Jami L. Josefson

Maternal Obesity and Vitamin D Sufficiency Are Associated with Cord Blood Vitamin D Insufficiency

CONTEXT An inverse relationship between total serum 25-hydroxyvitamin D (25-OH D) and increased adiposity has been established in children, adolescents, and adults. However, the relationship between neonatal adiposity and vitamin D status has not been reported. Both maternal obesity and vitamin D deficiency in pregnancy are common and are associated with adverse pregnancy outcomes. OBJECTIVE The aim of the study was to determine the relationship between vitamin D levels in mothers and newborns, as influenced by maternal obesity, and evaluate these associations with neonatal adiposity. DESIGN, SETTING, AND PATIENTS Sixty-one maternal-neonatal pairs participated in this cross-sectional study at an academic medical center. Mothers had a prepregnancy body mass index that was normal or obese. OUTCOME MEASURES Maternal and cord blood sera were assayed for 25-OH D, and neonatal body composition was measured by air displacement plethysmography. RESULTS Mothers had similar and sufficient levels of 25-OH D when measured at 36-38 wk gestation, irrespective of body mass index category (normal weight, 46.05, vs. obese, 49.84 ng/ml; P = not significant). However, cord blood 25-OH D was higher in neonates of normal-weight mothers compared to neonates of obese mothers (27.45 vs. 20.81 ng/ml; P = 0.02). The variance in cord blood 25-OH D was explained by four factors: maternal 25-OH D level, the presence of maternal obesity, maternal age, and neonatal adiposity (r(2) = 0.66). CONCLUSION Obese women transfer less 25-OH D to offspring than normal-weight women, despite similar serum levels. Cord blood 25-OH D levels directly correlate to neonatal percentage body fat. These novel findings underscore the evolving relationships between maternal obesity, vitamin D nutritional status, and adiposity in the neonatal period that may influence subsequent childhood and adulthood vitamin D-dependent processes.

Excessive weight gain in women with a normal pre‐pregnancy BMI is associated with increased neonatal adiposity

More than 40% of women with a normal pre‐pregnancy body mass index (BMI) exceed the 2009 Institute of Medicine (IOM) guidelines’ recommended weight gain of 25–35 lb. Excessive gestational weight gain is one modifiable factor that may be contributing to childhood overweight and obesity.

Maternal short-chain fatty acids are associated with metabolic parameters in mothers and newborns

During the course of pregnancy, dynamic remodeling of the gut microbiota occurs and contributes to maternal metabolic changes through an undefined mechanism. Because short chain fatty acids (SCFAs) are a major product of gut microbiome fermentation, we investigated whether serum SCFA levels during pregnancy are related to key metabolic parameters in mothers and newborns. In this prospective study, 20 pregnant women without gestational diabetes were evaluated at 36-38 weeks of gestation, and their newborns were assessed after parturition. In this cohort, which included normal (n = 10) and obese (n = 10) subjects based on prepregnancy body mass index, serum levels of SCFAs (acetate, propionate, and butyrate), maternal adipokines, maternal glucose, and C-peptide were measured at 36-38 weeks of gestation. Maternal weight gain and newborn anthropometrics were also determined. Data were analyzed using linear regression to test for associations, adjusting for prepregnancy obesity. In this cohort, serum acetate levels were associated with maternal weight gain and maternal adiponectin levels. In addition, serum propionate correlated negatively with maternal leptin levels, newborn length, and body weight. Taken together, this study observed that novel relationships exist among maternal SCFA levels and multiple interrelated maternal/newborn metabolic parameters.

Maternal Leptin Predicts Adiposity of the Neonate

Background: Increased adiposity at birth may identify infants at high risk of developing obesity. Maternal obesity and hyperglycemia in pregnancy are associated with increased neonatal adiposity; however, features of maternal obesity that contribute to increased neonatal adiposity need further study. Aims: To measure adiposity in neonates of obese and normal-weight women without gestational diabetes to test the hypothesis that obese women have neonates with increased adiposity compared to neonates of normal-weight women. Methods: Sixty-one pregnant women, with a normal or obese BMI, and their neonates participated in this cross-sectional study at an academic medical center. Neonatal adiposity, expressed as percent body fat (fat mass/body mass), was measured by air displacement plethysmography and cord blood was assayed for biomarkers. Results: Adiposity in neonates of obese and normal-weight mothers did not differ. Stratifying mothers by leptin level showed that neonates born to mothers with higher leptin had significantly higher adiposity (13.2 vs. 11.1%, p = 0.035). In the entire cohort, adiposity positively correlated with cord blood leptin (r = 0.48, p < 0.001) and adiponectin (r = 0.27, p = 0.04) levels. Conclusion: Obesity in normoglycemic pregnant women was not associated with increased neonatal adiposity. High maternal leptin levels identified neonates with increased adiposity.

Gestational Weight Gain and Neonatal Adiposity in the Hyperglycemia and Adverse Pregnancy Outcome Study-North American Region

To examine the associations between gestational weight gain (GWG) exceeding Institute of Medicine (IOM) guidelines and neonatal adiposity in the five North American field centers of the Hyperglycemia and Adverse Pregnancy Outcome study.

The Relationship of Insulin-Like Growth Factor 2 to Fetal Growth and Adiposity

Insulin-like growth factor 2 (IGF-2) is necessary for adequate human growth. Overexpression of the IGF2 gene is associated with fetal overgrowth and may play a role in the intrauterine programming of adipose tissue. As obesity in children is a major public health problem associated with early onset of comorbid metabolic diseases, identifying early life markers of obesity may serve as useful tool for counseling and implementation of preventive efforts before obesity develops. The relationship between IGF-2 and body composition is an emerging field of study and existing data are conflicting. In this review, we discuss the IGF2 gene and its function, highlight the proposed mechanisms for the effects of IGF-2 on adiposity, and examine the current literature studying the relationships between IGF-2 levels, changes within the IGF2 gene, weight, and adiposity. With additional study, IGF-2 may emerge as a useful marker of future obesity risk in infants.

Maternal BMI Associations with Maternal and Cord Blood Vitamin D Levels in a North American Subset of Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Participants

Objective Obesity in pregnancy may be associated with reduced placental transfer of 25-hydroxyvitamin D (25-OHD). The objective of this study was to examine associations between maternal BMI and maternal and cord blood levels of 25-OHD in full term neonates born to a single racial cohort residing at similar latitude. Secondary objectives were to examine associations between maternal glucose tolerance with maternal levels of 25-OHD and the relationship between cord blood 25-OHD levels and neonatal size. Methods This study was conducted among participants of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study meeting the following criteria: residing at latitudes 41–43°, maternal white race, and gestational age 39–41 weeks. Healthy pregnant women underwent measures of height, weight, and a 75-g fasting oral glucose tolerance test (OGTT) at approximately 28 weeks gestation. Maternal and cord blood sera were analyzed for total 25-OHD by HPLC tandem mass spectrometry. Statistical analyses included ANOVA and linear regression models. Results Maternal and cord blood (N = 360) mean levels (sd) of 25-OHD were 37.2 (11.2) and 23.4 (9.2) ng/ml, respectively, and these levels were significantly different among the 3 field centers (ANOVA p< 0.001). Maternal serum 25-OHD was lower by 0.40 ng/ml for BMI higher by 1 kg/m2 (p<0.001) in an adjusted model. Maternal fasting plasma glucose, insulin sensitivity, and presence of GDM were not associated with maternal serum 25-OHD level when adjusted for maternal BMI. Cord blood 25-OHD was lower by 0.26 ng/ml for maternal BMI higher by 1 kg/m2 (p<0.004). With adjustment for maternal age, field center, birth season and maternal serum 25-OHD, the association of cord blood 25-OHD with maternal BMI was attenuated. Neither birth weight nor neonatal adiposity was significantly associated with cord blood 25-OHD levels. Conclusion These results suggest that maternal levels of 25-OHD are associated with maternal BMI. The results also suggest that interpretation of neonatal 25-OHD levels may need to incorporate specific maternal factors in addition to season of birth and latitude.

Rapamycin Inhibits Growth Factor-Induced Cell Cycle Regulation in Pancreatic β Cells

ABSTRACT A progressive decline in islet function is a major obstacle to the success of islet transplantation. The cause of this decline in islet function is unclear, but immunosuppressive agents may contribute. Insulin-like growth factor-I (IGF-I) and betacellulin are important for islet cell survival and/or proliferation. In the present study, we performed studies in INS-1 cells and murine islets to define the effect of IGF-I and betacellulin on progression of islet cells through the cell cycle and the impact of immunosuppressive agents. Treatment of INS-1 cells for 24 hours with 20 ng/mL betacellulin or 50 ng/mL IGF-I increased cells in S phase by ∼2-fold. Treatment of INS-1 cells with IGF-I or betacellulin also increased cyclin D1 expression and nuclear exclusion of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1. In INS-1 cells and islets, betacellulin- and IGF-I increased Akt, extracellular signal-related kinase, and p70S6 kinase phosphorylation. Rapamycin, an immunosuppressant which inhibits mammalian target of rapamycin, inhibited the increase in p70S6 kinase phosphorylation stimulated by betacellulin- and IGF-I in INS-1 cells. Rapamycin also inhibited betacellulin- and IGF-I-induced entry of cells into S phase and 5′-Bromo-2′-deoxyuridine incorporation as well as the effect of betacellulin and IGF-I on cyclin D1 expression and nuclear exclusion of p21Cip1 and p27Kip1. Together, these data suggest that the effect of betacellulin and IGF-I on islet cell growth and proliferation is mediated, in part, via signaling through mammalian target of rapamycin. As rapamycin is used to treat islet transplant recipients, these results suggest that rapamycin could have deleterious effects on islet proliferation and function over time.

Neonatal adiposity increases with rising cord blood IGF-1 levels.

Infants with higher adiposity at birth may be at greater risk of developing obesity later in life. IGF‐1 is important for intrauterine growth and may be a useful early life marker of adiposity, and thus later obesity risk. The aim of this study was to determine the relationship between cord blood IGF‐1, neonatal anthropometrics and markers of neonatal adiposity.

Excessive gestational weight gain in the first trimester among women with normal glucose tolerance and resulting neonatal adiposity

Objective:To assess whether weight gain above or below Institute of Medicine (IOM) recommended amounts in an ethnically diverse obstetric population with normal glucose tolerance is associated with differences in neonatal adiposity.Study Design:In this prospective cohort study, healthy women with normal glucose tolerance based on the International Association of Diabetes and Pregnancy Study Groups guidelines were enrolled. Gestational weight at multiple time points were collected. Neonatal adiposity was measured by air displacement plethysmography at 24 to 72 h of life. Analyses included Fisher’s exact test, analysis of variance and a trajectory analysis using a group-based weight gain trajectory model with a censored normal distribution.Results:Overweight and obese women were more likely to exceed IOM weight gain guidelines. Regardless, there was no significant difference in %body fat of neonates born to mothers who either met or exceeded gestational weight gain (GWG) guidelines. GWG timing influenced neonatal anthropometrics: women who gained excessively by the first prenatal visit had neonates with significantly higher birth weight (3.91 vs 3.45 kg, P<0.001) and %body fat (13.7 vs 10.9%, P=0.0001) compared with women who had steady and moderate GWG.Conclusion:Avoidance of excessive GWG in the first trimester may prevent high amounts of neonatal adiposity.