P-546 History of caesarean births and risk of miscarriage - secondary analysis of three randomised controlled trials

Abstract Study question Does the history of caesarean births influence miscarriage risk in subsequent pregnancies? Summary answer In women with a history of 3 or more miscarriage(s), the subsequent miscarriage risk may increase with the presence and number of previous caesarean births. What is known already History of caesarean birth increases the risk of complications in subsequent pregnancies, including risks of spontaneous preterm birth. The evidence of association between caesarean births and subsequent miscarriage risk is scant and conflicting. Study design, size, duration We performed a secondary analysis of the dataset from three multicentre, prospective, double-blind, and placebo-controlled randomized trials. Study registration, duration, size, population, and intervention are as follows: 1) PROMISE; ISRCTN92644181; 2010 - 2013, 826 women with a history of unexplained recurrent miscarriages, progesterone. 2) PRISM; ISRCTN14163439; 2015 - 2017, 4038 women who experienced vaginal bleeding in early pregnancy, progesterone. 3) TABLET; ISRCTN15948785; 2011 - 2016, 940 euthyroid women with thyroid peroxidase antibodies, and miscarriages or infertility history, levothyroxine. Participants/materials, setting, methods The primary outcome for this analysis was miscarriage rate, defined as loss of pregnancy <24 weeks of gestation. RR with 95% CI was estimated using the Poisson regression model and adjusted for age, BMI, ethnicity, smoking status, and previous miscarriages. Random-effects two-stage individual participant data meta-analysis approach was used to account for treatment allocation effects. Subgroup analysis was conducted in women with a history of repeated miscarriages (3 or more) at randomisation. Main results and the role of chance After excluding pregnancies with incomplete data, we included 5,039 pregnancies in the final analysis. The overall miscarriage rate was 24.9% (1256/5039). In the non-specific population of women, there was no association between the history of caesarean births and subsequent miscarriage risk (aRR 1.00, 95% CI 0.86 to 1.17; 5,039 pregnancies). In contrast, for the subgroup of women with a history of 3 or more miscarriage(s) at randomisation, the miscarriage rate appears to increase with the history of caesarean births, although with some degree of statistical uncertainty (aRR 1.10, 95% CI 0.97 to 1.26; 1172 pregnancies). The association became significant when the analysis was categorised according to the number of previous caesarean births. With 1 previous caesarean birth, the miscarriage risk increased by 3% (aRR 1.03, 95% CI 1.00 to 1.06; 1080 pregnancies). This risk was increased by 37% with 2 previous caesarean births (aRR 1.37, 95% CI 1.03 to 1.83; 971 pregnancies), therefore indicating the presence of a biological gradient of effect which increases our confidence in the above findings. The history of previous caesarean births may be a valid prognostic risk factor for future miscarriage risk in women with a history of recurrent miscarriage. Limitations, reasons for caution Further analysis by the gestation at miscarriage (early vs. late), the type (elective vs. emergency), indication or cervical dilatation status at caesarean births is required to understand the possible mechanism behind this association and to better identify women at increased risk of miscarriage(s) related to caesarean births. Wider implications of the findings Our findings suggest that a history of caesarean births may be associated with a small increased risk of subsequent miscarriage risk in a subgroup of women with a history of recurrent miscarriage(s). This information may assist women and healthcare providers to reach more informed decisions regarding the mode of delivery. Trial registration number The study is registered with the OSF registry (ve5j4).