Fetal sex-specific differences in gestational age at delivery in pre-eclampsia : a meta-analysis

Background: Pre-eclampsia (PE) is a major pregnancy disorder complicating up to 8% of pregnancies. Increasing evidence indicates a sex-specific interplay between the mother,placenta and fetus. This may lead to different adaptive mechanisms during pregnancy. Methods: We performed an individual participant data meta-analysis to determine associations of fetal sex and PE, with specific focus on gestational age at delivery in PE. This was done on 219 575 independent live-born singleton pregnancies, with a gestational age at birth between 22.0 and 43.0 weeks of gestation, from 11 studies participating in a worldwide consortium of international research groups focusing on pregnancy. Results: Of the women, 9033 (4.1%) experienced PE in their pregnancy and 48.8% of the fetuses were female versus 51.2% male. No differences in the female/male distribution were observed with respect to term PE (delivered >= 37 weeks). Preterm PE (delivered <37 weeks) was slightly more prevalent among pregnancies with a female fetus than in pregnancies with a male fetus [odds ratio (OR) 1.11, 95% confidence interval (CI) 1.02-1.21]. Very preterm PE (delivered <34 weeks) was even more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus (OR 1.36, 95% CI 1.17-1.59). Conclusions: Sexual dimorphic differences in the occurrence of PE exist, with preterm PE being more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus and with no differences with respect to term PE.Peer reviewe

Fetal sex-specific differences in gestational age at delivery in pre-eclampsia: a meta-analysis

Background: : Pre-eclampsia (PE) is a major pregnancy disorder complicating up to 8% of pregnancies. Increasing evidence indicates a sex-specific interplay between the mother, placenta and fetus. This may lead to different adaptive mechanisms during pregnancy.Methods: We performed an individual participant data meta-analysis to determine associations of fetal sex and PE, with specific focus on gestational age at delivery in PE. This was done on 219 575 independent live-born singleton pregnancies, with a gestational age at birth between 22.0 and 43.0 weeks of gestation, from 11 studies participating in a worldwide consortium of international research groups focusing on pregnancy.Results: Of the women, 9033 (4.1%) experienced PE in their pregnancy and 48.8% of the fetuses were female versus 51.2% male. No differences in the female/male distribution were observed with respect to term PE (delivered ≥ 37 weeks). Preterm PE (delivered < 37 weeks) was slightly more prevalent among pregnancies with a female fetus than in pregnancies with a male fetus [odds ratio (OR) 1.11, 95% confidence interval (CI) 1.02-1.21]. Very preterm PE (delivered < 34 weeks) was even more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus (OR 1.36, 95% CI 1.17-1.59).Conclusions: Sexual dimorphic differences in the occurrence of PE exist, with preterm PE being more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus and with no differences with respect to term PE

Matrix metalloproteinase-2 activity, protein, mRNA, and tissue inhibitors in small arteries from pregnant and relaxin-treated nonpregnant rats

Vascular gelatinase activity is essential for pregnancy- and relaxin (Rlx)-induced renal vasodilation and hyperfiltration in rats. The objective of this study was to further elucidate the mechanisms for the increase in vascular matrix metalloproteinase (MMP)-2 activity caused by pregnancy and Rlx. We first corroborated our earlier work by showing that pro- and active forms of MMP-2 were increased in small renal arteries from pregnant compared with virgin rats and Rlx-treated compared with vehicle-treated nonpregnant rats. We next investigated other artery types and showed that MMP-2 activity was upregulated in mesenteric arteries from pregnant rats (pro-MMP-2 by 50% and active MMP-2 by 40%, both P<0.05) and from Rlx-treated nonpregnant rats (pro-MMP-2 by 50% and active MMP-2 by 90%, both P<0.005) compared with their respective controls. To corroborate these results obtained by gelatin zymography, pro-MMP-2 protein was determined by Western analysis in the same small arteries. Pro-MMP-2 protein was increased in small renal arteries from pregnant compared with virgin rats and from Rlx- compared with vehicle-treated nonpregnant rats: pro-MMP-2-to-beta-actin ratio=0.29 vs. 0.21 (P<0.01) and 0.43 vs. 0.32 (P<0.005). Findings were similar for mesenteric arteries. MMP-2 mRNA as measured by real-time PCR was increased in small renal arteries from pregnant and Rlx-treated nonpregnant rats compared with their respective controls. There were no significant differences in tissue inhibitor of metalloproteinase (TIMP-1 or TIMP-2) activity by reverse zymography in small renal arteries. Thus increases in MMP-2 mRNA and protein expression are major factors contributing to increased MMP-2 activity in small arteries from pregnant and Rlx-treated nonpregnant rats

Low Soluble Syndecan-1 Precedes Preeclampsia - Fig 3

<p><b>Representative images of Sdc1 immunoreactivity in preeclampsia (</b><u><b>A</b></u><b>) compared to uncomplicated pregnancy (</b><u><b>B</b></u><b>) villous tissue.</b> Note the more intense staining on syncytiotrophoblast of uncomplicated pregnancy (immunohistochemical score = 4) compared to preeclampsia (score = 1), and apparent absence of staining in fetal villous vasculature throughout. Gestational age at delivery was 36.6 weeks for both placentas. <u>C</u>: Sample Western blot of villous tissue homogenates from the preeclampsia and control patients; band densities at the expected 85 kDa are consistent with reduced Sdc1 protein mass in preeclampsia. See also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0157608#pone.0157608.t003" target="_blank">Table 3</a> for summary group data.</p

Placental and pre-delivery plasma data, corresponding to the uncomplicated pregnancy (n = 25) and preeclampsia (n = 19) groups described in Supplementary S4 Table.

<p>Placental and pre-delivery plasma data, corresponding to the uncomplicated pregnancy (n = 25) and preeclampsia (n = 19) groups described in Supplementary S4 Table.</p

Clinical characteristics of uncomplicated pregnancy control (n = 19), gestational hypertensive (n = 9), and preeclampsia (n = 9) groups; for comparison of soluble Sdc1 in gestational age-matched, 2^nd trimester maternal plasma.

<p>Clinical characteristics of uncomplicated pregnancy control (n = 19), gestational hypertensive (n = 9), and preeclampsia (n = 9) groups; for comparison of soluble Sdc1 in gestational age-matched, 2^nd trimester maternal plasma.</p

Soluble Sdc1 concentrations increased significantly with advancing gestation.

<p>Box-plot of soluble Sdc1 concentrations in maternal plasma as a function of successive gestational weeks (W) and postpartum stages, of n = 8 women with uncomplicated pregnancy outcome. The solid and dotted lines through the interior of the boxes correspond to median and mean values, respectively. The top and bottom of each box correspond to 75^th and 25^th percentiles, respectively. Horizontal lines on the top of the graph indicate significant differences between the time points (P<0.05; Repeated Measures Analysis of Variance on Ranks with post hoc Student-Newman-Keuls test).</p