It is now well known that maternal obesity, a high fat diet and a high GWG (gestational weight gain) have harmful effects on fetal metabolic programming; awareness of harmful effects on the fetal brain is less widespread. There are increased odds of cognitive deficits, decreased IQ and intellectual disability by 1.3 to 3.6 fold.
Maternal obesity is linked to decreases in offspring cognition, (2-5 points lower IQ) in obese women compared to non-obese women. For every increase of 1 unit in BMI in maternal BMI when not pregnant, there is a significant decrease in offspring’s verbal and non-verbal IQ.
The odds of ASD (autism spectrum disorders) are also increased, as well as the risk of IUGR (intrauterine growth restriction), as well as prematurity. Increased GWG (gestational weight gain) also can increase diabetes and pre-eclampsia (high blood pressure, renal problems and fetal problems with pre-mature delivery). There are also increased odds of ADHD (attention deficit hyperactivity disorder) as well as increased odds of CP (cerebral palsy): the underlying mechanisms are not fully elucidated, but it has been postulated that maternal inflammation may be causative since obesity induces a chronic inflammatory state; other maternal inflammatory conditions such as chorioamnionitis are know to increase the risk for CP (cerebral palsy).
Primary mechanisms proposed to underlie the risk of neurodevelopmental morbidity in offspring of obese women can include: inflammation induced malprogramming, relative excess or deficiencies of circulating nutrients, or metabolic hormone induced malprogramming. It is postulated that maternal and placental inflammation in the setting of obesity plays a key role in fetal brain inflammation and subsequent abnormal offspring neurodevelopment. Fetuses of obese women are chronically exposed to Insulin Resistance (IR) and a glucose rich environment. Insulin acts on the fetal brain as growth factor and can cause disruptions in neural circuitry, brain development and behavior. Maternal hyperinsulinema (HI) associated with type 2 diabetes or gestational diabetes (GD) is also associated with increased risk of ASD (autism spectrum disorders) and neurodevelopmental delay. Maternal obesity also increases the risk of neurodevelopmental and psychiatric disorders such as anxiety behavior and hyperactivity.
Maternal lifestyle, dietary changes and Metformin have been explored as interventions to improve offspring neurodevelopment. In animal studies, pre-pregnancy change from high fat diet to control diet reduced offspring obesity and anxiety behaviors.
In another animal study, Metformin treatment decreased fetal and placental inflammation. Some observational studies have postulated omega 3 and 6 fatty acids as possible therapies in maternal obesity. Omega 3 may protect against brain inflammation. Maternal omega 3 fatty acid deficiency is associated with an increased risk of offspring ASD and ADHD. Evidence is insufficient to recommend routine omega 3 or 6 fatty acid supplements or Metformin to obese women to decrease the risk of offspring neurodevelopmental morbidity.
Preconception counseling of obese women to encourage pre-pregnancy weight loss and a healthy diet as well as lifestyle changes, such as exercise, may also decrease the risk for pre-eclampsia and GDM (gestational diabetes mellitus) which are associated with prematurity causing an increased risk for ASD and other neurodevelopmental morbidities in offspring.
Reproductive Endocrinologists have a unique opportunity to counsel these patients before conceiving. Severely obese women may benefit from bariatric surgery, but then cannot conceive for at least 2 years, so this treatment is best for younger women who can tolerate 2 years removed from their “biologic clock”. Many women are very highly motivated to do the best for their fetus and ultimately their child, if not for themselves, but improvements in lifestyle may carry over after delivery for the long-term health of the Mother as well.
Reference: Andrea G. Edlow, MD, MSC and Larissa H. Mattei, BA. Comtemporary ObGyn June 2016, vol. 61(6) p. 16-22
Margaret Graf Garrisi, MD joined the Institute for Reproductive Medicine and Science in 1999. Dr. Garrisi brings more than 20 years of experience and achievement in Obstetrics, Gynecology and Infertility to her position as Medical Director of Assisted Reproduction in the Division of Reproductive Endocrinology.