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Obstet Gynecol. Author manuscript; available in PMC 2019 December 01.
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Published in final edited form as:

Obstet Gynecol. 2018 December ; 132(6): 1386–1393. doi:10.1097/AOG.0000000000002974.

Child Neurodevelopmental Outcomes by Prepregnancy Body

Mass Index and Gestational Weight Gain
Michelle A. Kominiarek, MD, MS,
Departments of Obstetrics and Gynecology of Northwestern University, Chicago, IL

Marcela C. Smid, MD,

University of Utah Health Sciences Center, Salt Lake City, UT
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Lisa Mele, ScM,

the George Washington University Biostatistics Coordinating Center, Washington, DC

Brian M Casey, MD,

University of Texas - Southwestern, Dallas, TX

Yoram Sorokin, MD,

Wayne State University, Detroit, MI

Uma M Reddy, MD, MPH,

the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-
Fetal Medicine Units Network, Bethesda, MD

Ronald J Wapner, MD,

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Columbia University, New York, NY

John M Thorp, Jr MD,

University of North Carolina, Chapel Hill, NC

George R Saade, MD,

University of Texas Medical Branch, Galveston, TX

Alan TN Tita, MD, PhD,

University of Alabama at Birmingham, Birmingham, AL

Dwight J Rouse, MD,

Brown University, Providence, RI

Baha Sibai, MD,

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Corresponding Author: Michelle A. Kominiarek, MD MS, Associate Professor, Northwestern University, 250 East Superior Street
Suite 05-2175, Chicago, IL 60611, (312)472-6747; (312)472-4687 fax, mkominia@nm.org. Each author has indicated that he or she
has met the journal’s requirements for authorship.
Financial Disclosure
Dr. Wapner serves as PI for several studies for which CUMC receives grants. Current funding from commercial entities includes
support from Natera Inc., Sequenom, and llumina, Inc. All funds go directly to CUMC. Dr. Wapner does not receive compensation
from any of these grants. He has also received consulting fees from Bioreference, Illumina Inc., and Natera Inc. The other authors did
not report any potential conflicts of interest.
Dr. Rouse, Associate Editor of Obstetrics & Gynecology, was not involved in the review or decision to publish this article.
* Other members of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal
Medicine Units Network are listed in Appendix 1, available online at http://links.lww.com/xxx.
 Kominiarek et al. Page 2

University of Texas – Houston, Houston, TX

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Jay D Iams, MD,

The Ohio State University, Columbus, OH

Brian M Mercer, MD,

Case Western Reserve University, Cleveland, OH

Jorge Tolosa, MD, and

Oregon Health Sciences University, Portland, OR

Steve N Caritis, MD
University of Pittsburgh, Pittsburgh, PA, for the Eunice Kennedy Shriver National Institute of Child
Health and Human Development Maternal-Fetal Medicine Units Network, Bethesda, MD, USA*

Abstract
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Objective: To study the association of pre-pregnancy body mass index (BMI) and gestational
weight gain with child neurodevelopmental outcomes.

Methods: We performed a secondary analysis of data from two parallel, multicenter, randomized,
double-masked, placebo-controlled, thyroxine replacement trials in pregnant women with either
hypothyroxinemia or subclinical hypothyroidism who delivered at term. Body mass index was
categorized as normal (18.5–24.9kg/m2), overweight (25.0–29.9kg/m2), or obese (≥30kg/m2). We
also evaluated early (≤20 weeks), late (>20 weeks) and total gestational weight gain and
categorized gestational weight gain as inadequate, adequate, and excessive per 2009 Institute of
Medicine guidelines. Neurodevelopmental outcomes included 5-year WPPSI-III and 3-year
Differential Ability Scales-II (DAS-II). Linear and logistic regression analyses were performed
and adjusted for maternal age, race–ethnicity, education, insurance status, parity, smoking and
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alcohol use, thyroid status (subclinical hypothyroidism or hypothyroxinemia), treatment group,

gestational age at delivery, and infant sex.

Results: Of the 948 women included, 380(40%), 305(32%) and 263(28%) had normal,
overweight, and obese prepregnancy BMI, respectively. A total of 106(11%), 212(22%), and
630(66%) of women had inadequate, adequate, and excessive total rates of gestational weight gain,
respectively. Maternal differences among the BMI categories included race–ethnicity, education,
insurance type, parity, and thyroid status (all p<0.01) whereas the gestational weight gain groups
only differed by parity (p<0.001). In unadjusted analysis, children of obese (93.2±12.8; 88.5±13.3)
and overweight (94.1±15.6; 89.6±16.0) women had lower WPPSI-III and DAS-II scores,
respectively than normal weight women (97.4±15.4; 93.9±16.0; p<0.001 for all comparisons);
however, in adjusted analysis, there were no differences in neurodevelopmental outcomes by
maternal BMI. The association was primarily accounted for by race-ethnicity and education. In
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unadjusted and adjusted analyses, there were no differences in neurodevelopmental outcomes by

adequacy of early, late, or total gestational weight gain.

Conclusion: In women with either subclinical hypothyroidism or hypothyroxinemia, neither

prepregnancy BMI nor gestational weight gain were associated with neurodevelopmental
outcomes among children born at term in adjusted analyses.

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Introduction
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Pregnancy is increasingly recognized as a window into the future health of not only the
mother, but also for her child. The maternal effects of obesity also may be intergenerational
with increased risks of childhood obesity along with cardiovascular, metabolic, and
neurodevelopmental problems in the offspring.(1–4) The developmental origins of health
and disease hypothesis suggests that in-utero effects can have long-term consequences on
offspring health.(5) Maternal obesity and peripheral systemic inflammation are associated
with impaired long-term cognition in the offspring in animal studies, suggesting that
cognitive programming occurs early in development.(6)

Although experts report that preventing excessive gestational weight gain may be one of the
most effective strategies to reduce both adverse perinatal outcomes and curb the obesity
epidemic,(7, 8) only 30–40% of women meet their gestational weight gain goals during
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pregnancy.(9, 10) Independent of maternal pre-pregnancy BMI, excessive gestational weight

gain is associated with an increased risk of abnormal cardiovascular and metabolic profiles
among offspring in adolescence and adulthood,(11–13) but less is understood about the
relationship between gestational weight gain and neurodevelopmental outcomes.

The objective of this study was to evaluate the association between pre-pregnancy BMI and
gestational weight gain and child neurodevelopmental outcomes as measured by intelligence
scales (IQ). We hypothesized that there would be an inverse relationship between pre-
pregnancy BMI and neurodevelopmental scores based on the association of obesity and
systemic inflammation and prior animal studies. We also hypothesized that excessive
gestational weight gain after 20 weeks would be associated with worse neurodevelopmental
outcomes as this period of gestation corresponds to the period of fetal brain myelination.(14,
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15)

Materials and Methods

This was a secondary analysis of data from two Eunice Kennedy Shriver National Institute
of Child Health and Human Development Maternal-Fetal Medicine Units Network parallel
randomized trials of thyroxine (T4) for either subclinical hypothyroidism (n=677) or
hypothyroxinemia (n=526). Women with a singleton gestation who were diagnosed with
either subclinical hypothyroidism (thyroid stimulating hormone [TSH] ≥ 4.0 mU/L and free
T4 0.86–1.9 ng/dL) or hypothyroxinemia (TSH 0.08–3.99 mU/L and free T4 <0.86 ng/dL) at
≤ 20 weeks gestation were offered participation in a trial that randomized them to either
placebo or levothyroxine at 15 centers from 2006–2009.(16) The original protocol was
approved by the Institutional Review Board at each center. For the current study, we limited
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the analysis to women with a term delivery (≥ 37 weeks) due to the a-priori risk for adverse
neurodevelopmental outcomes with prematurity, complete data on early pregnancy or pre-
pregnancy BMI, and childhood follow-up at 5 years. In the original trial, the primary
outcome was child IQ at 5 years.

The two exposures of interest were pre-pregnancy BMI and gestational weight gain. BMI
was calculated from maternal self-reported pre-pregnancy weight and height, defined as

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normal (BMI 18.5–24.9 kg/m2), overweight (BMI 25.0–29.9 kg/m2), or obese (BMI ≥ 30
kg/m2). We excluded underweight women (BMI<18.5 kg/m2) due to small sample size
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(n=17). Pre-pregnancy weight and study measured weights were used to calculate
gestational weight gain. Total gestational weight gain was defined as the difference between
the last study weight which typically occurred between 35–37 weeks, and pre-pregnancy
weight. Because of the high proportion of women who did not have a recorded weight after
36 weeks gestation, the gestational weight gain variable was compared to the gestational
weight gain guidelines based on weekly rates of gestational weight gain rather than total
gestational weight gain. We also calculated gestational weight gain according to the timing
during gestation (at ≤ 20 weeks “early” or > 20 weeks “late”) (see Appendix 2, available
online at http://links.lww.com/xxx, for sample calculations). For all BMI categories, the first
trimester gestational weight gain range is 0.5–2 kg whereas second and third trimester
gestational weight gain rate varies by BMI category (normal weight 0.35–0.50 kg/week;
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overweight 0.23–0.33 kg/week; obese 0.17–0.27 kg/week).(17) The total gestational weight
gain and gestational weight gain for the early and late gestational age periods were
compared with expected gestational weight gain based on these guidelines. Actual
gestational weight gain was categorized as inadequate, adequate, or excessive based on
guidelines for expected gestational weight gain for the first trimester plus second and third
trimester weekly weight gain rates.(17)

Our outcomes included the full-scale intelligence quotient (IQ) as measured by the Wechsler
Preschool and Primary Scale of Intelligence (WPPSI-III) at 5 years and Differential Ability
Scales-II (DAS-II) at 3 years. A child developmental specialist administered both the
WPPSI-III, a 1.5 hour full-scale IQ test, and the 1 hour DAS-II test which also measures
cognition and achievement levels and correlates highly with the WPPSI-III. The results were
expressed as age-standardized scores with an expected population mean of 100 and a
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standard deviation of 15. A WPPSI-III score < 85 at 5 years and a DAS-II score < 85 at 3
years were also evaluated as categorical outcomes. Spanish language study materials and
certified medical interpreters were available to participants whose preferred language was
Spanish. Maternal demographics (age, race-ethnicity, education, insurance type) and
characteristics (parity, tobacco and alcohol use, gestational age at randomization), thyroid
status (subclinical hypothyroidism vs. hypothyroxinemia), treatment group (levothyroxine
vs. placebo), and pregnancy outcomes (gestational diabetes, preeclampsia, gestational
hypertension, gestational age at delivery, Apgar scores, birth weight) were compared
between the three BMI categories and the three gestational weight gain categories with
Kruskal-Wallis, Chi-square, or Fisher’s exact tests, as appropriate. Chi-square linear tests for
trend or simple linear regression analysis were used to examine the association of BMI
category with child IQ measures. Chi-square and ANOVA tests were used to compare
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differences in the IQ measures among the three gestational weight gain categories
(inadequate, adequate, excessive) for early, late, and total gestational weight gain.

Multivariable linear regression for examination of continuous outcomes and logistic

regression for binomial outcomes were performed for the two IQ measures. We planned to
adjust for potentially confounding factors including maternal age, race–ethnicity, education,
insurance type, parity, smoking and alcohol use in pregnancy, thyroid status (subclinical
hypothyroidism or hypothyroxinemia), treatment group, gestational age at delivery, and

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infant sex. Backward proceeding stepwise regression models were used to examine the
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potentially confounding factors. Two way interaction terms for education, race–ethnicity,
and insurance type were also examined.

Final parsimonious models included BMI (or weight gain) and the significant factors
identified in the step-wise procedures. Unadjusted and adjusted odds ratios with 95%
confidence intervals were reported for binomial outcomes. For binary outcomes with small
numbers, adjusted odds ratios and 95% confidence intervals were generated using logistic
regression with Firth’s penalized likelihood estimation method.(18) A p-value <0.05 was
considered statistically significant and no imputation for missing data was performed.
Statistical analysis was performed using SAS 9.4 statistical software (SAS Institute Inc.,
Cary, NC).

Results
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Of the 1203 women in the original trials, complete data on 948 women were available for
analysis in the current study (Figure 1). There were 380 (40%) normal weight, 305 (32%)
overweight, and 263 (28%) obese women included. Among BMI categories, we found
significant baseline differences in race–ethnicity, education, insurance type, and parity (all
p<0.01, Table 1). Subclinical hypothyroidism was more common among normal weight
women, whereas hypothyroxinemia was more common among obese women (p<0.001). In
this study, 106 (11%), 212 (22%), and 630 (66%) women had inadequate, adequate, and
excessive total rates of gestational weight gain, respectively. Among the total gestational
weight gain rate categories, excessive gestational weight gain was more common in
nulliparas (p<0.001) and associated with higher mean birth weights (p<0.001, Table 2).

In univariable analyses, there were significant associations between BMI category and mean
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WPPSI-III at 5 years and mean DAS-II at 3 years (p<0.001 for both, Table 3). There also
were significant associations between BMI category and DAS-II < 85 at 3 years (OR 1.66,
95%CI 1.19–2.30 for overweight; OR 1.62, 95%CI 1.15–2.28 for obese, both compared with
normal weight women in unadjusted analyses); but not for WPPSI-III < 85 at 5 years. These
associations were no longer significant after adjustment for potential confounders (Table 3).
This was largely accounted for by specific covariables entered into the regression models.
Using stepwise regression to examine potentially confounding factors, only race–ethnicity,
education, insurance type, and infant sex were significantly associated with the WPPSI-III
score and WPPSI-III < 85. Race–ethnicity, education, and infant sex were also significantly
associated with the DAS-II score and DAS < 85. There were no significant interactions
between race–ethnicity, education, and insurance type. Final regression models that included
the significant factors and BMI, showed that BMI was no longer significantly associated
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with the neurodevelopmental outcomes but education, race–ethnicity, insurance type, and
infant sex remained significantly associated with WPPSI-III. Similarly, education, race–
ethnicity, and infant sex remained significantly associated with DAS-II. Early, late, and total
rates of gestational weight gain were not significantly associated with any of the
neurodevelopmental outcomes in either unadjusted (data not shown) or adjusted analyses
(Table 4).

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Discussion
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In this analysis of neurodevelopmental outcomes among women with either subclinical

hypothyroidism or hypothyroxinemia who delivered at term, we found that pre-pregnancy
obesity was associated with a 5.4 and 4.2-point lower mean IQ score in children at the ages
of 3 and 5 years, respectively compared with normal weight women. However, this
difference appears to be due to a confounding effect, as pre-pregnancy BMI was no longer
associated with childhood IQ when adjustments for race–ethnicity, education, and insurance
type were made, suggesting that other socioeconomic characteristics contribute to offspring
IQ. Similarly, although 66% of women in this study had excessive rates of gestational weight
gain, there were no differences in neurodevelopmental outcomes according to gestational
weight gain rate as either a total measure or when categorized as occurring early or late in
the pregnancy.
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Given the prevalence of obesity in reproductive-age women in the U.S., this factor’s
association with offspring health is of particular relevance. Accordingly, several other
studies have evaluated the relationship of maternal weight and gestational weight gain with
offspring’s neurocognitive outcomes. In a recent systematic review and meta-analysis of
maternal weight and childhood neurodevelopmental outcomes, Sanchez et al reported their
findings from 32 studies in 8 countries. Compared with children born to normal weight
women, children of overweight (OR 1.19, 95%CI 1.09–1.29) and obese women (OR 1.58,
95%CI 1.39–1.79) had higher odds for cognitive or developmental delay, but the effects of
gestational weight gain were not studied.(19) Data collected from the U.S. Collaborative
Perinatal Project from 1959–1976 showed that maternal pre-pregnancy BMI had an inverted
U-shaped association with child IQ at 7 years, after adjusting for potential confounders.(20)
Women with a pre-pregnancy BMI around 20 kg/m2 had children with the highest child IQ
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scores whereas women with pre-pregnancy obesity (BMI ≥ 30 kg/m2) had children with the
lowest child IQ scores when BMI was evaluated as a continuous variable.(20) Furthermore,
they found that children born to obese women who gained more than 40 pounds had a 6.5-
point deficit in IQ score compared with normal weight women who gained between 21–25
pounds. However, other studies have found no associations between maternal weight and
offspring cognition.(21, 22) For example, Brion et al studied 4712 infants at 3 years and
found no differences in cognition when they adjusted for maternal smoking and education,
family income, and paternal education.(22) Our findings corroborate that there does not
appear to be an association between gestational weight gain and offspring cognition.(21)
Altogether, these findings are important to consider when evaluating the association between
in utero exposures and long-term childhood health. It is particularly difficult to draw
conclusions about perinatal exposures and outcomes such as cognition without accounting
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for multi-factorial variables such as genetics, socioeconomic status, and education that may
influence fetal and childhood development.

We recognize that IQ scores assess just one aspect of the spectrum of neurodevelopment and
that many other biological and social factors contribute to these outcomes. Other studies
have evaluated the association between pre-pregnancy weight and behavioral problems such
as attention deficit disorder, cerebral palsy, autism, and emotional or behavioral problems,
also with inconsistent findings.(22–28) Two of these studies also showed an increased risk

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for autism in women with excessive gestational weight gain.(25, 26) In the meta-analysis of
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Sanchez et al, overweight and obese women had increased odds for attention deficit disorder
and autism compared with normal weight women.(19) Our study did not evaluate these other
neurodevelopmental outcomes.

We acknowledge limitations in our current study including unmeasured intrauterine effects

and residual confounding such as maternal and paternal IQ scores, maternal mental health,
breastfeeding, and other postnatal influences which are nearly impossible to separate out
from prenatal influences. Furthermore, women in this study had subclinical hypothyroidism,
therefore results may not be generalizable to all women. By restricting our study to term
deliveries, we excluded approximately 9% of the original cohort. Our intent was to simplify
the analytical approach since preterm deliveries are associated with neurodevelopmental
outcomes, although we acknowledge these findings may not generalize to all births.
Furthermore, the parent TSH trial was not specifically powered to address this study’s
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hypothesis. Nonetheless, the strengths of this study include its rigorous follow-up and
assessment of neurodevelopmental outcomes. The study also adds to the evidence base
because of its racial-ethnic diversity (Table 1), which is in contrast to other studies that had
lower representation from minority women. Future studies on this topic should measure
cognition and behavior in greater detail with consideration of additional prenatal and
postnatal factors related to cognition and behavior in offspring as well as comprehensive
assessments of adiposity and diet.

Supplementary Material
Refer to Web version on PubMed Central for supplementary material.
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Acknowledgments
Supported by grants (HD34116, HD40512, HD27917, HD34208, HD40485, HD40560, HD53097, HD27869,
HD40500, HD40545, HD27915, HD40544, HD53118, HD21410, and HD36801) from the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD) and the National Institute of Neurological
Disorders and Stroke and the National Center for Advancing Translational Sciences (UL1TR001070). The content
is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

The authors thank Lisa Moseley, R.N., B.S.N., and Gail Mallet, R.N., B.S.N., C.C.R.C., for protocol development
and coordination between clinical research centers; Barbara Jones-Binns, J.D., M.P.H., for protocol and data
management, overall coordination, and quality control; and Elizabeth A. Thom, Ph.D., Alan M. Peaceman, M.D.,
Michael W. Varner, M.D., Deborah G. Hirtz, M.D., and Catherine Y. Spong, M.D. for protocol development and
oversight.

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PRECIS:
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Maternal prepregnancy body mass index and gestational weight gain are not associated
with child neurodevelopmental outcomes.
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Figure 1:
Flow diagram of participant selection. BMI, body mass index.
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Table 1.

Baseline Characteristics by Pre-Pregnancy Body Mass Index Group

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Characteristic Normal Weight Overweight Obese P-value

N=380 N=305 N=263

Age (years) 27.8 ± 5.9 28.4 ± 5.8 27.7 ± 5.3 0.28

Race–Ethnicity <0.001

Hispanic 179 (47.1%) 182 (59.7%) 140 (53.2%)

Non-Hispanic white 150 (39.5%) 90 (29.5%) 60 (22.8%)

Non-Hispanic black 40 (10.5%) 29 (9.5%) 59 (22.4%)

Other 11 (2.9%) 4 (1.3%) 4 (1.5%)

Education <0.001

< High school 140 (36.8%) 142 (46.6%) 128 (48.7%)

High school 118 (31.1%) 105 (34.4%) 98 (37.3%)

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≥ College 122 (32.1%) 58 (19.0%) 37 (14.1%)

Government insurance 187 (49.2%) 179 (58.7%) 165 (62.7%) 0.002

Parity (number of births) <0.001

0 159 (41.8%) 87 (28.5%) 56 (21.3%)

1–3 212 (55.8%) 197 (64.6%) 188 (71.5%)

≥4 9 (2.4%) 21 (6.9%) 19 (7.2%)

Tobacco use in pregnancy 26 (6.8%) 13 (4.3%) 22 (8.4%) 0.13

Gestational age at randomization (weeks) 17.1 ± 2.9 17.4 ± 2.9 17.2 ± 3.0 0.54

Alcohol use in pregnancy 20 (5.3%) 20 (6.6%) 14 (5.3%) 0.73

Thyroid status <0.001

Subclinical hypothyroidism 238 (62.6%) 180 (59.0%) 115 (43.7%)

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Subclinical hypothyroxinemia 142 (37.4%) 125 (41.0%) 148 (56.3%)

Levothyroxine treatment group 189 (49.7%) 152 (49.8%) 130 (49.4%) 1.00

Gestational diabetes 11 (2.9%) 21 (6.9%) 30 (11.4%) <0.001

Gestational hypertension or preeclampsia 24 (6.3%) 27 (8.9%) 23 (8.8%) 0.38

TSH, mU/L 3.7 ± 2.7 3.5 ± 2.3 3.1 ± 2.3 <0.001

FT4, ng/dL 0.96 ± 0.14 0.94 ± 0.13 0.89 ± 0.12 <0.001

TPO > 50, IU/mL * 85 (22.6%) 73 (24.0%) 44 (16.9%) 0.10

Gestational age at delivery (weeks) 39.6 ± 1.1 39.6 ± 1.1 39.6 ± 1.1 0.89

Birth weight (g) 3387 ± 431 3507 ± 462 3478 ± 483 0.002

Apgar 1 min < 4 * 7 (1.8%) 7 (2.3%) 4 (1.5%) 0.80

Apgar 5 min < 7 * 1 (0.3%) 2 (0.7%) 2 (0.8%) 0.63

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Male sex 191 (50.3%) 157 (51.5%) 136 (51.7%) 0.92

*
Seven patients were missing TPO status and one patient was missing 1 minute and 5 minute Apgar scores.

Data presented as mean ± SD or n(%)

TSH thyroid stimulating hormone

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FT4 free thyroxine

TPO thyroid peroxidase antibody

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 Kominiarek et al. Page 14

Table 2.

Baseline Characteristics by Total Rate of Gestational Weight Gain

Author Manuscript

Characteristic Inadequate Adequate Excessive P-value

N=106 N=212 N=630

Age (years) 27.6 ± 5.7 28.5 ± 5.7 27.8 ± 5.7 0.31

Race–Ethnicity 0.10

Hispanic 67 (63.2%) 116 (54.7%) 318 (50.5%)

Non-Hispanic white 21 (19.8%) 63 (29.7%) 216 (34.3%)

Non-Hispanic black 17 (16.0%) 28 (13.2%) 83 (13.2%)

Other 1 (1.0%) 5 (2.4%) 13 (2.1%)

Education 0.13

< High school 56 (52.8%) 99 (46.7%) 255 (40.5%)

High school 29 (27.4%) 69 (32.6%) 223 (35.4%)

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≥ College 21 (19.8%) 44 (20.8%) 152 (24.1%)

Government insurance 68 (64.2%) 124 (58.5%) 339 (53.8%) 0.10

Parity (number of births) <0.001

0 24 (22.6%) 52 (24.5%) 226 (35.9%)

1–3 72 (67.9%) 145 (68.4%) 380 (60.3%)

≥4 10 (9.4%) 15 (7.1%) 24 (3.8%)

Tobacco use in pregnancy 5 (4.7%) 13 (6.1%) 43 (6.8%) 0.70

Alcohol use in pregnancy 4 (3.8%) 10 (4.7%) 40 (6.4%) 0.45

Gestational age at randomization (weeks) 17.2 ± 3.0 17.1 ± 3.0 17.3 ± 2.9 0.95

Thyroid status 0.68

Subclinical hypothyroidism 63 (59.4%) 115 (54.2%) 355 (56.3%)

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Subclinical hypothyroxinemia 43(41.6%) 97 (45.8%) 275 (43.7%)

Levothyroxine treatment group 55 (51.9%) 104 (49.1%) 312 (49.5%) 0.88

Gestational diabetes 13 (12.3%) 15 (7.1%) 34 (5.4%) 0.03

Gestational hypertension or preeclampsia 8 (7.6%) 11 (5.2%) 55 (8.7%) 0.25

TSH, mU/L 3.5 ± 2.2 3.4 ± 2.4 3.5 ± 2.6 0.92

FT4, ng/dL 0.95 ± 0.15 0.93 ± 0.13 0.93 ± 0.13 0.44

TPO > 50, IU/mL * 19 (18.5%) 50 (23.7%) 133 (21.2%) 0.55

Gestational age at delivery (weeks) 39.5 ± 1.2 39.5 ± 1.1 39.6 ± 1.1 0.25

Birth weight (g) 3275 ± 449 3371 ± 438 3507 ± 457 <0.001

Apgar 1 min < 4 * 2 (1.9%) 5 (2.4%) 11 (1.8%) 0.81

Apgar 5 min < 7 * 0 (0.0%) 2 (0.9%) 3 (0.5%) 0.63

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Male sex 42 (39.6%) 95 (44.8%) 347 (55.1%) 0.002

*
Seven patients were missing TPO status and one patient was missing 1 minute and 5 minute Apgar scores.

Data presented as mean ± SD or n(%)

TSH thyroid stimulating hormone

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 Kominiarek et al. Page 15

FT4 free thyroxine

TPO thyroid peroxidase antibody

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Table 3.

Neurodevelopment outcomes by pre-pregnancy body mass index group

Author Manuscript

Outcome Normal Weight Overweight Obese P-value

N=380 N=305 N= 263

WPPSI-III at 5 years 97.4 ± 15.4 94.1 ± 15.6 93.2 ± 12.8 0.84 *

WPPSI-III at 5 years < 85 86 (22.6%) Reference 75 (24.6%) aOR 95% CI: 0.90 64 (24.3%) aOR 95% CI: 0.70 0.22 †
(0.61, 1.32) (0.47, 1.05)

N=363 N=295 N=257

DAS-II at 3 years ∥ 93.9 ± 15.9 89.6 ± 16.0 88.5 ± 13.3 0.10 ‡

DAS-II at 3 years <85 100 (27.6%) Reference 114 (38.6%) aOR 95% CI: 1.35 98 (38.1%) aOR 95% CI: 1.18 0.28 §
(0.93, 1.96) (0.80, 1.73)

*
P value based on multivariable linear regression model adjusted for race-ethnicity, education, insurance type, and infant sex
†
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P value based on multivariable logistic regression model Wald test Type III effect adjusted for race-ethnicity, education, insurance type and infant
sex
‡∣
P value based on multivariable linear regression model adjusted for race-ethnicity, education, and infant sex
§
P value based on multivariable logistic regression model Wald test Type III effect adjusted for race-ethnicity, education, and infant sex
∥
The number of subjects varies from the WPPSI-III analysis because not all subjects that had WPPSI-III testing at 5 years had the DAS-II testing at
3 years.

Data presented as mean ± SD or n(%)

WPPSI-III Wechsler Preschool and Primary Scale of Intelligence

DAS-II Differential Ability Scales-II

OR, odds ratio

CI, confidence interval

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aOR, adjusted odds ratio

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 Kominiarek et al. Page 17

Table 4.

Neurodevelopment Outcomes by Early, Late, and Total Rates of Gestational Weight Gain
Author Manuscript

Outcome Inadequate Adequate Excessive P-value

Early Gestational Weight Gain *

N=255 N=236 N= 457

WPPSI-III at 5 years 94.6 ± 13.7 95.6 ± 14.0 95.4 ± 16.0 0.66 §

WPPSI-III at 5 years < 85 55 (21.6%) aOR 95% CI: 0.71 58 (24.6%) Reference 112 (24.5%) aOR 95% CI: 0.95 0.25 ∥
(0.46–1.12) (0.64–1.41)

N=251 N=220 N=444

DAS II at 3 years 89.7 ± 15.1 91.4 ± 14.8 91.5 ± 15.9 0.97 ¶

DAS-II at 3 years <85 89 (35.5%) aOR 95% CI: 1.18 66 (30.0%) Reference 157 (35.4%) aOR 95% CI: 1.46 0.15 #
(0.76–1.82) (0.98–2.16)

Late Gestational Weight Gain †

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N=164 N=142 N= 642

WPPSI-III at 5 years 94.3 ± 14.7 96.3 ± 15.3 95.2 ± 14.9 0.88 §

WPPSI-III at 5 years < 85 42 (25.6%) aOR 95% CI: 0.87 36 (25.4%) Reference 147 (22.9%) aOR 95% CI: 0.78 0.52 ∥
(0.50–1.52) (0.49–1.22)

N=158 N=135 N=622

DAS II at 3 years 92.1 ± 14.2 91.2 ± 16.7 90.7 ± 15.5 0.47 ¶

DAS-II at 3 years <85 46 (29.1%) aOR 95% CI: 0.70 46 (34.1%) Reference 220 (35.4%) aOR 95% CI: 0.97 0.29 #
(0.40–1.22) (0.62–1.51)

Total Gestational Weight Gain ‡

N=106 N=212 N= 630

WPPSI-III at 5 years 93.9 ± 13.6 95.0 ± 13.9 95.5 ± 15.4 1.00 §

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WPPSI-III at 5 years < 85 28 (26.4%) aOR 95% CI: 1.07 49 (23.1%) Reference 148 (23.5%) aOR 95% CI: 1.04 0.97 **
(0.61–1.88) (0.71–1.55)

N=104 N=206 N=605

DAS II at 3 years 88.9 ± 13.5 90.2 ± 15.2 91.6 ± 15.8 0.64 ¶

DAS-II at 3 years <85 37 (35.6%) aOR 95% CI: 0.96 69 (33.5%) Reference 206 (34.1%) aOR 95% CI: 1.11 0.78 ††
(0.55–1.66) (0.76–1.61)

*
Early gestational weight gain defined as weight gain rate at ≤ 20 weeks gestation
†
Late gestational weight gain defined as weight gain rate at > 20 weeks gestation
‡
Total gestational weight gain defined as last study visit weight minus pre-pregnancy weight and based on expected weight gain for the first
trimester plus second and third trimester weekly weight gain rates from guidelines.(17)
§
P value based on multivariable linear regression model adjusted for race-ethnicity, education, insurance type, and infant sex
∥
Author Manuscript

P value based on multivariable logistic regression model Wald test Type III effect adjusted for race-ethnicity, education, insurance type and infant
sex.
¶
P value based on multivariable linear regression model adjusted for race-ethnicity, education, and infant sex
#
P value based on multivariable logistic regression model Wald test Type III effect adjusted for race-ethnicity, education, and infant sex

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 Kominiarek et al. Page 18

**
P value based on multivariable logistic regression model using Firth’s likelihood estimation method adjusted for race-ethnicity, education,
insurance type, and infant sex
††
P value based on multivariable logistic regression model using Firth’s likelihood estimation method adjusted for race-ethnicity, education, and
infant sex
Author Manuscript

WPPSI-III Wechsler Preschool and Primary Scale of Intelligence

DAS-II Differential Ability Scales-II

OR, odds ratio

CI, confidence interval

aOR, adjusted odds ratio

Author Manuscript
Author Manuscript
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Obstet Gynecol. Author manuscript; available in PMC 2019 December 01.