Women with a History of Recurrent Pregnancy Loss Are a High-Risk Population for Adverse Obstetrical Outcome: A Retrospective Cohort Study

Abstract

Recurrent pregnancy loss (RPL), defined as three or more consecutive miscarriages, is hypothesized to share some of the same pathogenic factors as placenta-associated disorders. It has been hypothesized that a defect implantation causes pregnancy loss, while a partially impaired implantation may lead to late pregnancy complications. The aim of this retrospective register-based cohort study was to study the association between RPL and such disorders including pre-eclampsia, stillbirth, small for gestational age (SGA) birth, preterm birth and placental abruption. Women registered with childbirth(s) in the Swedish Medical Birth Register (MFR) were included in the cohort. Pregnancies of women diagnosed with RPL (exposed) in the National Patient Register (NPR), were compared with pregnancies of women without RPL (unexposed/reference). Obstetrical outcomes, in the first pregnancy subsequent to the diagnosis of RPL (n = 4971), were compared with outcomes in reference-pregnancies (n = 57,410). Associations between RPL and placental dysfunctional disorders were estimated by odds ratios (AORs) adjusting for confounders, with logistic regression. RPL women had an increased risk for pre-eclampsia (AOR 1.45; 95% CI; 1.24–1.69), stillbirth <37 gestational weeks (GWs) (AOR 1.92; 95% CI; 1.22–3.02), SGA birth (AOR 1.97; 95% CI; 1.42–2.74), preterm birth (AOR 1.46; 95% CI; 1.20–1.77), and placental abruption <37 GWs (AOR 2.47; 95% CI; 1.62–3.76) compared with pregnancies by women without RPL. Women with RPL had an increased risk of pregnancy complications associated with placental dysfunction. This risk population is, therefore, in need of improved antenatal surveillance.

Plasma level of mannose-binding lectin is associated with the risk of recurrent pregnancy loss but not pregnancy outcome after the diagnosis

“…Also, we found no association between low p-MBL levels and the incidence of preterm birth and low BW, although the latter analyses were based on very few observations. Nonetheless, the frequency of preterm birth after RPL in our patients corresponds to the frequency of 10.0% reported in a large Swedish register study ( Rasmark Roepke et al , 2021 ).…”

“…A significantly increased incidence of preterm birth, reduced birth weight (BW) and other perinatal complications is found in RPL patients ( Basso et al , 1998 ; Jivraj et al , 2001 ; Brown et al , 2008 ; Dempsey et al , 2014 ; Field and Murphy, 2015 ; Rasmark Roepke et al , 2021 ). Since low p-MBL levels may be associated with RPL, an obvious question is whether an aberrant p-MBL level is associated with a negative reproductive prognosis and an increased risk for adverse perinatal outcomes in RPL patients?…”

Human forkhead box protein 3 gene variants associated with altered susceptibility to idiopathic recurrent pregnancy loss: A retrospective case‐control study

“…30,31 Chronic hypertension did not constitute an exclusion criteria for RPL cases and control women. Unlike gestational hypertension (preeclampsia), which is a confirmed risk factor for pregnancy complications, 32,33 including RPL, chronic hypertension was not linked with adverse pregnancy complications. 34 Furthermore, we demonstrated that the association of the investigated FOXP3 variants with RPL was not affected by parity, as the allelic and genotypic distribution of rs2294021, rs2232365, and rs3761548 SNPs was comparable between nulliparous (no live births) and multiparous (one or more live births) RPL cases.…”

“…29 Our results were also contradictory to two independent Chinese (Han) studies, which reported no association of rs2294021 minor allele or genotypes with RPL. 27,32 These apparently contradictory findings are explained by case and control selection criteria, the ethnic background of study participants, and even differences in genotyping methods. 29 While not addressed here, epigenetic alteration, [33][34][35] including Foxp3 hypermethylation, 35 may increase the risk of RPL, in part through decreasing the number of Treg cells.…”

Tasked for Compassion: Initiating Reproductive Grief Care in the Neonatal Intensive Care Unit

“…Reproductive loss is common, occurring in up to a quarter of all pregnancies, and recurrent pregnancy loss is also related to subsequent neonatal morbidity and mortality. 1,2 Parents experiencing difficulty grappling with an infant enduring significant morbidity in the intensive care are more likely to have experienced reproductive loss or issues with infertility. 3 Additionally, advanced maternal age, multiple gestation pregnancies, and reproductive technology have been linked to increased neonatal morbidity and mortality.…”