Comparative impact of pharmacological treatments for gestational diabetes on neonatal anthropometry independent of maternal glycaemic control: A systematic review and meta-analysis

Fetal growth in gestational diabetes mellitus (GDM) is directly linked to maternal glycaemic control; however, this relationship may be altered by oral anti-hyperglycaemic agents. Unlike insulin, such drugs cross the placenta and may thus have independent effects on fetal or placental tissues. We investigated the association between GDM treatment and fetal, neonatal, and childhood growth. PubMed, Ovid Embase, Medline, Web of Science, ClinicalTrials.gov, and Cochrane databases were systematically searched (inception to 12 February 2020). Outcomes of GDM-affected pregnancies randomised to treatment with metformin, glyburide, or insulin were included. Studies including preexisting diabetes or nondiabetic women were excluded. Two reviewers independently assessed eligibility and risk of bias, with conflicts resolved by a third reviewer. Maternal outcome measures were glycaemic control, weight gain, and treatment failure. Offspring anthropometric parameters included fetal, neonatal, and childhood weight and body composition data. Thirty-three studies (n = 4,944), from geographical locations including Europe, North Africa, the Middle East, Asia, Australia/New Zealand, and the United States/Latin America, met eligibility criteria. Twenty-two studies (n = 2,801) randomised women to metformin versus insulin, 8 studies (n = 1,722) to glyburide versus insulin, and 3 studies (n = 421) to metformin versus glyburide. Eleven studies (n = 2,204) reported maternal outcomes. No differences in fasting blood glucose (FBS), random blood glucose (RBS), or glycated haemoglobin (HbA1c) were reported. No studies reported fetal growth parameters. Thirty-three studies (n = 4,733) reported birth weight. Glyburide-exposed neonates were heavier at birth (58.20 g, 95% confidence interval [CI] 10.10-106.31, p = 0.02) with increased risk of macrosomia (odds ratio [OR] 1.38, 95% CI 1.01-1.89, p = 0.04) versus neonates of insulin-treated mothers. Metformin-exposed neonates were born lighter (-73.92 g, 95% CI -114.79 to -33.06 g, p < 0.001) with reduced risk of macrosomia (OR 0.60, 95% CI 0.45-0.79, p < 0.001) than insulin-exposed neonates. Metformin-exposed neonates were born lighter (-191.73 g, 95% CI -288.01 to -94.74, p < 0.001) with a nonsignificant reduction in macrosomia risk (OR 0.32, 95% CI 0.08-1.19, I2 = 0%, p = 0.09) versus glyburide-exposed neonates. Glyburide-exposed neonates had a nonsignificant increase in total fat mass (103.2 g, 95% CI -3.91 to 210.31, p = 0.06) and increase