Family history and risk of miscarriage: A systematic review and meta-analysis of observational studies.

INTRODUCTION: Miscarriage, a spontaneous pregnancy loss at <24 weeks' gestation, is a common complication of pregnancy but the etiologies of miscarriage and recurrent miscarriage are not fully understood. Other obstetric conditions such as preeclampsia and preterm birth, which may share similar pathophysiology to miscarriage, exhibit familial patterns, suggesting inherited predisposition to these conditions. Parental genetic polymorphisms have been associated with unexplained miscarriage, suggesting there could be a genetically inherited predisposition to miscarriage. This systematic review and meta-analysis of observational studies aimed to assess the association between family history of miscarriage and the risk of miscarriage in women. MATERIAL AND METHODS: A systematic review and meta-analysis of observational studies was carried out in accordance with Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Electronic searches using databases (MEDLINE, EMBASE and CINAHL) were carried out to identify eligible studies from 1946 until 2019. Observational studies (cohort or case-control) were included. Human studies only were included. Participants were women of reproductive age. Exposure was a family history of one or more miscarriage(s). The primary outcome was miscarriage in women. Abstracts were screened and data were extracted by two independent reviewers. Study quality was assessed using Critical Appraisal Skills Program (CASP) tools. Data were pooled from individual studies using the Mantel-Haenszel method to produce pooled odds ratios (ORs) with 95% confidence intervals (95% CI). Systematic review registration number (PROSPERO): CRD42019127950. RESULTS: Thirteen studies were identified in the systematic review; 10 were eligible for inclusion in the meta-analysis. Twelve studies reported an association between family history of miscarriage and miscarriage in women. In all, 41 287 women were included in the meta-analysis. Women who miscarried were more likely to report a family history of miscarriage (pooled unadjusted OR 1.90, 95% CI 1.37-2.63). Overall study quality and size varied, with few adjusting for confounding factors. Results should be interpreted with caution as the associations presented are based on unadjusted analyses only. CONCLUSIONS: Women who miscarry may be more likely to have a family history of miscarriage. Further research is required to confirm or refute the findings.

Review of use of Mysodelle as a method of induction of labour.

BACKGROUND: Mysodelle is a 200 mcg misoprostol, vaginal delivery system. It is a PGE1 analogue and accepted as a method of IOL by Scottish medicine consortium in 2014 (Medicines Health and Regulatory Authority; Wing et al., 2013 ). AIMS: The main objective of this project was to determine efficacy of Mysodelle with regards to time interval between insertions to delivery. We also studied the safety profile of Mysodelle with regards to operative delivery rates, foetal concerns and incidence of hyperstimulation. METHODOLOGY: A protocol which outlined the criteria for suitability for the use of Mysodelle was developed. This method was used for IOL for primiparous women more than 38 weeks of gestations with unfavourable cervix and intact membranes with no foetal concerns on scan, i.e. suboptimal growth or reduced liquor. Mysodelle was left in situ for maximum duration of 24 hours and CTG was monitored every 4 hours. The data was collected prospectively over 1 year from January 2016. RESULTS: We reviewed 50 women for the study period of one year. All women were primiparous with singleton term gestations between 38 + 5 weeks to term +11 days. The indications for IOL included postdates, reduced foetal movement, big baby and advanced maternal age. Following the use of Mysodelle, 55% of the women progressed to active labour and did not require oxytocin on labour ward. In 20% of the women, Mysodelle was removed for suspicious CTG or tachysystole. Four women failed IOL with Mysodelle. 14% women had hyperstimulation response to Mysodelle and needed terbutaline. 46% women had spontaneous vaginal delivery and 24% needed instrumental delivery. Remaining 30% patients delivered by caesarean section. The median time from Mysodelle administration to vaginal delivery was 21 hours (95% confidence interval 18.8-26.8 hours). There were no neonatal adverse outcomes. CONCLUSIONS: Results at AMH overall are in keeping with those from EXPEDITE study (Wing et al. 2013 ). It was found to be more efficacious in terms of insertion to delivery time, however, was associated with more tachysystole and hyperstimulation requiring terbutaline as previously highlighted in Cochrane review (Alfirevic and Weeks 2006 ; Hofmeyr et al. 2010 ). There was no increased risk of operative delivery or adverse neonatal outcome with the use of Mysodelle. A reduction in time to vaginal delivery and time to active labour associated with misoprostol vaginal delivery system may be an advantage for patients and the service (ISD Scotland 2013 ), but it needs to be seen if this benefit is offset due to increased requirements for foetal monitoring due to uterine tachysystole and hyperstimulation. MHRA have advised that Mysodelle can cause uterine tachysystole, that might not respond to tocolytic treatment. (MHRA medicine update 2018).