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- Title
Comparative impact of pharmacological treatments for gestational diabetes on neonatal anthropometry independent of maternal glycaemic control: A systematic review and meta-analysis.
- Authors
Tarry-Adkins, Jane L.; Aiken, Catherine E.; Ozanne, Susan E.
- Abstract
Background: 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. Methods and findings: 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 increased abdominal (0.90 cm, 95% CI 0.03–1.77, p = 0.04) and chest circumferences (0.80 cm, 95% CI 0.07–1.53, p = 0.03) versus insulin-exposed neonates. Metformin-exposed neonates had decreased ponderal index (−0.13 kg/m3, 95% CI −0.26 to −0.00, p = 0.04) and reduced head (−0.21, 95% CI −0.39 to −0.03, p = 0.03) and chest circumferences (−0.34 cm, 95% CI −0.62 to −0.05, p = 0.02) versus the insulin-treated group. Metformin-exposed neonates had decreased ponderal index (−0.09 kg/m3, 95% CI −0.17 to −0.01, p = 0.03) versus glyburide-exposed neonates. Study limitations include heterogeneity in dosing, heterogeneity in GDM diagnostic criteria, and few studies reporting longitudinal growth outcomes. Conclusions: Maternal randomisation to glyburide resulted in heavier neonates with a propensity to increased adiposity versus insulin- or metformin-exposed groups. Metformin-exposed neonates were lighter with reduced lean mass versus insulin- or glyburide-exposed groups, independent of maternal glycaemic control. Oral anti-hyperglycaemics cross the placenta, so effects on fetal anthropometry could result from direct actions on the fetus and/or placenta. We highlight a need for further studies examining the effects of intrauterine exposure to antidiabetic agents on longitudinal growth, and the importance of monitoring fetal growth and maternal glycaemic control when treating GDM. This review protocol was registered with PROSPERO (CRD42019134664/CRD42018117503). Jane Tarry-Adkins and colleagues reveal the anthropometric impact of pharmacological treatments for gestational diabetes on babies. Author summary: Why was this study done?: Gestational diabetes mellitus (GDM) is an increasing healthcare concern that has significant short- and long-term health implications for mother and baby. Optimising clinical treatment of GDM is an important priority. Several current treatment options exist, including insulin or oral therapies, such as metformin or glyburide. We aimed to investigate the associations between different GDM treatments and the growth of the baby in the womb, at birth, during childhood, and in later life. What did the researchers do and find?: We performed a systematic review of 33 studies that included 4,944 mothers who were randomised to insulin, metformin, or glyburide for treatment of GDM. We included all studies that reported the weight and growth of their babies in the womb, at birth, or later in childhood. Babies exposed to glyburide are significantly heavier at birth compared to those whose mothers were randomised to insulin or metformin. Conversely, metformin-exposed babies are significantly lighter at birth than those whose mothers were randomised to insulin or glyburide. There may also be differences in body composition at birth. Babies exposed to glyburide tend to be born larger with increased fat mass, and babies exposed to metformin were born smaller and were thinner, compared to those treated with insulin. What do these findings mean?: There are significant differences in body mass between babies whose mothers were randomised to glyburide, metformin, and insulin to treat GDM. Our results highlight the importance of considering the effects of treatment on both mother and baby when managing GDM. There is a need for better understanding of exactly how oral treatments for GDM impact on growth of babies in the womb and in later life, particularly whether there are implications for long-term health.
- Subjects
GLYCEMIC control; FETAL macrosomia; GESTATIONAL diabetes; INFANT health; DIABETES in women; BIRTH weight; META-analysis; FETAL development
- Publication
PLoS Medicine, 2020, Vol 17, Issue 5, p1
- ISSN
1549-1277
- Publication type
Academic Journal
- DOI
10.1371/journal.pmed.1003126