Fetal Sex and Maternal Risk of Gestational Diabetes Mellitus: The Impact of Having a Boy

Abstract

OBJECTIVERetrospective analyses of perinatal databases have raised the intriguing possibility of an increased risk of gestational diabetes mellitus (GDM) in women carrying a male fetus, but it has been unclear if this was a spurious association. We thus sought to evaluate the relationship between fetal sex and maternal glucose metabolism in a well-characterized cohort of women reflecting the full spectrum of gestational glucose tolerance from normal to mildly abnormal to GDM. RESEARCH DESIGN AND METHODSA total of 1,074 pregnant women underwent metabolic characterization, including oral glucose tolerance test (OGTT), at mean 29.5 weeks' gestation. The prevalence of GDM, its pathophysiologic determinants (b-cell function and insulin sensitivity/ resistance), and its clinical risk factors were compared between women carrying a female fetus (n = 534) and those carrying a male fetus (n = 540). RESULTSWomen carrying a male fetus had lower mean adjusted b-cell function (insulinogenic index divided by HOMA of insulin resistance: 9.4 vs. 10.5, P = 0.007) and higher mean adjusted blood glucose at 30 min (P = 0.025), 1 h (P = 0.004), and 2 h (P = 0.02) during the OGTT, as compared with those carrying a female fetus. Furthermore, women carrying a male fetus had higher odds of developing GDM (odds ratio 1.39 [95% CI 1.01-1.90]). Indeed, male fetus further increased the relative risk of GDM conferred by the classic risk factors of maternal age >35 years and nonwhite ethnicity by 47 and 51%, respectively. CONCLUSIONSMale fetus is associated with poorer b-cell function, higher postprandial glycemia, and an increased risk of GDM in the mother. Thus, fetal sex potentially may influence maternal glucose metabolism in pregnancy.Fetal sex has been associated with differential risks of perinatal outcomes. Specifically, it has long been recognized that the presence of a male fetus carries increased risks of adverse outcomes, including preterm delivery, premature rupture of membranes, umbilical cord prolapse, true umbilical cord knot, failure to progress in the first and second stages of labor, nonreassuring fetal heart rate patterns, cesarean delivery, and lower Apgar scores (1,2). Although the mechanisms by which male sex may contribute to these events are not clearly understood, it seems probable that these outcomes relate primarily to biological factors determined by the fetus. In contrast, however, different pathophysiologic effects would likely need to be

Sex of the baby and risk of gestational diabetes mellitus in the mother: a systematic review and meta-analysis

“…The 20 studies [1,3,4,[14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] that met inclusion criteria provide data on 2,402,643 women. A study from Retnakaran and Shah [4] evaluated the risk for GDM conferred by fetal sex in a first pregnancy and, in those women in whom it was applicable, the analogous risk in a second pregnancy such that, in the pooled analyses, the first and second pregnancies from this study were entered as two separate reports.…”

“…Then, we performed a sensitivity analysis based on the stringency of the diagnostic approach for identifying GDM that was applied in the studies. In this analysis, we included only the seven studies [1,3,18,25,[28][29][30] that used the two-step approach to diagnose GDM (i.e. screening test followed by an OGTT) that was recently recommended by the National Institutes of Health (NIH) Consensus Panel [31].…”

“…1 Flow diagram of search to identify observational studies on fetal sex and maternal risk of GDM ACOG, American College of Obstetricians and Gynecologists; GCT, glucose challenge test; NDDG, National Diabetes Data Group underlying normal beta cell adaptation has not been fully elucidated, it is believed to involve placentally derived maternal hormones (including human placental lactogens and prolactin) acting through downstream mediators (including the transcription factor FoxMI, the serotonin synthetic enzyme Tph1 and the cell cycle regulator menin), ultimately leading to the expansion of beta cell mass and enhanced insulin secretion [33]. Importantly, it has recently emerged that, after adjustment for classical GDM risk factors (including age, ethnicity, BMI and family history of diabetes), the presence of a male fetus is independently associated with poorer maternal beta cell function [3], thereby providing a potential mechanistic basis through which fetal sex could affect the likelihood of GDM. Another potential explanation for the enhanced risk of maternal GDM conferred by a male fetus could be related to sex-specific selection in utero [34].…”

“…Persson et al [26] Retnakaran et al (b) [4] Gillman et al [19] Khalil et al [23] Okereke et al [25] Sarkar et al [29] Ricart et al [28] Aibar et al [14] Dionne et al [17] Xiao et al [30] Retnakaran et al (a) [4] Ehrlich et al [18] Kale et al [22] Janssen et al [21] Pirkola et al [27] Retnakaran et al [3] Lawlor et al [24] Author…”

“…have poorer pancreatic beta cell function in pregnancy, higher postprandial glycaemia and an elevated risk of gestational diabetes mellitus (GDM), independently of classical diabetes risk factors [3]. Furthermore, in women who develop GDM, the sex of the baby is a predictor of the mother's risk for early postpartum progression to type 2 diabetes after delivery [4].…”