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Importance: Preventive efforts in pregnancy-related alloimmunization have considerably decreased the prevalence of hemolytic disease of the fetus and newborn (HDFN). International studies are therefore essential to obtain a deeper understanding of the postnatal management and outcomes of HDFN. Taken together with numerous treatment options, large practice variations among centers may exist., Objectives: To assess variations in postnatal management and outcomes of HDFN among international centers and to identify opportunities to improve care., Design, Setting, and Participants: In this international, retrospective, cohort study, 31 expert centers from 22 countries retrieved data on neonates with HDFN managed between January 1, 2006, and July 1, 2021. Statistical analysis was performed from July 19, 2023, to October 28, 2024., Main Outcomes and Measures: Main outcomes included the frequency of exchange transfusions, administration of intravenous immunoglobulin, administration of erythropoiesis-stimulating agents, and red blood cell transfusions, as well as the association of gestational age at birth with exchange transfusion frequency and risk factors for adverse neonatal outcomes., Results: The study included 1855 neonates (median gestational age at birth, 36.4 weeks [IQR, 35.0-37.3 weeks]; 1034 boys [55.7%]), of whom 1017 (54.8%) received any form of antenatal treatment. Most neonates (1447 [78.0%]) had anti-D antibodies. Exchange transfusions were performed in 436 neonates (23.5%), with proportions in exchange transfusion frequency varying from 0% to 78% among centers. Intravenous immunoglobulin was administered to 429 of 1743 neonates (24.6%), with proportions varying from 0% to 100% among centers. A higher gestational age at birth was associated with a reduction in exchange transfusion frequency in neonates with intrauterine transfusion, decreasing from approximately 38.2% (13 of 34) at 34 weeks to 16.8% (18 of 107) after 37 weeks and 0 days. A weekly increase in gestational age at birth was associated with a 43.3% decrease (95% CI, 36.1%-49.7%) in the likelihood of adverse neonatal outcomes, and neonates who received an exchange transfusion were 1.55 (95% CI, 1.10-2.18) times more likely to experience unfavorable outcomes., Conclusions and Relevance: In this cohort study of neonates with HDFN managed at 31 centers in 22 countries, significant practice variations in the postnatal management of HDFN were identified, highlighting the lack of, and need for, consensus. The study suggests that there is a potential beneficial clinical association of waiting for delivery until after 37 weeks and 0 days with frequency of exchange transfusions among neonates with HDFN. The framework to implement international guidelines is provided.

Objectives: This study aimed to estimate the association between low first-trimester maternal serum PlGF (placental growth factor) and PAPP-A (pregnancy-associated plasma protein A) and the risk of placenta-mediated complications., Methods: We performed a secondary analysis of the PREDICTION study, including nulliparous participants recruited at 11 to 14 weeks of pregnancy. First-trimester PlGF and PAPP-A levels were reported in multiples of the median (MoM) adjusted for maternal characteristics and gestational age. Participants were stratified into 4 groups based on absence/presence of low (<0.4 MoM) PlGF and PAPP-A values. A composite of adverse pregnancy outcomes (including preeclampsia, fetal growth restriction, fetal death, and placental abruption) was calculated for deliveries occurring before 34 weeks, before 37 weeks, and at or after 37 weeks., Results: Out of the 7262 participants, 86 (1.2%) experienced the composite outcome before 37 weeks of gestation, including 35 (0.4%) before 34 weeks. The combination of low PAPP-A and low PlGF levels was associated with the greatest risk of adverse outcomes before 37 weeks (21%) and before 34 weeks (12%) compared with low PlGF alone (7% and 3%), low PAPP-A alone (2% and 1%), or neither marker (1% and 0.4%, respectively; P < 0.001). For preterm preeclampsia specifically, the combination of low PAPP-A and low PlGF was also associated with a greater risk (12%) compared with low PlGF alone (6%), low PAPP-A alone (0.5%), or neither marker (0.7%; P < 0.001)., Conclusions: The combination of low PAPP-A and low PlGF levels is associated with a very high risk for adverse outcomes before 34 and 37 weeks. An isolated low PAPP-A should not be considered a risk factor for adverse pregnancy outcomes., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Introduction: Preterm premature rupture of membranes (PPROM) is the main cause of premature delivery, complicating 1-3% of all pregnancies. Conventional hospitalization (CH) is the most frequent mode of follow-up, but homecare (HC) seems to be an alternative., Objectives: Study of the impact of the monitoring mode on the duration of the latency period and on the latency ratio after PPROM, and analysis of the risk factors modifying this ratio., Methods: This was a bicentric retrospective cohort study here-abouts including patients who presented a PPROM between 24 and 36weeks of gestation from 2016 to 2018. Patients had a follow-up in HC at Lille University Hospital center (UHC) and in CH at Nantes UHC according to two different follow-up protocols. The latency ratio corresponded to the real latency period divided by the latency period to theoretical term., Results: We included 154 patients: 102 in HC and 52 in CH. The mean latency period was significantly higher in HC: 36.9±21.8 days, corresponding to an 85.5±23.7% latency ratio versus 20.2±12 days, corresponding to an 66.9±29.8% latency ratio in CH (P<0.001). The latency ratio in CH was correlated with term at PPROM (P=0.001)., Conclusions: The duration of the latency period seems prolonged for PPROM followed by HC management versus CH in selected populations. This study suggests a benefit to HC in stable patients., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Advances in haemolytic disease of the fetus and newborn have led to numerous treatment options. We report practice variations in the management and outcomes of haemolytic disease of the fetus and newborn in at-risk pregnancies., Methods: In this international, retrospective, observational cohort study, data from cases with moderate or severe haemolytic disease of the fetus and newborn were retrieved from 31 centres in 22 countries. Eligible participants had pregnancies with haemolytic disease of the fetus that led to fetal death at 16 + 0 weeks or later, those treated antenatally with intrauterine transfusion or intravenous immunoglobulins, or neonates without antenatal treatment who were treated with intensive phototherapy, exchange transfusion, or red blood cell transfusions. All patients had confirmed maternal alloantibodies and an antigen-positive fetus incompatible with the maternal alloantibody. Patients with ABO-incompatibility only were excluded. We assessed serological diagnostics and referrals, antenatal treatment and timing, complications, delivery route, and gestational age at birth. Outcomes were analysed in all eligible participants who had complete data available., Findings: 2443 pregnancies with haemolytic disease of the fetus and newborn treated between Jan 1, 2006, and July 1, 2021, were shared by the centres and analysed between Dec 1, 2021, and March 1, 2023. 23 pregnancies were excluded due to missing information and we included 2420 for further analysis. 1764 (72·9%) of 2420 pregnancies were affected by D-antibodies. 95 (3·9%) of 2420 pregnancies resulted in fetal death. Of the 2325 liveborn neonates, 1349 (58·1%) received any form of antenatal treatment and 976 (41·9%) were only treated postnatally. Median gestational age at referral was 20·4 weeks (IQR 14·9-28·0) and ranged between medians of 10·0 and 26·3 weeks between centres. Severe hydrops at first intrauterine transfusion was present in 185 (14·5%) of 1276 pregnancies, with proportions ranging between 0 and 42% between centres. A median of two intrauterine transfusions (IQR 1-4) were done per pregnancy. The fetal access sites used in intrauterine transfusions varied widely between centres. Non-lethal complications in intrauterine transfusions by transfusion site occurred at a lower rate in intrahepatic approaches (2·0%, 95% CI 1·1-3·3) than in placental insertion (6·9%, 5·8-8·0) and free loop (13·3%, 8·9-18·9). The use and indication for intravenous immunoglobulin administration varied widely. Neonates with intrauterine transfusion were born at a median gestational age of 35·6 weeks (IQR 34·0-36·7), ranging between medians of 33·2 and 37·3 weeks between centres, while neonates without antenatal treatment were born at a median gestational age of 37·3 (IQR 36·3-38·1), ranging between medians of 34·9 and 38·9 weeks between centres., Interpretation: We found considerable variation in antenatal management and outcomes in haemolytic disease of the fetus and newborn between sites in different countries. Our study shows the capacity of the field to gather valuable data on a rare disease and to optimise care., Funding: None., Competing Interests: Declaration of interests DPdW is doing a PhD programme partly funded by Momenta Pharmaceuticals, which was acquired by Johnson & Johnson, and is an investigator for a phase 2 trial (NCT03842189) of a new drug for the treatment of haemolytic disease of the fetus and newborn. EL is a sub-investigator for a phase 2 trial (NCT03842189) of a new drug for the treatment of haemolytic disease of the fetus and newborn, which is sponsored by Janssen Pharmaceuticals. RD reports paid lectures and participation in studies for Janssen Pharmaceuticals. PM received payment for a lecture from CSL Behrin. PM and J-MJ reports participation in an advisory board for haemolytic disease of the fetus and newborn of Janssen Pharmaceuticals in December, 2023, and both report participation in a phase 3 trial (NCT05912517) of a new drug for the treatment of haemolytic disease of the fetus and newborn, which is sponsored by Janssen Pharmaceuticals. ET is the principal investigator for Janssen-sponsored trials Unity and Clarity in Sweden and an advisory Board Member and Steering Committee member for Janssen Pharmaceutical on haemolytic disease of the fetus and newborn and FNAIT programmes. TPS is a member of the board of the International Society of The Fetus as a Patient and member of the expert committee for Gynaecology and Obstetrics at Ministry of Health, Republic of Slovenia. EJTV is the principal investigator for a phase 2 trial (NCT03842189) and phase 3 trial (NCT05912517) of a new drug for the treatment of haemolytic disease of the fetus and newborn, which is sponsored by Janssen Pharmaceuticals. All other authors report no competing interests or financial disclosures., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: To review and compare existing guidelines on the intrapartum management and postpartum follow-up of obstetric anal sphincter injuries (OASIS) METHODS: We conducted a systematic review of clinical guidelines related to OASIS management, focusing on intrapartum care and postpartum follow-up. Searches were performed in July 2024 across multiple databases, including PubMed, Embase, and the Cochrane Library. Guidelines published after 2010 in English were included., Results: Nine national guidelines were included. There was a consensus on OASIS classification and immediate management, particularly regarding suture techniques, materials, and the necessity of adequate analgesia. However, notable variations were identified in the timing of repair, specialist involvement, use of prophylactic antibiotics, and post-operative care protocols. Postpartum follow-up practices also varied, especially regarding the role of physiotherapy and the timing of specialist consultations, reflecting inconsistencies in long-term care recommendations., Conclusion: Significant variability existed in the guidelines for the management and follow-up of OASIS, particularly in postpartum care. This study underscored the need for standardized, evidence-based guidelines to ensure consistent and optimal care for women affected by OASIS., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Professor M. Cosson has contracts from Ab medica, Promedon, Syliva, Proveday and receives consulting fees from Boston scientific and honoraria for educational events from Boston scientific and Promedon. He is also a founder of Digyne start-up.The other authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Incidence of complications following obstetrical anal sphincter injury (OASI) during vaginal delivery are poorly defined. They are only studied in high level maternities, small cohorts, all stages of perineal tear or in low-income countries. The aim of our study was to describe complications after primary OASI repair following a vaginal delivery in all French maternity wards at short and midterm and to assess factors associated with complication occurrence., Methods: We conducted a historical cohort study using the French nationwide claim database (PMSI) from January 2013 to December 2021. All women who sustained an OASI repair following a vaginal delivery were included and virtually followed-up for 2 years. Then, we searched for OASIS complications. Finally, we evaluated factors associated with OASIS complication repaired or not and OASIS complication repairs., Results: Among the 61,833 included women, 2015 (2.8%) had an OASI complication and 842 (1.16%) underwent an OASI complication repair. Women were mainly primiparous (71.6%) and 44.3% underwent an instrumental delivery. During a follow-up of 2 years, 0.6% (n = 463), 0.3% (n = 240), 0.2% (n = 176), 0.1% (n = 84), 0.06% (n = 43) and 0.01% (n = 5) of patients underwent second surgery for a perineal repair, a fistula repair, a sphincteroplasty, a perineal infection, a colostomy and a sacral nervous anal stimulation, respectively. Only one case of artificial anal sphincter was noticed. Instrumental deliveries (OR = 1.56 CI95%[1.29;1.9]), private for-profit hospitals (OR = 1.42 [1.11;1.82], reference group "public hospital"), obesity (OR = 1.36 [1;1.84]), stage IV OASIS (OR = 2.98 [2.4;3.72]), perineal wound breakdown (OR = 2.8 [1.4;5.48]), ages between 25 and 29 years old (OR = 1.59 [1.17;2.18], refence group "age between 13 and 24 years old") and 30 and 34 years old (OR = 1.57 [1.14; 2.16], refence group "age between 13 and 24 years old") were factors associated with OASIS complication repairs., Conclusions: Maternal age, stage IV OASIS, obesity, instrumental deliveries and private for-profit hospitals seemed to predict OASIS complications. Understanding factors associated with OASIS complications could be beneficial for the patient to inform them and to influence the patient's follow-up in order to prevent complications, repairs and maternal distress., (© 2024. The Author(s).)

Background: Fetal Medicine Foundation (FMF) studies suggest that preterm preeclampsia can be predicted in the first trimester by combining biophysical, biochemical, and ultrasound markers and prevented using aspirin. We aimed to evaluate the FMF preterm preeclampsia screening test in nulliparous women., Methods: We conducted a prospective multicenter cohort study of nulliparous women recruited at 11 to 14 weeks. Maternal characteristics, mean arterial blood pressure, PAPP-A (pregnancy-associated plasma protein A), PlGF (placental growth factor) in maternal blood, and uterine artery pulsatility index were collected at recruitment. The risk of preterm preeclampsia was calculated by a third party blinded to pregnancy outcomes. Receiver operating characteristic curves were used to estimate the detection rate (sensitivity) and the false-positive rate (1-specificity) for preterm (<37 weeks) and for early-onset (<34 weeks) preeclampsia according to the FMF screening test and according to the American College of Obstetricians and Gynecologists criteria., Results: We recruited 7554 participants including 7325 (97%) who remained eligible after 20 weeks of which 65 (0.9%) developed preterm preeclampsia, and 22 (0.3%) developed early-onset preeclampsia. Using the FMF algorithm (cutoff of ≥1 in 110 for preterm preeclampsia), the detection rate was 63.1% for preterm preeclampsia and 77.3% for early-onset preeclampsia at a false-positive rate of 15.8%. Using the American College of Obstetricians and Gynecologists criteria, the equivalent detection rates would have been 61.5% and 59.1%, respectively, for a false-positive rate of 34.3%., Conclusions: The first-trimester FMF preeclampsia screening test predicts two-thirds of preterm preeclampsia and three-quarters of early-onset preeclampsia in nulliparous women, with a false-positive rate of ≈16%., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02189148., Competing Interests: Disclosures None.

Background: Cardiovascular diseases (CVDs) are currently the leading cause of maternal death in Western countries. Although multidisciplinary cardio-obstetric teams are recommended to improve the management of pregnant women with CVD, data supporting this approach are scarce., Aims: To describe the characteristics and outcomes of pregnant patients with CVD managed within the cardio-obstetric programme of a tertiary centre., Methods: We included every pregnant patient with history of CVD managed by our cardio-obstetric team between June 2017 and December 2019, and collected all major cardiovascular events (death, heart failure, acute coronary syndromes, stroke, endocarditis and aortic dissection) that occurred during pregnancy, peripartum and the following year., Results: We included 209 consecutive pregnancies in 202 patients. CVDs were predominantly valvular heart diseases (37.8%), rhythm disorders (26.8%), and adult congenital heart diseases (22.5%). Altogether, 47.4% were classified modified World Health Organization (mWHO)>II, 66.5% had CARdiac disease in PREGnancy score (CARPREG II)≥2 and 80 pregnancies (38.3%) were delivered by caesarean section. Major cardiovascular events occurred in 16 pregnancies (7.7%, 95% confidence interval [CI] 4.5-12.2) during pregnancy and in three others (1.5%, 95% CI 0.3-4.1) during 1-year follow-up. Most events (63.1%) occurred in the 16.3% of patients with unknown CVD before pregnancy., Conclusions: The management of pregnant patients with CVD within a cardio-obstetric team seems encouraging as we found a relatively low rate of cardiovascular events compared to the high-risk profile of our population. However, most of the remaining events occurred in patients without cardiac monitoring before pregnancy., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objectives: COVID-19 has been associated with preterm birth (PTB) and placental-mediated complications, including fetal growth restriction and preeclampsia (PE). This study aimed to estimate the impact of COVID-19 and vaccination on adverse pregnancy outcomes and markers of placental function., Methods: We performed a study on a prospective cohort of women recruited in the first trimester of pregnancy during the early COVID-19 pandemic period (December 2020 to December 2021). At each trimester of pregnancy, the assessment included a questionnaire on COVID-19 and vaccination status; serological tests for COVID-19 (for asymptomatic infection); measurement of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in maternal blood; measurement of mean uterine artery pulsatility index (UtA-PI); and pregnancy outcomes (PTB, PE, birth weight below the fifth and the tenth percentile)., Results: Among 788 patients with complete data, we observed 101 (13%) cases of symptomatic infection and 74 (9%) cases of asymptomatic infection with SARS-CoV-2. Most cases (73%) of infection were among women with previous vaccination or COVID-19 infection before pregnancy. COVID-19 infection was not associated with adverse pregnancy outcomes, abnormal fetal growth, sFlt-1/PlGF ratio, or mean UtA-PI. Vaccination during pregnancy did not influence these outcomes either. We observed no case of severe COVID-19 infection requiring respiratory support., Conclusion: Mild symptomatic or asymptomatic COVID-19 during pregnancy did not influence the risk of adverse pregnancy outcomes and the markers of placental function in predominantly vaccinated women. Fetal growth monitoring is unlikely to be mandatory in women with mild symptoms of COVID-19., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)