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Journal of Pediatric Surgery (2010) 45, 2369–2372

Early developmental outcome of infants with infantilehypertrophic pyloric stenosis☆

Karen Walker a,⁎, Robert Halliday a, Andrew J.A. Hollandb,Caroline Karskens a, Nadia Badawi a

aGrace Centre for Newborn Care, The Children's Hospital at Westmead, Discipline of Paediatrics and Child Health,Sydney Medical School, The University of Sydney, New South Wales 2145, AustraliabDouglas Cohen Department of Paediatric Surgery, The Children's Hospital at Westmead, Discipline of Paediatrics and ChildHealth, Sydney Medical School, The University of Sydney, New South Wales 2006, Australia

Received 7 August 2010; accepted 12 August 2010

PoS9

0d

Key words:Infantile hypertrophicpyloric stenosis;

Neonate;Outcome;Survival

AbstractPurpose: The study aimed to compare the developmental outcome of infants with infantile hypertrophicpyloric stenosis (IHPS) who underwent pyloromyotomy with healthy control infants in New SouthWales (NSW), Australia.Methods: Infants diagnosed with IHPS requiring surgical intervention were enrolled prospectivelybetween August 1, 2006, and July 31, 2008. Healthy control infants were enrolled in the same period.The children underwent a developmental assessment at 1 year of age (corrected) using the Bayley Scalesof Infant and Toddler Development (Version III).Results: Of 52 infants with IHPS who were enrolled, 43 had developmental assessments. Most (90.6%)were term infants (N36 weeks gestation) with a median birth weight of 3237.8 g. Two infants (8%) hadan associated birth defect, and survival was 100%. Developmental assessments were also performed on211 control infants. Infants with IHPS scored significantly lower on the cognitive, receptive language,fine motor, and gross motor subscales compared to the control infants.Conclusions: This unique study found lower than expected developmental scores for infants aftersurgery for IHPS than for healthy control infants. These findings raise concerns over the potentialimpact of IHPS and its surgical treatment. Further studies, including continuing developmental reviewto determine whether these differences persist and their functional importance, should be performed.Crown Copyright © 2010 Published by Elsevier Inc. All rights reserved.

☆ Sponsor: Andrew J.A. Holland. Douglas Cohen Department ofaediatric Surgery, The Children's Hospital at Westmead, Disciplinef Paediatrics and Child Health, Sydney Medical School, The University ofydney, New South Wales, Australia. Tel.: +61 2 9845 1908; fax: +61 2845 3346. E-mail address: andrewh3@chw.edu.au.⁎ Corresponding author. Tel.: +61 2 9845 1923; fax: +61 2 9845 2251.E-mail address: karenw4@chw.edu.au (K. Walker).

022-3468/$ – see front matter. Crown Copyright © 2010 Published by Elsevieroi:10.1016/j.jpedsurg.2010.08.035

Infantile hypertrophic pyloric stenosis (IHPS) continuesto be a common pediatric surgical condition, with anincidence reported of 1 to 8 per 1000 live births [1,2]. Themusculature of the pyloric canal becomes thickened, usuallyin the first few months of life, causing a gastric outletobstruction [3]. The etiology of the condition is unknown [4],although there appears to be a familial tendency.

Inc. All rights reserved.

Table 1 Summary of developmental assessment

Group Mean P 95% CI ofthe difference

Cognition Controls 211PS 43

11.6210.77

.025 0.109 1.588

Receptivelanguage

Controls 211PS 43

10.979.67

.002 0.493 2.101

Expressivelanguage

Controls 211PS 43

9.729.07

.072 −0.058 1.350

Fine Motor Controls 211PS 43

9.938.91

.003 0.346 1.707

Gross Motor Controls 211PS 43

9.528.21

.006 0.386 2.243

2370 K. Walker et al.

The first clinical description of IHPS was in 1627 byFabricius Hildanus [5], but it was subsequently more clearlydefined at a conference by Harold Hirschsprung in 1888 [3].Surgical correction by the Ramstedt procedure under generalanesthesia (GA), initially reported in 1911, remains thestandard treatment for this condition and is considered a“relatively simple procedure with an excellent outcome” [3].

There have been many studies evaluating the incidenceand changing patterns of IHPS [6,7], methods of surgicalcorrection [8], and the impact of volume of surgical cases oncomplications [9]. Outcome data for these infants, however,have tended to focus on surgical results and immediatemorbidity [10]. These data demonstrate that this condition, atleast in contemporary practice, has been generally associatedwith a low mortality and a complication rate of around 2.7%[9]. Considered a relatively innocuous condition, there hasbeen little information on developmental outcomes aftersurgical treatment.

We aimed to describe the current survival and to comparethe developmental outcome of a cohort of infants with IHPSwho had surgery at a single tertiary pediatric hospital.

1. Methods

1.1. Patients and data collection

Data were obtained from the DAISy (Development afterInfant Surgery) study. Infants enrolled in this population-based study for a period of 2 years from August 1, 2006, toJuly 31, 2008, were eligible for inclusion. The DAISydatabase represents a prospectively collected database from 5participating tertiary centers in New South Wales. Three ofthese units perform major neonatal surgery, defined as theopening of a body cavity [11]. Criteria for inclusion in theDAISy database were either major cardiac or noncardiacsurgery within the first 90 days of age, with healthy controlsenrolled from co-located maternity units. During the studyperiod, there were 52 infants enrolled with a diagnosis ofIHPS who required a pyloromyotomy under GA and 211control infants.

1.2. Developmental assessment

Infants were assessed at a corrected age of 1 year using theBayley Scales of Infant and Toddler Development, VersionIII (BSITD) [12]. The assessment consisted of 5 scales:cognition, receptive language, expressive language, finemotor, and gross motor. The parents also completed a social-emotional questionnaire. This assessment has been wellvalidated as developmentally appropriate and the previousversion had been used widely in Australia and in ourpreliminary work [13-15]. Each infant was assessed by 2Bayley-trained assessors, one of whom was blinded to theinfants' study group. Parents were asked not to identify theirchild's surgical status to the assessor.

The scores for infants with IHPS on the 5 subscales of theBSITD were then compared with the scores for the controlinfants, and P b 0.05 was considered statistically significant.Statistical analysis was performed using SPSS statisticalsoftware version 17 (SPSS, Chicago, Ill) [16]. Normalprobability plots were calculated to determine normality ofthe data and the t test was used to determine differencesbetween the means for the subscales.

2. Results

Fifty-two infants with a diagnosis of IHPS were enrolledin the study. Of these, 43 infants (83%) returned for follow-up assessment at 1 year of age (corrected). Two infants werewithdrawn, with the reason for one cited as, he was “fine anddid not require follow-up.” Seven infants were lost to follow-up, 3 of whom had moved interstate.

The mean gestational age of the control infants was 40weeks (SD, ±1.2 weeks), with a mean birth weight of3538 g (SD, ±490 g). All control infants were from asingleton pregnancy and were term, with most of the babiesbeing male (54%).

The mean gestational age of infants with IHPS was 38.4weeks (SD, ±2.0 weeks), with a mean birth weight of 3238 g(SD, ±667 g). Only 4 of the infants with IHPS were preterm,defined as delivery at less than 37 weeks of gestation. Mostof the babies were male (77%), with one set of twins whoboth underwent surgery. There were no reported deathswithin the cohort.

The median age at presentation was 30.8 days (10-77days). The clinical diagnosis was confirmed by ultrasound in83% of infants. Most (86%) had an open pyloromyotomy,whereas 14% had a laparoscopic pyloromyotomy based onthe treating surgeon's preference. The median length of staywas 4 days (range, 2 -13 days). Two infants (8%) hadassociated anomalies (one an anorectal malformation andanother unilateral hydronephrosis).

At 1 year of age, there was no difference in the meanweight or height between the 2 groups of infants. Infants withPS had a mean weight of 10.5 kg compared with a mean

2371Infantile hypertrophic pyloric stenosis outcome

weight of 10.6 kg for the control infants. Mean height for theinfants with PS was 76.3 cm compared with 75.6 cm for thecontrol infants.

Infants with IHPS scored significantly lower on 4 of thesubscales of the BSITD. They scored lower on the cognitive,receptive language, fine motor, and gross motor subscalesthan the healthy control infants (P b .05), although theconfidence intervals were narrow indicating that themagnitude of effect was small Table 1.

3. Discussion

In modern times, pyloromyotomy has been considered arelatively minor surgical procedure, reported to haveexcellent survival and minimal adverse outcomes [6,9].The etiology of IHPS remains unclear, with many hypoth-eses, including genetic, extrinsic factors, structural, andmolecular factors [1]. Research has therefore focused on thepathogenesis of this condition, with outcome studiesgenerally only related to surgical aspects and associatedcomplications [2,8]. It has generally been assumed thatinfants with IHPS have “normal development” afterpyloromyotomy. As far as we can ascertain, there havebeen no prospective studies in the English-languageliterature that have documented the developmental progressof this group of children compared with normal, controlinfants of the same age and gestation.

Most of our patients presented after 3 weeks of life, withonly 8 (18.6%) presenting earlier. The infants with IHPSwere not different in their gestation or birth weight from thecontrol infants and only 2 has associated birth defects.Surprisingly, we found significant differences betweeninfants with IHPS and controls. Specifically, infants withIHPS scored below average in cognition, receptive language,fine motor, and gross motor. Although these differences weresmall, they were statistically significant and clearly persistentbeyond the perioperative period at 12 months of age.

Current neurodevelopmental research suggests that earlylanguage skills appear associated with cognitive skills laterin childhood [17]. It is therefore particularly important toidentify any delay as early intervention programs have beenshown to improve cognitive development in at-risk childrenby up to 25%. Subsequently, such interventions may reduceadverse social outcomes including school absenteeism,delinquency, and long-term unemployment [18].

Although this study clearly identified adverse neurode-velopmental outcomes in infants after surgical treatment ofIHPS, the etiology may only be speculated upon at this stage.The differences observed may be related to the IHPS througha common genetic etiology, a result of nutritional compro-mise secondary to IHPS at a critical time in early braindevelopment, potentially through the effect of GA or acombination of these factors [19-21]. Given the promptnessof contemporary diagnosis of IHPS, in part as a result of theincreasing use of ultrasound, significant malnutrition wouldseem unlikely to be a major contributing factor [22]. In

contrast, there has been increasing interest in the effects ofanesthesia on young infants, with several animal studiessuggesting a neurotoxic effect including neurodegenerationand possible long-term cognitive sequelae [23-25]. Onestudy has even demonstrated a central neurapoptoticresponse in a murine model after even subanesthetic dosesof propofol [26].

A recent population-based study investigated the associ-ation between GA before 4 years of age and subsequentdevelopment of reading, written language, and math learningabilities. Although the authors found that multiple exposureto GA was a significant risk factor for the development oflearning disabilities, this was confounded by complexmedical conditions requiring multiple surgery [19]. Incontrast, DiMaggio et al compared the incidence ofbehavioral and developmental disorders in children whounderwent hernia surgery before 3 years of age with matchedcontrol infants. Their results showed that the surgical infantswere more than twice as likely to be diagnosed withbehavioral or developmental problems than control infants[20]. It is unclear from these studies whether the actualanesthesia or the underlying condition may be responsiblefor the differences.

4. Limitations of the study

This study was limited by the relatively small sample sizeof the IHPS cohort. As a result of this, it was not possible todetermine any potential impact that might result fromdifferent surgical approaches to the treatment of IHPS. Thesetting of our study precluded evaluation of infants withIHPS, albeit controversially, managed nonsurgically. Such astudy would assist in determining the relative contributionsof GA vs genetic or other factors associated with IHPS.

Perhaps more importantly, to date, we have performedonly one developmental assessment at the relatively earlyage of 12 months. To this end, we plan to follow thesechildren and reassess their development when they are 3years of age to ascertain fully their developmental progress.

Although the infants with IHPS treated by a pyloromyot-omy under GA performed significantly worse than controlinfants on the cognitive, receptive language, fine motor, andgross motor subscales of the BSITD at 12 months of age,they still had a mean score within the average range for theassessment, which is reassuring.

After a relatively minor surgical procedure, with mostinfants having a short hospital stay, this finding should alertpaediatric clinicians to the need for further evaluation.Additional studies should include an assessment of thepotential for alternative anesthetic approaches, includingspinal, epidural, and local anesthesia, to potentially amelio-rate any associated adverse neurodevelopmental sequelae[27]. Potentially all infants that require GA for a surgicalprocedure may need to be enrolled in newborn developmen-tal follow-up clinics.

2372 K. Walker et al.

Acknowledgments

We thank our neonatal and paediatric surgical colleaguesfor permission to enroll their patients in this study.

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