The 100 most-cited articles in American Journal of Obstetrics and Gynecology, 2024

Psychological birth trauma and childbirth-related posttraumatic stress disorder represent a substantial burden of disease with 6.6 million mothers and 1.7 million fathers or co-parents affected by childbirth-related posttraumatic stress disorder worldwide each year. There is mounting evidence to indicate that parents who develop childbirth-related posttraumatic stress disorder do so as a direct consequence of a traumatic childbirth experience. High-risk groups, such as those who experience preterm birth, stillbirth, or preeclampsia, have higher prevalence rates. The main risks include antenatal factors (eg, depression in pregnancy, fear of childbirth, poor health or complications in pregnancy, history of trauma or sexual abuse, or mental health problems), perinatal factors (eg, negative subjective birth experience, operative birth, obstetrical complications, and severe maternal morbidity, as well as maternal near misses, lack of support, dissociation), and postpartum factors (eg, depression, postpartum physical complications, and poor coping and stress). The link between birth…

BACKGROUND: National Vital Statistics System reports show that maternal mortality rates in the United States have nearly doubled, from 17.4 in 2018 to 32.9 per 100,000 live births in 2021. However, these high and rising rates could reflect issues unrelated to obstetrical factors, such as changes in maternal medical conditions or maternal mortality surveillance (eg, due to introduction of the pregnancy checkbox). OBJECTIVE: This study aimed to assess if the high and rising rates of maternal mortality in the United States reflect changes in obstetrical factors, maternal medical conditions, or maternal mortality surveillance. STUDY DESIGN: The study was based on all deaths in the United States from 1999 to 2021. Maternal deaths were identified using the following 2 approaches: (1) per National Vital Statistics System methodology, as deaths in pregnancy or in the postpartum period, including deaths identified solely because of a positive pregnancy checkbox, and (2) under an alternative formulation, as deaths in pregnancy or in the postpartum period, with at least 1 mention of pregnancy…

BACKGROUND: Placenta accreta spectrum disorders are associated with severe maternal morbidity and mortality. Placenta accreta spectrum disorders involve excessive adherence of the placenta preventing separation at birth. Traditionally, this condition has been attributed to excessive trophoblast invasion; however, an alternative view is a fundamental defect in decidual biology. OBJECTIVE: This study aimed to gain insights into the understanding of placenta accreta spectrum disorder by using single-cell and spatially resolved transcriptomics to characterize cellular heterogeneity at the maternal-fetal interface in placenta accreta spectrum disorders. STUDY DESIGN: To assess cellular heterogeneity and the function of cell types, single-cell RNA sequencing and spatially resolved transcriptomics were used. A total of 12 placentas were included, 6 placentas with placenta accreta spectrum disorder and 6 controls. For each placenta with placenta accreta spectrum disorder, multiple biopsies were taken at the following sites: placenta accreta spectrum adherent and nonadherent sites in the…

BACKGROUND: There are limited data to guide the diagnosis and management of vasa previa. Currently, what is known is largely based on case reports or series and cohort studies. OBJECTIVE: This study aimed to systematically collect and classify expert opinions and achieve consensus on the diagnosis and clinical management of vasa previa using focus group discussions and a Delphi technique. STUDY DESIGN: A 4-round focus group discussion and a 3-round Delphi survey of an international panel of experts on vasa previa were conducted. Experts were selected on the basis of their publication record on vasa previa. First, we convened a focus group discussion panel of 20 experts and agreed on which issues were unresolved in the diagnosis and management of vasa previa. A 3-round anonymous electronic survey was then sent to the full expert panel. Survey questions were presented on the diagnosis and management of vasa previa, which the experts were asked to rate on a 5-point Likert scale (from "strongly disagree"=1 to "strongly agree"=5). Consensus was defined as a median score of 5. Following…

OBJECTIVE: To evaluate the effectiveness of nonpharmacological conservative therapies for women with CPP. DATA SOURCES: A systematic search of electronic databases (Amed, CINAHL, PsycINFO, SportDiscuss, Medline, PubMed, Embase, and Cochrane Central Register of Controlled Trials) was performed in January 2023, and updated in December 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing a nonpharmacological conservative therapy to inert (eg, placebo, usual care) or nonconservative (eg, surgical, pharmacological) treatment were included. Conservative therapies of interest to this review were: multimodal physical therapy, predominantly psychological approaches, acupuncture, and other tissue-based monotherapies (eg, electrophysical agents, manual stretching). STUDY APPRAISAL AND SYNTHESIS METHODS: All study data were aggregated, and analyses of the included studies were performed. Effects on pain; sexual measures; psychological and physical function; health-related quality of life; symptom severity/bother; pelvic floor muscle function and morphometry; perceived…

OBJECTIVE: Care bundles are a promising approach to reducing postpartum hemorrhage-related morbidity and mortality. We assessed the effectiveness and safety of care bundles for postpartum hemorrhage prevention and/or treatment. DATA SOURCES: We searched MEDLINE, Embase, Cochrane CENTRAL, Maternity and Infant Care Database, and Global Index Medicus (inception to June 9, 2023) and ClinicalTrials.gov and the International Clinical Trials Registry Platform (last 5 years) using a phased search strategy, combining terms for postpartum hemorrhage and care bundles. STUDY ELIGIBILITY CRITERIA: Peer-reviewed studies evaluating postpartum hemorrhage-related care bundles were included. Care bundles were defined as interventions comprising ≥3 components implemented collectively, concurrently, or in rapid succession. Randomized and nonrandomized controlled trials, interrupted time series, and before-after studies (controlled or uncontrolled) were eligible. METHODS: Risk of bias was assessed using RoB 2 (randomized trials) and ROBINS-I (nonrandomized studies). For controlled studies, we reported…

OBJECTIVE: Type 2 diabetes (T2D) now accounts for the majority of pre-existing diabetes affecting pregnancy in the UK. Our aim was to determine its impact on pregnancy outcomes compared to type 1 diabetes (T1D), gestational diabetes (GDM), and nondiabetes pregnancies. DATA SOURCES: PubMed was searched 1 January 2009 to 2024. STUDY ELIGIBILITY CRITERIA: Cohort observational studies reporting original data on at least one of the primary outcomes in ten or more T2D pregnancies were eligible for inclusion. Comparative diabetes and nondiabetes pregnancies were also collected. METHODS: Primary outcomes included congenital anomalies, stillbirths, neonatal and perinatal mortality, birthweight, rates of large for gestational age (LGA), small for gestational age (SGA), and macrosomia. PROSPERO ID CRD42023411057. RESULTS: Forty seven studies were analyzed. The number of pregnancies in each analysis varied depending on the available data from the outcome being analyzed but ranged from 723 to 4,469,053 pregnancies. When compared with T1D pregnancies, T2D were more likely to have SGA babies as…

OBJECTIVE: Hypertensive disorders of pregnancy, including preeclampsia, are associated with an increased risk for maternal cardiovascular disease, stroke, and chronic kidney disease. However, their association with subsequent maternal dementia or cognitive impairment is less well understood. This study aimed to review and synthesize the published literature on hypertensive disorders of pregnancy and the subsequent risk for maternal dementia or cognitive impairment. DATA SOURCES: PubMed, Web of Science, Pyschinfo, and CINAHL were searched from database inception until July 31, 2022, for observational studies of hypertensive disorders of pregnancy and maternal dementia or cognitive impairment. STUDY ELIGIBILITY CRITERIA: Selected studies included the following: a population of pregnant women, exposure to a hypertensive disorder of pregnancy of interest, and at least 1 primary outcome (dementia) or secondary outcome (cognitive impairment). Two reviewers were involved in study selection. METHODS: We followed the Meta-analyses of Observational Studies in Epidemiology guidelines…

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19,…

BACKGROUND: Robotic-assisted laparoscopy has become a widely and increasingly used modality of minimally invasive surgery in the treatment of endometrial cancer. Due to its technical advantages, robotic-assisted laparoscopic surgery offers benefits, such as a lower rate of conversions compared to conventional laparoscopy. Yet, data on long-term oncological outcomes after robotic-assisted laparoscopy is scarce and based on retrospective cohort studies only. OBJECTIVE: This study aimed to assess overall survival, progression-free survival, and long-term surgical complications in patients with endometrial cancer randomly assigned to robotic-assisted or conventional laparoscopy. STUDY DESIGN: This randomized controlled trial was conducted at the Department of Gynecology and Obstetrics of Tampere University Hospital, Finland. Between 2010 and 2013, 101 patients with low-grade endometrial cancer scheduled for minimally invasive surgery were randomized preoperatively 1:1 either to robotic-assisted or conventional laparoscopy. All patients underwent laparoscopic hysterectomy, bilateral…

BACKGROUND: An imbalance of the antiangiogenic factor, soluble fms-like tyrosine kinase-1, and proangiogenic factor, placental growth factor, in the circulation is a reliable predictor for the development of preeclampsia with severe features and related adverse outcomes. In 2023, the US Food and Drug Administration approved a serum soluble fms-like tyrosine kinase-1/placental growth factor test at a cutoff of 40 to aid in the risk assessment of women hospitalized for hypertensive disorders of pregnancy for the progression to preeclampsia with severe features between 23 and 35 weeks. OBJECTIVE: This study aimed to generate real-world evidence for clinical utility for serum soluble fms-like tyrosine kinase-1/placental growth factor test when made available to clinicians in a timely fashion as an aid in risk stratification of development of preeclampsia with severe features within 2 weeks of testing among hospitalized patients with hypertensive disorders of pregnancy. STUDY DESIGN: Hospitalized patients with hypertensive disorders of pregnancy between 23 weeks to 34 weeks and 6 days of…

Attention-deficit/hyperactivity disorder is a childhood-onset neurodevelopmental disorder that frequently persists into adulthood with 3% of adult women having a diagnosis of attention-deficit/hyperactivity disorder. Many women are diagnosed and treated during their reproductive years, which leads to management implications during pregnancy and the postpartum period. We know from clinical practice that attention-deficit/hyperactivity disorder symptoms frequently become challenging to manage during the perinatal period and require additional support and attention. There is often uncertainty among healthcare providers about the management of attention-deficit/hyperactivity disorder in the perinatal period, particularly the safety of pharmacotherapy for the developing fetus. This guideline is focused on best practices in managing attention-deficit/hyperactivity disorder in the perinatal period. We recommend (1) mitigating the risks associated with attention-deficit/hyperactivity disorder that worsen during the perinatal period via individualized treatment planning; (2) providing…

BACKGROUND: The levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used for the treatment of menorrhagia, dysmenorrhea, and for contraception. However, the association between the use of LNG-IUD and the risk of site-specific gynecologic and breast cancers remains inconclusive. OBJECTIVE: We aim to address this knowledge gap by investigating whether the use of LNG-IUD is associated with a significant risk of site-specific gynecologic and breast cancers. This will be achieved by accessing the nationwide Swedish Registers, with consideration given to the influence and potential interaction of family history of cancer. STUDY DESIGN: A total of 514,719 women aged 18 to 50 years who have used LNG-IUD between July 2005 and December 2018 were identified from the Swedish Prescribed Drug Register and randomly matched with 1,544,157 comparisons who did not use LNG-IUD at a ratio of 1:3. The propensity score was calculated and matched among women who used LNG-IUD and the matched comparisons. The follow-up period started from the date of the first prescription of LNG-IUD for users…

BACKGROUND: Respiratory syncytial virus is associated with significant neonatal and infant morbidity and mortality. Maternal bivalent respiratory syncytial virus prefusion F respiratory syncytial virus vaccination to protect neonates and infants was approved in September 2023 for administration between 32+0 and 36+6 weeks to protect neonates and infants. This approved timeframe is narrower than the 24 to 36 week window evaluated in the clinical trial, due to the possible association between preterm birth and vaccine administration. Currently, data are lacking on how maternal vaccine timing within the approved window affects the transfer of antibodies from mother to fetus, critical information that could influence clinical practice. OBJECTIVE: We sought to examine how gestational age at vaccination and time elapsed from maternal respiratory syncytial virus vaccination to delivery impacted transfer of maternal antibodies measured in the umbilical cord at delivery and in peripheral blood of 2-month infants. We also examined differences in maternal and cord respiratory syncytial virus…

OBJECTIVE: This study aimed to examine the impact of maternal metformin use during pregnancy on offspring neurodevelopmental outcomes. DATA SOURCES: MEDLINE, Embase, and Web of Science (Core Collection) were searched from inception until July 1, 2023. STUDY ELIGIBILITY CRITERIA: Studies of women who received treatment with metformin at any stage of pregnancy for any indication with neurodevelopmental data available for their offspring were included. Studies without a control group were excluded. Randomized controlled trials, case-control, cohort, and cross-sectional studies were included in the review. METHODS: Studies were screened for inclusion and data were extracted independently by 2 reviewers. Risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale for nonrandomized studies, and the Risk of Bias 2 tool for randomized trials. RESULTS: A total of 7 studies met the inclusion criteria, including a combined cohort of 14,042 children with 7641 children who were exposed and followed for up to 14 years of age. Metformin use during pregnancy was not associated…

BACKGROUND: Primary ovarian insufficiency refers to the loss of ovarian function before the age of 40 years and leads to amenorrhea and infertility. Primary ovarian insufficiency has diverse causes, but a common cause is exposure to gonadotoxic chemotherapy used in cancer treatment. Because of the risk for developing primary ovarian insufficiency, patients who want to preserve their fertility may consider various procedures for fertility preservation. However, current fertility preservation options are highly invasive, carry substantial risks, and have uncertain success rates. Recent studies from our group and others reported that mesenchymal stem cells and mesenchymal stem cell-derived exosomes can restore ovarian function in preclinical models of primary ovarian insufficiency by restoring damaged cells and inhibiting apoptosis. Although the restorative effect of mesenchymal stem cell-derived exosomes has been well reported in previous studies, the potential of mesenchymal stem cell-derived exosomes in preventing ovarian damage has not been fully elucidated. OBJECTIVE: This study…

Background In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression. Objective This study aimed to describe human papillomavirus HPV type–specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. Study Design We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after…

BACKGROUND: Elagolix, an approved oral treatment for endometriosis-associated pain, has been associated with hypoestrogenic effects when used as monotherapy. Hormonal add-back therapy has the potential to mitigate these effects. OBJECTIVE: To evaluate efficacy, tolerability, and bone density outcomes of elagolix 200 mg twice daily with 1 mg estradiol/0.5 mg norethindrone acetate (add-back) therapy once daily compared with placebo in premenopausal women with moderate-to-severe endometriosis-associated pain. STUDY DESIGN: This ongoing, 48-month, phase 3 study consists of a 12-month double-blind period, with randomization 4:1:2 to elagolix 200 mg twice daily with add-back therapy, elagolix 200 mg twice daily monotherapy for 6 months followed by elagolix with add-back therapy, or placebo. The coprimary endpoints were proportion of patients with clinical improvement (termed "responders") in dysmenorrhea and nonmenstrual pelvic pain at month 6. We report 12-month results on efficacy of elagolix with add-back therapy vs placebo in reducing dysmenorrhea, nonmenstrual pelvic pain,…

BACKGROUND: Accurate individualized assessment of preeclampsia risk enables the identification of patients most likely to benefit from initiation of low-dose aspirin at 12 to 16 weeks of gestation when there is evidence for its effectiveness, and enables the guidance of appropriate pregnancy care pathways and surveillance. OBJECTIVE: The primary objective of this study was to evaluate the performance of artificial neural network models for the prediction of preterm preeclampsia (<37 weeks' gestation) using patient characteristics available at the first antenatal visit and data from prenatal cell-free DNA screening. Secondary outcomes were prediction of early-onset preeclampsia (<34 weeks' gestation) and term preeclampsia (≥37 weeks' gestation). METHODS: This secondary analysis of a prospective, multicenter, observational prenatal cell-free DNA screening study (SMART) included singleton pregnancies with known pregnancy outcomes. Thirteen patient characteristics that are routinely collected at the first prenatal visit and 2 characteristics of cell-free DNA (total cell-free DNA and…

BACKGROUND: Adverse pregnancy outcomes, including hypertensive disorders of pregnancy and gestational diabetes mellitus, influence maternal cardiovascular health long after pregnancy, but their relationship to offspring cardiovascular health following in-utero exposure remains uncertain. OBJECTIVE: To examine associations of hypertensive disorders of pregnancy or gestational diabetes mellitus with offspring cardiovascular health in early adolescence. STUDY DESIGN: This analysis used data from the prospective Hyperglycemia and Adverse Pregnancy Outcome Study from 2000 to 2006 and the Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study from 2013 to 2016. This analysis included 3317 mother-child dyads from 10 field centers, comprising 70.8% of Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study participants. Those with pregestational diabetes and chronic hypertension were excluded. The exposures included having any hypertensive disorders of pregnancy or gestational diabetes mellitus vs not having hypertensive disorders of pregnancy or gestational diabetes mellitus,…

BACKGROUND: Intrapartum cardiotocographic monitoring of fetal heart rate by abdominal external ultrasound transducer without simultaneous maternal heart rate recording has been associated with increased risk of early neonatal death and other asphyxia-related neonatal outcomes. It is unclear, however, whether this increase in risk is independently associated with fetal surveillance method or is attributable to other factors. OBJECTIVE: This study aimed to compare different fetal surveillance methods and their association with adverse short- and long-term fetal and neonatal outcomes in a large retrospective cohort of spontaneous term deliveries. STUDY DESIGN: Fetal heart rate and maternal heart rate patterns were recorded by cardiotocography during labor in spontaneous term singleton cephalic vaginal deliveries in the Hospital District of Helsinki and Uusimaa, Finland between October 1, 2005, and September 30, 2023. According to the method of cardiotocography monitoring at birth, the cohort was divided into the following 3 groups: women with ultrasound transducer, women with both…

BACKGROUND: Optimal management of fetuses diagnosed as small for gestational age based on an estimated fetal weight of <10th percentile represents a major clinical problem. The standard approach is to increase fetal surveillance with serial biometry and antepartum testing to assess fetal well-being and timing of delivery. Observational studies have indicated that maternal rest in the left lateral position improves maternal cardiac output and uterine blood flow. However, maternal bed rest has not been recommended based on the results of a randomized clinical trial that showed that maternal rest does not improve fetal growth in small-for-gestational-age fetuses. This study was conducted to revisit this question. OBJECTIVE: This study aimed to determine whether maternal bed rest was associated with an increase in the fetal biometric parameters that reflect growth after the diagnosis of a small-for-gestational-age fetus. STUDY DESIGN: A retrospective study was conducted on fetuses who were diagnosed as small for gestational age because of an estimated fetal weight of <10th percentile…

BACKGROUND: Antenatal betamethasone and dexamethasone are prescribed to women who are at high risk of premature birth to prevent neonatal respiratory distress syndrome (RDS). The current treatment regimens, effective to prevent neonatal RDS, may be suboptimal. Recently, concerns have been raised regarding possible adverse long-term neurological outcomes due to high fetal drug exposures. Data from nonhuman primates and sheep suggest maintaining a fetal plasma concentration above 1 ng/mL for 48 hours to retain efficacy, while avoiding undesirable high fetal plasma levels. OBJECTIVE: We aimed to re-evaluate the current betamethasone and dexamethasone dosing strategies to assess estimated fetal exposure and provide new dosing proposals that meet the efficacy target but avoid excessive peak exposures. STUDY DESIGN: A pregnancy physiologically based pharmacokinetic (PBPK) model was used to predict fetal drug exposures. To allow prediction of the extent of betamethasone and dexamethasone exposure in the fetus, placenta perfusion experiments were conducted to determine placental transfer.…

Objective Postpartum depression is one of the most common complications after childbearing. Urinary incontinence is a frequent symptom during pregnancy and the postnatal period, often being the first time that women experience it. This systematic review and meta-analysis aimed to synthesize the evidence on the association between urinary incontinence and postpartum depression and to assess whether this association becomes weaker at 6 months after childbirth. Data Sources MEDLINE, Embase, Cochrane Library, Web of Science, and PsycINFO were searched from inception to December 26, 2023. Study Eligibility Criteria Cross-sectional and cohort studies addressing the association between urinary incontinence and postpartum depression were included. Methods Pooled odds ratios and their 95% confidence intervals, and 95% prediction intervals were estimated using a DerSimonian and Laird random-effects model for the association between urinary incontinence and postpartum depression. Subgroup analyses were conducted on the basis of time after delivery (<6 or ≥6 months). The risk of bias was…

BACKGROUND: The United States suffers from an increasing rate of severe maternal morbidity, paired with a wide disparity in maternal health by race. Doulas are posited to be a useful resource to increase positive outcomes and to decrease this disparity. OBJECTIVE: This study aimed to evaluate the association between doula care and a broad range of maternal and neonatal outcomes in various subpopulations. STUDY DESIGN: This was a retrospective cohort study of deliveries that were recorded from January 2021 to December 2022 at a single institution where they received prenatal care. The exposure was receipt of doula care prenatally and at delivery. We evaluated both the maternal (cesarean delivery, cesarean delivery of nulliparous, term, singleton, vertex infant, vaginal birth after cesarean, gestational hypertension, preeclampsia, postpartum emergency department visit, readmission, and attendance of postpartum office visit) and neonatal (neonatal intensive care unit admission, unexpected complications in term newborns, breastfeeding, preterm delivery, and intrauterine growth…

BACKGROUND: A significant proportion of major fetal structural anomalies can be detected in the first trimester by ultrasound examination. However, the test performance of the first-trimester anomaly scan performed in a low-risk population as part of a nationwide prenatal screening program is unknown. Potential benefits of the first-trimester anomaly scan include early detection of fetal anomalies, providing parents with more time for reproductive decision-making. OBJECTIVE: To investigate the uptake, test performance, and time to a final prenatal diagnosis after referral. STUDY DESIGN: A nationwide implementation study was conducted in the Netherlands (November 2021-November 2022). The FTAS was performed between 12+3 and 14+3 weeks of gestation by certified sonographers using a standard protocol. Women were referred to a tertiary care center if anomalies were suspected. Uptake, test performance, and time to a final prenatal diagnosis (days between referral and date of final diagnosis/prognosis for reproductive decision-making) were determined. Test performance was calculated for…

BACKGROUND: Nonchromosomal congenital anomalies (NCAs) are the most common cause of infant mortality and morbidity. The role of maternal age is well known, although the specifics are not thoroughly elucidated in the literature. OBJECTIVE: To evaluate the role of maternal age in the incidence of NCAs and to pinpoint age groups at higher risk to refine screening protocols. STUDY DESIGN: A systematic review and meta-analysis were conducted following the PRISMA 2020 guidelines and Cochrane Handbook. Searches were performed on October 19, 2021, across MEDLINE (via PubMed), Cochrane Library (CENTRAL), and Embase. Population-based studies assessing the impact of maternal age on the incidence of NCAs in pregnant women were included, without restrictions on age range, country, or comorbidities. A random-effects model was used for pooling effect sizes, considering the heterogeneity across studies. RESULTS: From 15,547 studies, 72 were synthesized. Maternal age >35 showed an increased NCA risk (risk ratio [RR]: 1.31, confidence interval [CI]: 1.07 -1.61), rising notably after>40 (RR: 1.44, CI:…

BACKGROUND: Preeclampsia is characterized by maternal endothelial activation and placental dysfunction. Imbalance in maternal angiogenic and vasoactive factors has been linked to the pathophysiology. The contribution of the placenta as a source of these factors remains unclear. Furthermore, little is known about fetal angiogenic and vasoactive proteins and the relation between maternal and fetal levels. OBJECTIVE: We describe placental growth factor, soluble Fms-like tyrosine kinase 1, soluble endoglin, and endothelin 1-3 in 5 vessels in healthy pregnancies, early- and late-onset preeclampsia. Specifically, we aimed to (1) compare protein abundance in vessels at the maternal-fetal interface between early- and late-onset preeclampsia, and healthy pregnancies, (2) describe placental uptake and release of proteins, and (3) describe protein abundance in the maternal vs fetal circulations. STUDY DESIGN: Samples were collected from the maternal radial artery, uterine vein and antecubital vein, and fetal umbilical vein and artery in 75 healthy and 37 preeclamptic mother-fetus pairs…

Background Pregnancies with large-for-gestational-age fetuses are at increased risk of adverse maternal and neonatal outcomes. There is uncertainty about how to manage birth in such pregnancies. Current guidelines recommend a discussion with women of the pros and cons of options, including expectant management, induction of labor, and cesarean delivery. For women to make an informed decision about birth, antenatal detection of large for gestational age is essential. Objective To investigate the ability of antenatal ultrasound scans to predict large for gestational age at birth. Study Design In this retrospective cohort study, we analyzed data from a routinely collected database from the West Midlands, United Kingdom. We included pregnancies that had an antenatal ultrasound-estimated fetal weight between 35+0 and 38+0 weeks gestation for any indication and a subgroup where the reason for the scan was that the fetus was suspected to be big. Large for gestational age was defined as >90th customized GROW percentile for estimated fetal weight as well as neonatal weight. In addition, we…

BACKGROUND: There are few studies in unselected populations describing reproductive outcomes in women with polycystic ovary syndrome (PCOS) at the end of their reproductive years. OBJECTIVE: To compare parity and maternal age at deliveries and explore factors associated with advanced maternal age in a large, unselected population-based cohort, followed prospectively for 25 years. STUDY DESIGN: Women randomly selected from the general population and included in the prospective Australian Longitudinal Study on Women's Health were assessed approximately every third year from 1996 (age 18-23 years) to 2021 (age 43-48 years). Women with and without self-reported PCOS diagnosis (n=981 and n=13,266, respectively) were compared. RESULTS: Overall 9.9% of women reported having PCOS by 43 to 48 years. Compared to women without PCOS, those with PCOS had fewer births (1.7±1.3 vs 1.9±1.2, P<.001), and more were nulliparous (23% vs 18%, P=.003). Women with PCOS were older at their first and second childbirths (29.5±5.5 vs 28.8±5.5 years and 32.1±5.2 vs 31.1±5.0 years, P<.001 for both). PCOS was…

BACKGROUND: One in 5 females will have surgery to treat pelvic organ prolapse in their lifetime. Uterine-preserving surgery involving suspension of the uterus is an increasingly popular alternative to the traditional use of hysterectomy with vaginal vault suspension to treat pelvic organ prolapse; however, comparative evidence with native tissue repairs remains limited in scope and quality. OBJECTIVE: To compare 1-year outcomes between hysterectomy-based and uterine-preserving native tissue prolapse surgeries performed through minimally invasive approaches. STUDY DESIGN: We used a nonrandomized design with patients self-selecting their surgical group to integrate a pragmatic, patient-centered, and autonomy-focused approach. Participants chose between uterine-preserving surgery or hysterectomy-based surgery, guided by neutral evidence-based discussions and individualized decision-making, with support from fellowship-trained urogynecologists. Inverse probability of treatment weighting based on high-dimensional propensity scores was used to balance baseline differences across surgical…

BACKGROUND: The effect of primary cytoreductive surgery vs interval cytoreductive surgery on International Federation of Gynecology and Obstetrics stage IV ovarian cancer outcomes remains uncertain and may vary depending on the stage and the location of extraperitoneal metastasis. Emulating target trials through causal assessment, combined with propensity score adjustment, has become a leading method for evaluating interventions using observational data. OBJECTIVE: This study aimed to assess the effect of primary vs interval cytoreductive surgery on progression-free and overall survival in patients with International Federation of Gynecology and Obstetrics stage IV ovarian cancer using target trial emulation. STUDY DESIGN: Using the comprehensive French national health insurance database, we emulated a target trial to explore the causal impacts of primary vs interval cytoreductive surgery on stage IV ovarian cancer prognosis (Surgery for Ovarian cancer FIGO 4: SOFI-4). The clone method with inverse probability of censoring weighting was used to adjust for informative censoring and…

BACKGROUND: Previous studies demonstrated that placental dysfunction leads to intrapartum fetal distress, particularly when an abnormal pattern of angiogenic markers is demonstrated at 36 weeks of gestation. The prediction of intrapartum fetal compromise is particularly important in patients undergoing induction of labor because of different indications for delivery, as this can be a useful in optimizing the method and timing of induction of labor. OBJECTIVE: This study aimed to examine whether the risk of preeclampsia assessed using the Fetal Medicine Foundation algorithm (derived from a combination of maternal risk factors, mean arterial pressure, uterine arteries pulsatility index, placental growth factor, and soluble fms-like tyrosine kinase-1) is associated with the risk of intrapartum fetal compromise requiring cesarean delivery in a population of patients with singleton pregnancies undergoing induction of labor for various indications. STUDY DESIGN: This was a retrospective analysis on prospectively collected data from women with singleton pregnancies who underwent routine…

BACKGROUND: Stress urinary incontinence affects approximately 40% of adult females and is often treated surgically. Minimally invasive vaginal laser therapy to treat stress urinary incontinence has become widely available, but the efficacy of this novel therapy is unclear. OBJECTIVE: This study aimed to determine the efficacy of erbium-doped yttrium aluminum garnet laser as a therapy for stress urinary incontinence. STUDY DESIGN: This was a double-blind randomized sham-controlled trial with 6-week and 6-month follow-ups at a single tertiary hospital setting with 144 adult female patients with symptomatic stress urinary incontinence. Each participant received 2 vaginal laser therapies 6 weeks apart, with patients randomized to either laser or sham. The primary outcome was patients' subjective reporting of no urinary incontinence at 6 months after treatment on question 3 of the International Consultation on Incontinence Questionnaire-Short Form. The secondary outcomes included objective measures of urine loss with 24-hour pad tests, 3 incontinence symptom questionnaires (Urogenital…

BACKGROUND: Gestational diabetes mellitus affects up to 10% of pregnancies and is classified into subtypes gestational diabetes subtype A1 (GDMA1) (managed by lifestyle modifications) and gestational diabetes subtype A2 (GDMA2) (requiring medication). However, whether these subtypes are distinct clinical entities or more reflective of an extended spectrum of normal pregnancy endocrine physiology remains unclear. OBJECTIVE: Integrated bulk RNA-sequencing (RNA-seq), single-cell RNA-sequencing (scRNA-seq), and spatial transcriptomics harbors the potential to reveal disease gene signatures in subsets of cells and tissue microenvironments. We aimed to combine these high-resolution technologies with rigorous classification of diabetes subtypes in pregnancy. We hypothesized that differences between preexisting type 2 and gestational diabetes subtypes would be associated with altered gene expression profiles in specific placental cell populations. STUDY DESIGN: In a large case-cohort design, we compared validated cases of GDMA1, GDMA2, and type 2 diabetes mellitus (T2DM) to healthy controls…

BACKGROUND: Adults with developmental disabilities often have less access to reproductive health services than adults without these disabilities. However, little is known about how adolescents with developmental disabilities, including autism, access reproductive healthcare. OBJECTIVE: We aimed to characterize the use of reproductive healthcare services among adolescents with autism and those with other developmental disabilities in comparison with adolescents with typical development. STUDY DESIGN: We conducted a cohort study of a sample of adolescents who were continuously enrolled members of Kaiser Permanente Northern California, an integrated healthcare system, from ages 14 to 18 years. The final analytical sample included 700 adolescents with autism, 836 adolescents with other developmental disabilities, and 2187 typically developing adolescents who sought care between 2000 and 2017. Using the electronic health record, we obtained information on menstrual conditions, the use of obstetrical-gynecologic care, and prescriptions of hormonal contraception. We compared healthcare use…

BACKGROUND: Occiput posterior position is associated with labor arrest, need for operative delivery, and failed instrumental vaginal delivery, with resulting adverse peripartum outcomes. Vacuum extraction is the most commonly performed type of instrumental delivery worldwide. OBJECTIVE: This study aimed to investigate the outcome of vacuum extraction in fetuses with sonographically confirmed occiput posterior position before the procedure. STUDY DESIGN: Singleton pregnancies at term with sonographically confirmed fetal occiput posterior position before the vacuum extraction were enrolled in 3 academic maternity units. Fetal head station was assessed using transperineal sonography measuring the angle of progression and the head-perineum distance. The primary outcome was failed vacuum extraction, defined as the need for cesarean delivery. Secondary outcomes included adverse maternal and/or adverse neonatal outcomes and complicated vacuum extraction, with the latter defined as failed vacuum extraction or at least 3 out of the following 6 parameters: 5-minute Apgar score <7, neonatal…

BACKGROUND: Previous evidence showed that placental dysfunction triggers spontaneous preterm or term births and intrapartum fetal compromise and often requires urgent delivery, thereby exposing both the fetus and the mother to significant risks. Predicting spontaneous labor onset and intrapartum fetal compromise could improve obstetrical management and outcomes, but this is currently difficult, particularly in low-risk populations. OBJECTIVE: The objective of this study was to examine whether placental dysfunction, as assessed at 36 weeks' gestation by the soluble fms-like tyrosine kinase-1 to placental growth factor ratio, is associated with the interval to spontaneous onset of labor and intrapartum fetal compromise that requires cesarean delivery in a routinely examined population. STUDY DESIGN: This was a retrospective analysis of prospectively collected data of women with singleton pregnancies who underwent routine assessment at 35+0 to 36+6 weeks' gestation at the King's College Hospital (London, England). Using a general linear model, the study examined the outcomes related to…

OBJECTIVE: To investigate the association between actual and planned modes of delivery, neonatal mortality, and short-term outcomes among preterm pregnancies ≤32 weeks of gestation. DATA SOURCES: A systematic literature search was conducted in 3 main databases (PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to November 16, 2022. The protocol was registered in advance in the International Prospective Register of Systematic Reviews (CRD42022377870). STUDY ELIGIBILITY CRITERIA: Eligible studies examined pregnancies ≤32nd gestational week. All infants received active care, and the outcomes were reported separately by different modes of delivery. Singleton and twin pregnancies at vertex and breech presentations were included. Studies that included pregnancies complicated with preeclampsia and abruptio placentae were excluded. Primary outcomes were neonatal mortality and intraventricular hemorrhage. STUDY APPRAISAL AND SYNTHESIS METHODS: Articles were selected by title, abstract, and full text, and disagreements were resolved by consensus. Random…

BACKGROUND: In recent years, pragmatic metformin use in pregnancy has stretched to include prediabetes mellitus, type 2 diabetes mellitus, gestational diabetes mellitus, and (most recently) preeclampsia. However, with its expanded use, concerns of unintended harm have been raised. OBJECTIVE: This study developed an experimental primate model and applied ultrahigh performance liquid chromatography coupled to triple-quadrupole mass spectrometry for direct quantitation of maternal and fetal tissue metformin levels with detailed fetal biometry and histopathology. STUDY DESIGN: Within 30 days of confirmed conception (defined as early pregnancy), 13 time-bred (timed-mated breeding) Rhesus dams with pregnancies designated for fetal necropsy were initiated on twice-daily human dose-equivalent 10 mg/kg metformin or vehicle control. Pregnant dams were maintained as pairs and fed either a control chow or 36% fat Western-style diet. Metformin or placebo vehicle control was delivered in various treats while the animals were separated via a slide. A cesarean delivery was performed at gestational…

BACKGROUND: Fear of pain associated with intrauterine device (IUD) placement has been identified as a significant barrier to the adoption of long-acting reversible contraception, contributing to lower utilization of the most effective reversible contraceptive methods. OBJECTIVE: To assess whether instillation of intrauterine mepivacaine before IUD placement alleviates pain more effectively than a placebo. STUDY DESIGN: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving nulliparous women undergoing IUD placement. An intrauterine instillation of 10 mL of 20 mg/mL mepivacaine or 0.9 mg/mL sodium chloride was administrated through a hydrosonography catheter 2 minutes prior to IUD placement. Pain scores were assessed using a 100 mm visual analog scale (VAS) at prespecified time points. Primary outcome measured the difference in VAS pain scores between the intervention group and the placebo group during IUD placement. Secondary outcomes included VAS pain scores at instillation and 10 minutes after placement, tolerability of the placement pain, as well…

Background Cytomegalovirus is responsible for the most common congenital infection, affecting 0.5% to 1.0% of live births in Europe. Congenital cytomegalovirus infection can be diagnosed during pregnancy by viral DNA amplification in the amniotic fluid, but the prognosis of fetuses without severe brain abnormalities remains difficult to establish on the basis of prenatal imaging alone. Objective To identify predictors of moderate to severe symptomatic cytomegalovirus infection among fetal blood parameters and to propose an algorithm on the basis of these parameters and on prenatal imaging that would provide the best positive and negative predictive values. Study Design Fetal blood sampling at 21–28 weeks gestation was performed in fetuses with congenital cytomegalovirus infection confirmed by amniocentesis after maternal infection in the first-trimester or periconceptional period. We compared the levels of hemoglobin, thrombocytes, γ-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, β2-microglobulin, immunoglobulins G and M, and cytomegalovirus DNA viral…

BACKGROUND: Endometriosis is a prevalent chronic gynecological condition characterized by severe pelvic pain, negatively affecting women's health-related quality of life. The Common-Sense Model of Illness Self-regulation has revealed the importance of illness perceptions and coping strategies in explaining the impact of illness on across several conditions. These aspects have never been assessed in endometriosis. OBJECTIVE: We aimed to explore the relationship between pelvic pain severity and health-related quality of life in women with endometriosis, hypothesizing that illness representations and pain-specific cognitive and behavioral maladaptive coping strategies influence this relationship. STUDY DESIGN: This cross-sectional study analyzed data from 273 women with endometriosis who completed an online questionnaire assessing pelvic pain severity, illness perceptions, specific pain-related coping strategies, and health-related quality of life. A path analysis through MPlus was conducted to examine the direct and indirect relationships between variables. RESULTS: The analysis…

BACKGROUND: Birthing people with de novo postpartum hypertensive disorders continue to be among the populations at highest risk for severe maternal morbidity. Randomized controlled trials demonstrate a benefit of oral loop diuretics in decreasing postpartum hypertensive morbidity in patients with an antenatal diagnosis of preeclampsia. It is not known whether this same therapy benefits patients at risk for new-onset postpartum hypertension. OBJECTIVE: This study aimed to evaluate whether oral furosemide can reduce the risk for de novo postpartum hypertension among high-risk birthing people by reducing postdelivery blood pressure. STUDY DESIGN: From October 2021 to April 2022, we conducted a randomized triple-masked placebo-controlled clinical trial of individuals at high risk for de novo postpartum hypertension at a single university-based tertiary care medical center. A total of 82 postpartum patients with no antenatal diagnosis of chronic hypertension or a hypertensive disorder of pregnancy who were at high risk for the development of de novo postpartum hypertension based on a…