation group and 50 in thesupination-flexion group. The hyper pronation groupwas found to be more efficient on reduction at the firstattempt. There is no mention of adverse events made inthis study [37].

A medium quality RCT compared the efficiency ofhyper pronation and supination flexion maneuvers inthe reduction of pulled elbow on 66 children (34 hyperpronation-flexion and 32 supination-flexion) with anaverage age of 28 months. Successful reduction was con-sidered by the observation of the child being able to usethe arm after the reduction. Although the authors con-cluded that final reduction rates were similar in bothgroups they found that the hyper pronation maneuverwas more efficient on the first attempt. There is no men-tion of adverse events made in this study [38].Overall Summary:Moderate (positive) evidence for use of CMT/CST for

children with SIB.

2.6.Temporomandibular dysfunction (TMD)

One study was found that investigated the use ofOMT for TMD dysfunction [39].A low quality RCT conducted by Monaco et al. evalu-

ated the effects of OMT on mandibular kinematics in 28children diagnosed with non-specific temporomandibu-lar disorders. Kinesiographic tracings using K71 mea-sured mandibular incisor-point movement in threedimensions was the only outcome assessed. The resultsof this study showed a significantly statistical improve-ment in the maximal mouth opening velocity in thestudy group. It was reported that the use of OMT im-proved non-specific TMD. There is no mention of ad-verse events made in this study [39].Overall Summary:Inconclusive (favorable) evidence for OMT in

pediatric TMD.

3. Respiratory and eyes, ears, nose, and throat (EENT)conditions

Table 8 summarizes the eight studies that investigatedrespiratory, EENT conditions. In total, there were twostudies that investigated children with asthma [40, 41],one study that investigated children with obstructiveapnea [42], and five studies investigated children withotitis media [43–47].

3.1.Asthma

Two studies were identified that investigated the useof manual therapy for the treatment of pediatric asthma.One study was a medium quality and investigated OMT[40]. The other study was a high quality pilot RCT andinvestigated CMT [41].Guiney et al. conducted a medium quality RCT and re-

ported favorable results with the use of OMT in 140 pa-tients (90 treatment group, 50 control group), ages 5–17

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 22 of 38

Table

8Dataextractio

nforrespiratory

stud

ies

Con

ditio

nAutho

r/year

Stud

yob

jective

Stud

yde

sign

samplesize

interven

tion

Patient

descrip

tion/

cond

ition

Prim

ary/mainou

tcom

e(s)

Mainresults/con

clusions

Adverse

even

ts

Asthm

aGuine

yP,

etal.2005[40]

Tode

mon

strate

the

therapeutic

relevanceof

osteop

athicmanipulationin

thepe

diatric

asthma

popu

latio

n.

RCT

n=140

OMT

Childrenages

5–17,d

iagn

osed

with

asthmaby

guidelines

from

NIH

Peak

Expiratory

Flow

Rates

Therewas

statistically

sign

ificant

improvem

ent

of7Lpe

rminuteto

9L

perminuteforpe

akexpiratory

flow

ratesin

thetreatm

entgrou

p.

Therewas

nomen

tionof

adverse

even

tsmadein

thisstud

y.

Bron

fortG,

etal.2001[41]

Tode

term

ineifchiro

practic

manipulativetherapyin

additio

nto

optim

almed

ical

managem

entresultedin

clinicallyim

portantchange

sin

asthma-relatedou

tcom

es.

RCT

n=34

CMT

Childrenages

6–17,w

ithpe

rsistent

asthma

Pulm

onaryfunctio

ntests,

diaryrecordingpe

akexpiratory

flow

andinhaler

use,qu

estio

nnaires

assessingqu

ality

oflife,

asthmaseverityand

improvem

ent

Littleto

nochange

inpu

lmon

aryfunctio

ntestsat

12weeks

and

nochange

inpatient,

parent/guardianor

pulm

onolog

istrated

improvem

ent

Therewas

nomen

tionof

adverse

even

tsmadein

thisstud

y.

Obstructive

Apn

eaVand

enplas

Y,et

al.2008[42]

Toevaluate

ifosteop

athy

can

influen

cetheincide

nceof

obstructiveapne

adu

ringsleep

ininfants.

RCT

n=34

OMT

Infantsaged

1.5–4

mon

ths,with

obstructiveapne

aas

determ

ined

bya po

lysomno

graphic

test

Decreasein

thenu

mbe

rof

obstructiveapne

asas

measuredby

polysomno

graphy.

Infantsaged

1.5–4mon

ths,

with

obstructiveapne

aas

determ

ined

bypo

lysomno

graphic

Therewas

nomen

tionof

adverse

even

tsmadein

thisstud

y.

OtitisMed

iaSteeleD,

etal.2014[43]

Toevaluate

theefficacyof

anosteop

athicmanipulative

treatm

entprotocol

onmiddle

eareffusion

resolutio

nfollowingacuteotitismed

ia.

RCT

n=52

OMT

Infant

ages

6–24

mon

ths,with

acute

otitismed

iaand

abno

rmal

tomog

ram

Tympano

meter

and

acou

sticreflectom

eter

Both

tympano

meter

data

andacou

stic

reflectom

eter

analysis

demon

stratedsign

ificantly

sign

ificant

improvem

ent

inmiddleeareffusion

atvisit3in

thestandard

care

plus

osteop

athic

treatm

entgrou

p.

Therewereno

serio

usadverseeven

tsrepo

rted

durin

gthestud

y.

WahlR

,etal.

2008

[44]

Toassess

theefficacyof

Echinaceaandosteop

athic

manipulativetreatm

entfor

preven

tingacuteotitismed

ia.

RCT

n=90

OMT

Childrenaged

12–

60mon

ths,with

recurren

totitis

med

ia

Redu

ctionin

future

episod

esof

OM

Nointeractionwas

foun

dbe

tweenEchinaceaand

osteop

athicmanipulation.

Echinaceawas

associated

with

abo

rderlineincreased

riskof

having

atleaston

eep

isod

eof

acuteotitis

med

iadu

ring6-mon

thfollow-upcomparedto

placeb

o.Osteo

pathic

manipulationdidno

tsign

ificantlyaffect

risk

comparedto

sham

.

“One

subjectwith

drew

from

thestud

yfollowingan

adverseeffect

(vom

iting

aftertaking

theEchinaceaplaceb

o).

One

additio

nalsub

ject

repo

rted

adverse

effects(vom

iting

andno

n-urticarialrash

2days

afterstartin

gEchinaceaforaviralu

pper

respiratory

illne

ss)bu

tdidno

twith

draw

.Neither

adverseeffect

was

considered

tohave

been

caused

bythestud

ymed

ication.

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 23 of 38

Table

8Dataextractio

nforrespiratory

stud

ies(Con

tinued)

Con

ditio

nAutho

r/year

Stud

yob

jective

Stud

yde

sign

samplesize

interven

tion

Patient

descrip

tion/

cond

ition

Prim

ary/mainou

tcom

e(s)

Mainresults/con

clusions

Adverse

even

ts

Deg

enhardtB

&Ku

cheraM,

2006

[45]

Doe

sosteop

athic

manipulationde

crease

the

recurren

ceof

otitismed

ia?

Before-Afte

rn=8

OMT/CST

Infantsages

7–35

mon

ths,with

recurren

totitis

med

ia

Decreased

incide

nce

ofacuteotitismed

ia5participantshadno

recurren

ceafter1year

follow-up.

1participanthad1

recurren

ce.2

participants

hadashort-term

ofno

recurren

ceon

ly.

Thereisno

men

tionof

adverseeven

tsmadein

thisstud

y.

ZhangJ&

Snyder

B,2004

[46]

Tostud

ytheeffect

ofToftn

ess

chiro

practic

adjustmen

tfor

acuteotitismed

ia.

Before-Afte

rn=22

CMT

Childrenages

9mon

ths−9years,

with

acuteotitis

med

ia

TympanicMem

brane

visualizationvia

otoscopicexam

and

oraltempe

rature

After

Toftne

sschiro

practic

adjustmen

t,redandbu

lging

tympanicmem

brane

returned

tono

rmalin

95%

ofchildren.Ade

crease

inaverageoraltempe

rature

was

noted.

“Duringthestud

yprotocol,noside

effectsor

deterio

ratio

nof

clinical

presen

tatio

nswerefoun

dam

ong

21childrenwith

otitismed

ia.”

MillsM,etal.

2003

[47]

Toevaluate

theeffect

ofusual

care

andosteop

athic

manipulationforchildrenwith

acuteotitismed

ia.

RCT

n=57

OMT

Childrenages

6mon

ths-6years,

with

recurren

totitismed

ia

Decreased

frequ

ency

ofacuteotitismed

ia,

antib

iotic

us,surgical

interven

tions,and

improved

tympano

metric

andaudiom

etric

perfo

rmance

Interven

tiongrou

phadfewer

episod

esof

acuteotitis

med

ia,few

ersurgical

proced

ures

andan

increased

frequ

ency

ofmoreno

rmal

tympano

gram

readings.

Therewereno

adverseeven

tsrepo

rted

durin

gthestud

y.

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 24 of 38

with asthma. The primary outcome was improved peakexpiratory flow rates. Their results show a statisticallysignificant improvement from 7 L/min to 9 L/min forpeak expiratory flow rates. No mention of adverse eventswas noted in this study [40].Bronfort et al. conducted a high quality pilot RCT

that investigated if CMT in addition to medical man-agement would result in clinically important changesin asthma-related outcomes. This study included anobservation component, but no actual data was avail-able to include in this review. Their study included34 children aged 6–17 years of age with persistentasthma. The main outcomes were determined by pul-monary technicians at baseline and at 12 weeks. Theylooked at diaries of recording peak expiratory flowand inhaler use, questionnaires assessing quality oflife, asthma severity, and improvements. They foundlittle to no change in pulmonary function tests at 12weeks and no change in patient or pulmonologistrated improvement with the use of CMT. However,Bronfort et al. did report improvement in patient-cen-tered outcomes such as quality of life, even 1 yearafter the last treatment. No mention of adverse eventswas noted in this study [41].Overall Summary:Inconclusive (favorable) for OMT in treating asthma.Inconclusive (unclear) for CMT in treating asthma.

3.2.Obstructive apnea

One study was found that investigated the use ofOMT on obstructive apnea [42].A medium quality pilot RCT by Vandenplas et al.

sought to investigate if OMT can influence the incidenceof obstructive apnea during sleep in infants. This studyof 34 infants, ages 1.5–4 months diagnosed with ob-structive apnea showed a significant decrease in thenumber of observed apnea episodes in the OMT groupcompared to the control group. The main outcome mea-sured was a decrease in the incidence of apnea with thesuggestion for additional research. No mention of ad-verse events was noted in this study [42].Overall Summary:Inconclusive (favorable) evidence for OMT in treating

obstructive apnea.

3.3.Otitis media

Five studies investigated the clinical effectiveness ofmanual therapy on otitis media that met our inclusioncriteria. Four of the studies investigated the use of OMT.Of these, two were of high quality and two were ofmedium quality [43–45, 47]. One medium quality studylooked at the use of CMT (specifically Toftness

technique) for acute otitis media [46]. All but one of theOMT studies showed favorable results on the use of MTfor acute otitis media.Steele et al. conducted a medium quality prospective,

pilot RCT (stopped before it reached its recruitmentgoal of 80 patients) that evaluated 52 infants ages 6–24months with acute otitis media and abnormal tomo-grams. The primary outcome was measured with a tym-panometer and an acoustic reflectometer. Theydetermined there was faster resolution in middle ear ef-fusion in 2 weeks with what they described as “standard-ized OMT”. There were no serious adverse eventsreported during this study [43].A high quality RCT evaluated the use of Echinacea

purpurea and OMT on 90 (84 completed the study) in-fants aged 12–60 months with recurrent otitis media.The main outcome of the study was a reduction in theincidence of recurrent otitis media. As reported inmonthly telephone interviews and at the 3- and6-month visits, there was no statistically significant dif-ference in reporting of any side effects between placeboand treatment groups for either echinacea or OMT. Oneparticipant withdrew from the study following adverseevents (vomiting after taking the echinacea placebo).One additional participant reported adverse events(vomiting and non-urticarial rash 2 days after startingechinacea for a viral upper respiratory illness) but didnot withdraw [44].A medium quality before-after cohort, practice

based study evaluated 8 infants ages 7–35 monthswith recurrent acute otitis media was undertaken byDegenhardt et al. The main outcome was a decreasedincidence of otitis media. The results of this studywere that 5 of the 8 children had no recurrence after1 year follow up, one had 1 recurrence, and 2 of the8 children had a short period of no recurrence afterreceiving OMT. In the method section of this study,the OMT used met the description of craniosacraltherapy (CST). It is also important to note that allparticipants in this study were also under concurrentmedical care. No mention of adverse events was noted inthis study [45].A medium quality study before-after case series in-

vestigated 22 children ages 9 months to 9 years withacute otitis media showed favorable results utilizingToftness chiropractic technique, a type of low forcetechnique chiropractic system. The primary outcomemeasures utilized in the study was otoscopicvisualization and oral temperature. The researchers ofthis study state that otitis media may benefit fromToftness CMT and that the data justified a clinicaltrial be undertaken. During the study, no side effectsor deterioration of clinical presentations were notedamong the pediatric participants [46].

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 25 of 38

A second high quality RCT investigated the use ofOMT for 57 children with acute otitis media. In thisstudy, Mills et al. grouped 25 participants into the treat-ment group that received OMT in addition to routinepediatric care and 32 subjects in the control group whoreceived only routine pediatric care. The average agewas 26months in the treatment group and 20 months inthe control group. Decreased symptoms and improvedtympanogram scores were only reported in the OMTgroup. The researchers stated there were no adverseevents reported during the study [47].Overall Summary:Inconclusive (favorable) evidence for OMT in treating

acute otitis media.Inconclusive (unclear) evidence for CMT (Toftness

technique) in treating acute otitis media.

4. Special needs

Table 9 summarizes the ten studies investigating theuse of manual therapy for pediatric conditions catego-rized as special needs that met our inclusion criteria.One study investigated OMT on children with AttentionDeficit Hyperactive Disorder (ADHD) [48], two studiesinvestigated the use of manual therapy for autistic chil-dren [49, 50], (one used VOMT and the other usedCMT). Three studies investigated the use of OMT onchildren with cerebral palsy [51–53] and four of thestudies investigated the use of OMT on premature in-fants [54–57].

4.1.Attention deficit hyperactive disorder (ADHD)

One study was found that investigated the use ofOMT on patients with ADHD [48].Accorsi et al. conducted a high quality RCT evaluat-

ing the efficacy of OMT in the treatment of 28 childrenages 5 to 15 years old with ADHD. One half of the par-ticipants (n = 14) were placed in a treatment group,which received OMT plus conventional treatment, andone half of participants (n = 14) were placed in the con-trol group, receiving conventional therapy alone. Theoutcome measures were better accuracy and rapidityscores on the Biancardi-Stroppa Modified Cancellationtest, a test that is used to measure visual-spatial atten-tion. Accorsi et al. reported the children in the inter-vention group demonstrated statistically significantimprovement in selective and sustained attentive per-formances, as measured using the Biancardi-StroppaModified Cancellation Test. These findings promptedthe researchers to recommend a larger study be under-taken. There is no mention of adverse events in thisstudy [48].Overall Summary:

Inconclusive (favorable) evidence for OMT in treatingADHD in children.

4.2.Autism

Two studies were found that investigated the use ofmanual therapy on patients with autism. One looked atthe use of visceral osteopathic manual therapy (VOMT)the other CMT [49, 50].A medium quality interrupted time-series without

comparison was conducted by Bramati-Casterllarian etal. They investigated the influence of VOMT on behav-ior and GI symptoms on children with autism. Theirstudy included 49 autistic children ages 3 1/2 to 8 yearsof age with GI symptoms and impaired social interac-tions and communication. The primary outcome meas-ure they utilized was parental completion of theModified Autism Research Institute survey and secretinassessment to assess the GI signs and symptoms. Overallsignificant symptomatic improvement for social behav-iors and communication, as well as improvement in di-gestive issues such as vomiting and poor appetite, werereported. They concluded VOMT could have a signifi-cant improvement in quality of life and well-being forchildren suffering from both autism and GI signs andsymptoms. There was no mention of adverse eventsmade in this study [49].A low quality RCT without a control group intended

to identify the differences in efficacy between UpperCervical CMT and Full Spine (Diversified) CMT in 14autistic children. The clinical effects of the autistic chil-dren were evaluated using the Autism Treatment Evalu-ation Checklist, a questionnaire that assessed thechildren’s development and progress that is answered bythe parents. Although autistic children in both groupsdemonstrated improvements in their autistic behaviours,the ATEC score for the upper cervical group was 32%versus 19% for the full spine group. The authors con-cluded autistic children receiving Upper Cervical CMTexperienced better improvement in their autistic behav-iors compared to autistic children receiving DiversifiedCMT. There is no mention of adverse events in thisstudy [50].Overall Summary:Inconclusive (unclear) evidence for VOMT in treating

autism.Inconclusive (favorable) evidence for CMT in treating

autism.

4.3.Cerebral palsy

Three RCT’s were found that met our criteria investi-gated the use of OMT on children with cerebral palsy[51–53].

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 26 of 38

Table

9Dataextractio

nforthespecialn

eeds

stud

ies

Con

ditio

nAutho

r/year

Stud

yob

jective

Stud

yde

sign

samplesize

interven

tion

Patient

descrip

tion/

cond

ition

Prim

ary/mainou

tcom

e(s)

Mainresults/con

clusions

Adverse

even

ts

ADHD

AccorsiA,etal.

2014

[48]

Toevaluate

efficacyof

osteop

athicmanipulative

treatm

entof

children

with

ADHD.

RCT

n=28

OMT

Childrenages

5–15,

with

prim

arydiagno

sis

ofADHD

Biancardi-Strop

paMod

ified

BellCancellatio

nTest,

accuracy

andrapidity

scores

Osteo

pathicmanipulative

treatm

entwas

positively

associated

with

change

sin

theBiancardi-Strop

paTestaccuracy

andrapidity

scores.

Therewas

nomen

tion

ofadverseeven

tsmadein

thisstud

y.

Autism

Bram

ati-C

astellarin

I,et

al.2016[49]

Investigatetheinfluen

ceof

visceralosteop

athic

techniqu

eon

the

behaviou

randGI

symptom

sof

children

with

autism.

Interrup

ted

TimeSeries

(with

out

controlg

roup

)n=49

VOMT

Autistic

childrenages

31/2–8,with

GI

symptom

s,im

paired

socialinteractions

andcommun

ication

Parentalcompletionof

the

Mod

ified

Autism

Research

Institu

teou

tcom

essurvey

form

(9S.O.S.q

uestionn

aires)

andsecretin

assessmen

tused

toassess

GIsigns

and

symptom

s

Sign

ificant

improvem

ents

repo

rted

in“socialb

ehavior

andcommun

ication”

and

“digestivesign

s”subscale

ofthequ

estio

nnaire

and

invomiting

andpo

orappe

titecomparin

gbe

fore

andafterVO

MT.

“The

rewas

nomen

tionof

adverse

even

tsmadein

this

stud

y.”

Khorshid

K,et

al.

2006

[50]

Iden

tifythedifferences

inefficacybe

tween

uppe

rcervicalandfull

spineadjustmen

tin

autistic

children

RCT

n=14

CMT

Childrendiagno

sed

with

autism

ATECaveragescores

and

parentalob

servations

Clinicalim

provem

ents

observed

throug

hparental

observations

andthroug

hade

crease

intheATEC

scores

inbo

thgrou

ps.U

pper

cervicalgrou

phadim

proved

ATECaveragescores

of32%.Full

spinegrou

phadim

proved

ATEC

scores

of19%.

Clinicalde

terio

ratio

nwas

show

nin

oneof

thechildrenof

thefull

spinegrou

p,bu

ton

lymarginalinon

echild

oftheup

percervical

grou

p.

Cereb

ral

Palsy

WyattK,et

al.

2011

[51]

Evaluate

thege

neral

health

andwellbeing

effect

ofcranial

osteop

athy

oncerebral

palsychildren.

RCT

n=142

Cranial

Osteo

pathy

Childrenwith

CP,

ages

5–12

GrossMotor

FunctionMeasure-

(GMFM

M-66)Qualityof

life

Child

Health

Questionn

aire-

(CHQ)PF50

Nostatisticalchange

inGMFM

-66or

CHQ.PF50

Parents(unb

linde

d)repo

rted

better

glob

alhe

alth.

Noserio

usadverse

even

tswererepo

rted

.

Dun

canB,et

al.

2004

[52]

Evaluate

effectiven

ess

ofosteopathicmanipulation

oracupunctureas

asupp

lementaltherapies

forchildrenwith

spastic

cerebralpalsy.

RCT

n=50

OMT

Childrenwith

spastic

CP,ages

20mon

ths

-12

years

Parent

repo

rtingof

change

sob

served

(ope

n-en

ded

questio

ns)

96%

repo

rted

improvem

ents.

Mostfre

quen

tseen

inuse

ofarmsandlegs

(61and

68%)andmorerestfulsleep

(39and68%)in

osteop

athic

andacup

uncturerespectively.

Add

ition

alim

provem

entsalso

notedin

moo

dandbo

wel

functio

ns.

Therewas

nomen

tion

ofadverseeven

tsmadein

thisstud

y.

Dun

canB,et

al.

2008

[53]

Evaluate

effectiven

ess

ofosteop

athic

manipulation(cranial

field,m

yofascialrelease

orbo

th)vs.acupu

ncture

inspastic

cerebralpalsy

patients.

RCT

n=55

OMT/

Acupu

ncture

Childrenwith

CP,

ages

20mon

ths-

12years

11ou

tcom

esused

:Prim

ary-

GMFC

S,GMFM

totalp

ercent,

PEDIm

obility,PED

Iself-care,

WeeFIM

mob

ility,W

eeFIM

self-

care;Secon

dary-DOratin

gof

spasticity,M

ASbiceps,M

AS

hamstrin

g,parent/guardian

ratin

gof

arched

back,p

aren

t/gu

ardian

ratin

gof

startle

reflex

Osteo

pathicmanipulation

was

associated

with

improvem

entsin

2of

11ou

tcom

es;G

MFM

total

percen

tandWeeFIM

Mob

ility.A

cupu

ncture

was

notassociated

with

improvem

entsin

any

oftheou

tcom

esvariables.

Therewas

nomen

tion

ofadverseeven

tsmadein

thisstud

y.

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 27 of 38

Table

9Dataextractio

nforthespecialn

eeds

stud

ies(Con

tinued)

Con

ditio

nAutho

r/year

Stud

yob

jective

Stud

yde

sign

samplesize

interven

tion

Patient

descrip

tion/

cond

ition

Prim

ary/mainou

tcom

e(s)

Mainresults/con

clusions

Adverse

even

ts

Prem

aturity

Raith

W,etal.

2016

[54]

Investigatene

urolog

ical

shortterm

effectsof

craniosacraltherapyon

gene

ralm

ovem

entsin

preterm

infants.

RCT

n=30

OMT/CST

Preterm

infantsages

25–33weeks,free

from

med

ical

complications

inNICU

Prim

aryou

tcom

e:Gen

eral

movem

entassessmen

ttool.Secon

dary

outcom

es:

Gen

eralmovem

ent

optim

ality

score

Nodifferencein

thege

neral

movem

entcouldbe

observed

betw

eenthegrou

ps.N

ochange

inge

neralm

ovem

ent

optim

ality

scorewas

noted.

Therewas

nomen

tion

ofadverseeven

tsmadein

thisstud

y.

CerretelliF,et

al.

2015

[55]

Investigatewhe

ther

osteop

athicmanipulation

redu

cestheleng

thof

hospitalstay,costs,and

weigh

tgain

forpreterms.

RCT

n=695

OMT/CST

Preterm

infantsages

29–37weeks,w

ithou

tcongenitalcom

plications

inNICU

1.Redu

cing

leng

thof

hospitalstay

2.Weigh

tgain

andho

spital

saving

s

Osteo

pathictreatm

ent

redu

ceddays

hospital

(3.9days)a

ndredu

ced

costsby

1250.65€

per

newbo

rnpe

rleng

thof

stay.N

ochange

inweigh

tgain

was

noted.

Therewereno

complications

associated

tothe

interven

tion.

Pizzolorusso

G,

etal.2014[56]

Investigatewhe

ther

osteop

athicmanipulation

redu

cesleng

thof

hospital

stay,w

hateffect

thetim

ing

ofintrod

uctio

nof

osteop

athic

treatm

entmay

have

onthe

outcom

eandho

spitalcosts

inpreterm

infants.

RCT

n=110

OMT/CST

Preterm

infantsages

32–37weeks,free

from

med

ical

complications

inNICU

1.Redu

cing

leng

thof

hospital

stay

andim

pact

onleng

thof

stay

oftim

ingof

introd

uctio

nof

osteop

athic

manipulation

2.Redu

cing

hospitalcost

Soonerosteopathic

manipulationintro

duced,

shorterlengthofstay.There

isapositiveassociationof

osteop

athicmanipulationwith

overallreductionincost

ofcare.

Therewereno

complications

associated

tothe

interven

tion.

CerretelliF,et

al.

2013

[57]

Determineeffectiven

essof

osteop

athicmanipulative

therapyin

redu

cing

the

leng

thof

hospitalstay,

hospitalcostsandweigh

tgain

inpreterm

infants.

RCT

n=110

OMT/CST

Preterm

infantsages

>28

and<38

weeks,

freefro

mmed

ical

complications

inNICU

1.Decreased

leng

thof

hospitalstay

2.Im

proved

weigh

tgain

andredu

cedNICUcosts

Osteo

pathicmanipulation

redu

cedleng

thof

stay

andho

spitalcostsbu

tno

teffect

weigh

tgain.

Noserio

usadverse

even

tswererepo

rted

.

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 28 of 38

A high quality pragmatic RCT evaluated the effect ofOMT using cranial therapy on the general health andwell-being of 142 children ages 5–12 with cerebral palsy.In this study, Wyatt et al. placed 71 children in treatmentgroup, who received 6 OMT sessions over 6 months and71 children in a control group, which they referred to as“waiting list”. Primary outcome measures included: GrossMotor Function Measure 66 (GMFMM-66) and Qualityof Life Child Health Questionnaire (CHQ) PF50. Second-ary outcomes measures used in this study included: Paren-tal Assessment of Global Health and Sleep at 6months,Pain and Sleep Questionnaire at 10 weeks and 6months,CHQ PF50 at 10 weeks and the Quality of Life ShortForm-36. This trial showed no statistically significant evi-dence that OMT led to sustained improvement in motorfunction, pain, sleep, quality of life of the subjects or inthe quality of life of their caretakers. No serious adverseevents were reported and none of the children withdrewfrom the study due to side effects of the treatment [51].Duncan et al. conducted a high quality assessor blinded

wait-list controlled pilot RCT that investigated the effect-iveness of OMT (cranial therapy), myofascial release orboth versus acupuncture on 55 cases of children ages 20months to 12 years with moderate to severe spastic cere-bral palsy. Participants were grouped into one of threegroups: OMT (which included osteopathy, myofascial re-lease or both) (n = 15), acupuncture (n = 19) and wait-listcontrol (non-therapeutic attention) (n = 22). The six pri-mary outcome measures were: Gross Motor FunctionalClassification, Gross Motor Measurement Total percent-age, Pediatric Evaluation of Disability Inventory mobilityand self-care, and Functional Independent Measure forChildren mobility and self-care. Duncan et al. reportedthat OMT resulted in an improvement in the child’s grossmotor function as indicated by the outcome measures inchildren with moderate to severe spastic cerebral palsy.There was no mention of adverse events in this study [53].A low quality RCT evaluated the effectiveness of

OMT, acupuncture or both for 50 children aged 11months to 2 years with spastic cerebral palsy. Partici-pants were grouped into four groups: OMT (n = 23),acupuncture (n = 19), both OMT and acupuncture(n = 8) and wait-list control (n = 19). Multiple out-come variables were used to determine if these inter-ventions would decrease muscle tone, improvefunction and quality of life. Evaluation in this studyincluded parental interviews to assess perceptions andchanges observed. Only 2 of 17 parents reported posi-tive gains while their child was in a wait-list controlperiod, but all 17 parents reported gains while in thetreatment phase of the study. Improvement wasclaimed by 96% (48 of 50) of the parents while theirchild was receiving treatments, but the gains varied.The most frequent gains were seen in improvement

in the use of arms or legs (61 and 68%) and morerestful sleep (39 and 68%) in the OMT and the acu-puncture groups, respectively. Improvement in moodand improved bowel function were also very commonbenefits noted by the parents in both groups. Thereis no mention of adverse events in this study [52].Overall Summary:Inconclusive (unclear) evidence for OMT in treating

children with cerebral palsy.

4.4.Prematurity

Four high quality RCTs were found, that investigatedthe use of OMT on various clinical outcomes of childrenborn preterm [54–57].A high quality RCT was conducted by Raith et al. on

30 preterm infants between 25 and 33 weeks in the neo-natal intensive care unit, free from medical complica-tions, with OMT/CST. The aim was to investigateneurological short term effects of craniosacral therapyon general movement in preterm infants. The primaryoutcome utilized was improvement in general move-ment assessment tool. Secondary outcomes includedimprovement in general movement optimality score.They found no differences between the control orstudy group for all outcome measures and at all timepoints. There was no mention of adverse events madein this study [54].Cerretelli et al. conducted a high quality RCT in 2015

that investigated the effectiveness of OMT/CST onlength of hospital stay, hospitalization costs, and weightgain in 695 preterm infants’ ages 29–37 weeks. (Studygroup, n = 352; control group, n = 343) The primary ob-jective was in determining the effect of OMT/CST in re-ducing the length of the hospital stay. Secondaryobjectives evaluated the effect on weight gain and NICUcost savings. They found a reduction in days in hospital(3.9 days) and associated cost savings, but no significantchange in weight gain after OMT/CST compared to thecontrol group. Similar to the Pizzolorusso et al. 2014study, the description of the intervention listed as “ma-nipulation” met the characteristics of cranial/craniosacraltherapy. No complications were associated with the inter-vention [55].Pizzolorusso et al. investigated whether OMT (cra-

nial sacral) reduced the length of the hospital stay in110 preterm infants ages 32–37 weeks in a high qual-ity RCT. Fifty-five infants were placed in the studygroup who received routine pediatric care and OMT/CST and compared to 55 infants in the control groupwho received routine pediatric care only. The primaryobjective of the study was to determine the effect ofOMT/CST on reducing the length of stay and whateffect the timing of introduction OMT/CST may have

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 29 of 38

on the outcome. The secondary objective was to esti-mate the potential savings in terms of hospital costs.Pizzolorusso et al. reported that length of stay andneonatal intensive care unit costs were improved afterintroduction of OMT. It was also concluded that theearlier the OMT/CST had the shorter the hospital stay.No adverse events were recorded in this study [56].Lastly, Cerretelli et al. conducted another high

quality RCT that sought to determine the clinical ef-fects of OMT in 110 preterm infants ages range 29–37 weeks. The treatment group had 55 assigned toreceive OMT/CST plus routine pediatric care. Theywere compared to 55 infants in the control groupwho received only routine pediatric care. The pri-mary outcome measure was to determine the effect-iveness of OMT/CST in reducing the length of thehospital stay. Secondary objectives included deter-mining the effect of OMT/CST on weight gain andin reducing NICU costs. The results of this studyshow that OMT reduced the length of stay (− 5.9days) and NICU costs, but did not impact weightgain. They suggested that further studies based onmulti-center design are required to confirm these re-sults. No adverse or side effects were shown in ei-ther group [57].Overall Summary:Moderate (favorable) evidence for OMT/CST in redu-

cing length of stay and hospital costs for preterm infants.Inconclusive (unclear) evidence for OMT/CST in im-

proving general movement in preterm infants.

5. Structural conditions

Table 10 provides a summary of ten studies thatwere categorized as “structural” conditions. Two stud-ies assessed changes to cranial asymmetry [58, 59],one evaluated postural asymmetry [60], five studiesinvestigated scoliosis [61–65], one study evaluatedtorticollis [66], and one study evaluated upper cervicaldysfunction [67].

5.1.Cranial asymmetry (non-synostotic plagiocephaly)

Two studies investigated the use of manual therapy oncranial asymmetry.One high quality RCT evaluated the use of MT/CST

[58], the other a medium quality before-after observa-tional study looked at OMT [59].Cabrera-Martos conducted a high quality RCT that

evaluated the effects of CST in infants with severenonsynostotic plagiocephaly. Forty-six children meet-ing eligibility were randomized into control and studygroups. Twenty-three children allocated to the controlgroup received standard treatment which included

positional changes and the use of an orthotic helmet.The study group included 23 infants who receivedCST in addition to standard treatment to evaluatetreatment duration and motor development. The pri-mary outcome utilized was the Alberta Infant MotorScale at baseline and at discharge of the patients. Theresults of the study showed that CST added to usualtreatment for severe nonsynostotic plagiocephaly re-sulted in significant improvement in asymmetry, lesstreatment duration, and improved motor behavior.There were no adverse events seen during the treat-ment period [58].One medium quality pilot before-after study re-

ported favorable results utilizing OMT (the most fre-quently used techniques used in the study weredescribed as “cranial” work) on 12 infants with cranialasymmetry. Twelve infants with cranial asymmetriesreceived four OMT treatments over 2 weeks. An-thropometric, plagiocephalometric, and qualitativemeasures were administered pre-intervention, duringthe third treatment and 2 weeks after the fourth treat-ment. The study group showed a significant decreasein cranial vault asymmetry, skull base asymmetry, andtrans-cranial vault asymmetry. The researchers con-cluded that OMT contributes to improvements in cra-nial asymmetries in infants younger than 6.5 monthspresenting with nonsynostotic occipital plagiocephalycharacteristics. There was no mention of adverseevents in this study [59].Overall Summary:Inconclusive (favorable) evidence for both OMT and

MT/CST in treating cranial asymmetry in children.

5.2.Postural asymmetry

One high quality RCT reported improved infant pos-tural asymmetry utilizing OMT/CST on 32 infants,(18 males, 14 females) with gestational age of at least36 weeks. Infants were assigned to intervention (n = 16) orsham (n = 16) groups. Outcomes were measured usinga standardized video-based asymmetry scale frombaseline to final visit. In the control group, the meanimprovement was 1.2 points. In the treatment group,the mean improvement was 5.9 points. The re-searchers concluded that OMT/CST in the firstmonths of life is beneficial for infants with idiopathicasymmetry. At least two of the seven vegetative symp-toms aggravated for 2 days after the intervention in sixpatients of the control group and in four patients ofthe treatment group. No other adverse events weredescribed [60].Overall Summary:Inconclusive (favorable) evidence for OMT/CST in

treating postural asymmetry in children.

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 30 of 38

Table

10Dataextractio

nforstructuralstud

ies

Con

ditio

nAutho

r/year

Stud

yob

jective

Stud

yde

sign

samplesize

interven

tion

Patient

descrip

tion/

cond

ition

Prim

ary/mainou

tcom

e(s)

Mainresults/con

clusions

Adverse

even

ts

Cranial

Asymmetry

Cabrera-M

artosI,

etal.2016[58]

Evaluate

theeffectsof

manualthe

rapy

asan

adjuvant

optio

non

treatm

entdu

ratio

nandmotor

developm

entin

infantswith

severe

nonsynostotic

plagioceph

aly.

RCT

n=46

MT/CS

T

Infantsages

4–8mon

ths,

with

severe

nonsynostotic

plagioceph

aly

Treatm

entdu

ratio

nand

motor

developm

ent

assessed

with

Alberta

Infant

Motor

Scale

Treatm

entdu

ratio

nwas

sign

ificantlyredu

cedin

manualthe

rapy

grou

p(109.84+/−

14.45)

comparedto

thecontrol

grou

p(148.65+/−

11.53)

days.A

symmetry

afterthe

treatm

entwas

minim

alType

0or

Type

1.Motor

behaviou

rwas

norm

alin

allthe

infantsafter

treatm

ent.

Stud

yrepo

rted

noadverse

effectswereseen

durin

gthetreatm

entpe

riod.

LessardS,et

al.

2011

[59]

Doe

sosteop

athic

manipulationalter

cranialasymmetry

ininfants.

Before-Afte

rn=12

OMT

Infantsages

<6.5mon

ths,

diagno

sedwith

nonsynostotic

plagioceph

aly

Anthrop

ometric

change

sOsteo

pathictreatm

ent

ledto

improvem

entsin

cranialasymmetry.

Thereisno

men

tionof

adverseeven

tsmadein

thisstud

y.

Postural

Asymmetry

Philipp

iH,etal.

2006

[60]

Toassess

the

therapeutic

efficacy

ofosteop

athic

manipulationin

infantswith

postural

asym

metry.

RCT

n=32

OMT/CST

Infant

ages

6–12

weeks,w

ithpo

sturalasym

metry

Vide

o-based

measuremen

tsSign

ificant

improvem

ent

inpo

sturalasym

metry

(mean5.9po

ints)

observed

with

osteop

athicmanipulation.

“Atleasttw

oof

theseven

vege

tativesymptom

saggravated

for2days

after

theinterven

tions

insix

patientsof

thecontrol

grou

pandin

four

patients

ofthetreatm

entgrou

p.Otherwiseno

adverse

effectswereseen

.”

Scoliosis

Byun

S&Han

D,

2016

[61]

Exam

inewhe

ther

chiro

practic

techniqu

eswou

ldredu

cethecurvature

ofidiopathicscoliosis.

Before-Afte

rn=5

CMT

Childrenages

10–13,with

Cob

bangles

>10

degrees

Redu

ctionin

Cob

bangle

Nosign

ificant

differencein

Cob

banglewas

noted

afterthe4thweekof

chiro

practic

manipulation.

Thereisno

men

tionof

adverseeven

tsmadein

thisstud

y.

HaslerC,etal.

2010

[65]

Testto

seeif

osteop

athy

alters

trun

kmorph

olog

y,to

unload

the

concaveside

ofthe

scoliosisto

haltcurve

prog

ression.

RCT

n=20

OMT

Post-pub

ertalfem

ales

ages

12–18,with

Cob

bangles

20–40

Trun

kmorph

olog

y,spineflexibilityand

scoliometer

measuremen

ts

Repe

atmeasuremen

tsrevealed

notherapeutic

effect

onrib

hump,

lumbarprom

inen

ce,

plum

bline,sagittal

profile

andglob

alflexibility.

“Nointerven

tion-related

side

effectsor

complications

wereno

ted”

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 31 of 38

Table

10Dataextractio

nforstructuralstud

ies(Con

tinued)

Con

ditio

nAutho

r/year

Stud

yob

jective

Stud

yde

sign

samplesize

interven

tion

Patient

descrip

tion/

cond

ition

Prim

ary/mainou

tcom

e(s)

Mainresults/con

clusions

Adverse

even

ts

RoweD,etal.

2006

[62]

Tocond

uctapilot

(feasibility)study

andexploreissues

ofpatient

safety,

patient

recruitm

ent

andcompliance,

treatm

ent

standardization,

sham

treatm

ent

refinem

ent,

interprofessional

coop

eration,qu

ality

assurance,and

outcom

emeasure

selection.

RCT

n=6

CMT

Childrenages

10–16,with

Cob

bangles

20–40de

grees

Redu

ctionin

Cob

bangle

Feasibleto

recruitAIS

patientsforarand

omized

clinicaltrialtocompare

chiro

practic

care

and

standard

med

ical

treatm

ent.

CMTde

livered

on52

visits

resultedin

twobe

nign

reactio

nson

ewith

mod

eratepain

lasting

24h;theothe

rprod

uced

mild

pain

lasting6h.

Morning

star

M,

etal.2004[63]

Evaluate

ofscoliosis

treatm

entusinga

combinatio

nof

manipulativeand

rehabilitativetherapy.

Before-Afte

rn=19

(6pe

diatrics)

CMT

Scoliotic

patientsaged

15–65(6

patients18

andun

der-iden

tified

inTable3of

stud

y)

Redu

ctionin

Cob

bangle

Redu

ctionin

Cob

bangles

inallp

atients.

Thereisno

men

tionof

adverseeven

tsmade

inthisstud

y.

LantzC&

Che

nJ,2001

[64]

Effect

ofchiro

practic

manipulationon

small

scoliotic

curves

inyoun

gersubjects.

Before-Afte

rn=42

CMT

Childrenaged

6–17,

with

Cob

bangles

6–25

Redu

ctionin

Cob

bangle

Nooverallred

uctio

nin

Cob

bangleafter

6.5–28.5mon

thsof

care.

Thereisno

men

tionof

adverseeven

tsmadein

thisstud

y.

Torticollis

Hauge

nE,

2011

[66]

Evaluate

measuremen

tmetho

dsandexam

ine

short-tim

eeffect

ofmanualthe

rapy

inadditio

nto

physiotherapyin

infantswith

torticollis.

RCT

n=32

MT

Infant

aged

3–6mon

ths,

diagno

sedwith

torticollis

Prim

aryou

tcom

e:Vide

oclip

recordings,

Second

aryou

tcom

es:

12parametersof

body

functio

n,activity,

participation

Nosign

ificant

difference

inprim

aryou

tcom

e.Foun

dno

n-sign

ificant

tend

ency

togreater

improvem

entin

lateral

flexion

andhe

adrig

htingin

interven

tion

grou

p.

Thereisno

men

tionof

adverseeven

tsmadein

thisstud

y.

Upp

erCervical

Dysfunctio

nSaed

tE,et

al.

2018

[67]

Togain

insigh

tinto

thepatient

characteristicsand

reason

sforseeking

care

ininfantswith

indicatio

nsof

uppe

rcervicaldysfun

ction

referred

formanual

therapy.

Before-Afte

rn=295

MT

Infantsaged

<27

weeks,

with

positio

nalp

reference,

restlessne

ss,abn

ormal

head

positio

n,excessive

crying

Improved

flexion

-rotation

testandlateralflexion

tests

Parentalpe

rcep

tionof

treatm

enteffectsPre-

andpo

sttreatm

ent

self-repo

rted

questio

nnaires

Flexion-

rotatio

ntest

decreasedfro

m78.8to

6.8%

.Lateralflexion

test

decreasedfro

m91.5%

tp6.2%

.Allparents

perceivedpo

sitive

treatm

enteffects.

Noserio

usadverse

even

tswererepo

rted

durin

gthisstud

y.

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 32 of 38

5.3.Scoliosis

Five studies looked at the use of manual therapy in thetreatment of scoliosis. Four looked at the use of CMT[61–64]. Of these, one was a high quality RCT, threebefore-after, two medium and one of low quality. Thefifth study was a high quality RCT that looked at the useof OMT [65].A medium quality before-after observational study by

Byun and Han examined whether chiropractic tech-niques would reduce the curve of adolescent idiopathicscoliosis in 5 healthy children with an average age of11.8 years with Cobb angles greater than 10 degrees(average 11.2 degrees). The primary outcome was thechange in the Cobb angle that was measured after 4 andat 8 weeks of treatment. The results of this study werethat the Cobb angle was noticeably decreased after 4weeks, but no further reduction in Cobb angle wasnoted after 8 weeks, except in one male. They concludedthat chiropractic techniques effectively reduced theCobb angle in adolescent idiopathic scoliosis after 4weeks. There was no mention of adverse events made inthis study [61].Rowe et al. conducted a high quality pilot RCT that in-

vestigated the clinical effects of CMT on children withscoliosis. This was a feasibility study whose purpose wasto explore issues of safety, patient recruitment, patientcompliance, treatment standardization, sham treatmentrefinement, inter-professional cooperation, quality assur-ance, and outcome measure selection. The primary out-come measured was the Cobb angle. Secondary outcomewas the Scoliosis Quality of Life Index (SQLI). The re-searchers reported improved Cobb angles in 5 of the 6patients that received CMT and an improved SQLI in 1of the 6. Due to the small sample size, no conclusionscould be made regarding effectiveness. Regarding ad-verse events, CMT delivered on 52 visits resulted in twobenign reactions; 1 with moderate pain lasting 24 h, theother produced mild pain lasting 6 h [62].Morningstar et al. conducted a low quality before-after

case series that reviewed the clinical files of 22 patients,6 of whom were 18 years or younger, who received acombination of CMT and rehabilitative therapy. The au-thors found reductions in Cobb angle (average 17 degreereduction) in all the patients, including the patientsunder the age of 18 years. No mention of any adverseevents was noted in this study [63].Lantz et al. conducted a medium quality before-after

case series of 42 children, 16 males, 26 females, withscoliotic curves ranging from 4 to 22 degrees, ages 6–17years, to determine the clinical effects of full spine CMT,use of heel lifts, and lifestyle counseling on the progres-sion of the curves. Participants were treated for between6.5 to 28.5 months. The main outcome was a reduction

in scoliotic curvature. The authors reported no overallimprovement in scoliotic curves using CMT. No men-tion of adverse events was made in this study [64].Hasler et al. conducted a high quality prospective RCT

that sought to determine if OMT altered trunk morph-ology to unload the concave side of the scoliosis in orderto halt curve progression. The study included 20pre-pubertal women with curves that ranged from 20 to40 degrees. The primary outcomes was trunk morph-ology and spine flexibility. The authors concluded thatthere was no evidence to support the use of OMT in thetreatment of mild idiopathic scoliosis. Nointervention-related side effects or complications werenoted [65].Overall Summary:Inconclusive (unclear) evidence for use of CMT in

childhood scoliosis.Inconclusive (unfavorable) evidence for use of OMT

in childhood scoliosis.

5.4.Torticollis

One medium quality pilot RCT investigated whetherMT improved torticollis in 32 patients between the agesof 3–6 months. There were 15 infants in the study groupwho received MT plus physiotherapy (PT) and 16 in-fants in the control group who received child physio-therapy alone. The study did not describe the type ofMT provided. The primary outcome measured wasevaluating the torticollis symptoms via videotape footageof the child using a 4-point scale in which the child wasrated as “much better”, “better”, “no significant change”or “worse”. Secondary outcomes included 12 measure-ment parameters that involved body function, activity,and participation corresponding to the InternationalClassification of Function The study reported no signifi-cant improvement in the MT and PT group in the pri-mary outcome, but improvement in two of thesecondary outcome measures of improved passive andactive lateral flexion of the neck. No mention of adverseevents were noted in this study [66].Overall Summary:Inconclusive (unfavorable) evidence for MT for

torticollis.

5.5.Upper cervical dysfunction

A high quality before-after observational study by Saedtet al. sought to gain insight into the patient characteris-tics and reasons for seeking care in infants with uppercervical dysfunction (UCD). A group of 295 infants(mean age of 11.2 weeks) with positional preference, rest-lessness, abnormal head position and excessive cryingwere treated with mobilization. The primary outcomes

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 33 of 38

were assessed with pre- and post-treatment self-reportedquestionnaires used to assess diagnostics, treatment pro-cedures, outcomes, and harms from parents and manualtherapists. The questionnaires consisted of two sections:one collected at baseline; the other posttreatment byboth the parents and the manual therapists. The re-searchers concluded that the majority of infants withupper cervical dysfunction showed positional preferenceof the head and reduced the active and passive mobilityof the upper cervical spine. After gentle upper cer-vical mobilization techniques, active and passive cer-vical mobility increased. They also reported that theparents reported a reduction in symptoms. No seriousadverse events were reported during this study [67].Overall Summary:Inconclusive (unclear) evidence for the use of MT in

infants with upper cervical dysfunction.

DiscussionThis review identified 50 RCTs and observational ori-ginal studies that evaluate manual therapy for pediatricconditions, which updates several previously publishedsystematic reviews. Of particular importance, our reviewincluded studies investigating the effects of manual ther-apy on musculoskeletal conditions, including pediatriclow back pain and headache. Other conditions not previ-ously reported in some previous systematic reviews in-clude: constipation, suboptimal infant breastfeeding,clubfoot, cuboid syndrome, headache, pulled (nurse’s)elbow, asthma, obstructive apnea, autism, cranial asym-metry, postural asymmetry, scoliosis, torticollis, andupper cervical dysfunction.Of the 50 studies, 32 were RCTs (18 high-quality, 10

medium-quality, and 4 low-quality). The remaining 18 stud-ies were observational (1 high-quality, 13 medium-quality,and 4 low-quality). Observational studies were furtherbroken down by study design (13-before-after, 4 interruptedtime-series without comparison group, and 1 interruptedtimes-series with comparison group). Thirty-six studies re-ported ‘favorable’ results, five showed ‘no improvement’, andnine showed ‘no difference’ between study groups. In five ofthe nine ‘no difference’ studies, ‘favorable’ results were notedin both groups, of which two of these studies had MT inboth groups.Pediatric conditions assessed as ‘moderate-favorable’

were:

� Low Back Pain (using CMT);� Pulled (or Nurse’s) Elbow (using MT); and� Preterm Infants (using OMT/CST to reduce days

and costs in hospital).

Pediatric conditions assessed to be ‘inconclusive-favorable’ were:

� ADHD (using OMT);� Autism (using CMT);� Asthma (using OMT);� Clubfoot (using MT);� Cranial Asymmetry (using MT/CST);� Dysfunctional Voiding (using OMT);� Infantile Colic (using OMT/CST);� Obstructive Apnea (using OMT);� Otitis Media (using OMT);� Postural Asymmetry (using OMT/CST);� Suboptimal Infant Breastfeeding (using CMT/CST); and� Temporomandibular Joint Dysfunction (using OMT).

Pediatric conditions assessed to be ‘inconclusive-unclear’ were:

� Asthma (using CMT);� Autism (using VOMT);� Cerebral Palsy (using OMT);� Constipation (using OMT);� Cranial Asymmetry (using OMT);� Cuboid Syndrome (using MT);� Headache (using CMT, OMT, and MT);� Infantile Colic (using CMT);� Low Back Pain (using MT);� Otitis Media (using CMT);� Nocturnal Enuresis (using CMT);� Preterm Infants (using OMT/CST for general

movement);� Scoliosis (using CMT); and� Upper Cervical Dysfunction (using MT).

Pediatric conditions assessed to be ‘inconclusive-unfa-vorable’ were:

� Scoliosis (using OMT) and� Torticollis (using MT).

Our findings had a few notable updates from prior sys-tematic reviews, especially the UK Update, of which“inconclusive-unclear” or “inconclusive-favorable” wasthe outcome for all conditions [10]. The UK Update wasunable to review any musculoskeletal conditions becauseno studies were available at that time [10]. Evans et al.published the first high-quality RCT on adolescent lowback pain, which allowed for this review to report a“moderate-positive” evidence for low back pain usingCMT [33]. Another musculoskeletal condition that has anongoing study is headaches (ClinicalTrials.gov Identifier:NCT02684916); we anticipate the results of this study willallow for better practitioner guidance because of the highrigor described in the protocol. Pulled (Nurse’s) elbowusing MT was also not in the UK Update, and was foundto have a “moderate-positive” result in this study [37, 38].

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 34 of 38

Additional evidence ratings changed in a positive direc-tion in our study from the UK Update for preterm infants(reducing length of stay and hospital costs) using OMT/CST. Three new high-quality RCT’s not previously identi-fied by the UK Update were identified showing favorableresults, which accounted for this modification [55–57].We were able to change the evidence ratings from “incon-clusive-unclear” to “inconclusive-favorable” for two add-itional conditions: otitis media, based on data gatheredfrom two medium quality RCT’s [43, 45], reporting favor-able results and for ADHD, based on the results of a highquality RCT showing favorable results [48].We amended the evidence from “inconclusive-favor-

able” to “inconclusive-unclear” for infantile colic andpediatric enuresis using CMT. Regarding the change forinfantile colic, our study included four studies, the mostrecent of which is a high-quality with improved out-comes [19]. However, the remaining studies showed ei-ther “no improvement” or “no difference” [20–22]. Ourevidence rating is similar to the recent 2018 systematicreview and meta-analysis of infantile colic and manualtherapy conducted by Carnes et al. [68]. Carnes et al.concluded that while small benefits were found for theoverall outcome, the benefit of manual therapy for in-fantile colic is still unclear [68]. For pediatric enuresis,our search identified only one observational study show-ing favorable results; however, this level of evidence wasnot enough to substantiate a “favorable” rating [25]. TheUK Update conclusion was based off the Huang et al.systematic review, which included clinical trials that didnot meet our eligibility criteria for manual therapy andyear of publication [69].Similar to the previous systematic review on this topic,

and despite using only recent literature, this review con-tinued to find serious methodological limitations withinthe included studies. Our most common methodologicalconcern was the lack of standardization of the interven-tion, which varied across the professions and even be-tween studies within the same profession. Many studiesfailed to adequately describe the methods used by thepractitioner; most of the studies also failed to describethe number of treatments the patients received and overwhat duration of time. In addition, the provider’s experi-ence, training, and type of intervention used in the samestudy varied considerably. Another notable methodo-logical concern was small sample size, which was notaccounted for in the quality assessment. Finally, manystudies failed to report on the incidence of adverse events.Adverse events were addressed in only 20 of the 50 in-

cluded studies reviewed. No lasting or significant adverseevents were reported for children receiving any form ofMT. Two previous systematic reviews have been pub-lished regarding the incidence of adverse events associatedwith pediatric spinal manipulation [7]. These reviews

report that adverse events are rare, but that the true inci-dence is unknown as they have not been evaluated pro-spectively. The current “Best Practices for ChiropracticCare of Children: A Consensus Update” report states thatthe best way to minimize adverse events is by conductinga thorough history and examination, as the majority of ad-verse event cases in the literature are often due to under-lying pre-existing pathology that was not diagnosed [9].Our review is in agreement with previous studies inrecommending that prospective-population-based studiesshould be conducted to identify the true incidence of ser-ious adverse events due to MT in the pediatric population.Such a clinical trial is currently ongoing (ClinicalTrials.govIdentifier: NCT02268331).Additionally the “Best Practice” report states that manual

procedures should be modified when treating children totake into account the differences in patient size, structuraldevelopment and flexibility of the joints [9]. Modificationsshould include using gentler, lighter biomechanical forcesproportioned to the size and structural development of thechild. BothTriano et al. and Todd et al. [8, 70]. have positedthat healthcare providers using SMT are able to modulatethe amount of forces used. We agree this ability to modu-late for pediatric, geriatric, and other special populationsought to be included in undergraduate training programsor during continuing education workshops for fieldpractitioners.

LimitationsAside from using rigorous methodology in this system-atic review and conducting a comprehensive search, it ispossible that our search failed to identify every relevantstudy, especially considering the restriction of the searchto English-language studies. Our knowledge of unpub-lished trials have influenced our conclusions; unpub-lished trials may be more likely to produce negative orequivocal results. Although the independent reviewersperformed this review, and in spite of utilizing system-atic strategies for assessing the quality of the includedstudies, there is still room for subjective interpretation.While we deliberately chose widely accepted recommen-dations for assessing quality and determining bias, ouradaptation of some recommendations to better fit ourstudy design may have impacted our conclusions. Also,each reviewer has varying degrees of familiarity with theassessment tools a priori, which could influence theinter-reviewer reliability of the primary quality and biasassessments. Finally, all six reviewers are chiropractors;this expertise, as well, may be considered a source ofbias.

ConclusionsFavorable, albeit inconclusive, results were reported in 36of the 50 studies we assessed that used different types of

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 35 of 38

manual therapies for pediatric conditions. Compared toprevious reviews of the literature, we found a number ofclinical trials investigating the effects of manual therapieson pediatric musculoskeletal conditions. Twenty-fourstudies included information on adverse events that wereall transient and mild to moderate in nature. Clearly moreresearch investigating the clinical effectiveness of manualtherapies for pediatric conditions, along with the inci-dence of adverse events, is required in order to allow prac-titioners and parents to make better informed choiceswith respect to care planning for children with pediatricconditions.

AbbreviationsADHD: Attention deficit hyperactivity disorder; AHRQ: Agency for HealthcareResearch and Quality; CAM: Complementary and alternative medicine;CMT: Chiropractic manipulative therapy; CST: Cranial-sacral therapy;EENT: Eyes, ears, nose, and throat; HHS: Department of Health and HumanServices; HVLA: High velocity, low amplitude; LBP: Low back pain; MT: Manualtherapy; NHIS: National Health Interview Statistics; OMT: Osteopathic manualtherapy; RCT: Randomized controlled trial; SMT: Spinal manipulation therapy;TMD: Temporomandibular dysfunction; UK: United Kingdom; US: UnitedStates; VOMT: Visceral osteopathic manipulation

AcknowledgmentsThe authors would like to thank Edward Murphy of Palmer College ofChiropractic-Port Orange, FL Campus, Kent Murnaghan of CanadianChiropractic University and Simone Brand of Cleveland University- KansasCity for their assistance in performing the literature search.

FundingNot Applicable

Availability of data and materialsAll data generated or analysed during this study are included in thispublished article.

Authors’ contributionsStudy Design: CPP, BG, KA, BC, KAP. Data Extraction: CPP, BG, KA, BC, MC,KAP. Data Interpretation: CPP, BG, KA, BC, MC, KAP. Critical Review andApproval of Final Manuscript: CPP, KA, BC, BG, MC, KAP.

Ethics approval and consent to participateNot Applicable

Consent for publicationNot Applicable

Competing interestsThe authors declare that they have no competing interests.

Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.

Author details1Palmer College of Chiropractic, 4777 City Center Parkway, Port Orange, FL32129, USA. 2Canadian Memorial Chiropractic College, 6100 Leslie St., NorthYork, ON M2H 3J1, Canada. 3Performance Chiropractic, 4350 SouthWashington Street Suite 100, Grand Forks, ND 58201, USA. 4Parker University,2540 Walnut Hill Lane, Dallas, TX 75229, USA.

Received: 24 July 2018 Accepted: 21 January 2019

References1. Black LI, Clarke TC, Barnes PM, Stussman BJ, Nahin R. Use of complementary

health approaches among children aged 4-17 years in the United States:National Health Interview Survey 2007-2012. Natl Health Stat Report. 2015;(78):1–19.

2. Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicineuse among adults and children: United States, 2007. Natl Health Stat Report.2008;12:1–23.

3. Christensen MG, Kollasch MW, Martin W, Hyland JK. Practice analysis ofchiropractic: a project report, survey analysis and summary of the practiceof chiropractic within the United States — 2010. Greeley: National Board ofChiropractic Examiners; 2010.

4. Pohlman K, Hondras M, Long C, Haan A. Practice patterns of doctors ofchiropractic with pediatric diplomate: a cross sectional survey. BMCComplement Altern Med. 2010;10:26.

5. Ndetan H, Evans M, Hawk C, Walker C. Chiropractic or Osteopathic Manipulationfor Children in the United States: An analysis of data from the 2007 NationalHealth interview survey. J Altern Complement Med. 2012;18:347–53.

6. McClafferty H, Vohra S, Bailey M, Brown M, Esparham A, Gerstbacher D, et al.Pediatric Integrative Medicine. Pediatrics. 2017;140(3):e20171961.

7. Vohra S, Johnston B, Cramer K, Humphreys K. Adverse events associatedwith pediatric spinal manipulation: a systematic review. Pediatrics. 2007;119(1):e275–83.

8. Todd A, Carroll M, Robinson A, Mitchell E. Adverse events due tochiropractic and other manual therapies for infants and children: a reviewof the literature. J Manip Physiol Ther. 2015;38(9):699–712.

9. Hawk C, Schneider M, Vallone S, Hewitt E. Best practices for chiropracticcare of children: a consensus update. J Manip Physiol Ther. 2016;39:158–68.

10. Clar C, Tsertsvadze A, Court R, Lewando H, Clarke A, Sutcliffe P. Clinicaleffectiveness of manual therapy for the management of musculoskeletaland non-musculoskeletal conditions: systematic review and update of UKevidence report. Chiropr Man Therap. 2014;22(1):12.

11. Gotlib A, Rupert R. Assessing the evidence for the use of chiropracticmanipulation in paediatric health conditions: a systematic review. PaediatrChild Health. 2005;10(3):157–61.

12. Gotlib A, Rupert R. Chiropractic manipulation in pediatric health conditions-an updated systematic review. Chiropr Osteopat. 2008;16:11.

13. Gleberzon B, Arts J, Mei A, McManus EL. The use of spinal manipulativetherapy for pediatric health conditions: a systematic review of the literature.J Can Chiropr Assoc. 2012;56:128–41.

14. Posadzki P, Lee MS, Ernst E. Osteopathic manipulative treatment forpediatric conditions: A systematic review. Pediatrics. 2013;132(1):140–52.

15. Viswanathan M, Berkman N, Dryden D, Hartling L. Assessing risk of bias andconfounding in observational studies of interventions or exposures: furtherdevelopment of the RTI item bank. Agency for Healthcare Research andQuality (US). 2013. Report No.:13-EHC106-EF.

16. Higgins J, Altman D, Gøtzsche PC, Jüni P, Moher D, Oxman A, et al. TheCochrane collaboration’s tool for assessing risk of bias in randomised trials.BMJ. 2011;343:d5928.

17. Liberati A, Altman DG, Tatzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al.The PRISMA statement for reporting systematic reviews and meta-analysesfor studies that evaluate health care interventions: explanation andelaboration. PLoS Med. 2009;6(7):e1000100.

18. Tarsuslu T, Bol H, Simşek IE, Toylan IE, Cam S. The effects of osteopathictreatment on constipation in children with cerebral palsy: a pilot study. JManip Physiol Ther. 2009;32(8):648–53.

19. Miller J, Newell D, Bolton J. Efficacy of chiropractic manual therapy on infantcolic: a pragmatic singleblind, randomized controlled trial. J Manip PhysiolTher. 2012;35(8):600–7.

20. Wiberg K, Wiberg J. A retrospective study of chiropractic treatment of 276Danish infants with infantile colic. J Manip Physiol Ther. 2010;33(7):536–41.

21. Browning M, Miller J. Comparison of the short-term effects of chiropracticspinal manipulation and occipito-sacral decompression in the treatment ofinfant colic: a single-blinded, randomized, comparison trial. Clin Chiropr.2008;11(3):122–9.

22. Olafsdottir E, Forshei S, Fluge G, Markestad T. Randomised controlled trial ofinfantile colic treated with chiropractic spinal manipulation. Arch Dis Child.2001;84(2):138–41.

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 36 of 38

23. Hayden C, Mullinger B. A preliminary assessment of the impact of cranialosteopathy for the relief of infantile colic. Complement Ther Clin Pract.2006;12(2):83–90.

24. Nemett D, Fivush B, Mathews R, Camirand N, Eldrigde M, Finney K, et al. Arandomized controlled trial of the effectiveness of osteopathy-basedmanual physical therapy in treating pediatric dysfunctional voiding. JPediatr Urol. 2008;4(2):100–6.

25. Van Poecke A, Cunliffe C. Chiropractic treatment for primary nocturnalenuresis: a case series of 33 consecutive patients. J Manip Physiol Ther.2009;32(8):675–81.

26. Miller J, Miller L, Sulesund A, Yevtushenko A. Contribution of chiropractictherapy to resolving suboptimal breastfeeding: a case series of 114 infants. JManip Physiol Ther. 2009;32(8):670–4.

27. Vallone S. Chiropractic evaluation and treatment of musculoskeletaldysfunction in infants demonstrating difficulty breastfeeding. J Clin ChiroprPed. 2004;6(1):349–68.

28. Nilgün B, Suat E, Engin Şİ, Fatma U, Yakut Y. Short-term results of intensivephysiotherapy in clubfoot deformity treated with the Ponseti method.Pediatr Int. 2011;53(3):381–5.

29. Jennings J, Davies G. Treatment of cuboid syndrome secondary to lateralankle sprains: a case series. J Orthop Sports Phys Ther. 2005;35(7):409–15.

30. Przekop P, Przekop A, Haviland M. Multimodal compared to pharmacologictreatments for chronic tension-type headache in adolescents. J Bodyw MovTher. 2016;20(4):715–21.

31. Borusiak P, Biedermann H, Boberhoff S, Opp J. Lack of efficacy of manualtherapy in children and adolescents with suspected cervicogenic headache:results of a prospective, randomized, placebocontrolled, and blinded trial.Headache. 2010;50(2):224–30.

32. Marchand A, Miller J, Mitchell C. Diagnosis and chiropractic treatment ofinfant headache based on behavioral presentation and physical findings: aretrospective series of 13 cases. J Manip Physiol Ther. 2009;32(8):682–6.

33. Evans R, Haas M, Schulz C, Leininger B, Hanson L, Bronfort G. Spinalmanipulation and exercise for low back pain in adolescents: a randomizedtrial. Pain. 2018;159(7):1297–307.

34. Walston Z, Yake D. Lumbar thrust manipulation and exercise for thetreatment of mechanical low back pain in adolescents: a case series. JOrthop Sports Phys Ther. 2016;46(5):391–8.

35. Selhorst M, Selhorst B. Lumbar manipulation and exercise for the treatmentof acute low back pain in adolescents: a randomized controlled trial. J ManManipulative Ther. 2015;23(4):226–33.

36. Hayden J, Mior S, Verhoef M. Evaluation of chiropractic management ofpediatric patients with low back pain: a prospective cohort study. J ManipPhysiol Ther. 2003;26(1):1–8.

37. Garcia-Mata S, Hidalgo-Ovejero A. Efficacy of reduction maneuvers for“pulled elbow” in children: a prospective study of 115 cases. J PediatrOrthop. 2014;34(4):432–6.

38. Bek D, Yildiz C, Köse O, Sehirlioğlu A, Başbozkurt M. Pronation versussupination maneuvers for the reduction of ‘pulled elbow’: a randomizedclinical trial. Eur J Emerg Med. 2009;16(3):135–8.

39. Monaco A, Cozzolino V, Cattaneo R, Cutilli T, Spadaro A. Osteopathicmanipulative treatment (OMT) effects on mandibular kinetics: kinesiographicstudy. Euro Arch Pediatr Dent. 2008;9(1):37–42.

40. Guiney P, Chou R, Vianna A, Lovenheim J. Effects of osteopathicmanipulative treatment on pediatric patients with asthma: a randomizedcontrolled trial. J Am Osteopath Assoc. 2005;105(1):7–12.

41. Bronfort G, Evans R, Kubic P, Filkin P. Chronic pediatric asthma andchiropractic spinal manipulation: a prospective clinical series andrandomized clinical pilot study. J Manip Physiol Ther. 2001;24(6):369–77.

42. Vandenplas Y, Denayer E, Vandenbossche T, Vermet L, Hauser B,Deschepper, et al. Osteopathy may decrease obstructive apnea in infants: apilot study. Osteopath Med Prim Care. 2008;2:8.

43. Steele K, Carreiro J, Viola J, Conte J, Ridpath L. Effect of osteopathicmanipulative treatment on middle ear treatment on middle ear effusionfollowing acute otitis media in young children: a pilot study. J AmOsteopath Assoc. 2014;114(6):436–47.

44. Wahl RA, Aldous MB, Worden KA, Grant KL. Echinacea purpurea andosteopathic manipulative treatment in children with recurrent otitis media:a randomized controlled trial. BMC Complement Altern Med. 2008;8:56.

45. Degenhardt B, Kuchera M. Osteopathic evaluation and manipulativetreatment in reducing the morbidity of otitis media: a pilot study. J AmOsteopath Assoc. 2006;106(6):327–34.

46. Zhang JQ, Snyder BJ. Effect of the Toftness chiropractic adjustments forchildren with acute otitis media. J Vertebral Sublux Res. 2004:1–4.

47. Mills M, Henley C, Barnes L, Carreiro J, Degenhardt B. The use of osteopathicmanipulative treatment as adjuvant therapy in children with recurrent acuteotitis media. Arch Pediatr Adolesc Med. 2003;157(9):861–6.

48. Accorsi A, Lucci C, Di Mattia L, Granchelli C, Barlafante G, Fini F, et al. Effectof osteopathic manipulative therapy in the attentive performance ofchildren with attention-deficit/hyperactivity disorder. J Am Osteopath Assoc.2014;114(5):374–81.

49. Bramati-Castellarin I, Patel V, Drysdale I. Repeat-measures longitudinal studyevaluating behavioural and gastrointestinal symptoms in children withautism before, during and after visceral osteopathic technique (VOT). JBodyw Mov Ther. 2016;20(3):461–70.

50. Khorshid KA, Sweat RW, Zemba D, Zemba B. Clinical efficacy of uppercervical versus full spine chiropractic care on children with autism: arandomized clinical trial. J Vertebral Subluxation Res. 2006:1–7.

51. Wyatt K, Edwards V, Franck L, Britten N, Creanor S, Maddick A, et al. Cranialosteopathy for children with cerebral palsy: a randomised controlled trial.Arch Dis Child. 2011;96(6):505–12.

52. Duncan B, Barton L, Edmonds D, Blashill BM. Parental perceptions of thetherapeutic effect from osteopathic manipulation or acupuncture inchildren with spastic cerebral palsy. Clin Pediatr (Phila). 2004;43(4):349–54.

53. Duncan B, McDonough-Means S, Worden K, Schnyer R, Andrews J,Meaney F. Effectiveness of osteopathy in the cranial field andmyofascial release versus acupuncture as complementary treatment orchildren with spastic cerebral palsy: a pilot study. J Am OsteopathAssoc. 2008;108(10):559–70.

54. Raith W, Marschik, Sommer C, Maurer-Fellbaum U, Amhofer C, Avian A, et al.General movements in preterm infants undergoing craniosacral therapy: arandomized controlled pilot trial. BMC Complement Altern Med. 2016;16:12.

55. Cerretelli F, Pizzolorusso G, Renzetti C, Cozzolino V, D’Orazio M, LupacchiniM, et al. A multicenter, randomized, controlled trial of osteopathicmanipulative treatment on preterms. PLoS One. 2015;10(5):e0127370.

56. Pizzolorusso G, Cerritelli F, Accorsi A, Lucci C, Tubaldi L, Lancellotti J, et al.The effect of optimally timed osteopathic manipulative treatment on lengthof hospital stay in moderate and late preterm infants: results from a RCT.Evid Based Complement Alternat Med. 2014;2014:243539.

57. Cerretelli F, Pizzolorusso G, Ciardelli F, La Mola E, Cozzolino V, Renzetti C, et al.Effect of osteopathic manipulative treatment on length of stay in a populationof preterm infants: a randomized controlled trial. BMC Pediatr. 2013;13:65.

58. Cabrera-Martos I, Valenza M, Valenza-Demet G, Benítez-Feliponi A, Robles-Vizcaíno C, Ruiz-Extrmera A. Effects of manual therapy on treatmentduration and motor development in infants with severe nonsynostoticplagiocephaly: a randomized controlled pilot study. Childs Nerv Syst. 2016;32(11):2211–7.

59. Lessard S, Gagnon I, Trottier N. Exploring the impact of osteopathictreatment on cranial asymmetries associated with nonsynostoticplagiocephaly in infants. Complement Ther Clin Pract. 2011;17(4):193–8.

60. Phillippi H, Faldum A, Schleupen A, Pabst B, Jung T, Bergmann H, et al.Infantile postural asymmetry and osteopathic treatment: a randomizedtherapeutic trial. Dev Med Child Neurol. 2006;48(1):5–9.

61. Byun S, Han D. The effect of chiropractic techniques on the Cobb angle inidiopathic scoliosis arising in adolescents. J Phys Ther Sci. 2016;28(4):1106–10.

62. Rowe D, Feise R, Crowther E, Grod J, Menke JM, Goldsmith CH, et al.Chiropractic manipulation in adolescent idiopathic scoliosis: a pilot study.Chiropr Osteopat. 2006;14:15.

63. Morningstar MW, Woggon D, Lawrence G. Scoliosis treatment using acombination of manipulative and rehabilitative therapy: a retrospective caseseries. BMC Musculoskelet Disord. 2004;5:32.

64. Lantz CA, Chen J. Effect of chiropractic intervention on small scoliotic curvesin younger subjects: a timeseries cohort design. J Manip Physiol Ther. 2001;24(6):385–93.

65. Hasler C, Schmid C, Enggist A, Neuhaus C, Erb T. No effect of osteopathictreatment on trunk morphology and spine flexibility in young women withadolescent idiopathic scoliosis. J Child Orthop. 2010;4(3):219–26.

66. Haugen E, Benth J, Nakstad B. Manual therapy in infantile torticollis: arandomized, controlled pilot study. Acta Paediatr. 2011;100(5):687–90.

67. Saedt E, Driehuis F, Hoogeboom TJ, van der Woude BH, de Bie R. Nijhuis-van der Sanden MWG. Common manual therapy practices in theNetherlands for infants with upper cervical dysfunction: a prospectivecohort study. J Manip Physiol Ther. 2018;41(1):52–61.

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 37 of 38

68. Carnes D, Plunkett A, Ellwood J, Miles C. Manual therapy for unsettled,distressed and excessively crying infants: a systematic review and meta-analyses. BMJ Open. 2018;8(1):e019040.

69. Huang T, Shu X, Huang YS, Cheuk DK. Complementary and miscellaneousinterventions for nocturnal enuresis in children. Database Syst Rev. 2011;12:CD005230.

70. Triano J, Lester S, Starmer D, Hewitt EG. Manipulation peak forces acrossspinal regions for children using mannequin simulators. J Manip PhysiolTher. 2017;40(3):139–46.

71. Cooperstein R, Gleberzon BJ. Technique Systems in Chiropractic. ChurchillLivingstone. Edinburgh, UK. 2004.

72. Byfield D. Techniques Skills in Chiropractic. Churchill Livingstone. Edinburgh,UK. 2012.

73. Gleberzon BJ, Ross K. Manual of Diversified Diagnostic and TherapeuticProcedures. Self-Published (CMCC). 2017.

74. Triano JJ, McGregor M, Howard L. Enhanced learning of manipulationtechniques using Force-Sensing Table Technology (FSTT). Toronto: HigherEducation Quality Council of Ontario.

Parnell Prevost et al. BMC Complementary and Alternative Medicine (2019) 19:60 Page 38 of 38