Sex-specific basis of severe placental dysfunction leading to extreme preterm delivery

Walker, Mark; Fitzgerald, Brendan; Keating, Sarah; Ray, Joel G.; Windrim, Rory; Kingdom, John

doi:10.1016/j.placenta.2012.03.011

Cited by 87 publications

(71 citation statements)

References 36 publications

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“…Khalil (2013) and demonstrate that male foetuses have a higher vulnerability in the perinatal phase and a high obstetric risk [7,10,11]. The high tendency towards premature births or, respectively, the higher rate of preterm births for boys revealed by these data confirms the results of previous studies [2,3,6,7]. Di Renzo et al assumed that the higher incidences of premature rupture of membranes and preterm births among boys can be attributed to their relatively higher weights and lower gestational ages [7].…”

Section: Perinatal Outcomesupporting

confidence: 82%

“…Various studies have shown that placental dysfunctions, especially severe pre-eclampsia and intrauterine growth retardation, occur significantly more frequently in pregnancies involving a male foetus. The placentas of male foetuses exhibit significantly higher rates of deciduitis and velamentous navel insertions as well as a significantly lower incidence of placental infarction than the placenta of female foetuses [2][3][4][5][6]. In the mothers of male infants, in comparison to the mothers of female babies, higher incidences of premature rupture of membranes and premature births can be observed [7].…”

mentioning

confidence: 99%

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Foetal Gender and Obstetric Outcome

Schildberger

Leitner

2016

Geburtshilfe Frauenheilkd

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Introduction: Data on specific characteristics based on the gender of the unborn baby and their significance for obstetrics are limited. The aim of this study is to analyse selected parameters of obstetric relevance in the phases pregnancy, birth and postpartum period in dependence on the gender of the foetus. Materials and Methods: The selected study method comprised a retrospective data acquisition and evaluation from the Austrian birth register of the Department of Clinical Epidemiology of Tyrolean State Hospitals. For the analysis all inpatient singleton deliveries in Austria during the period from 2008 to 2013 were taken into account (live and stillbirths n?=?444?685). The gender of the baby was correlated with previously defined, obstetrically relevant parameters. Results: In proportions, significantly more premature births and sub partu medical interventions (vaginal and abdominal surgical deliveries. episiotomies) were observed for male foetuses (p?

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Section: Perinatal Outcomesupporting

confidence: 82%

mentioning

confidence: 99%

Foetal Gender and Obstetric Outcome

Schildberger

Leitner

2016

Geburtshilfe Frauenheilkd

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“…30 This is particularly interesting, given that male placentas exhibit significantly higher rates of chronic deciduitis in incidences of PTB and preeclampsia. 31 Although chronic deciduitis would most likely be associated with recruitment of macrophages, it is unclear whether fetal sex directly affects the infiltration into, or the population of these inflammatory cells within, the decidua. The decidua also contains fetal chorionic cells, which have been previously reported to produce renin 32 ; however, we and others have failed to detect REN mRNA in the chorion and in fact isolated choriodecidual explants contain only half the REN mRNA abundance of decidual explants (unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

Regulation of the Renin—Angiotensin System Pathways in the Human Decidua

et al. 2015

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Pregnancy outcome is influenced, in part, by the sex of the fetus. Decidual renin messenger RNA (REN) abundance is greater in women carrying a female fetus than a male fetus. Here, we explore whether the sex of the fetus also influences the regulation of decidual RAS expression with a known stimulator of renal renin and cyclic adenosine monophosphate (cAMP). Cyclic adenosine monophosphate had no affect on decidual REN expression, since REN abundance was still greater in decidual explants from women carrying a female fetus than a male fetus after cAMP treatment. Cyclic adenosine monophosphate decreased prorenin levels in the supernatant if the fetus was female (ie, prorenin levels were no longer sexually dimorphic) and altered the fetal sex-specific differences in other RAS genes seen in vitro. Therefore, fetal sex influences the decidual renin-angiotensin system response to cAMP. This may be related to the presence of fetal cells in the maternal decidua.

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“…All phenotypes of severe preeclampsia are associated with placental pathology; however, it is not entirely clear which placental diseases were targeted in previous trials due to a lack of reported pathology [50,51]. The main limitation of previous clinical trials evaluating the effectiveness of LMWH for preeclampsia prevention is therefore the singular diagnosis of 'severe preeclampsia', which is a heterogeneous syndrome rather than a single disease of different severity, and an incomplete understanding of the underlying cause of severe preeclampsia [52].…”

Section: Patient Selectionmentioning

confidence: 99%

Low molecular weight heparin for the prevention of severe preeclampsia: where next?

McLaughlin

Scholten

Parker

et al. 2018

Brit J Clinical Pharma

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Low molecular weight heparin has been extensively evaluated for the prevention of preeclampsia in high-risk pregnant women; however, the results from these trials have been conflicting. This review discusses the potential mechanisms of action of low molecular weight heparin for the prevention of severe preeclampsia, how to optimize the selection of high-risk women for participation in future trials, and the importance of trial standardization. Preeclampsia preventionPreeclampsia is a hypertensive disorder of pregnancy, clinically diagnosed by new-onset hypertension after 20 weeks' gestation with evidence of organ injury [1]. The potential maternal and perinatal complications of preeclampsia are significant, including maternal seizures, fetal growth restriction (FGR) and stillbirth. Approximately 5% of women develop preeclampsia, with the majority of women experiencing mild preeclampsia that occurs near term and is safely managed by delivery [2]. Only 1% of pregnant women develop early-onset preeclampsia, where both the maternal and fetal implications are substantially greater, typically resulting in FGR and the need for iatrogenic preterm delivery before 34 weeks' gestation [2]. Early-onset preeclampsia is hypothesized to be a direct consequence of the interactions between a dysfunctional placenta and maternal cardiovascular system, while late-onset preeclampsia is hypothesized to be largely triggered by maternal constitutional factors [3][4][5]. Typically, women with early-onset preeclampsia present with an acute, severe syndrome that threatens the life of both the mother and her fetus. In contrast, late-onset preeclampsia is a less severe illness with a favourable clinical outcome in countries with well-developed maternity systems. However, in countries with limited medical resources, preeclampsia remains among the most frequent causes of maternal death [6].The early-and late-onset subsets of preeclampsia exhibit different types and severity of placental pathologies and express divergent maternal haemodynamics. Early-onset preeclampsia is strongly associated with placental disease characterized by maternal vascular malperfusion, where the abnormal placental villi secrete excessive amounts of antiangiogenic proteins and reduced levels of pro-angiogenic proteins into the maternal circulation [7][8][9]. Women with early-onset disease, typically associated with FGR, develop hypertension earlier in pregnancy that is characterized by increased systemic vascular resistance, reduced cardiac output and stroke volume along with relative bradycardia [5]. In contrast, late-onset preeclampsia is less commonly associated with severe placental disease, and consequently exhibits less British Journal of Clinical Pharmacology Br J Clin Pharmacol (2018) 84 673-678 673

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Sex-specific basis of severe placental dysfunction leading to extreme preterm delivery

Cited by 87 publications

References 36 publications

Foetal Gender and Obstetric Outcome

Foetal Gender and Obstetric Outcome

Regulation of the Renin—Angiotensin System Pathways in the Human Decidua

Low molecular weight heparin for the prevention of severe preeclampsia: where next?

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