SLC9B1 methylation predicts fetal intolerance of labor.

Fetal intolerance of labor is a common indication for delivery by Caesarean section. Diagnosis is based on the presence of category III fetal heart rate tracing, which is an abnormal heart tracing associated with increased likelihood of fetal hypoxia and metabolic acidemia. This study analyzed data from 177 unique women who, during their prenatal visits (7-15 weeks and/or 24-32 weeks) to Atlanta area prenatal care clinics, consented to provide blood samples for DNA methylation (HumanMethylation450 BeadChip) and gene expression (Human HT-12 v4 Expression BeadChip) analyses. We focused on 57 women aged 18-36 (mean 25.4), who had DNA methylation data available from their second prenatal visit. DNA methylation patterns at CpG sites across the genome were interrogated for associations with fetal intolerance of labor. Four CpG sites (P value <8.9 × 10-9, FDR <0.05) in gene SLC9B1, a Na+/H+ exchanger, were associated with fetal intolerance of labor. DNA methylation and gene expression were negatively associated when examined longitudinally during pregnancy using a linear mixed-effects model. Positive predictive values of methylation of these four sites ranged from 0.80 to 0.89, while negative predictive values ranged from 0.91 to 0.92. The four CpG sites were also associated with fetal intolerance of labor in an independent cohort (the Johns Hopkins Prospective PPD cohort). Therefore, fetal intolerance of labor could be accurately predicted from maternal blood samples obtained between 24-32 weeks gestation. Fetal intolerance of labor may be accurately predicted from maternal blood samples obtained between 24-32 weeks gestation by assessing DNA methylation patterns of SLC9B1. The identification of pregnant women at elevated risk for fetal intolerance of labor may allow for the development of targeted treatments or management plans.

Intrauterine programming of ageing.

Ageing is an unavoidable corollary to being alive; the most intuitive interpretation of ageing being that it is the consequence of progressive body degeneration. In agreement with this, current models propose that ageing occurs through a stepwise accumulation of DNA damage, which ultimately limits the regenerative capacity of tissues. On the other hand, there is increasing evidence that fetal distress can influence the development of disease in adult life, a phenomenon known as 'intrauterine programming'. The extent to which an intrauterine exposure to DNA damage can compromise lifespan remains unclear. My group has recently generated a murine model of a human syndrome linked to defective DNA repair and observed that these animals age prematurely, but the accumulation of DNA damage is restricted mostly to the embryonic period. Here, I discuss the implications of this finding and propose that ageing can be influenced by fetal distress.

Maternal race/ethnicity and predictors of pregnancy and infant outcomes.

OBJECTIVE: To examine predictors of pregnancy and infant outcomes, including maternal race/ethnicity. DESIGN: Prospective and observational follow-up of high-risk pregnancies and births. PARTICIPANTS: Three hundred fifty-four mothers and their preterm and/or high-risk live-born neonates were closely followed in three tertiary care centers from the prenatal to postnatal periods for potential high-risk and/or preterm births that required neonatal resuscitations. MAJOR OUTCOME MEASURES: Pregnancy complications, birth complications, and infant outcomes were examined in conjunction with maternal factors, including preexisting health problems, health behaviors (smoking, alcohol consumption, prenatal visits), and the birth setting (tertiary care centers or community hospitals). RESULTS: About 22% of these infants were transferred into the tertiary care centers from the community hospitals right after birth; the rest were born in the centers. According to regression analyses, predictors of the birth setting were race (White vs. non-White), maternal health behaviors, pregnancy complications, fetal distress, and the presence of congenital defects for infants (p < .001). Predictors for fetal distress included race (Whites) and pregnancy-induced hypertension (p < .003). Predictors for lower birth weight included race (non-Whites), maternal cigarette smoking, pregnancy complications, fetal distress, and congenital defects (p < .001). Infant mortality rate was 3.9% for these high-risk infants, with the highest rate in infants born to Black mothers (8%). CONCLUSIONS: There are obvious health disparities among White and non-White women experiencing high-risk pregnancies and births. Future studies are needed to develop interventions targeted to different racial/ethnic groups during pregnancy to reduce preterm and high-risk births.

[Neonatal chylothorax with trisomy 21]. / Neonataler Chylothorax bei Trisomie 21.

Neonatal chylothorax is an uncommon cause of respiratory distress in the newborn. It may result from anomalous lymph drainage with or without association with aneuploidy syndromes (trisomy, Turner's syndrome, Noonan's syndrome), from injury to the thoracic duct, and from obstruction of the superior vena cava. We report a term newborn and a premature infant with neonatal chylothorax, both associated with trisomy 21. In the case of the term infant, bilateral pleural effusions were diagnosed immediately before birth. The baby suffered from respiratory distress. The physical findings were characteristic of trisomy 21. In the premature infant (gestational age 24 weeks, 735 g) the ductus arteriosus was ligated on day nine after birth. Four days after surgery a central venous line was inserted via the left vena mediana cubiti into the left vena subclavia. Nine days after surgery a left-sided chylothorax occurred. The infant had subtle signs of a trisomy 21 (slightly enlarged tongue, brachycephalic head. questionable simian crease). In both children, cytogenetic studies were done and confirmed the diagnosis of trisomy 21. Infants with neonatal chylothorax should be carefully evaluated for dysmorphic signs of a trisomy or monosomy. Premature infants may present with only subtle clinical signs requiring cytogenetic studies to confirm an aneuploidy syndrome.

Family patterns in handedness: evidence for indirect inheritance mediated by birth stress.

The most common alternative to a genetic explanation of left-handedness is that sinistrality arises because of birth stress factors. In a sample of 1398 subjects, the association between birth stress and left-handedness was confirmed. More importantly, it was found that left-handed mothers are more likely to have birth-stressed offspring and that the presence of any left-handed sibling increases the likelihood of a history of birth stress in the proband. This was interpreted as suggesting that a plausible alternative to the genetic explanation for the usual pattern of association observed in family studies of handedness (where a left-handed mother increases the probability of left-handed offspring) is that the mother-offspring association may actually be mediated by birth stress rather than representing heritable aspects of handedness.