Association between HbA1c Levels and Fetal Macrosomia and Large for Gestational Age Babies in Women with Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis of 17,711 Women

Abstract

Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy. GDM is associated with serious maternal and fetal complications, in particular, fetal macrosomia and large for gestational age (LGA), which predisposes to a higher risk of childhood obesity and type 2 diabetes mellitus later in life. Early prediction and diagnosis of GDM leads to early interventions such as diet and lifestyle, which could mitigate the maternal and fetal complications associated with GDM. Glycated haemoglobin A1c (HbA1c) has been widely used for monitoring, screening for and diagnosing diabetes and prediabetes. Increasing evidence has also showed that HbA1c could indicate fetal glucose supply. Thus, we hypothesise that the HbA1c level at around 24 to 28 weeks may predict the development of fetal macrosomia or an LGA baby in women with GDM, which could be useful for better prevention of fetal macrosomia and LGA. We searched MEDLINE, EMBASE, Cochrane and Google Scholar databases from inception to November 2022 for relevant studies that reported at least one HbA1c level during 24–28 weeks of pregnancy and fetal macrosomia or an LGA baby. We excluded studies that were not published in the English language. No other search filters were applied during the search. Two independent reviewers selected eligible studies for meta-analysis. Two independent reviewers performed data collection and analyses. The PROSPERO registration number is CRD42018086175. A total of 23 studies were included in this systematic review. Of these, 8 papers reported data of 17,711 women with GDM that allowed for inclusion in a meta-analysis. The obtained results demonstrated the prevalence of fetal macrosomia was 7.4% and of LGA, 13.36%. Meta-analyses showed that the estimated pooled risk ratio (RR) for LGA in women with high HbA1c values compared to normal or low values was 1.70 (95% CI: 1.23–2.35), p = 0.001; and the pooled RR for fetal macrosomia was 1.45 (95% CI: 0.80 to 2.63), p = 0.215. Further research is needed to evaluate the utility of HbA1c levels in predicting the delivery of a baby with fetal macrosomia or LGA in pregnant women.

Comparisons of the Rates of Large-for-Gestational-Age Newborns between Women with Diet-Controlled Gestational Diabetes Mellitus and Those with Non-Gestational Diabetes Mellitus

“…Certainly, GDM is an independent risk factor for LGA infants [28][29][30][31], directly dosagedependent on blood glucose levels [29,32,33]. In GDM, maternal hyperglycemia causes fetal hyperglycemia via placental transportation of glucose, leading to fetal hyperinsulinemia.…”

Influence of Physical Activity during Pregnancy on Birth Weight: Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…For example, gestational weight gain and birth weight are positively correlated, and therefore, preventing excessive gestational weight gain may also affect the reduction in birth weight [ 105 ]. Similarly, gestational diabetes increases the risk for large-for-gestational-age newborns [ 106 ]. Physical activity in pregnancy reduces the risk for excessive gestational weight gain by 32% and gestational diabetes by 38% [ 102 , 103 ], and accordingly, may be attributed to also improving newborn birth weight.…”