Soluble fms-like tyrosine kinase 1 is increased in preeclampsia but not in normotensive pregnancies with small-for-gestational-age neonates: relationship to circulating placental growth factor.

CONTEXT: An excess of the soluble receptor, fms-like tyrosine kinase 1 (sFlt-1) may contribute to maternal vascular dysfunction in women with preeclampsia by binding and thereby reducing concentrations of free vascular endothelial growth factor and placental growth factor (PlGF) in the circulation. The putative stimulus for increased sFlt-1 during preeclampsia, placental hypoxia due to poor perfusion, is common to both preeclampsia and idiopathic intrauterine growth restriction. However, the latter condition occurs without maternal vascular disease. OBJECTIVE: We asked whether, as with preeclampsia, sFlt-1 is increased and free PlGF is decreased in villous placenta and maternal serum of normotensive women with small-for-gestational-age (SGA) neonates. STUDY DESIGN: This was a case-control study using banked samples. Groups of women with SGA neonates (birth weight centile < 10th) and women with preeclampsia were matched to separate sets of normal pregnancy controls based on gestational age at blood sampling (serum) or gestational age at delivery (placenta). RESULTS: sFlt-1 levels were higher in preeclamptics than controls (serum, P < 0.0001; placental protein, P = 0.03; placental mRNA, P = 0.007) but not increased in SGA pregnancies. PlGF was lower in both preeclampsia (serum, P < 0.0001; placental protein, P = 0.05) and SGA (serum, P = 0.0008; placental protein, P = 0.03) compared with their controls. PlGF in preeclampsia and SGA groups did not differ. CONCLUSIONS: These data are consistent with a role for sFlt-1 in the maternal manifestations of preeclampsia. In contrast to preeclampsia, sFlt-1 does not appear to contribute substantially to decreased circulating free PlGF in SGA pregnancies in the absence of a maternal syndrome.

Contemporary management of preterm premature rupture of membranes: determinants of latency and neonatal outcome.

Preterm premature rupture of membranes (PPROM) is responsible for 30% of neonatal morbidity and mortality in premature gestations. We sought to evaluate pregnancy outcomes in PPROM managed uniformly with antibiotics and steroids, and to determine what maternal factors influence latency. This was a retrospective analysis of 134 patients at 24 to 31.9 weeks with PPROM. Associations of maternal and pregnancy characteristics with latency were evaluated by chi-square for linear trend, nonparametric tests, or multivariable linear regression, as appropriate. Forty-three of 134 women (32%) had latencies greater than a week. Gestational age ( p < 0.001), admission white blood cell count ( p = 0.001), and amniotic fluid index ( p = 0.02) were independently predictive of latency. Histopathologic funisitis increased with pregnancy length. There were no fetal deaths or significant intraventricular hemorrhage past 28 weeks.

The Trp64Arg polymorphism of the beta3-adrenergic receptor is not increased in women with preeclampsia.

OBJECTIVE: Insulin resistance is greater and obesity is more common in women with preeclampsia. The Trp64Arg polymorphism in the beta(3)-adrenergic receptor is associated with these metabolic changes. This study investigated whether the Trp64Arg polymorphism is more common in women with preeclampsia. STUDY DESIGN: beta(3)-Adrenergic receptor genotypes were determined in 177 women with a history of preeclampsia and in 179 normal pregnancies. We also compared prepregnancy body mass index (BMI), length of gestation, baby weight percentile, and glucose values during an oral tolerance test in women with and without the polymorphism. RESULTS: The genotypes and allele frequency did not differ significantly between women with preeclamptic and normal pregnancies (P=.17). Women with and without the polymorphism had similar prepregnancy BMI, glucose at 1-hour screening, gestational age at delivery, and adjusted baby weight. CONCLUSION: The Trp64Arg polymorphism of the beta(3)-receptor does not predispose to preeclampsia, and it is it not associated with obesity and carbohydrate intolerance in a population of young pregnant women.

Smoking during pregnancy is associated with alterations in markers of endothelial function.

OBJECTIVE: Alterations in endothelial function may explain the reduced risk of preeclampsia that is associated with smoking. We hypothesized that markers of endothelial function increase over pregnancy but decrease with smoking. STUDY DESIGN: Plasma samples were obtained throughout pregnancy from 63 primiparous women with normal pregnancies. The samples were assayed for cellular fibronectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1. Smoking status was determined by urinary cotinine concentrations. RESULTS: Mean cellular fibronectin concentrations were different by time (P<.001) and smoking status (P=.01); the lowest concentrations were found in smokers. In contrast, intracellular adhesion molecule-1 was different by smoking status (P=.046); the highest concentrations were found in smokers. Vascular cell adhesion molecule-1 was different over time (P<.001), but not by smoking status. CONCLUSION: Smoking during pregnancy is associated with reduced cellular fibronectin and increased intracellular adhesion molecule-1. These differences may be the result of different aspects of endothelial function or the source of the marker. The explanation for reduced preeclampsia in smokers remains elusive.