OBSTETRICS

Pregnancy, obstetric, and perinatal healthoutcomes in eating disordersMilla S. Linna, MD; Anu Raevuori, MD, PhD; Jari Haukka, PhD;Jaana M. Suvisaari, MD, PhD; Jaana T. Suokas, MD, PhD; Mika Gissler, MD, PhD

OBJECTIVE: The purpose of this study was to assess pregnancy,obstetric, and perinatal health outcomes and complications in womenwith lifetime eating disorders.

STUDY DESIGN: Female patients (n 2257) who were treated at theEating Disorder Clinic of Helsinki University Central Hospital from 1995-

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slow fetal growth, premature contractions, short duration of the firststage of labor, very premature birth, small for gestational age, lowbirthweight, and perinatal death. Increased odds of premature con-tractions, resuscitation of the neonate, and very low Apgar score at 1minute were observed in mothers with BN. BED was associatedpositively with maternal hypertension, long duration of the first and

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J, et al. Pregnancy, obstetric, and perinatal health outcomes in eating disorders. Am J Obstet Gynecol

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Research ajog.orgPsychiatry, Tampere School of Public Health, Tampere (Dr Suvisaari), Finland, and Nordic School of Public Health, Gothenburg, Sweden (Dr Gissler).

Received Dec. 10, 2013; revised Feb. 18, 2014; accepted March 31, 2014.

Supported by doctoral programs in Public Health, Academy of Finland, and by research grants from Helsinki University Central Hospital.

The funders were not involved in the conduct of the study, collection, management, or analysis and interpretation of the data.

J.T.S. and J.M.S. have been involved in a research collaboration with Janssen-Cilag. J.T.S. has received fees for giving expert opinions to LightlakeSinclair and attended one international conference supported by Janssen-Cilag. J.M.S. has received a lecturing fee from AstraZeneca. J.H. has been inresearch collaboration with Janssen-Cilag and Eli Lilly and has been a member of the expert advisory group for Astellas. The other authors report noconict of interest.

Presented at the International Conference on Eating Disorders, Montreal, QC, Canada, May 2-4, 2013.

Reprints: Milla Linna, MD, Hjelt Institute, Department of Public Health, PO Box 41, 00014 University of Helsinki, Finland. milla.linna@helsinki.

0002-9378/$36.00 2014 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.ajog.2014.03.067E psychiatric disorders amongwomen at childbearing age. Accordingto epidemiologic studies, at least 1 in20 women experiences some form ofED during pregnancy.1-3 Salient symp-toms of EDs include disturbed eatingbehavior, pronounced fear of weightgain, and dissatisfaction with onesbody. Accompanying dysfunctional

eating, binge and pusive exercise, and laon the ED subtypecompromise the hof the body. Anxsymptoms are alsodisorders. Residualmon even yearsfrom ED.4-6

From the Department of Public Health, Hjelt Institute, University of HelsinkiHelsinki University Central Hospital (Dr Raevuori); Department of Mental He(Drs Raevuori, Haukka, Suvisaari, and Suokas); Department of Psychiatry,Health andWelfare (Dr Gissler), Helsinki; Institute of Clinical Medicine, Child P392.e1 American Journal of Obstetrics& Gynecology OCTOBER 2014ge episodes, exces-ative abuse dependand often severelymeostatic balancety and depressivebiquitous in thesemptoms are com-fter the recovery

healthy women experience worry relatedto weight gain and their changing bodyduring pregnancy and the postpartumperiod,7 and food cravings and uctua-tions in eating patterns are physiologicduring these periods. With this back-ground, it is evident that pregnancy andthe postpartum period represent extrachallenges for women with EDs.

rs Linna, Raevuori, and Haukka); Department of Adolescent Psychiatry,h and Substance Abuse Services, National Institute for Health and Welfareelsinki University Central Hospital (Dr Suokas); and National Institute forychiatry, University of Turku, Turku (Dr Raevuori); and Department of Social2014;211:392.e1-8.

ating disorders (EDs) are common behaviors, such as very restrictive On the other hand, many otherwiseobserved in women with BED. Maternal AN w

Cite this article as: Linna MS, Raevuori A, Haukka2010 were compared with unexposed women fr9028). Register-based information on pregnannatal health outcomes and complications were abirths during the follow-up period among womnervosa (AN; n 302 births), broad bulimia nbinge eating disorder (BED; n 52), and unexpoRESULTS: Women with AN and BN gave birtbirthweight compared with unexposed womenm the population (n, obstetric, and peri-quired for all singletonn with broad anorexiarvosa (BN; n 724),d women (n 6319).to babies with lowerbut the opposite wass related to anemia,

second stage of labor

CONCLUSION: Eatingadverse perinatal outcclose monitoring of peating disorder. Attenthese mothers.

Key words: eating dipregnancy, reproductind birth of large-for-gestational-age infants.

sorders appear to be associated with severales, particularly in offspring. We recommendgnant women with either a past or currentn should be paid to children who are born to

rder, obstetric complication, perinatal health,health

Perinatal health outcomes andcomplications

ajog.org Obstetrics ResearchAdequate nutrition and weight gainare crucial for fetal development, andmaternal stress has potentially detri-mental effects on offspring.8 Currentevidence on the effects of maternalEDs on pregnancy, delivery, and peri-natal outcomes suggests increased risksfor several complications,9-19 althoughstudies are not fully conclusive. This isthe reason that we aimed to examine therisk of pregnancy and obstetric com-plications and adverse perinatal healthoutcomes in a large patient cohort whowas treated for EDs. Based on currentevidence, we hypothesized that womenwith anorexia nervosa (AN) wouldhave higher risk of pregnancy, obstetric,and perinatal complications related toundernourishment (eg, anemia, lowbirthweight, small-for-gestational-age[SGA]), that women with binge eatingdisorder (BED) would have an elevatedrisk of complications related to binge-eating and obesity (eg, hypertension,gestational diabetes mellitus, pretermbirth, large-sized infants), and thatcomplications of women with bulimianervosa (BN) would be a mixture ofthese. In addition, we hypothesized thatcomplications related to stress, anxiety,and depressive symptoms (eg, prematurecontractions, preterm birth) would bepresent in patients from all 3 EDcategories.

MATERIALS AND METHODSFrom hospital records, we manuallyidentied all patients who had beentreated in the ED clinic at the Hel-sinki University Central Hospital from1995-2010. Matched unexposed controlwomen were selected randomly fromthe Central Population Register as de-scribed previously.20,21A register searchon pregnancy, obstetric, and perinataloutcomes was conducted on 2257 pa-tients and 9028 unexposed women for thefollow-up period (extending from ad-mission to Dec. 31, 2010/death/movingabroad/reaching age 50 years). We focushereby on pregnancies that led to child-birth. All births during the follow-upperiod were included; however, multiplebirths were excluded (n 104).The ED diagnoses were set byattending physicians at the clinic with theuse of International Statistical Classica-tion of Diseases and Related Health Prob-lems, 10th revision (ICD-10) criteria,22

where F50.0, F50.1, F50.2, and F50.3indicate AN, atypical AN, BN, andatypical BN, respectively. We used broadcriteria for AN and BN, with atypicalforms combined with full disorders. Inthe clinic, diagnosis of BED was set withthe use of Diagnostic and StatisticalManual of Mental Disorders, fourth edi-tion (DSM-IV), research criteria.

Outcome measuresData on outcome measures were ob-tained from the Medical Birth Register,which covers all delivery hospitals inFinland (live births and stillbirths with22 weeks gestation or birthweight500 g). Data quality studies indicatethat most of the register content cor-responds well/satisfactorily with hospitalrecords.23

Pregnancy complicationsThe following pregnancy complications(recorded since 2004) were included:gestational diabetes mellitus (pathologicoral glucose tolerance test), initiation ofinsulin treatment during pregnancy,anemia, antenatal corticosteroid treat-ment, and pregnancy-related ICD-10diagnoses of the mother (since 2004).ICD-10 diagnoses included preeclamp-sia (O14), hypertension (O13, O16),slow fetal growth (O36.5, P05.0, P05.1,P05.9), fast fetal growth (O36.6), oligo-hydramnios (O41.0), infection of amni-otic uid (O41.1), premature rupture ofmembrane (O42), any placental disorder(O43, O44, O45, O73, and a separatecheck-box on placenta previa in theMedical Birth Register data collectionform), fear of childbirth (O99.80), pre-mature contractions (O47), proteinuria(O12.1), hyperemesis gravidarum(O21.0, O21.1, O21.2, O21.9), any veincomplication (O22), urogenital infec-tion (O23), hepatogestosis (O26.6),exhaustion (O26.82), symphyseolysis(O26.7), cervix insufciency (O34.3),suspected fetal injury because of alcohol/drugs (O35.4, O35.5), and suspectedfetal hypoxia (O36.3). Information oneclampsia was available for the whole

duration of the follow-up period.

OCTOBER 2014 AmeriThe following perinatal outcomes wereincluded: perinatal death, gestational age(by fetal ultrasound examination at therstmaternity care visit), premature birth(

growth was observed more frequently in

unexposed women (P not signicant).

Research Obstetrics ajog.orgEthical considerationsThe Ethics committee of National Insti-tute of Health and Welfare has reviewedthe study with a positive statement(DnroTHL/184/6.02.00/2011). Datahandling was performed according tothe Finnish data protection legislationand the rules of National Institute ofHealth andWelfare. All institutions gavetheir permission to use their registerdata in this study. The authors did nothave access to the personal identicationdata; only research codes were used in allanalyses.

RESULTSWe identied 1078 singleton birthsamong patients and 6319 among unex-posed women during the follow-upperiod. Mothers with broad AN (n 182) delivered 302 babies; mothers withbroad BN (n 436) and BED (n 39)delivered 724 and 52 babies, respectively.Unexposed mothers (n 3642) deliv-ered 6319 babies. Only singleton child-births are reported here.

Demographic characteristicsThe mean age at childbirth was 29.4 5.0 (SD) years in women with AN, 30.4 1.2 years in women with BN, 30.2 1.0 years in women with BED, and29.1 4.8 years in unexposed women.Being married was less common amongwomen with AN compared with unex-posed women (P < .001), and beingdivorced was more common in womenwith AN and BED (P< .001 and .005,respectively). There were no differencesacross the groups in being single.Among those who gave birth, parity wasdistributed equally in women with ANand BED compared with unexposedwomen, whereas the number of previ-ous births was lower among womenwith BN (P .005). Smoking duringpregnancy was less common amongwomen with an ED compared withunexposed women (P .04 for BN;not signicant for AN and BED).

Prenatal careThe total number of prenatal carevisits was higher among women withBN and BED compared with unexposed

women, and all patient groups had an

392.e3 American Journal of Obstetrics& GynecolDuration of the rst stage of laborwas the shortest among women withAN (mean, 733 401 minutes, adjustedP .031) and the most lengthy amongwomen with BED (mean, 1249 309minutes; adjusted P < .001) relative tounexposed women (mean, 811 503minutes). Similarly, the second stage oflabor was prolonged among womenwithBED (mean, 110 73 minutes) com-paring with unexposed women (mean,43 55 minutes; adjusted P .018).There were no statistically signicantdifferences between the exposure groupswomen with AN compared with unex-posed women. Women with AN andBN had increased odds of prematurecontractions compared with unexposedwomen.

Obstetric complicationsThe rate of induction of labor was14.8% in women with AN, 18.2% inwomen with BN, 26.4% in women withBED, and 15.5% in unexposed women(P not signicant). The elective ce-sarean section rate was 7.1% in womenwith AN, 7.3% in women with BN,11.3% in women with BED, and 5.9% inelevated number of hospital outpatientvisits before delivery. The mean numberof prenatal care visits was 16.7 0.3(P not signicant) in women withAN, of which 3.6 0.2 (P < .001) werehospital outpatient visits, 17.2 0.2(P< .001) in women with BN, of which3.7 0.1 (P < .001) were in the hos-pital, 19.6 0.9 (P < .001) in womenwith BED, of which 4.7 0.5 (P< .001)were in the hospital, and 16.4 0.06in unexposed women, of which 2.9 0.03 were in the hospital.

Pregnancy complicationsMost of the pregnancy complicationsoccurred in similar percentages acrossthe exposure groups (Table 1).Anemia was more frequent among

women with AN compared with unex-posed women. The risk of maternalhypertension was elevated in womenwith BED. Furthermore, slow fetalin terms of other obstetric outcomes.

ogy OCTOBER 2014Perinatal health outcomes andcomplicationsWomen with AN and BN gave birth tobabies with lower birthweight comparedwith unexposed women (mean, 3302 562 g; adjusted P < .001 in womenwith AN; mean, 3464 563 g; adjustedP .037 inwomenwith BN; mean, 3520 539 g in unexposed women), whereasbirthweight was higher among babies ofwomen with BED (mean, 3812 519 g;adjusted P < .001). Similarly, womenwith AN had an increased odds for SGAinfants and infants with low birthweight(Table 2), whereas odds for LGA infantswas increased among women with BED.Gestational age was the lowest amongwomen with AN and the highest amongwomenwith BED (AN:mean, 39.6 2.1weeks; adjusted P .032; BN: mean39.7 1.9 weeks; adjusted P .026;BED: mean, 40.1 1.4 weeks; adjustedP .27; unexposed: mean, 39.9 1.8weeks). Women with AN had anincreased risk of very premature birth.All 3 cases of very premature birthamong women with AN were sponta-neous in nature. Assisted ventilation andmonitoring of the neonate occurred insimilar percentages across the groups,whereas resuscitation and very low Apgarscore at 1 minute after the birth weremore common among infants born towomen with BN compared with unex-posed women. Babies of womenwith ANhad a 4-fold risk of perinatal death(adjusted odds ratio, 4.06; 95% con-dence interval, 1.15e14.35). All of these3 babies were born prematurely; 2 ofthemwere born very prematurely at

hor

ajog.org Obstetrics ResearchTABLE 1Pregnancy complications in womenPregnancy complication An

Gestational diabetes mellitussurprisingly, risks of resuscitation of theneonate and very low Apgar score at1 minute from birth were increased. Inline with previous studies, elevated risksof hypertension, prolonged rst andsecond stage of labor, higher birthweightof infants, and, in a similar vein, LGA

n (%) 5 (1

Odds ratio (95% CI)

Crude 0.4

Adjusted 0.3

Anemia

n (%) 12 (3

Odds ratio (95% CI)

Crude 2.6

Adjusted 2.3

Hypertensionb

n (%) 3 (1

Odds ratio (95% CI)

Crude 0.6

Adjusted 0.6

Slow fetal growthb

n (%) 14 (4

Odds ratio (95% CI)

Crude 2.4

Adjusted 2.5

Fast fetal growthb

n (%) 0

Odds ratio (95% CI)

Crude

Adjusted

Premature contractionsa

n (%) 7 (3

Odds ratio (95% CI)

Crude 2.1

Adjusted 2.3

Results of logistic regression models are provided.

CI, confidence interval; ICD-10, International Statistical Classific

a Statistically significant findings; b Information is based on ICD-

Linna. Pregnancy outcomes in eating disorders. Am J Obstewith an eating disorder compared witexia nervosa Bulimia nervosainfants were observed among motherswith BED. Despite these observed ad-verse outcomes, the course of pregnancywas favorable for most women whohad been treated for an ED.Our nding of lower birthweight of

infants in mothers with AN parallels

.66) 27 (3.73)

0 (0.14e1.13) 0.91 (0.57e1.46)

8 (0.13e1.10) 0.81 (0.51e1.31)

.97) 12 (1.66)

5 (1.38e5.11)a 1.08 (0.57e2.06)

9 (1.20e4.76)a 1.05 (0.54e2.03)

.4) 6 (1.22)

2 (0.19e1.98) 0.54 (0.21e1.4)

3 (0.20e2.00) 0.51 (0.20e1.33)

.64) 22 (3.04)

7 (1.36e4.48)a 1.59 (0.99e2.55)

9 (1.43e4.71)a 1.53 (0.94e2.48)

7 (1.42)

1.54 (0.68e3.51)

1.54 (0.69e3.47)

.26) 16 (3.25)

8 (0.99e4.83) 2.18 (1.18e4.00)a

1 (1.05e5.11)a 2.20 (1.17e4.14)a

ation of Diseases and Related Health Problems, 10th revision.

10 diagnosis.

t Gynecol 2014.

OCTOBER 2014 Ameriunexposed womenBinge eating disorder Unexposedthe ndings of a recent metaanalysis.14

A similar pattern was found for SGA.Our study also provides evidence forhigher risk of very premature birth inmothers with AN. However, it should benoted that the number of very prematurebirths was small. Previous literature on

2 (3.85) 257 (4.07)

0.94 (0.24e3.75) 1

0.85 (0.22e3.23) 1

0 97 (1.54)

1

1

4 (22.22) 87 (2.24)

12.48 (3.82e40.82)a 1

13.29 (4.03e43.81)a 1

0 122 (1.93)

1

1

1 (5.56) 36 (0.93)

6.29 (0.80e49.67) 1

6.06 (0.72e50.99) 1

1 (5.56) 59 (1.52)

3.82 (0.49e29.77) 1

3.96 (0.51e30.95) 1

can Journal of Obstetrics& Gynecology 392.e4

Research Obstetrics ajog.orgTABLE 2prematurity is conicting, but most ofthe literature suggests an elevated riskof preterm birth in EDs in general18,26

Perinatal health complications in infPerinatal health complication

Resuscitation

n (%)

Odds ratio (95% CI)

Crude

Adjusted

Perinatal death

n (%)

Odds ratio (95% CI)

Crude

Adjusted

Small for gestational age

n (%)

Odds ratio (95% CI)

Crude

Adjusted

Large for gestational age

n (%)

Odds ratio (95% CI)

Crude

Adjusted

Premature birth

n (%)

Odds ratio (95% CI)

Crude

Adjusted

Very premature birth

n (%)

Odds ratio (95% CI)

Crude

Adjusted

Low birthweight

n (%)

Odds ratio (95% CI)

Crude

Adjusted

Linna. Pregnancy outcomes in eating disorders. Am J Obste

392.e5 American Journal of Obstetrics& Gynecoland specically in women with AN,11,15

in women with BN,17 in women witheating disorder not otherwise speciede

ants of women with an eating disorderAnorexia nervosa Bulimia nervosa

3 (0.99) 15 (2.07)

1.08 (0.34e3.45) 2.28 (1.29e4.03)a

1.06 (0.33e3.37) 2.12 (1.18e3.79)a

3 (0.99) 3 (0.41)

3.00 (0.89e10.2) 1.25 (0.37e4.20)

4.06 (1.15e14.35)a 1.78 (0.51e6.19)

13 (4.30) 23 (3.18)

2.09 (1.17e3.73)a 1.53 (0.94e2.47)

2.20 (1.23e3.93)a 1.51 (0.92e2.48)

1 (0.33) 19 (2.62)

0.13 (0.02e0.94)a 1.07 (0.65e1.78)

0.13 (0.02e0.91)a 1.10 (0.66e1.84)

15 (4.98) 36 (5.01)

1.22 (0.67e2.22) 1.23 (0.82e1.84)

1.28 (0.71e2.33) 1.28 (0.85e1.91)

3 (0.99) 3 (0.42)

3.51 (1.02e12.09)a 1.46 (0.43e5.01)

4.59 (1.25e16.87)a 1.84 (0.51e6.62)

19 (6.31) 30 (4.16)

2.05 (1.23e3.40)a 1.32 (0.88e1.98)

2.16 (1.30e3.58)a 1.37 (0.90e2.07)

t Gynecol 2014.

ogy OCTOBER 2014purging, and in women with BED.12

A lower risk of preterm births in womenwith AN and BN has been reported by

compared with unexposed womenBinge eating disorder Unexposed

0 58 (0.92)

1

1 (1.92) 21 (0.33)

5.88 (0.79e43.57) 1

9.51 (1.33e68.26)a

0 133 (2.10)

1

5 (9.62) 155 (2.45)

4.23 (1.64e10.92)a 1

4.32 (1.64e11.36)a

0 259 (4.11)

1

0 18 (0.29)

1

0 201 (3.19)

1

(continued)

f r

ajog.org Obstetrics ResearchTABLE 2Perinatal health complications in in(continued)

Perinatal health complication

Very low birthweight

n (%)

Odds ratio (95% CI)

Crude

Adjusted

Low Apgar score at 1 min (

delivery complications increase the risk

comes in women with eating disorders. Obstet

Research Obstetrics ajog.orgdelivery,45 cesarean delivery,44,46,47

LGA,44,48 congenital anomalies,49 andstillbirth,35,36,44,50 whereas obesity iscommon in women with BED. Bingeeating persists in many women withBED during pregnancy. Moreover, preg-nancy is shown to present a risk windowfor incident BED,1 and binge eatingtends to lead to greater gestational weightgain and related complications amongthesewomen.1,12,51 In our study, BEDwasrelated to maternal hypertension andprolonged rst and second stage of labor.The large sample size and compre-

hensive register-based data allowed us toinvestigate a large spectrum of specicoutcomes and complications. However,some limitations need to be considered:rst, our sample was drawn from aspecialized clinic, which implies that se-vere cases of EDs may be over-presented.Second, the diagnoses in this studywere intake diagnoses, and we did nothave information on continuation ofED symptoms or diagnostic cross-over.Third, we were limited to variables thatwere recorded in national registries.Gestational weight gain may have con-founded or mediated the observed asso-ciations; unfortunately, this informationis not recorded in national registries.Furthermore, there may be differencesbetween individual clinicians and localcustoms within hospitals in the diagnosisand reportage of ICD-10 diagnoses re-lated to pregnancy and childbirth, whichmay have led to biased classication.Fourth, we were unable to assess the ef-fects of medication on pregnancy andbirth complications within the frame-work of this study. Overall, the ndingsof this study were largely consistent withthe hypotheses. However, consideringthe high number of outcomes, it mustbe acknowledged that some of the ob-served associations may have occurredby chance. Studies that will use well-powered datasets are needed to assessfurther the risk of severe perinatal healthcomplications with EDs.This study showed a surprisingly high

risk of severe adverse perinatal healthoutcomes in offspring of mothers withan ED, which may affect later develop-ment of the child. Indeed, Koubaa et al52recently reported delayed neurocognitive

392.e7 American Journal of Obstetrics& Gynecolof EDs in the offspring55,56 and a cycle ofrisk has been hypothesized in womenwith AN.57 This cycle is characterized byelevated risks of preterm birth, SGA,lower gestational weight gain, and lowerbirthweight, which later lead to anincreased risk of EDs in the child him/herself. Among other things, the effectsof these adverse outcomes on the fetusmight be mediated through metabolicprogramming. Because genetic and en-vironmental factors further contributeto the overall risk, it is plausible biologi-cally that children of mothers with anED may be at elevated risk of laterEDs and other psychologic problems.Future research should focus on thehealth and psychologic development ofthese children.Our ndings suggest an increased risk

for severe negative health outcomes ininfants who are born to women with ahistory of EDs. We thus recommendclose monitoring of pregnant womenwith either past or current EDs and thefollow-up evaluation of children who areborn to these mothers. -

ACKNOWLEDGMENT

The authors are most grateful to M. Grainger forher contribution to data management andcomputational issues.

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Pregnancy, obstetric, and perinatal health outcomes in eating disordersMaterials and MethodsOutcome measuresPregnancy complicationsObstetric complicationsPerinatal health outcomes and complicationsCovariates

Statistical analysesEthical considerations

ResultsDemographic characteristicsPrenatal carePregnancy complicationsObstetric complicationsPerinatal health outcomes and complications

CommentAcknowledgmentReferences