Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist—including insulin and lifestyle interventions—there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.

Background Infant cognitive development is influenced by maternal factors that range from obesity to early feeding and breast milk composition. Animal studies suggest a role for human milk oligosaccharide (HMO), 2'-fucosyllactose (2'FL), on learning and memory, yet no human studies have examined its impact on infant cognitive development relative to other HMOs and maternal factors. Objective To determine the impact of 2'FL from breast milk feeding on infant cognitive development at 24 months of age relative to maternal obesity and breast milk feeding frequency. Methods and materials Hispanic mother-infant pairs (N = 50) were recruited across the spectrum of pre-pregnancy BMI. Breast milk was collected at 1 and 6 months, and feedings/day were reported. Nineteen HMOs were analyzed using high-performance liquid chromatography, with initial interest in 2'FL. Infant cognitive development score was assessed with the Bayley-III Scale at 24 months. Linear regressions were used for prediction, and bootstrapping to determine mediation by 2'FL.

Background Human milk oligosaccharides (HMOs) are complex glycans that are highly abundant in human milk. While over 150 HMOs have been identified, it is unknown how individual HMOs change in concentration over 24 months of lactation. Objectives To understand how HMO concentrations change over 24 months of lactation. Methods Breast milk samples were collected from participants in a longitudinal cohort study of Hispanic mother-infant pairs at 1, 6, 12, 18, and 24 months postpartum. Concentrations of 19 of the most abundant HMOs were measured using HPLC. Because the parent study is ongoing and not all participants have finished all time points yet, the sample sizes ranged per time point (n = 207 at 1 month; n = 109 at 6 months; n = 83 at 12 months; n = 59 at 18 months; and n = 28 at 24 months). Approximately 88% of participants were classified as HMO secretors—a genetic factor that affects concentrations of HMOs such as 2’fucosyllactose (2’FL) and lacto-N-fucopentaose I—while the remaining 12% were classified as nonsecretors. Mixed models were used to examine changes in HMO concentrations and relative abundances over the course of lactation. Results The majority of HMOs significantly decreased in concentration over the course of lactation. The exceptions were 2’FL, sialyl-lacto-N-tetraose b, and disialyl-lacto-N-tetraose, which did not change with time, and 3-fucosyllactose (3FL) and 3′-sialyllactose (3’SL), which significantly increased. The concentration of 3FL increased 10-fold, from 195 (IQR 138–415) μg/mL at 1 month to 1930 (1100–2630) μg/mL at 24 months, while 3’SL increased 2-fold, from 277 (198–377) μg/mL to 568 (448–708) μg/mL over the same time period. Conclusions These results indicate that HMOs do not decrease in concentration uniformly across lactation. In particular, 3FL and 3’SL increased over the course of lactation in this cohort. Future studies are required to fully understand the functions of these HMOs.

Among all the body fluids, breast milk is one of the richest sources of microRNAs (miRNAs). MiRNAs packaged within the milk exosomes are bioavailable to breastfeeding infants. The role of miRNAs in determining infant growth and the impact of maternal overweight/obesity on human milk (HM) miRNAs is poorly understood. The objectives of this study were to examine the impact of maternal overweight/obesity on select miRNAs (miR-148a, miR-30b, miR-29a, miR-29b, miR-let-7a and miR-32) involved in adipogenesis and glucose metabolism and to examine the relationship of these miRNAs with measures of infant body composition in the first 6 months of life. Milk samples were collected from a cohort of 60 mothers (30 normal-weight [NW] and 30 overweight [OW]/obese [OB]) at 1-month and a subset of 48 of these at 3 months of lactation. Relative abundance of miRNA was determined using real-time PCR. The associations between the miRNAs of interest and infant weight and body composition at one, three, and six months were examined after adjusting for infant gestational age, birth weight, and sex. The abundance of miR-148a and miR-30b was lower by 30% and 42%, respectively, in the OW/OB group than in the NW group at 1 month. miR-148a was negatively associated with infant weight, fat mass, and fat free mass, while miR-30b was positively associated with infant weight, percent body fat, and fat mass at 1 month. Maternal obesity is negatively associated with the content of select miRNAs in human milk. An association of specific miRNAs with infant body composition was observed during the first month of life, suggesting a potential role in the infant’s adaptation to enteral nutrition.

Consumption of sugar and alternative low- or no-energy sweeteners has increased in recent decades. However, it is still uncertain how consumption of sugar and alternative sweeteners during pregnancy affects pregnancy outcomes and long-term offspring health. This review aims to collate the available evidence surrounding the consequences of sugar and alternative sweetener consumption during pregnancy, a so-called secondhand sugar effect. We found evidence that sugar consumption during pregnancy may contribute to increased gestational weight gain and the development of pregnancy complications, including gestational diabetes, preeclampsia and preterm birth. Further, we found a growing body of the animal and human evidence that maternal sugar intake during pregnancy may impact neonatal and childhood metabolism, taste perception and obesity risk. Emerging evidence also suggests that both maternal and paternal preconception sugar intakes are linked to offspring metabolic outcomes, perhaps via epigenetic alterations to the germline. While there have been fewer studies of the impacts of alternative sweetener consumption before and during pregnancy, there is some evidence to suggest effects on infant outcomes including preterm birth risk, increased infant body composition and offspring preference for sweet foods, although mechanisms are unclear. We conclude that preconception and gestational sugar and alternative sweetener consumption may negatively impact pregnancy outcomes and offspring health and that there is a need for further observational, mechanistic and intervention research in this area.