Obesity in pregnancy: What do recent trials deliver?

Pre-existing obesity and excessive weight gain in pregnancy have significant consequences for maternal and fetal health and may also have consequences for the offspring and future generations. Potential complications include gestational diabetes, pre-eclampsia, caesarean delivery, maternal haemorrhage and infant mortality. Obesity also presents difficulties in the initiation and maintenance of breastfeeding, which has been suggested to be protective against future obesity.

A recent systematic review examined the impact of dietary interventions on excess weight and obesity in pregnancy (Flynn et al, 2016). The studies reviewed had different participant numbers, interventions, intervention delivery approaches and assessment tools. Although several of the studies were encouraging and reported beneficial maternal effects, the majority failed or were not powered to demonstrate an impact on neonatal outcomes.

Recently, prevention of excessive weight gain through lifestyle intervention and/or medication has been studied in randomised clinical trials. Dodd et al (2014) compared a dietary and lifestyle intervention against standard care in 2212 overweight or obese women across three centres in Australia. They reported improved maternal diet and activity in the intervention arm, as well as an 18% reduction in the risk of infants being born weighing more than 4 kg. However, only 40% of eligible women took up the programme.

UPBEAT (UK Pregnancies Better Eating and Activity Trial; n=1556) was conducted across eight centres in the UK and involved dietary and lifestyle sessions (Poston et al, 2015). Participants randomised to the intervention arm had a 0.55 kg reduction in mean gestational weight gain and improved diet and activity. Adherence was good, with 83% attending the majority of the sessions.

In EMPOWaR (Efficacy of Metformin in Pregnant Obese Women, a Randomised Controlled Trial), the authors compared metformin (highest tolerated dose up to 2500 mg) with placebo in 449 obese women without diabetes (Chiswick et al, 2015). No difference in birth weight was observed. In a similar new study (summarised alongside), Syngelaki and colleagues examined the impact of metformin (maximum dose, 3000 mg) in obese pregnant women without diabetes across three centres in the UK. The study included a more ethnically diverse population than EMPOWaR. The participants were randomised to metformin (n=225) or placebo (n=225), with a total of 400 subjects included in the analysis.

Side effects were more common in the metformin group. Median maternal weight gain was lower in the metformin group compared to placebo (4.6 kg vs 6.3 kg; P<0.001), and the risk of pre-eclampsia was reduced (3.0% vs 11.3%; P<0.001). There were five stillbirths and miscarriages in the placebo group, compared to one stillbirth in the metformin group. Metformin had no significant effect on birth weight.

Both this study and EMPOWaR generally show benefits of metformin in terms of several outcomes, although many of the differences did not reach significance because of insufficient statistical power.

Both lifestyle intervention and metformin may have a role in reducing maternal weight gain in pregnancy, but further study is required. Lifestyle advice may also have an impact on birth weight, but the optimal content and delivery of the lifestyle intervention need to be determined. At best, the evidence only shows modest effects on pregnancy weight outcomes. However, maternal weight gain is complex, involving many factors beyond adiposity (e.g. fluid shifts). The potential impact of metformin on pre-eclampsia is promising, but has not been consistently observed. No significant harm from metformin has been observed, although side effects are more common, and longer-term outcomes in the offspring are unknown. The best approach for avoiding the complications of obesity is yet to be determined, but focus should be on avoiding excessive weight gain during pregnancy through lifestyle intervention, and also concentrating on tackling overweight and obesity prior to conception.

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