In an 8-year prospective study of the perinatal risk factors associated with childhood obesity, we similarly found that maternal pregravid BMI – independent of maternal glucose status or gestational weight gain – was the strongest predictor of childhood obesity and metabolic dysfunction (Am. J. Clin. Nutr. 2009;90:1303-13).
Other studies have teased apart the roles of maternal obesity and GDM in long-term health of offspring. This work has found that maternal obesity during pregnancy is associated with metabolic syndrome in the offspring and an increased risk of type 2 diabetes in youth, independent of maternal diabetes during pregnancy. A recent meta-analysis also reported that, although maternal diabetes is associated with an increased BMI z score, this was no longer significant after adjustments were made for prepregnancy BMI (Diabetologia 2011;54:1957-66).
Maternal pregravid obesity, therefore, is not only a risk factor for neonatal adiposity at birth, but also for the longer-term risk of obesity and metabolic dysfunction in the offspring – independent of maternal GDM or excessive gestational weight gain.
Interventions in Pregnancy
Numerous prospective trials have examined lifestyle interventions for obese women during pregnancy. One randomized controlled study of a low glycemic index diet in pregnancy (coined the ROLO study) involved 800 women in Ireland who had previously delivered an infant weighting greater than 4,000 g. Women were randomized to receive the restricted diet or no intervention at 13 weeks. Despite a decrease in gestational weight gain in the intervention group, there were no differences in birth weight, birth weight percentile, ponderal index, or macrosomia between the two groups (BMJ 2012;345:e5605).
Another randomized controlled trial reported by a Danish group involved an intervention that consisted of dietary guidance, free membership in a fitness center, and personal coaching initiated between 10 and 14 weeks of gestation. There was a decrease in gestational weight gain in the intervention group, but paradoxically, the infants in the intervention group also had significantly higher birth weight, compared with controls (Diabetes Care 2011;34:2502-7).
Additionally, there have been at least five meta-analyses published in the past 2 years looking at lifestyle interventions during pregnancy. All have concluded that interventions initiated during pregnancy have limited success in reducing excessive gestational weight gain but not necessarily to within the IOM guidelines. The literature contains scant evidence to support further benefits for infant or maternal health (in other words, fetal overgrowth, GDM, or hypertensive disorders).
A recent Cochrane review also concluded that the results of several randomized controlled trials suggest no significant difference in GDM incidence between women receiving exercise intervention versus routine care.
Just this year, three additional randomized controlled trials of lifestyle interventions during pregnancy were published. Only one, the Treatment of Obese Pregnant Women (TOP) study, showed a modest effect in decreasing gestational weight gain. None found a reduction in GDM or fetal overgrowth.
Focus on prepregnancy
Obesity is an inflammatory condition that increases the risk of insulin resistance, impaired beta-cell function, and abnormal adiponectin concentrations. In pregnancy, maternal obesity and hyperinsulinemia can affect placental growth and gene expression.
We have studied lean and obese women recruited prior to a planned pregnancy, as well as lean and obese women scheduled for elective pregnancy termination in the first trimester. Our research, some of which we reported recently in the American Journal of Physiology , has shown increased expression of lipogenic and inflammatory genes in maternal adipose tissue and in the placenta of obese women in the early first trimester, before any phenotypic change becomes apparent (Am. J. Physiol. Endocrinol. Metab. 2012;303:e832-40).
Specifically, hyperinsulinemia and/or defective insulin action in obese women appears to affect the placental programming of genes relating to adipokine expression and lipid metabolism, as well as mitrochondrial function. Altered inflammatory and lipid pathways affect the availability of nutrients for the fetus and, consequently, the size and body composition of the fetus. Fetal overgrowth and neonatal adiposity can result.
In addition, our research has shown that obese women have decreased insulin suppression of lipolysis in white adipose tissue, which during pregnancy results in improved lipid availability for fetal fat accretion and lipotoxicity.
When interventions aimed at weight loss and improved insulin sensitivity are undertaken before pregnancy or in the period between pregnancies, we have the opportunity to increase fat oxidation and reduce oxidative stress in early pregnancy. We also may be able to limit placental inflammation and favorably affect placental growth and gene expression. By the second trimester, our research suggests, gene expression in the placenta and early molecular changes in the white adipose tissue have already been programmed and cannot be reversed (Am. J. Physiol. Endocrinol. Metab. 2012;303:e832-40).