Primary sclerosing cholangitis in pregnancy refractory to ursodeoxycholic acid treatment: a case report.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease associated with fibrosis and inflammation of the bile ducts. Its complications include symptoms from pruritis and fatigue to dominant strictures, cholangiocarcinoma and liver failure necessitating liver transplant. Due to its predominance in young males, little is reported regarding PSC and pregnancy. CASE: We report a case of a pregnant woman with PSC whose symptoms were initially unresponsive to the traditional treatment of ursodeoxycholic acid (UDCA) early in her pregnancy but subsequently did well using high dose steroids for the duration of her pregnancy. CONCLUSION: With close management, successful pregnancy outcomes seem possible with patients with PSC, even when diagnosed multiple years prior to pregnancy, if not with UDCA, then possibly with steroid treatment.

Placental system A transporter mRNA is not different in preeclampsia, normal pregnancy, or pregnancies with small-for-gestational-age infants.

OBJECTIVE: System A amino acid transporter activity is reduced in placentas from small-for-gestational-age (SGA) compared to normal pregnancies. We compared the expression of the system A transporters between preeclamptic and control and between small-for-gestational-age and controls pregnancies. METHODS: We used placental samples from 18 preeclamptic pregnancies matched with 17 normal pregnancies and from 16 SGA pregnancies matched with 15 different normal pregnancies. Using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) we quantified the mRNA for two system A subtype target genes ATA1 and ATA2 as well as beta-actin for normalization. RESULTS: There was no significant difference of mRNA for ATA1 or ATA2 transporters between preeclamptic and their controls or SGA pregnancies and their controls. CONCLUSIONS: Despite previous studies reporting reduced activity for system A transporters in small-for-gestational-age pregnancies, we found no difference in steady-state concentrations of the mRNA, of the system A transporters among preeclamptic, SGA, and normal control pregnancies. These results do not exclude differences in actual protein levels or activity of the amino acid transporters, which warrant further study.

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.

Maternal serum oestrogen and androgen concentrations in preeclamptic and uncomplicated pregnancies.

BACKGROUND: Epidemiological studies show a substantially reduced risk of breast cancer in adult daughters of preeclamptic pregnancies, and modest risk reductions have been demonstrated for mothers also. Alterations in pregnancy hormone concentrations, particularly lower in utero exposure to oestrogen, are hypothesized to mediate this association. METHODS: Pregnancy hormone concentrations were measured in maternal sera collected at hospital admission for labour and delivery from 86 preeclamptic and 86 uncomplicated, singleton pregnancies matched on length of gestation, maternal age, parity, and type of delivery. RESULTS: Case and control pregnancies were similar in several maternal and pregnancy factors. Serum unconjugated oestradiol, oestrone, and oestriol concentrations were not lower in preeclamptic pregnancies in a matched analysis with adjustment for race and whether blood was collected before or after labour commenced. Serum unconjugated androstenedione (506.3 versus 316.0 ng/dl; P = 0.0007) and testosterone concentrations (214.5 versus 141.9 ng/dl; P = 0.004), however, were significantly higher in preeclamptic compared with control pregnancies, whereas dehydroepiandrosterone (DHEA) and DHEA sulphate did not differ. CONCLUSIONS: These data do not support the hypothesis that cancer risk in mothers and offspring of preeclamptic pregnancies is explained by exposure to lower maternal blood oestrogen concentrations, but raise the possibility that androgens play a role.