Plasma asymmetric dimethylarginine levels are increased in neonates with bronchopulmonary dysplasia-associated pulmonary hypertension.

OBJECTIVE: To test the hypothesis that levels of the endogenous inhibitor of nitric oxide production, asymmetric dimethylarginine (ADMA), would be greater in preterm infants with bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH) than in infants with BPD alone. STUDY DESIGN: A case-control study of 23 patients with both BPD and PH (cases) and 95 patients with BPD but no evidence of PH (controls). Levels of ADMA were compared between cases and controls by t test. RESULTS: Patients with both BPD and PH had greater plasma levels of ADMA than patients with BPD alone (P = .04). In samples drawn before 28 days of life, greater levels of ADMA were again found in cases compared with controls (P = .02). The plasma arginine-to-ADMA ratio was lower in cases than in controls (P = .03), suggesting a greater likelihood of inhibition of nitric oxide production in patients with both BPD and PH than in patients with BPD alone. CONCLUSION: In this neonatal BPD cohort, ADMA levels are increased in patients with BPD who develop PH. We speculate that ADMA may be both a biomarker and a potential therapeutic target for preterm infants with BPD-associated PH.

Maternal and cord blood 25(OH)-vitamin D concentrations in relation to child development and behaviour.

BACKGROUND: Animal studies have linked in utero vitamin D exposure to various aspects of offspring brain development. Limited research has translated these findings to humans, and none have employed cord blood to measure exposure late in gestation. METHODS: Our objective was to examine the associations between maternal 25(OH)D measured at ≤26 weeks' gestation or cord blood 25(OH)D and offspring global development, IQ, achievement, and behaviour in the US Collaborative Perinatal Project (1959-73). This was a secondary analysis of data from a case-cohort study, with 3896 women and children who participated in at least one outcome assessment. Psychologists assessed global development at 8 months, IQ and behaviour at 4 and 7 years, and achievement at 7 years. Multiple linear and logistic regression was used to examine the associations between 25(OH)D and child outcomes, controlling for maternal education, age, parity, race, maternal body mass index, marital status, smoking, gestational age and month of blood draw, and study site. RESULTS: Positive associations for many outcomes were greatly attenuated upon adjustment for confounders and were generally null. Only IQ at age 7 was associated with both maternal and cord blood 25(OH)D, but the effect estimates were very small (ß for 5 nmol/L increment of maternal 25(OH)D = 0.10; [95% CI 0.00, 0.19]). CONCLUSION: We observed very little indication that maternal or cord blood 25(OH)D are associated with cognitive development, achievement, and behaviour between 8 months and 7 years of age.

Relationship between 17-alpha hydroxyprogesterone caproate concentration and spontaneous preterm birth.

OBJECTIVE: 17-alpha hydroxyprogesterone caproate 250 mg weekly reduces recurrent spontaneous preterm birth in women with a prior spontaneous preterm birth by 33%. The dose is not based on pharmacologic considerations. A therapeutic concentration has not been determined hampering any attempt to optimize treatment. This study evaluated the relationship between 17-alpha hydroxyprogesterone caproate plasma concentrations and the rate of spontaneous preterm birth in women with singleton gestation. STUDY DESIGN: A single blood sample was obtained between 25 and 28 weeks' gestation from 315 women with a spontaneous preterm birth who participated in a placebo-controlled, prospective, randomized clinical trial evaluating the benefit of omega-3 supplementation in reducing preterm birth. All women in the parent study received 17-alpha hydroxyprogesterone caproate and 434 received omega-3 supplementation and 418 received a placebo. Plasma from 315 consenting women was analyzed for 17-alpha hydroxyprogesterone caproate concentration. RESULTS: There were no differences between placebo and omega-3 supplemented groups in demographic variables, outcomes or in mean 17-alpha hydroxyprogesterone caproate concentration. Plasma concentrations of 17-alpha hydroxyprogesterone caproate ranged from 3.7-56 ng/mL. Women with plasma concentrations of 17-alpha hydroxyprogesterone caproate in the lowest quartile had a significantly higher risk of spontaneous preterm birth (P = .03) and delivered at significantly earlier gestational ages (P = .002) than did women in the second to fourth quartiles. The lowest preterm birth rates were seen when median 17-alpha hydroxyprogesterone caproate concentrations exceeded 6.4 ng/mL. CONCLUSION: Low plasma 17-alpha hydroxyprogesterone caproate concentration is associated with an increased risk of spontaneous preterm birth. This finding validates efficacy of this treatment but suggests that additional studies are needed to determine the optimal dosage.

Prenatal Chlamydia trachomatis infection increases the risk of preeclampsia.

The relationship between Chlamydia trachomatis (CT) and preeclampsia was examined longitudinally among 205 cases and 423 normotensive controls nested within the Collaborative Perinatal Project. Antibodies were analyzed at a first prenatal visit (mean 14.2 weeks) and at delivery. Prenatal infections were identified as IgG/IgM seroconversion or a four-fold rise in IgG antibody titers. Although serological evidence of incident prenatal CT infection was uncommon (n=9, 1.4%) in this general pregnant population, infected women were more likely to develop preeclampsia, after adjustment for maternal age, body mass index, smoking status, race and time between blood draws (ORadj 7.2, 95% CI 1.3 - 39.7).

Prospective identification of pregnant women drinking four or more standard drinks (> or = 48 g) of alcohol per day.

We aimed to identify drinking rates in a prospectively identified cohort of pregnant women, and subsequently, to identify the drinkers of 48 g or more alcohol/day among them, by using complementary methods for verifying self-reported drinking habits. A research team of social workers and health professionals at the Maipú Clinic, located in a lower middle class neighborhood of Santiago, Chile, conducted interviews of women attending a prenatal clinic between August 1995 and July 2000. Women whose interview responses met predefined criteria (identified in the text) were further evaluated by home visits. We interviewed 9,628 of 10,917 (88%) women receiving prenatal care. By initial interview, 42.6% of women reported no drinking, 57.4% some alcohol consumption, and 3.7% consuming at least one standard drink (15 mL of absolute alcohol) per day. Of the 887 women who had home visits, 101 were identified as consuming on average at least 4 drinks/day (48 g). To determine the best home visit questionnaire items for identifying those drinking at least 4 drinks per day, 48 women who openly admitted drinking this amount were compared with 786 women who were not considered drinkers after the home visit. The 48 self-reported 48 g/day drinkers were significantly more likely to get tipsy when drinking before (p = 0.01) or during (p < 0.0001) pregnancy, to have started drinking at a younger age (p = 0.007), or to exhibit signs of low self-esteem (p < 0.0001), sleep or appetite problems (p < 0.0001), bad interpersonal relationships (p < 0.0001) or having family members with fetal alcohol syndrome features (p < 0.009). In conclusion, using complementary methods of alcohol misuse ascertainment during pregnancy, we found that at least 1% of pregnant women in a Santiago, Chile, clinic population were drinking at levels that are clearly dangerous to the fetus (48 g/day or more). We identified specific interview questions that may help screen for alcohol use of 48 g/day or more in pregnant women.

Childhood cancer following neonatal oxygen supplementation.

OBJECTIVE: To evaluate the relationship between neonatal oxygen supplementation (O2) and childhood cancer in the Collaborative Perinatal Project (CPP). STUDY DESIGN: The CPP consisted of 54,795 children born between 1959 and 1966 and followed to age 8 years. We used Cox proportional hazards modeling to examine the association between history of neonatal O2 and cancer (n = 48). RESULTS: The hazard ratio (HR) for any O2 was 1.77 (95% confidence interval [CI] = 0.94 to 3.35). The HR for continuous duration of O2 was near 1 and not significant. However, the HRs were 0.69 (95% CI = 0.17 to 2.88) and 2.87 (95% CI = 1.46 to 5.66) when comparing 0 to 2 and 3 or more minutes of O2, respectively, to no O2. The latter association was weaker (HR = 2.00; 95% CI = 0.88 to 4.54) and not significant ( P = .10) when analysis was restricted to cancers diagnosed after age 1 year (n = 41). CONCLUSIONS: These findings are consistent with an association between O 2 for 3 minutes or longer and cancer in childhood, and should serve as a basis for further study.

Peripheral nerve conduction abnormalities in children exposed to alcohol in utero.

OBJECTIVE: We performed a longitudinal study of nerve conduction velocity to determine the effect of prenatal alcohol exposure on the peripheral nervous system. Study design We studied 17 children exposed to >2 oz of absolute alcohol/day prenatally and 13 unexposed children, identified prospectively from a cohort of pregnant women screened during prenatal care. Nerve conduction assessment was done on the median, ulnar, peroneal and tibial nerves during the newborn period and between 12 and 14 months of age. RESULTS: At both assessments the alcohol-exposed subjects had significantly slower ulnar motor nerve velocity (P=.007), smaller proximal (P=.018) and distal amplitude (P=.051). They also showed reduced tibial nerve velocity (P=.06) and a decrease in distal amplitude. CONCLUSIONS: This study demonstrates that prenatal alcohol exposure is associated with abnormalities in nerve electrical properties, and that the pattern is different from that seen in adults. Electrophysiologic abnormalities in peripheral nerves should be added to the problems found in children of alcohol abusing mothers.