Optimizing healthy gestational weight gain in women at high risk of gestational diabetes: A randomized controlled trial

Objective:

Optimizing gestational weight gain (GWG) in early pregnancy is of clinical and public health importance, especially in higher risk pregnancies.

Design and Methods:

In a robustly designed, randomized controlled trial, 228 pregnant women at risk of developing gestational diabetes mellitus (GDM) were allocated to either control (written health information only) or intervention (four‐session lifestyle program). All women received standard maternal care. Measures were completed at 12‐15 and 26‐28 weeks gestation. Measures included anthropometrics (weight and height), physical activity (pedometer and International Physical Activity Questionnaire), questionnaires (risk perception), and GDM screening.

Results:

The mean (SD) age [31.7 (4.5) and 32.4 (4.7) years] and body mass index [BMI; 30.3 (5.9) and 30.4 (5.6) kg/m²] were similar between control and intervention groups, respectively. By 28 weeks, GWG was significantly different between control and intervention groups [6.9 (3.3) vs. 6.0 (2.8) kg, P < 0.05]. When stratified according to baseline BMI, overweight women in the control group gained significantly more weight compared to overweight women in the intervention group [7.8 (3.4) vs. 6.0 (2.2) kg, P < 0.05], yet in obese women, GWG was similar in both groups. Physical activity levels declined by 28 weeks gestation overall (P < 0.01); however, the intervention group retained a 20% higher step count compared to controls [5,203 (3,368) vs. 4,140 (2,420) steps/day, P < 0.05]. Overall, GDM prevalence was 22%, with a trend toward less cases in the intervention group (P = 0.1).

Conclusions:

Results indicate that a low‐intensity lifestyle intervention, integrated with antenatal care, optimizes healthy GWG and attenuates physical activity decline in early pregnancy. Efficacy in limiting weight gain was greatest in overweight women and in high‐risk ethnically diverse women.     

Modeling the pediatric paradox: Birth weight by gestational age

Abstract

The “pediatric paradox” of African versus European American infant mortality is often observed with respect to birth weight, but rarely to gestational age, even though the two measures are biologically related. This paper models the pediatric paradox by birth weight and gestational age simultaneously, using Covariate Density Defined mixture of logistic regressions (CDDmlr) fitted to 1985–1988 New York State births. The model controls for unobserved heterogeneity and isolates the pediatric paradox in the “compromised” subpopulation. The paradox is not limited to low birth weights and/or short gestational ages, but surrounds the normal birth range. Nevertheless, the pediatric paradox is only observed in the marginal distribution of birth weight and not the marginal distribution of gestational age. These results are consistent with the hypothesis that higher fetal losses in the “compromised” subpopulation may be responsible for the pediatric paradox and that African versus European American infant mortality differentials are underestimated.     

Association between gestational diabetes and biomarkers: a role in diagnosis

Background: We investigated the association between markers of insulin resistance, chronic inflammation, and adipokines and GDM.

Methods: In our case-cohort study in Johannesburg we included women with GDM and controls. We tested the ability of biomarkers to identify women at high risk of GDM.

Results: Of the 262 pregnant women, 83 (31.7%) had GDM. Women with GDM were heavier (p?=?0.04) and had more clinical risk factors (p?=?0.008). We found a significant difference in fasting insulin (p?p?=?0.046), HOMA (p?p?Conclusions: Insulin sensitivity markers are promising tools to identify women at high risk of GDM.     

Lung protein leaks in ventilated lambs: effects of gestational age

To study the protein permeability properties of the ventilated premature lung, we delivered groups of eight lambs at 122 and 135 days gestational age and ventilated the lambs equivalently. The lambs at 122 days gestational age had been treated with natural sheep surfactant at birth, and both groups of lambs had similar pH and blood gas values to 3 h of age. Three groups of lambs at 146 days gestational age also were studied for comparison; four lambs were ventilated to normalized PCO2 values, four lambs were ventilated equivalently to the premature lambs with supplemental CO2 used to normalize PCO2 values, and four lambs were treated with natural surfactant and ventilated similarly to the preterm lambs. The percent recovery into an alveolar wash and lung tissue of 131I-albumin given by intravascular injection and of 125I-albumin given into the airways was measured in each animal after killing at 3 h of age. Full-term lambs had a small bidirectional leak of albumin to and from the alveoli and lung tissue. The recovery of intravascular 131I-albumin in the alveolar wash was 5.8- and 4.1-fold higher in lambs at 122 and 135 days gestational age, respectively, than in full-term lambs. The loss of 125I-albumin from the airways and alveoli also increased as gestational age decreased. The bidirectional flux of albumin to and from the alveoli increased as gestational age decreased in the prematurely delivered and ventilated lambs.     

Relationship between gestational cocaine use and pregnancy outcome: a meta-analysis.

Despite a growing number of studies that have investigated the reproductive effects of maternal cocaine use, a homogeneous pattern of fetal effects has not been established and there is little consensus on the adverse effects of the drug. We used meta-analysis to evaluate the reproductive risks of cocaine. We reviewed the 45 scientific papers published in the English language dealing with effects of cocaine used during pregnancy on pregnancy outcome in humans, and identified 20 papers eligible for meta-analysis (cocaine use in pregnancy, pregnancy/fetal outcome studies, human studies, original work, cohort or case control studies, control group present, English language). Our analysis revealed that very few adverse reproductive effects could be shown to be significantly associated with cocaine use by polydrug users when compared to control groups of polydrug users not using cocaine [genitourinary malformations; odds ratio of 6.08 (95% CI 1.18-31.3); gestation age: Cohen's d 0.37 (CI 0.2-0.55)]. When the control groups consisted of no drug users, the polydrug users abusing cocaine had a higher risk for spontaneous abortions [odds ration 10.50 (CI 11.74-64.1)]. Similarly, comparison of users of cocaine alone or no drug users revealed a higher risk for in utero death, in addition to genitourinary tract malformations. Analysis of continuous variables (head circumference, gestational age, birth weight and length) revealed that the effect size was dependent upon the nature of the comparison. Comparison of cocaine users to no drug users consistently yielded a medium effect size (Cohen's d) between 0.50 and 0.58, while comparison of polydrug/cocaine users to polydrug/no cocaine users provided effect sizes small to non existent (0.06-0.37). These discrepancies suggest that a variety of adverse reproductive effects commonly quoted to be associated with maternal use of cocaine may be caused by confounding factors clustering in cocaine users.     

Postnatal gestational age estimation via newborn screening analysis: application and potential

ABSTRACT

Introduction: Preterm birth is a major global health concern, contributing to 35% of all neonatal deaths in 2016. Given the importance of accurately ascertaining estimates of preterm birth and in light of current limitations in postnatal gestational age (GA) estimation, novel methods of estimating GA postnatally in the absence of prenatal ultrasound are needed. Previous work has demonstrated the potential for metabolomics to estimate GA by analyzing data captured through routine newborn screening.

Areas covered: Circulating analytes found in newborn blood samples vary by GA. Leveraging newborn screening and demographic data, our group developed an algorithm capable of estimating GA postnatally to within approximately 1 week of ultrasound-validated GA. Since then, we have built on the model by including additional analytes and validating the model’s performance through internal and external validation studies, and through implementation of the model internationally.

Expert opinion: Currently, using metabolomics to estimate GA postnatally holds considerable promise but is limited by issues of cost-effectiveness and resource access in low-income settings. Future work will focus on enhancing the precision of this approach while prioritizing point-of-care testing that is both accessible and acceptable to individuals in low-resource settings.     

Glycaemia dynamics in gestational diabetes mellitus

Pregnant women may develop gestational diabetes mellitus (GDM), a disease of pregnancy characterised by maternal and fetal hyperglycaemia with hazardous consequences to the mother, the fetus, and the newborn. Maternal hyperglycaemia in GDM results in fetoplacental endothelial dysfunction. GDM-harmful effects result from chronic and short periods of hyperglycaemia. Thus, it is determinant to keep glycaemia within physiological ranges avoiding short but repetitive periods of hyper or hypoglycaemia. The variation of glycaemia over time is defined as ‘glycaemia dynamics’. The latter concept regards with a variety of mechanisms and environmental conditions leading to blood glucose handling. In this review we summarized the different metrics for glycaemia dynamics derived from quantitative, plane distribution, amplitude, score values, variability estimation, and time series analysis. The potential application of the derived metrics from self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) in the potential alterations of pregnancy outcome in GDM are discussed.     

Molecular basis of gestational trophoblastic diseases

Gestational trophoblastic disease (GTD) encompasses a diverse group of lesions with specific pathogenesis, morphological characteristics and clinical features. The modified World Health Organization-classification of GTD includes complete and partial hydatidiform mole, invasive mole, choriocarcinoma, placental site trophoblastic tumor, epithelioid trophoblastic tumor, exaggerated placental site, and placental site nodule. The various forms of gestational trophoblastic disease can be defined and related to discrete pathologic aberrations occurring at different stages of trophoblastic differentiation. Some of these lesions are true neoplasms, whereas others represent abnormally formed placentas with a predisposition for neoplastic transformation of the trophoblast. Except hydatidiform moles in which the cytogenetic studies have been extensively reported, the pathogenesis of other trophoblastic lesions is poorly understood. Recent studies have shed light on the molecular mechanisms of trophoblastic function, especially as it relates to trophoblastic disease. This review will focus on these advances with special emphasis on the pathogenesis of each specific form of GTD. In addition, the morphology and clinical behavior of each of these entities will be briefly discussed.     

Predictive parameters of gestational diabetes mellitus

Gestational diabetes mellitus is a carbohydrate intolerance recognized in pregnancy. The objective of this study was to determine the prevalence of gestational diabetes mellitus (GDM) of all deliveries at the University Hospital Rijeka, Croatia (34 997 deliveries over 10-year period) using 2-hour 75 g oral glucose tolerant test and to evaluate the impact of GDM on neonatal outcomes and mother's health. Gestational diabetes was diagnosed in 55 of 128 pregnant women with suspected glucose intolerance. Logistic regression analysis was used to examine the relationship between fasting plasma glucose, age, family history, body mass index, maternal weight gain, neonatal weight, neonatal head diameter and Apgar score in the gestational diabetes group and in the non-diabetes group. The results indicate that fasting plasma glucose greater than 7.0 mmol/L and maternal overweight are strong predictors for GDM and macrosomia. There was no difference in the mode of delivery, and vitality and metabolic complications among the infants of all analyzed mothers. We concluded that to prevent GDM as well as to reduce the rate of macrosomic infants good glycemic control should be initiated as soon as possible. The 2-hour 75 g OGTT is worth enough to evaluate GDM. Women should be counseled and encouraged to lose weight before or at the beginning of the conception period.     

Placental structure in gestational diabetes mellitus

The placenta is a transitory organ, located between the mother and the foetus, which supports intrauterine life. This organ has nutritional, endocrine and immunologic functions to support foetal development. Several factors are related to the correct functioning of the placenta including foetal and maternal blood flow, appropriate nutrients, expression and function of receptors and transporters, and the morphology of the placenta itself. Placental morphology is crucial for understanding the pathophysiology of the organ as represents the physical structure where nutrient exchange occurs. In pathologies of pregnancy such as diabetes mellitus in humans and animal models, several changes in the placental morphology occur, related mainly with placental size, hypervascularization, higher branching capillaries of the villi and increased glycogen deposits among others. Gestational diabetes mellitus is associated with modifications in the structure of the human placenta including changes in the surface area and volume, as well as histological changes including an increased volume of intervillous space and terminal villi, syncytiotrophoblast number, fibrinoid areas, and glycogen deposits. These modifications may result in functional changes in this organ thus limiting the wellbeing of the developing foetus. This review gives an overview of recurrent morphological changes at macroscopic and histological levels seen in the placenta from gestational diabetes in humans and animal models. This article is part of a Special Issue entitled: Membrane Transporters and Receptors in Pregnancy Metabolic Complications edited by Luis Sobrevia.     

Babies born small for gestational age: insulin sensitivity and growth hormone treatment

Epidemiological studies have identified an association between size at birth and adult risk for type 2 diabetes mellitus and cardiovascular disease. In contemporary populations, children who are relatively small at birth and show rapid infancy weight gain are at greatest risk for the development of childhood obesity, increased visceral fat and insulin resistance: possible early markers of adult disease risk. Individuals presenting to growth clinics with short stature and a history of low birthweight will not have shown post-natal catch-up growth and may be a very heterogeneous group. Nevertheless, there are some data to suggest that as a group they are insulin resistant with decreased lean mass. Growth hormone treatment leads to reversible worsening of the insulin resistance, and short-term data do not indicate an increased risk for type 2 diabetes. However, further long-term follow-up is required, and particular care should be taken in monitoring children with a strong family history of type 2 diabetes and those from ethnic groups in which there is a high background prevalence of the disease.