W.L.D.M. Nelen

Homocysteine and folate levels as risk factors for recurrent early pregnancy loss

Objective To estimate the relative risk of recurrent early pregnancy loss for different total plasma homocysteine and serum folate concentrations. Methods In a case-control study, we measured homocysteine (fasting and afterload), folate (serum and red cells), pyridoxal 5′-phosphate, and cobalamin concentrations in 123 women who had at least two consecutive spontaneous early pregnancy losses each and compared concentrations with those of 104 healthy controls. Results Women with recurrent early pregnancy losses had significantly lower serum folate concentrations than controls, whereas the other measurements were similar to those of controls. Elevated homocysteine, fasting greater than 18.3 μmol/L and afterload greater than 61.5 μmol/L, was a risk factor for recurrent early pregnancy loss, with odds ratios (ORs) and 95% confidence intervals (95% CIs) of 3.6 (1.2, 12.7) and 2.7 (0.9, 8.8) in the group with recurrent miscarriages: 6.4 (1.9, 24.3) and 4.3 (1.2, 17.3) in primary aborters, and 4.2 (1.3, 15.4) and 3.4 (1.0, 12.8) in those with three or more miscarriages. The ORs (95% CIs) in the same study populations for serum folate concentrations less than 8.4 nmol/L were 2.1 (0.9, 4.8), 2.7 (1.0, 7.8), and 3.2 (1.3, 8.1), respectively. A significant dose-response relationship between serum folate concentrations and risk of recurrent early pregnancy loss suggested a protective effect by high serum folate concentrations. Conclusion Elevated homocysteine and reduced serum folate concentrations were risk factors for recurrent spontaneous early pregnancy losses. Folic acid supplementation might be beneficial in women with histories of early pregnancy loss.

Genetic risk factor for unexplained recurrent early pregnancy loss.

mutation in the methylenetetrahydrofolate reductase gene a risk factor for neural tube defects? A meta-analysis. Q J Med 1997; 90: 111–15. 3 Kluijtmans LAJ, Kastelein JJP, Lindemans J, et al. Thermolabile methylenetetrahydrofolate reductase in coronary artery disease. Circulation (in press). 4 Wouters MGAJ, Boers GHJ, Blom HJ, et al. Hyperhomocysteinemia: a risk factor in women with unexplained recurrent early pregnancy loss. Fertil Steril 1993; 60: 820–25. 5 Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10: 111–13.

Neonatal complications in newborns with an umbilical artery pH <7.00

OBJECTIVE Our purpose was to determine the significance of an umbilical artery pH < 7.00 in relation to neonatal morbidity and mortality. STUDY DESIGN Between 1986 and 1993 acid-base assessment of the umbilical artery was performed routinely in 10,699 deliveries. In a retrospective cohort study 84 nonanomalous neonates with an umbilical artery pH < 7.00 were individually matched with 84 neonates with an umbilical artery pH > 7.24. Matched variables included year of delivery, gender, parity, maternal age, delivery mode, fetal presentation, gestational age, and birth weight. Differences in morbidity between the two groups during the neonatal period (until 28 days after delivery) were investigated. RESULTS Neonates with an umbilical artery pH < 7.00 versus > 7.24 showed significant differences in the following: neonatal condition directly post partum; neurologic, respiratory, cardiovascular, and gastrointestinal complications; and neonatal intensive care unit admissions. No significance was found in renal dysfunction and mortality rate. The proportion of premature infants (< 37 weeks) was 17% in both groups. In the acidotic group a 1-minute Apgar score < or = 3 and a 5-minute Apgar score < 7 was predictive for neonatal complications. CONCLUSIONS Severe intrapartum asphyxia, quantified by an umbilical artery pH < 7.00, poses a threat to the neonates health.

The intercostal-to-phrenic-inhibitory reflex (IPIR) in normal and intra-uterine growth-retarded (IUGR) human fetuses from 26 to 40 weeks of gestation

The existence of an IPIR in the healthy fetus between 37 and 40 weeks of gestation has already been demonstrated: compression of the fetal thoracic wall during an epoch of fetal breathing movements (FBM) consistently caused a fetal apnea (> or = 4 s). The apnea durations were similar in fetal behavioural states 1F and 2F, with a wide inter- and intrafetal variability. We therefore hypothesized that the duration of the IPIR-apnea would increase during gestation and would be increased in IUGR-fetuses as compared to healthy fetuses of the same age. Twenty-six healthy fetuses between 28 and 40 weeks (mean 34.3 weeks) and 14 IUGR-fetuses between 26 and 38 weeks (mean 33.5 weeks) were studied. If FBM were present, the caudolateral part of the fetal thoracic wall was shortly compressed manually and the duration of the resulting apnea was measured. In a random order a sham-compression was also carried out on the fetal head. In normal fetuses 21/28 real compressions were followed by an apnea in 1F, while this was only the case in 3/21 sham-compressions (P < 10(-4)). For 2F these results were 47/57 and 7/51, respectively (P < 10(-4)). In IUGR-fetuses 43/51 real compressions (1F and 2F together) and 7/46 sham-procedures provoked an apnea (P < 10(-4)). These results prove the existence of the IPIR in normal and IUGR-fetuses. The mean (+/- S.D.) duration of apnea in the IUGR-fetuses was 15.8 s (+/- 4.0) (range 4-80 s) and 15.2 s (+/- 4.3) (range 4-106 s) in the normal group.(ABSTRACT TRUNCATED AT 250 WORDS)