Maternal obesity and long-term neuropsychiatric morbidity of the offspring

We examined whether metabolic conditions (MCs) during pregnancy (diabetes, hypertension, and obesity) are associated with autism spectrum disorder (ASD), developmental delays (DD), or impairments in specific domains of development in the offspring. Children aged 2 to 5 years (517 ASD, 172 DD, and 315 controls) were enrolled in the CHARGE (Childhood Autism Risks from Genetics and the Environment) study, a population-based, case-control investigation between January 2003 and June 2010. Eligible children were born in California, had parents who spoke English or Spanish, and were living with a biological parent in selected regions of California. Children's diagnoses were confirmed by using standardized assessments. Information regarding maternal conditions was ascertained from medical records or structured interview with the mother. All MCs were more prevalent among case mothers compared with controls. Collectively, these conditions were associated with a higher likelihood of ASD and DD relative to controls (odds ratio: 1.61 [95% confidence interval: 1.10-2.37; odds ratio: 2.35 [95% confidence interval: 1.43-3.88], respectively). Among ASD cases, children of women with diabetes had Mullen Scales of Early Learning (MSEL) expressive language scores 0.4 SD lower than children of mothers without MCs (P < .01). Among children without ASD, those exposed to any MC scored lower on all MSEL and Vineland Adaptive Behavior Scales (VABS) subscales and composites by at least 0.4 SD (P < .01 for each subscale/composite). Maternal MCs may be broadly associated with neurodevelopmental problems in children. With obesity rising steadily, these results appear to raise serious public health concerns.

To estimate the association between maternal overweight and obesity on complications during pregnancy and delivery in Denmark. A population-based study on a cohort consisting of all Danish women giving birth to a singleton from 2004 through June 30, 2010 (N = 403,092) was undertaken. Women were identified from the Danish Medical Birth Registry, which contains data on 99.8% of all deliveries in Denmark. Maternal complications during pregnancy and delivery and fetal complications were classified according to the International Classification of Diseases, 10th Revision. The final study population consisted of 369,347 women, 20.9% being overweight (body mass index [BMI] 25-29.9), 7.7% obese (BMI 30-35), and 4% severely obese (BMI higher than 35). Overweight, obese, and severely obese women had more complications than did normal weight women. Adjusted odds ratios (ORs) were significantly increased as follows: for gestational diabetes mellitus, 3.5, 7.7, and 11.0 for each BMI category; for preeclampsia 1.9, 3, and 4.4. Planned and especially emergency cesarean delivery was significantly increased with increasing BMI (OR ranging from 1.2 to 2.1). The risk of giving birth to a macrosomic neonate (greater than 4,500 g) increased significantly with increasing BMI (1.6, 2.2, and 2.7), as did the risks of having a neonate with a low Apgar score (1.3, 1.4, and 1.9) and having a stillborn fetus (1.4, 1.6, and 1.9). For shoulder dystocia the risk was significantly increased in the unadjusted analysis, but the significance disappeared in the adjusted analysis. No statistically significance was seen for hemorrhage and thrombosis. This study shows a significant increased risk of a wide variety of pregnancy, birth, and neonatal complications in overweight, obese, and severely obese women. II.

There is a growing body of evidence from both human epidemiologic and animal studies that prenatal and lactational exposure to maternal obesity and high-fat diet are associated with neurodevelopmental and psychiatric disorders in offspring. These disorders include cognitive impairment, autism spectrum disorders, attention deficit hyperactivity disorder, cerebral palsy, anxiety and depression, schizophrenia, and eating disorders. This review synthesizes human and animal data linking maternal obesity and high-fat diet consumption to abnormal fetal brain development and neurodevelopmental and psychiatric morbidity in offspring. In addition, it highlights key mechanisms by which maternal obesity and maternal diet might impact fetal and offspring neurodevelopment, including neuroinflammation; increased oxidative stress, dysregulated insulin, glucose, and leptin signaling; dysregulated serotonergic and dopaminergic signaling; and perturbations in synaptic plasticity. Finally, the review summarizes available evidence regarding investigational therapeutic approaches to mitigate the harmful effects of maternal obesity on fetal and offspring neurodevelopment. © 2016 John Wiley & Sons, Ltd.