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BSTETRICS

aternal obesity and risk of neuralube defects: a metaanalysis
onja A. Rasmussen, MD, MS; Susan Y. Chu, PhD, MSPH; Shin Y. Kim, MPH; Christopher H. Schmid, PhD; Joseph Lau, MD
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long with the rapid increase in obe-sity prevalence in the United States

nd many other countries in the last 2ecades,1,2 a substantial increase in obe-ity prevalence among women of repro-uctive age has occurred. In a recenttudy,3 data from 9 US states showed thatrepregnancy obesity had risen nearly0% from 1993-2004 among womenith a previous live birth; based on Na-

ional Health and Nutrition Examina-ion Survey data, approximately 30% ofS women aged 20-39 years were obeseuring 2003 and 2004.2 Given this highrevalence of maternal obesity, it is crit-

cal to understand fully its effects on theealth outcomes of the mother and herffspring.Several studies have suggested that

bese women are at increased risk of de-ivering an infant with a birth defect,4,5

articularly with a neural tube defectNTD), which is a defect that is caused byailure of neural tube closure 3-4 weeksfter conception.6 Although most stud-es have demonstrated an increased riskf NTDs among obese women,5,7-14 aew have not.15,16 In addition, the degreef risk that is estimated by these studies

rom the Divisions of Birth Defects andevelopmental Disabilities (Dr Rasmussen)

nd Reproductive Health (Dr Chu and Msim), Centers for Disease Control andrevention, Atlanta, GA; Institute forlinical Research and Health Policy Studies,ufts Medical Center (Drs Schmid and Lau),oston, MA.

eceived Feb. 10, 2008; accepted April 9,008

eprints not available from the authors.

he findings and conclusions in this report arehose of the authors and do not necessarilyepresent the official position of the Centers forisease Control and Prevention.

002-9378/$34.00ublished by Mosby, Inc.

doi: 10.1016/j.ajog.2008.04.021

as varied from no increase16 to a nearly-fold increase in risk.5 An estimate ofhe magnitude of the risk of NTDs thatre associated with maternal obesity isecessary to estimate the public healthurden and economic costs of maternalbesity, both of which are substantial forTDs.17-20 This information will alsoelp clarify the relative effect of changes

n obesity prevalence on trends in NTDrevalence, trends that have been moni-ored closely in countries where cerealrain fortification with folic acid haseen instituted.21-24 Analysis of theserends suggests that folic acid fortifica-ion efforts have reduced NTD preva-ence; however, it is important to evalu-te whether other factors, such asaternal obesity, could be affecting

hese changes.In this study, we performed a system-

tic review and metaanalysis of the avail-ble epidemiologic evidence to provide auantitative estimate of the associationetween maternal obesity and NTDs.

aterials and methodsearch processith recommendations from the Meta-

nalysis of Observational Studies in Epi-

We conducted a metaanalysis of publishedobesity and the risk of neural tube defects3 sources: (1) PubMed search of articles thJanuary 2007, (2) reference lists of publisearch, and (3) reference lists of review arwere published from January 2000 throughcriteria. A Bayesian random effects moderegression. Unadjusted odds ratios for an0.99-1.49), 1.70 (95% CI, 1.34-2.15), andobese, and severely obese women, respecNone of the study characteristics includedresults significantly. Maternal obesity is aaffected pregnancy.

Key words: anencephaly, metaanalysis, ne

emiology guidelines,25 we identified c

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tudies for possible inclusion in thisnalysis using 3 sources. First, weearched PubMed records for the periodanuary 1980 to January 2007 using theollowing criteria: (abnormalities ORirth defects OR congenital anomal* ORalformations OR congenital malfor-ations OR neural tube defects) AND

overweight OR obesity OR body massndex OR BMI OR maternal weight)ND (pregnancy OR prepregnancy).rom this search, the full text was re-rieved for articles in which the abstracts

entioned a relationship between ma-ernal obesity and 1 of the terms for con-enital anomalies just cited.Second, we reviewed the reference lists

f the publications that we retrieved pre-iously and obtained the entire text oftudies that potentially could be in-luded in the metaanalysis. Finally, weearched the reference lists of review ar-icles on obesity and maternal outcomeshat were published from January 2000o January 2007 for additional potentialtudies. We did not attempt to locate anynpublished studies.Studies that were considered poten-

ially eligible were then screened for in-

ence on the relationship between maternalDs). Eligible studies were identified fromere published from January 1980 through

ons that were selected from the PubMeds on obesity and maternal outcomes thatnuary 2007. Twelve studies met inclusionas used for the metaanalysis and meta-D-affected pregnancy were 1.22 (95% CI,1 (95% CI, 1.75-5.46) among overweight,ly, compared with normal-weight women.the metaregression analysis affected the

ciated with an increased risk of an NTD-

l tube defect, obesity, spina bifida

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erican Journal of Obstetrics & Gynecology 611

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owing criteria: (1) provided obesityeasures (maternal weight, percentage

ver ideal weight, BMI) that reflectedtatus preceding any significant preg-ancy weight gain (ie, measured or re-orted prepregnancy or during the firstrimester or first prenatal visit); (2) con-ained a comparison group of normal-eight women; (3) reported NTDs as anutcome measure (NTDs were defineds any of the following defects: spinaifida, anencephaly, encephalocele,raniorachischisis, or iniencephaly); and4) provided data in tables, figures, orext that allowed for a quantitative mea-urement of obesity and the risk ofTDs.If there were multiple articles from the

ame study population that met thetudy criteria, we included only the pub-ication with the most complete or mostecent data.

ata abstractionll articles were read and abstracted by 2

eviewers (S.A.R.; S.Y.K.) who used theame structured data form. A final ab-traction was compiled from the 2 formsfter correction or resolution of minimalifferences between the reviewers. Ab-tracted information included study de-

TABLE 1Characteristics of cohort studies ex

Citation CountryType and scohort, stu

Feldman et al.,199915

United States Retrospectlaboratoryyears not s

...................................................................................................................

Kallen, 19989 Sweden Retrospectnational meregistry, 19

...................................................................................................................

Moore et al,200016

United States Prospectivescreening wobstetrical1987

...................................................................................................................

Ray et al,200526

Canada Retrospectscreening wantenatal vdischarge d1994-2000

...................................................................................................................

NA, not available.

Rasmussen. Maternal obesity and risk of neural tube defec

ign, setting, location, and time period; c

12 American Journal of Obstetrics & Gynecology

he number and characteristics of studyarticipants; the source and categoriza-ion of obesity measures; the diagnosticriteria and the source(s) for NTDs (eg,edical records, clinical databases), and

tatistical methods, that included adjust-ent factors. We abstracted data only

or NTDs as a combined group becauseeveral studies did not report findings forpecific NTDs (eg, spina bifida,nencephaly).

tatistical analysisor each study, we constructed separate� 2 tables to calculate the odds ratios

ORs) and 95% CIs of NTDs for eachMI/weight category that was analyzedie, overweight, obese, and severelybese vs normal BMI/weight). In 6 stud-

es, we collapsed narrow intervals intoroupings that more appropriately fitormal-weight, overweight, obese, andeverely obese categories (eg, 19.8-22.0g/m2 and 22.1-24.9 kg/m2 were com-ined into one 19.8-24.9 kg/m2 normal-eight category; Tables 1 and 2). Given

hat NTDs are rare events, we were ableo combine results from cohort and case-ontrol studies, rather than analyzinghem separately. One-third of the studiesresented adjusted ORs; however, be-

ining the relation between BMI and

rce ofperiod

Cohortsize (n)

BMI (kg/m2)/weight

Normal

cohort frombase,ified

72,915 100-140 lb

.........................................................................................................................

cohort fromal birth1993

665,706 19.8-26.0 kg/m2

.........................................................................................................................

hort fromen in 100

ics, 1984-

22,951 �25.0 kg/m2

.........................................................................................................................

cohort fromen duringand

base,

406,191 52.0-64.1 kg

.........................................................................................................................

m J Obstet Gynecol 2008.

ause the adjusted estimates were not d

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ufficiently comparable across studieseg, underweight was used as the refer-nce group; adjusted estimates wereiven for more narrow or more wideroupings than what was defined overalls normal, overweight, obese, and se-erely obese; studies adjusted for differ-nt factors), we could not calculate aummary OR of the adjusted ORs.herefore, only crude ORs were used in

he metaanalysis.Sources for information on prepreg-

ancy BMI/weight included self-re-ort from maternal interview andedical records or databases (Tables 1

nd 2).5,7-9,11-16,26,27 Information onTDs was obtained from birth defects

urveillance systems, hospital records,r clinical databases (Tables 1 and 2).he conditions that were included asTDs varied among the studies: 3

tudies included spina bifida and anen-ephaly; 7 studies included spina bi-da, anencephaly, and encephalocele;nd 2 studies did not specify individualonditions.

Metaanalyses combining the ORscross studies were conducted with aayesian random effects model,28,29 inhich the effects of obesity vary ran-

Dsor lbs) categories

rweight ObeseSeverelyobese

-180 lb 181-260 lb 261-300 lb

..................................................................................................................

.1-29.0 kg/m2 �29.0 kg/m2 NA

..................................................................................................................

.0-27.9 kg/m2 �28.0 kg/m2 NA

..................................................................................................................

.2-85.6 kg �85.6 kg NA

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orates both within and between studyariances. Because the Bayesian modelncorporates uncertainty in the between-tudy variance, it gives wider CIs. It ishus more conservative than empiricalayes models, such as that of DerSimo-ian and Laird.28

The Bayesian model assumes that theounts in the exposed and unexposedroups follow binomial distributions,

TABLE 2Characteristics of case-control stu

Citation Country

Type and sourcecases/control sustudy period

Anderson et al,20057

United States Birth defects survsystem; cases: anspina bifida; contbirths randomly ssame hospital; 19

...................................................................................................................

Hendricks et al,20018

United States Birth defects survsystem; cases: anspina bifida, encecontrol subjects:previous year from1995-2000

...................................................................................................................

Mikhail et al,200527

United States Perinatal databasrecords; cases: Nsubjects: live birtselected from sam1981-1994

...................................................................................................................

Shaw et al,199611

United States Birth defects survsystem; cases: anspina bifida cysticcraniorachischisiscontrol subjects:randomly selectehospitals; 1989-1

...................................................................................................................

Waller et al,199412

United States Perinatal databasrecords; cases: aspina bifida, encecontrol subjects:subjects (normalinfants and fetusegeography; 1985-

...................................................................................................................

Watkins et al,199613

United States Birth defects survsystem; cases: anspina bifida; contbirths matched frcertificates; 1968

...................................................................................................................

Watkins et al,20035

United States Birth defects survsystem; cases: anspina bifida, encecontrol subjects:of births from are1993-1997

...................................................................................................................

Werler et al,199614

United Statesand Canada

Surveillance progtertiary and birthcases: anencephaencephalocele; comalformed infant1988-1994.

...................................................................................................................

NA, not available.

Rasmussen. Maternal obesity and risk of neural tube defec

ith different mean probabilities. These w

eans are modeled on the logit scale sohat their difference represents the logR. The mean and variance of the study

og ORs are random variables in theayesian model. To represent our lack ofrevious knowledge about the value ofhese means and variances, we used dif-use priors that encompassed a wideange of possible values. For means andegression coefficient parameters, these

s that examined the relation betwee

ts Case/control (n)

BMI (kg/m2)/weight (kg)

Normal O

ncephaly,bjects: liveed from001

254/413 18.5-24.9 kg/m2

.........................................................................................................................

ncephaly,

ocele;irths from

me facility;

149/178 18.5-24.9 kg/m2

.........................................................................................................................

d clinicalcontrolndomlyatabase;

17/144 �27.0 kg/m2 �

.........................................................................................................................

ncephaly,

ncephaly;irths

m area

538/539 19.0-27.0 kg/m2

.........................................................................................................................

d geneticephaly,ocele;trol

abnormalatched by7

499/534 19.0-27.0 kg/m2

.........................................................................................................................

ncephaly,bjects: liveirth0

307/2755 19.9-26.0 kg/m2

.........................................................................................................................

ncephaly,

ocele;om samplespitals;

43/330 18.5-24.9 kg/m2

.........................................................................................................................

based onitals;pina bifida,l subjects:etuses;

604/1658 50-69 kg

.........................................................................................................................

m J Obstet Gynecol 2008.

ere normal distributions with mean 0 e

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nd extremely large variance 106; for theariance parameters, we used inverseamma (1.0, 0.1) distributions. To com-ute the Bayesian estimates, we used aarkov chain Monte Carlo algorithm

unning 3 parallel chains and monitor-ng convergence with the Gelman-Rubiniagnostic.30 On convergence, whichenerally occurred within 1000 runs, weaved 15,000 samples from each chain to

MI and NTDsgories

eight ObeseSeverelyobese

-29.9 kg/m2 30.0-39.9 kg/m2 �40 kg/m2

..................................................................................................................

-29.9 kg/m2 �30 kg/m2 NA

..................................................................................................................

g/m2 NA NA

..................................................................................................................

-30.0 kg/m2 31.0-37.0 kg/m2 �38 kg/m2

..................................................................................................................

-30.0 kg/m2 31.0-37.0 kg/m2 �38 kg/m2

..................................................................................................................

-29.0 kg/m2 �29.0 kg/m2 NA

..................................................................................................................

-29.9 kg/m2 �30 kg/m2 NA

..................................................................................................................

9 kg 90-109 kg �110 kg

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odel parameters. The Markov chainonte Carlo algorithm that was used is

escribed in greater detail by Schmidt al.29

We also conducted a Bayesian meta-egression analysis29 to assess whetherhe relationship between log odds ofTDs and obesity varied by certain

tudy characteristics. These includedtudy design (cohort or case-control),ate of publication (1994-1998, 1999-004, and 2005 or later), whether thetudy excluded or adjusted for the pres-nce of diabetes, and whether the studyas adjusted for folic acid intake.

esultshe PubMed search identified 3259

tudies; of these, 63 abstracts reported anding on the relationship between ma-

ernal obesity and congenital anomaliesr NTDs; the full texts of these articlesere retrieved for detailed examination

Figure 1). After review of these articles,0 articles were excluded, either becausehey did not report the results of a cohortr case-control study (including 12 re-iew articles) or because they clearly didot address an association between ma-

FIGURE 1Flow diagram of the study selectio

asmussen. Maternal obesity and risk of neural tube defects.

ernal obesity and NTDs; thus, 33 studies S


ere considered further for inclusion.e reviewed the reference lists of the 63

tudies and identified another 5 studiesor possible inclusion. One additionaltudy was identified from our examina-ion of reference lists of 12 recent reviewrticles.31-42 Therefore, a total of 39 stud-es, including 4 non-English publica-ions that were translated for consider-tion, were screened for final inclusionn the metaanalysis. We excluded 1 studyecause there was no normal-weightomparison group,10 11 studies becauseTDs were not reported as a separate

ategory,43-53 6 studies because other ar-icles reported results on the same studyopulation,54-59 and 9 studies becauseata were not presented in a way to allowhe construction of appropriate 2 � 2ables.60-68

A total of 12 studies (4 cohort9,15,16,26

nd 8 case-control5,7,8,11-14,27) met thenclusion criteria. Of these, 12, 11, and 5tudies presented data for overweight,bese, and severely obese pregnantomen, respectively, compared withormal-weight pregnant women. All butstudies were conducted in the United

rocess

Obstet Gynecol 2008.

tates (Tables 1 and 2). Based on our w

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etaanalysis, the unadjusted ORs for anTD-affected pregnancy were 1.22

95% CI, 0.99-1.49), 1.70 (95% CI, 1.34-.15), and 3.11 (95% CI, 1.75-5.46)mong overweight, obese, and severelybese women, respectively, comparedith women of normal weight (Figures-4). Inclusion of covariates that re-ected the study design in the randomffects model did not alter the estimatedRs meaningfully.

ommentn the basis of the results of this meta-

nalysis, we estimate that maternal obe-ity is associated with a 1.7-fold in-reased risk of NTDs, and severe obesitys associated with a �3-fold increasedisk. Given the high prevalence of mater-al obesity in the United States and otherountries1,2 and the significant morbid-ty, mortality, and disability rates and theosts associated with NTDs,17-20 thesendings have considerable public healthignificance.

Possible mechanisms that led to thebserved association between maternalbesity and increased NTD risk are un-lear, but several possible mechanismsave been suggested. One possibleechanism is related to problems with

lucose metabolism. Animal studiesave provided evidence that hyperglyce-ia is teratogenic to the developing em-

ryo.69 Obesity is known to increase theikelihood of development of diabetes

ellitus,70 and most people who later ex-erience type 2 diabetes mellitus initiallyave impaired glucose tolerance.71 Anssociation between maternal prepreg-ancy diabetes mellitus and an elevatedisk of NTDs and other birth defects isell-recognized72,73; this risk is higher

mong women with poor glucose con-rol in early pregnancy.74 A recent studyuggests that features of metabolic syn-rome (defined in that study as presencef prepregnancy diabetes mellitus, bodyeight �90th percentile value of control

ubjects, nonwhite ethnicity, and/or se-um highly sensitive C-reactive protein

75th percentile of control subjects)ncreased the risk of NTDs. The risk

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nd �2 features of metabolic syndrome,espectively.75

Gestational diabetes mellitus is foundore frequently among obese women,76

nd women with gestational diabetesellitus have been shown in some stud-

es to be at increased risk of having annfant with certain birth defects.43 Thisisk appears to be higher among womenith higher prepregnancy BMI.43,46 The

arly closure of the neural tube (at 3-4eeks before conception)6 precedes theevelopment of gestational diabetesellitus in most women,77 but womenho later experience gestational diabetesellitus might have altered glucose con-

rol earlier in pregnancy. The findingshat hyperinsulinemia (measured afterelivery) was associated independentlyith an increased risk of having an NTD-

ffected pregnancy8 and that obeseomen were more likely to have hyper-

nsulinemia78 also support a role for al-eration in glucose metabolism in the re-ationship between obesity and NTDisk.

Other explanations for the relation-hip between maternal obesity andTDs are that obese and normal-weightomen differ in nutritional require-ents or responses for critical nutrients

r that the diets of obese women are de-cient in critical nutrients. The relation-hip between folic acid and NTDs is well-ecognized6; a daily intake of 400 �g ofolic acid has been shown to decreaseTD risk,79 and higher plasma and red-

ell folate levels in early pregnancy haveeen associated with a lower risk ofn NTD-affected pregnancy.80 Obeseomen could be less responsive to the

ntake of folic acid at the standard00-�g dose than are women of normaleight. A study by Werler et al14 pro-ides support for this hypothesis. Theseuthors found that, among women whoeigh �70 kg, an average daily intake of

olic acid of �400 �g reduced the risk ofn NTD-affected pregnancy by 40%, buthis protective effect was not observedmong women who weigh �70 kg. In atudy of women of childbearing age, hav-ng a higher BMI was associated withower serum folate levels, even after con-rol for intake.81 Using data from that
tudy, the author estimated that obese
FIGURE 2Association of neural tube defects with maternaloverweight status versus normal weight

asmussen. Maternal obesity and risk of neural tube defects. Am J Obstet Gynecol 2008.

FIGURE 3Association of neural tube defects with maternalobesity versus normal weight

asmussen. Maternal obesity and risk of neural tube defects. Am J Obstet Gynecol 2008.

JUNE 2008 American Journal of Obstetrics & Gynecology 615

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omen would require an additional 350g of folic acid to achieve the same se-

um folate level as women in the under-eight category; however, the author

autioned against changing recommen-ations for folic acid supplementationithout further supportive data.Another explanation for the observed

ssociation is that obese women alsoould be more likely to be on diets to loseeight or to have a poor quality diet. In a

ecent study, overweight or obese adultsere more likely to have low levels of sev-

ral micronutrients, when comparedith adults of normal weight, with theighest likelihood of having low levels ofultiple nutrients observed in premeno-

ausal women who were overweight orbese.82 Consistent with this hypothesis,omen who diet to lose weight, espe-

ially those who use fasting diets or thoseith poor-quality diets, have been

hown to have an increased risk of anTD-affected pregnancy.55,83,84

Several limitations should be consid-red when interpreting our findings.ome of the studies in this metaanalysis

FIGURE 4Association of neural tube defectssevere obesity versus normal weig

asmussen. Maternal obesity and risk of neural tube defects.

ere based on outcome sources (eg, w


irth defects surveillance systems) thatometimes did not include pregnanciesn which NTDs were diagnosed prena-ally and followed by pregnancy termi-ation. Because visualization of fetal or-ans on ultrasonography in obeseomen is more difficult,85,86 prenatal as-

ertainment of NTDs might be less com-lete for obese women than for normal-eight women. If this is true, moreTD-affected pregnancies among obeseomen would result in live births or fetaleaths and more would be ascertained byome birth defects surveillance systemshan NTD-affected pregnancies amongormal-weight women. This would haveesulted in an overestimate of the risk ofTDs that were associated with mater-al obesity in those studies,87 which in

urn would have affected our summarystimate.

The variability among studies in theefinitions that were used for maternalbesity could have affected our findings.tudies used different definitions forormal weight, overweight, obese, andevere obese categories and varied in

th maternal

Obstet Gynecol 2008.

hether body weights and heights were b

JUNE 2008

elf-reported or measured. Seven of thetudies did not include a severely obeseategory in their analysis and instead in-luded those mothers in the obese group.lthough this could possibly overesti-ate the risk estimates that are associ-

ted with obesity, we expect the magni-ude of this effect to be small, given thathe number of severely obese women iselatively small. Most of the studies usedelf-reported heights and weights, whichould also result in misclassification ofaternal overweight and obesity.88 The

esulting exposure misclassification, ifignificant, could have resulted in signif-cant heterogeneity in the metaanalysis

odel and bias in the summary estimate,ost likely towards the null. The resultsere somewhat heterogeneous for the

ssociation between maternal over-eight status and NTDs (Figure 2) butere relatively consistent for the associ-

tions for obesity and severe obesityFigures 3 and 4), which suggests thathis effect was minimal. Self-report ofeight and weight also raises the possibil-

ty of recall bias; however, it seems un-ikely that mothers with NTD-affectedregnancies would be more likely toverestimate or underestimate theireight and weight than other mothers.The definition of NTDs also varied

mong the studies; all types of NTDsere included in some studies, and other

tudies focused on the most commonlybserved types (ie, anencephaly andpina bifida). Given that anencephalynd spina bifida make up the vast major-ty of NTDs,6 these differences in defini-ion are not likely to have had a signifi-ant effect on the summary estimate. Andditional study by Waller et al4 that ad-ressed the association between mater-al obesity and birth defects, includingTDs, became available after our cutoff

or inclusion of January 2007. Separatedjusted ORs for anencephaly and spinaifida were presented in that study (ad-

usted OR, 0.96 [95% CI, 0.62-1.48] and.10 [95% CI, 1.62-2.71], respectively).ased on the data from that study, wealculated a crude OR (OR,1.83; 95% CI,.46-2.28) for the association betweenbesity (BMI, �30 kg/m2) and NTDsanencephaly and spina bifida com-

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ummary OR that was calculated in ouretaanalysis; thus, inclusion of this

tudy would not have changed our re-ults substantially. Of note, this studyuggests that obesity may affect the risksor anencephaly and spina bifida differ-ntly. Given that most of the studies thatere included in our metaanalysis didot present data on anencephaly andpina bifida separately, we were unableo address this issue.

Another important issue was thatomen who were obese were more likely

o have prepregnancy diabetes mellitus,hich is a well-known risk factor forTDs89; thus, the association with ma-

ernal obesity and NTD risk could haveeen related to the fact that some obeseomen also had diabetes mellitus. In an

ttempt to control for this issue, 4 studiesn this metaanalysis excluded womenith prepregnancy diabetes melli-

us5,7,13,27; 4 studies performed sub-nalyses with women, with diabetes mel-itus excluded, and noted no materialhange in the risk estimates8,11,12,14; andstudy adjusted for the presence of pre-

estational diabetes mellitus and otheractors, and the adjusted OR did not sub-tantially differ from the unadjusted es-imate. However, if some women had di-betes mellitus that had not beenecognized, these exclusions or adjust-ents for prepregnancy diabetes melli-

us would not have controlled effectivelyor this issue.

Because adjustment for potential con-ounding factors varied among studies,e used only crude study estimates inur metaanalysis. If there were strong ef-ects from confounding factors, ourummary estimate would have been bi-sed. However, in general, adjusted andrude estimates were similar in studies inhich both estimates were presented. Fi-ally, our metaanalysis included onlyublished studies; if studies that sup-orted the association between maternalbesity and NTDs were more likely toave been submitted and published, ourummary estimate would have overesti-

ated the risk of NTDs that are associ-ted with obesity.90

In conclusion, based on our meta-nalysis, maternal obesity was associated
ith a significantly higher risk of an 1
TD-affected pregnancy. The reasonsor this association are unknown. Thisuantitative estimate of the risk adds tour understanding of the total publicealth effects of obesity among womenf reproductive age and provides addi-ional information for appropriate inter-retation of trends in NTD prevalence.uture assessments of trends in NTDrevalence might benefit from taking

nto account the effects of the changingrevalence of maternal obesity. f

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