Association of glucocorticoid and type 1 corticotropin-releasing hormone receptors gene variants and risk for depression during pregnancy and post-partum.

Women with postnatal depression (PND) appear to have abnormal hypothalamic pituitary adrenal (HPA) axis responses to stress, which might involve a genetic variability component. We investigated association of genetic variants in the glucocorticoid receptor (GR, NR3C1) and corticotropin releasing hormone receptor 1 (CRHR1) genes with increased risk for PND. Two hundred pregnant women were recruited prospectively and PND risk was assessed by the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy and again 2-8 weeks post-natally (CW-GAPND study). The BclI and ER22/23EK single nucleotide polymorphisms (SNPs) of the GR and the haplotype-tagged rs1876828, rs242939 and rs242941 SNPs of the CRHR1 associated with genetic risk to depressive disorders were genotyped. A cut-off score of 10 was used to detect increased risk of PND. Association analysis was carried out in 140 patients that completed the study protocol. The BclI and rs242939 SNPs were over-represented in women with postnatal EPDS score ≥10 with significant allele association (p = 0.011 and <0.001, respectively) and risk ratios of 2.9 (95% CI: 1.2-6.9) for BclI, 4.9 (2-12) for rs242939 and 5.48 (2.13-14.10) for both. The rs242939 SNP was also associated with increased EPDS values during pregnancy. Moreover, the G-G-T haplotype of the CRHR1 was significantly over-represented in patients with high EPDS scores, with risk ratio of 3.22 (95% CI: 1.91-5.42). This is the first evidence that specific SNPs of genes involved in 'stress' responses might contribute in the genetics of high-risk for depression during pregnancy and postpartum.

Perinatal variables and neonatal outcomes in severely growth restricted preterm fetuses.

OBJECTIVE: To investigate the impact of severe preterm intrauterine growth restriction on perinatal and neonatal outcomes. DESIGN: Retrospective cohort study. SETTING: Tertiary referral fetal medicine unit in London. POPULATION: A total of 60 pregnancies affected by early onset severe intrauterine growth restriction with fetal abdominal circumference below the third centile and abnormal arterial or venous Dopplers between October 2003 and October 2007, and control cohort of 77 appropriate-for-gestational age preterm neonates. METHODS: Cases were identified from the departmental databases. The neonatal outcomes in 44 growth restricted survivors were compared with 77 gestation matched appropriate-for-gestational age preterm neonates. MAIN OUTCOME MEASURES: Neonatal morbidity and neonatal mortality. RESULTS: Of the 60 pregnancies affected by severe intrauterine growth restriction, seven were terminated, nine resulted in stillbirth and 44 resulted in live births. The growth restricted neonates had increased odds of developing respiratory distress compromise (odds ratio (OR) 2.5, 95% confidence interval (CI) 1.1-6.2) and thrombocytopenia (OR 9.4, 95%CI 2.9-30.8) in comparison to average-for-gestational age cohorts. We also noted an increased risk of neonatal sepsis (OR 2.5, 95%CI 1.1-6.0) and necrotising enterocolitis (OR 9.7, 95%CI 1.1-86.0). Sepsis was the major contributing factor towards neonatal mortality in the growth restricted cohorts. CONCLUSION: Despite intensive fetal surveillance and tertiary level neonatal care, the survival for growth restricted fetuses before 28 weeks gestation remains poor with neonatal outcome predominantly affected by respiratory morbidity, sepsis and metabolic compromise.

The effect of polyhydramnios on cervical length in twins: a controlled intervention study in complicated monochorionic pregnancies.

OBJECTIVE: To test the hypothesis that cervical shortening in polyhydramnios reflects the degree of excess amniotic fluid, and increases with normalisation of amniotic fluid volume. STUDY DESIGN: Prospective cohort study of 40 women with monochorionic twins undergoing interventional procedures between 16-26 weeks. Cervical length was assessed via transvaginal sonography pre-procedure, 1 and 24 hours post-procedure, and results compared between amnioreduction and control procedures. Amniotic fluid index (AFI) was measured pre- and post-procedure. RESULTS: Pre-procedural cervical length correlated with AFI (linear fit = 5.07 -0.04x, R(2) = 0.17, P = 0.03) in patients with polyhydramnios (n = 28). Drainage of 2000 ml fluid (range 700-3500 ml), reduced AFI from 42 cm to 21 cm (P<0.001). Their pre-procedural cervical length did not change at one (mean Delta:-0.1cm, 95%CI, -0.4 to 0.2) or 24 hours (0.2 cm, -0.1 to 0.6) after amnioreduction. There was no change in cervical length at control procedures. CONCLUSION: Cervical shortening in twins with polyhydramnios does not appear to be an acute process; cervical length can be measured before or after therapeutic procedures.

Influence of extracellular matrix on cytokine stimulated pro-labour gene expression in human uterine myocytes.

Cellular function is modulated by the interaction with the extracellular matrix within the myometrium. We formed the hypothesis that the cytokine-stimulated pro-labour gene expression by human uterine smooth muscle cells would be increased by growing the cells on collagen-coated plates. Primary cultures of human uterine smooth muscle cells grown on uncoated plates and on plates coated with collagen were exposed to the inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta and interleukin-6) and assessed the messenger RNA expression of oxytocin receptor, interleukin-8, prostaglandin H synthase type-2 and prostaglandin F(2) alpha receptor. Basal pro-labour gene expression was unaffected by collagen coating and the response to the inflammatory cytokines was similar for oxytocin receptor and prostaglandin H synthase type-2, but appeared to be reduced for interleukin-8 and enhanced for FP. Collagen coating made no significant impact on basal integrin expression and interleukin-1beta induced phosphorylation of extracellular-regulated-kinase1/2 and RelA subunit of nuclear factor-kappa B (p65). We conclude that growing human uterine smooth muscle cells on collagen-coated plates may modulate the pro-labour gene response to the inflammatory cytokines.

Pro-labour myometrial gene expression: are preterm labour and term labour the same?

Preterm labour (PTL) is the most important cause of neonatal morbidity and mortality. While some causes have been identified, the mechanisms involved remain elusive. This study investigates whether term labour (TL) is an appropriate model for PTL by examining pro-labour gene expression, using quantitative rtPCR, and protein synthesis, using Western analysis, in preterm and term myometrial samples obtained from the upper and lower uterine segments before and after the onset of labour. In the lower segment, the levels of prostaglandin H synthase type-2 (PGHS-2), interleukin-1beta (IL-1beta), IL-6 and IL-8 mRNA expression were significantly higher in TL compared with PTL samples. Compared with non-labour controls, the expression of IL-1beta and IL-8 mRNA was increased in both PTL and TL samples and the expression of PGHS-2 and IL-6 mRNA was increased in TL samples only. In the upper segment, there were no differences between PTL and TL samples and the mRNA expression of PGHS-2 and IL-1beta was increased in TL compared with term no labour samples. No effect of PTL or TL was seen on either oxytocin receptor or connexin-43 mRNA expression or protein levels. The multiple regression analysis and studies in primary cultures of uterine myocytes suggest that the inflammatory cytokines, IL-1beta and tumour necrosis factor-alpha, are the most important regulators of PGHS-2 and IL-8. Our data show that preterm and term labouring myometrium are significantly different and that the most marked labour-induced changes in gene expression are in the lower segment. These changes may occur in response to the release of inflammatory cytokines by the labour-associated inflammatory infiltration.

A case report of polysplenia syndrome associated with genital tract duplication anomaly.

Polysplenia syndrome is a condition that persists as a defect of lateralisation, the embryonic process by which the site of body organs is determined. The most frequent manifestations of this syndrome, in addition to polysplenia are complex cardiac malformations, situs inversus, and bilobed lungs. Laterality defects have been known to be due to autosomal recessive inheritance. We report a unique case of polysplenia syndrome in association with genital tract duplication anomaly.