Effects of Maternal Pre-pregnancy Obesity and Diabetes

on Autism Spectrum Disorder (ASD) and Other Developmental

Disabilities: A Prospective Birth Cohort Study
Mengying Li, MSPH1, M Daniele Fallin, PhD1,2, Anne Riley, PhD1,
Rebecca Landa, PhD, CCC-SLP2,3, Deanna Caruso, MS1, Colleen
Pearson, BA4, Shannon Kiang, BA4, Xiaobin Wang, MD1,2

Background
Rising prevalence of autism spectrum
disorder (ASD) parallels the epidemic of
obesity and diabetes in the US.
Obesity and diabetes are prevalent
amongst pregnant women, particularly in
U.S. urban low-income minorities.
Maternal obesity and diabetes may
contribute to ASD in children through
immunologic and metabolic disturbances

Objectives
In a prospective birth cohort of a lowincome minority population, this study
aims to:
1. Examine the independent and joint
effects of maternal obesity and diabetes
on the development of ASD in children
2. Compare if the effects differ for
intellectual disability (ID) and other
developmental disorders (other DD)
3. Calculate the population attributable
fractions (PAF) of maternal obesity and
diabetes on ASD.

Participants
2734 children who were
Enrolled at birth at Boston Medical
Center (BMC) between 1998 and 2014,
AND
Followed-up at least once through
pediatric care at BMC
Length of follow up: 6.0 years (interquartile range 3.6 to 9.0 years).
60% African American, 11% Hispanic, 7%
White, 21% other.
Median annual family income $ 15-19 K

1Wendy

Klag Center for Autism and Developmental Disabilities and Center on Early Life Origins of Disease, Johns
Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States; 2Johns Hopkins School of Medicine,
Baltimore, Maryland, United States; 3The Kennedy Krieger Institute, Baltimore, Maryland, United States;
4The Boston University Medical Center, Boston, Massachusetts, United States

Measures
Outcome
ICD9 diagnosis in childrens postnatal
electronic medical records (EMR)
ASD - 102 children (3.7%) w/ autism,
Asperger syndrome or pervasive
developmental disorder not otherwise
specified.
ID 131 children (4.8%) w/ Downs
syndrome, intellectual disability not
otherwise specified, developmental delay
not elsewhere classified, or tuberculosis
with developmental delay
Other DD 864 children (31.6%) w/
language delay, coordination disorders or
learning disorders, and w/o ASD, ID or
attention deficit hyperactivity disorder
(ADHD)
Typically developing 1749 children
(64.0%) w/o ASD, ID, other DD or ADHD

Exposures
Obesity
Defined based on body mass index (BMI)
using postpartum maternal report of prepregnancy weight and height
Diabetes
Identified through maternal prenatal EMR
and medical record abstraction.
Differentiating
oPre-gestational diabetes (PGDM)
oGestational diabetes (GDM)
Other covariates
o Maternal age, parity; child year of birth, sex;
gestational age, birth weight, mode of delivery,
pre-eclampsia, hypertension, smoking, alcohol
use and drug use during pregnancy

Statistical analysis
1. Cox proportional hazard regression
Compared the incidence of ASD by
exposure status, accounting for length of
follow-up
Adjusted for other covariates associated
with ASD risk (p-value 0.10)
2. Repeated step 1 for ID and other DD
3. Derived PAF using relative risk and
prevalence of exposures.

1. Maternal obesity and diabetes are

independently and jointly associated with
ASD risk
2. The associations are similar between ASD
and ID, but strength of the associations are
much smaller for other DD
Hazard ratios of ASD, ID & Other DD associated w/
maternal obesity and diabetes
ID

Other DD

Obesity
Normal/underweight

Reference

Reference

Reference

Overweight

1.05 (0.65-1.71)

0.78 (0.50-1.23)

0.99 (0.84-1.17)

Obese

1.91 (1.19-3.05)** 1.55 (1.03-2.33)* 1.22 (1.02-1.45)*

Diabetes
Reference

9
8
7
6
5
3.91

4
3.04

3
2
1

No DM

Reference

GDM

1.87 (0.92-3.77) 1.49 (0.74-2.98)

Reference

PGDM

2.25 (1.14-4.42)* 2.33 (1.28-4.22)** 1.31 (0.96-1.77)

1.11 (0.82-1.51)

Obesity & Diabetes

Not obese, no DM Reference

Reference

Reference

Not obese, GDM 1.44 (0.51-4.02)

1.29 (0.47-3.59)

0.98 (0.63-1.53)

Not obese, PGDM 1.32 (0.41-4.29)

1.73 (0.69-4.37)

1.15 (0.75-1.76)

Obese, no DM

1.54 (0.93-2.53) 1.51 (0.98-2.34) 1.17 (0.98-1.40)

Obese, GDM

3.04 (1.21-7.63)* 2.07 (0.83-5.17)

Obese, PGDM

3.91 (1.76-8.68)** 3.65 (1.74-7.67)** 1.63 (1.07-2.49)*

1.34 (0.89-2.02)

All models adjusted for child year of birth, child sex, maternal age, parity and smoking
during pregnancy and preterm birth
** p-value 0.01, * p-value 0.05, p-value 0.10

1.44

1.32

1.54

0
Nonobese,
no DM

Results

ASD

Joint effect of maternal obesity and

diabetes on the risk of ASD

Nonobese,
GDM

Nonobese,
PGDM

Obese,
no DM

Obese,
GDM

Obese,
PGDM

3. Maternal obesity and diabetes together

accounts for 17.5% of the ASD cases.

Conclusion
In this urban low-income minority birth
cohort, maternal obesity and diabetes
appear to jointly increase the risk of ASD
and ID in children.
Similar findings in ASD and ID but not
other DD may suggest possible shared
etiologic pathways between ASD and ID.
Maternal obesity and diabetes may
contribute to substantial burden of ASD
and are potentially preventable.

Acknowledgments
This study is supported in part by a grant from the
Maternal and Child Health Bureau (R40MC27443). The
parent study is supported in part by the March of Dimes
PERI grants (20-FY02-56); NIEHS (R21 ES011666); and
NICHD (2R01 HD041702). The follow-up study is
supported in part by the Bunning Family Food Allergy
Project/Food Allergy Initiative; the Ludwig Family
Foundation; the National Institute of Allergy and
Infectious Diseases (U01AI090727, and R21AI079872);
Mengying Li is supported by Bernard and Jane Guyer
Scholarship in her current training.