Ceramides during Pregnancy and Obstetrical Adverse Outcomes.

Ceramides are a group of sphingolipids located in the external plasma membrane layer and act as messengers in cellular pathways such as inflammatory processes and apoptosis. Plasma ceramides are biomarkers of cardiovascular disease, type 2 diabetes mellitus, Alzheimer's disease, various autoimmune conditions and cancer. During pregnancy, ceramides play an important role as stress mediators, especially during implantation, delivery and lactation. Based on the current literature, plasma ceramides could be potential biomarkers of obstetrical adverse outcomes, although their role in metabolic pathways under such conditions remains unclear. This review aims to present current studies that examine the role of ceramides during pregnancy and obstetrical adverse outcomes, such as pre-eclampsia, gestational diabetes mellitus and other complications.

Vitamin D receptor Fokl polymorphism is a determinant of both maternal and neonatal vitamin D concentrations at birth.

Maternal vitamin D deficiency is considered to be the key determinant of the development of neonatal vitamin D deficiency at birth and during early infancy. Specific vitamin D receptor (VDR) gene polymorphisms have been associated with adverse pregnancy and offspring outcomes. The aim of this study was to evaluate the effect of maternal and neonatal VDR polymorphisms (ApaI, TaqI, BsmI, FokI, Tru9I) on maternal and neonatal vitamin D status. VDR polymorphisms were genotyped in 70 mother-neonate pairs of Greek origin, and classified according to international thresholds for Vitamin D status. Mean neonatal and maternal 25-hydroxy-vitamin D [25(OH)D] concentrations were 35 ± 20 and 47 ± 26 nmol/l, respectively. Neonatal VDR polymorphisms were not associated with neonatal 25(OH)D concentrations. In contrast, mothers with the Fokl FF polymorphism had a 70 % lower risk of vitamin D deficiency [25(OH)D <30 nmol/l] compared with ff ones, after adjustment for several confounders. They were also in 73 % and 88 % lower risk of giving birth to vitamin D deficient [25(OH)D <30 nmol/l] neonates compared with Ff and ff mothers, respectively. These results suggest a protective role of maternal Fokl FF genotype against both maternal and neonatal vitamin D deficiency. Further studies are needed to clarify the complex gene-gene and gene-environment interactions that determine vitamin D status at birth.

Characterizing neonatal vitamin D deficiency in the modern era: A maternal-neonatal birth cohort from Southern Europe.

Absence of adequate maternal vitamin D supplementation and decreased maternal ultraviolet exposure during pregnancy are key determinants for the manifestation of neonatal hypovitaminosis D at birth. These parameters may vary, according to country-specific dietary patterns, health policies and sunshine exposure. We aimed to investigate differences in calcium metabolism and anthropometric profiles according to neonatal vitamin D status at birth, in a sunny region of Northern Greece. A secondary aim was to identify maternal parameters as risk factors for developing neonatal vitamin D deficiency at birth. A total of 129 mother-neonate pairs were included in the study and classified into three groups, according to neonatal 25-hydroxy-D [25(OH)D)] concentrations at birth [deficiency (<30 nmol/l), insufficiency (30-50 nmol/l) and sufficiency (>50 nmol/l)]. Neonatal biochemical and anthropometric profiles and maternal demographic, social, dietary and biochemical profiles were comparatively evaluated between the three groups. Univariate and multivariate logistic regression was performed to identify independent associations of maternal factors with neonatal vitamin D status. Vitamin D deficient-neonates manifested higher parathyroid hormone (7.20 ± 2.60 vs 5.50 ± 1.50 pg/ml, p = 0.01) and lower corrected calcium (10.70 ± 0.70 vs 11.30 ± 1.30 mg/dl, p = 0.02) concentrations compared with vitamin d-insufficient neonates. Mothers of vitamin D deficient and insufficient neonates had a lower total of 25(OH)D (31.7 ± 19.2 and 36.5 ± 22.3 vs 53.3 ± 39.0 nmol/l, p < 0.01) and 25(OH)D3 (27.4 ± 17.5 and 33.3 ± 19.9 vs 47.3 ± 36.7 nmol/l, p < 0.01 and p = 0.04, respectively) concentrations respectively, compared with those of vitamin D-sufficient neonates. Maternal use of alcohol during pregnancy was associated with a 5.57-fold higher risk for neonatal vitamin D deficiency at birth (OR 5.57, 95 % CI1.17-26.56, p = 0.03). Newborns with vitamin D deficiency presented a 6.89-fold higher risk of having been given birth by vitamin D deficient mothers (OR 6.89, 95 % CI 3.09-15.38, p < 0.01). In conclusion, neonatal vitamin D deficiency is associated with maternal 25(OH)D concentrations at birth and maternal alcohol use. Further studies are required to replicate these findings in other regions and populations.

Comments on gestational diabetes mellitus: from pathophysiology to clinical practice.

Gestational diabetes mellitus (GDM) is a topic of major interest, as it affects up to 16% of pregnant women and may lead to adverse pregnancy outcomes, which, however, are preventable by appropriate treatment. The aim of the present study was to discuss basic concepts and to critically appraise recent updates on practical issues in the field of GDM. GDM pathophysiology, long-term complications including "fetal programming" and GDM diagnosis are discussed, while clinical practice guidelines on follow-up, medical nutrition therapy, oral hypoglycemic agents and insulin treatment are also reviewed. GDM comprises a serious yet preventable public health problem and prevention by lifestyle changes, early detection and adequate treatment can lead to better health outcomes for both mothers with GDM and their offspring.

An observational study reveals that neonatal vitamin D is primarily determined by maternal contributions: implications of a new assay on the roles of vitamin D forms.

BACKGROUND: Vitamin D concentrations during pregnancy are measured to diagnose states of insufficiency or deficiency. The aim of this study is to apply accurate assays of vitamin D forms [single- hydroxylated [25(OH)D2, 25(OH)D3], double-hydroxylated [1α,25(OH)2D2, 1a25(OH)2D3], epimers [3-epi-25(OH)D2, 3-epi-25(OH)D3] in mothers (serum) and neonates (umbilical cord) to i) explore maternal and neonatal vitamin D biodynamics and ii) to identify maternal predictors of neonatal vitamin D concentrations. METHODS: All vitamin D forms were quantified in 60 mother- neonate paired samples by a novel liquid chromatography -mass spectrometry (LC-MS/MS) assay. Maternal characteristics [age, ultraviolet B exposure, dietary vitamin D intake, calcium, phosphorus and parathyroid hormone] were recorded. Hierarchical linear regression was used to predict neonatal 25(OH)D concentrations. RESULTS: Mothers had similar concentrations of 25(OH)D2 and 25(OH)D3 forms compared to neonates (17.9 ± 13.2 vs. 15.9 ± 13.6 ng/mL, p=0.289) with a ratio of 1:3. The epimer concentrations, which contribute approximately 25% to the total vitamin D levels, were similar in mothers and neonates (4.8 ± 7.8 vs. 4.5 ± 4.7 ng/mL, p=0.556). No correlation was observed in mothers between the levels of the circulating form (25OHD3) and its active form. Neonatal 25(OH)D2 was best predicted by maternal characteristics, whereas 25(OH)D3 was strongly associated to maternal vitamin D forms (R²=0.253 vs. 0.076 and R2=0.109 vs. 0.478, respectively). Maternal characteristics explained 12.2% of the neonatal 25(OH)D, maternal 25(OH)D concentrations explained 32.1%, while epimers contributed an additional 11.9%. CONCLUSIONS: By applying a novel highly specific vitamin D assay, the present study is the first to quantify 3-epi-25(OH)D concentrations in mother-newborn pairs. This accurate assay highlights a considerable proportion of vitamin D exists as epimers and a lack of correlation between the circulating and active forms. These results highlight the need for accurate measurements to appraise vitamin D status. Maternal characteristics and circulating forms of vitamin D, along with their epimers explain 56% of neonate vitamin D concentrations. The roles of active and epimer forms in the maternal-neonatal vitamin D relationship warrant further investigation.