Precision stratification of prognostic risk factors associated with outcomes in gestational diabetes mellitus: a systematic review.

Background: The objective of this systematic review is to identify prognostic factors among women and their offspring affected by gestational diabetes mellitus (GDM), focusing on endpoints of cardiovascular disease (CVD) and type 2 diabetes (T2D) for women, and cardiometabolic profile for offspring.

Methods: This review included studies published in English language from January 1st, 1990, through September 30th, 2021, that focused on the above outcomes of interest with respect to sociodemographic factors, lifestyle and behavioral characteristics, traditional clinical traits, and 'omics biomarkers in the mothers and offspring during the perinatal/postpartum periods and across the lifecourse. Studies that did not report associations of prognostic factors with outcomes of interest among GDM-exposed women or children were excluded.

Bringing precision medicine to the management of pregnancy in women with glucokinase-MODY: a study of diagnostic accuracy and feasibility of non-invasive prenatal testing.

Aims/hypothesis: In pregnancies where the mother has glucokinase-MODY (GCK-MODY), fetal growth is determined by fetal genotype. When the fetus inherits a maternal pathogenic GCK variant, normal fetal growth is anticipated, and insulin treatment of maternal hyperglycaemia is not recommended. At present, fetal genotype is estimated from measurement of fetal abdominal circumference on ultrasound.

Predictors and risk factors of short-term and long-term outcomes among women with gestational diabetes mellitus (GDM) and their offspring: Moving toward precision prognosis?

As part of the American Diabetes Association Precision Medicine in Diabetes Initiative (PMDI) - a partnership with the European Association for the Study of Diabetes (EASD) - this systematic review is part of a comprehensive evidence evaluation in support of the 2 International Consensus Report on Precision Diabetes Medicine. Here, we sought to synthesize evidence from empirical research papers published through September 1 , 2021 to evaluate and identify prognostic conditions, risk factors, and biomarkers among women and children affected by gestational diabetes mellitus (GDM), focusing on clinical endpoints of cardiovascular disease (CVD) and type 2 diabetes (T2D) among women with a history of GDM; and adiposity and cardiometabolic profile among offspring exposed to GDM We identified a total of 107 observational studies and 12 randomized controlled trials testing the effect of pharmaceutical and/or lifestyle interventions. Broadly, current literature indicates that greater GDM severity, higher maternal body mass index, belonging to racial/ethnic minority group; and unhealthy lifestyle behaviors would predict a woman's risk of incident T2D and CVD, and an unfavorable cardiometabolic profile among offspring.

Assessing whether genetic scores explain extra variation in birthweight, when added to clinical and anthropometric measures.

Background: Human birthweight is a complex, multifactorial trait. Maternal characteristics contribute to birthweight variation by influencing the intrauterine environment. Variation explained by genetic effects is also important, but their contributions have not been assessed alongside other key determinants.

Identification of GCK-maturity-onset diabetes of the young in cases of neonatal hyperglycemia: A case series and review of clinical features.

Heterozygous mutations in GCK result in a persistent, mildly raised glucose from birth, but it is usually diagnosed in adulthood as maturity-onset diabetes of the young (MODY), where hyperglycemia is often an incidental finding. The hyperglycemia of GCK-MODY is benign and does not require treatment, but is important to be aware of, particularly in females where it has implications for managing pregnancy. We present three cases of neonatal hyperglycemia resulting from a heterozygous mutation in GCK, illustrating its clinical presentation and evolution in early life.

All thresholds of maternal hyperglycaemia from the WHO 2013 criteria for gestational diabetes identify women with a higher genetic risk for type 2 diabetes.

Using genetic scores for fasting plasma glucose (FPG GS) and type 2 diabetes (T2D GS), we investigated whether the fasting, 1-hour and 2-hour glucose thresholds from the WHO 2013 criteria for gestational diabetes (GDM) have different implications for genetic susceptibility to raised fasting glucose and type 2 diabetes in women from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) and Atlantic Diabetes in Pregnancy (DIP) studies. Cases were divided into three subgroups: (i) FPG ≥5.1 mmol/L only, n=222; (ii) 1-hour glucose post 75 g oral glucose load ≥10 mmol/L only, n=154 (iii) 2-hour glucose ≥8.

Two decades since the fetal insulin hypothesis: what have we learned from genetics?

In 1998 the fetal insulin hypothesis proposed that lower birthweight and adult-onset type 2 diabetes are two phenotypes of the same genotype. Since then, advances in research investigating the role of genetics affecting insulin secretion and action have furthered knowledge of fetal insulin-mediated growth and the biology of type 2 diabetes. In this review, we discuss the historical research context from which the fetal insulin hypothesis originated and consider the position of the hypothesis in light of recent evidence.

The association between first trimester AFP to PAPP-A ratio and placentally-related adverse pregnancy outcome.

Introduction: Low maternal serum levels of pregnancy-associated plasma protein A (PAPP-A) measured in the first trimester and high levels of alpha fetoprotein (AFP) measured in the second trimester have been associated with adverse pregnancy outcomes reflective of placental insufficiency, and there is a synergistic relationship between the two. We investigated the utility as a screening test of a simple ratio of maternal serum AFP to PAPP-A (AFP:PAPP-A) measured in the first trimester.

Methods: We studied 4057 nulliparous women with a singleton pregnancy from the Pregnancy Outcome Prediction (POP) study.

A Lower Maternal Cortisol-to-Cortisone Ratio Precedes Clinical Diagnosis of Preterm and Term Preeclampsia by Many Weeks.

Context: Previous studies have shown reduced placental levels of 11-β-hydroxysteroid dehydrogenase type 2 (11βHSD2) in preeclampsia (PE). However, it is unknown if the maternal cortisol-to-cortisone ratio is predictive of placental complications of pregnancy.

Objective: To determine the relationship between the maternal serum cortisol-to-cortisone ratio at different stages of pregnancy and the risk of PE or fetal growth restriction (FGR).

Fetal Genotype and Maternal Glucose Have Independent and Additive Effects on Birth Weight.

Maternal glycemia is a key determinant of birth weight, but recent large-scale genome-wide association studies demonstrated an important contribution of fetal genetics. It is not known whether fetal genotype modifies the impact of maternal glycemia or whether it acts through insulin-mediated growth. We tested the effects of maternal fasting plasma glucose (FPG) and a fetal genetic score for birth weight on birth weight and fetal insulin in 2,051 European mother-child pairs from the Exeter Family Study of Childhood Health (EFSOCH) and the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.