Abstract
Biomarkers commonly assessed in prenatal screening have been associated with a number of adverse perinatal and birth outcomes. However, it is not clear whether first trimester measurements of prenatal screening biomarkers are associated with subsequent risk of gestational diabetes mellitus (GDM). We aimed to systematically review and statistically summarize studies assessing the relationship between first trimester prenatal screening biomarker levels and GDM development. We comprehensively searched PubMed/MEDLINE, EMBASE, CINAHL, and Scopus (from inception through January 2018) and manually searched the reference lists of all relevant articles. We included original, published, observational studies examining the association of first trimester pregnancy associated plasma protein-A (PAPP-A) and/or free β-human chorionic gonadotropin (free β-hCG) levels with GDM diagnosis. Mean differences were calculated comparing PAPP-A and free β-hCG multiples of median (MoM) levels between women who developed GDM and those who did not and were subsequently pooled using two-sided random-effects models. Our meta-analysis of 13 studies on PAPP-A and nine studies on free β-hCG indicated that first trimester MoM levels for both biomarkers were lower in women who later developed GDM compared to women who remained normoglycemic throughout pregnancy (MD -0.17; 95% CI -0.24, -0.10; MD -0.04; 95% CI -0.07–0.01). There was no evidence for between-study heterogeneity among studies on free β-hCG (I2 = 0%). A high level of between-study heterogeneity was detected among the studies reporting on PAPP-A (I2 = 90%), but was reduced after stratifying by geographic location, biomarker assay method, and timing of GDM diagnosis. Our meta-analysis indicates that women who are diagnosed with GDM have lower first trimester levels of both PAPP-A and free β-hCG than women who remain normoglycemic throughout pregnancy. Further assessment of the predictive capacity of these biomarkers within large, diverse populations is needed.
Highlights
Gestational diabetes mellitus (GDM), characterized by abnormal glucose tolerance with onset or first recognition during pregnancy, is the most common metabolic complication in pregnancy and is associated with substantial maternal and neonatal morbidities [1,2,3]
The pooled mean differences (MDs) showed lower multiples of median (MoM) levels of first trimester free β-hCG among women who later developed GDM compared to women who remained normoglycemic throughout pregnancy (Fig 2(B))
Our meta-analysis indicates that women diagnosed with GDM have lower first trimester levels of both plasma protein-A (PAPP-A) and free β-hCG than women who remain normoglycemic throughout pregnancy
Summary
Gestational diabetes mellitus (GDM), characterized by abnormal glucose tolerance with onset or first recognition during pregnancy, is the most common metabolic complication in pregnancy and is associated with substantial maternal and neonatal morbidities [1,2,3]. Glucose testing for GDM diagnosis is usually performed between 24–28 weeks’ gestation, [6, 7] when maternal insulin resistance increases to preserve nutrients for the rapidly growing fetus [8]. Evidence of the association between elevated first trimester fasting glucose levels, within the nondiabetic range, and increased risk of GDM diagnosis later in pregnancy and adverse pregnancy outcomes indicate that women with GDM may exhibit metabolic alterations earlier in pregnancy [9,10,11]. Measurement of first trimester biomarkers representative of these metabolic changes may allow for early detection and management of GDM, improved understanding of GDM pathogenesis, and enhanced targeted intervention [9, 11, 12]
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