Am. J. Obstet. Gynecol. [JOURNAL]
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200 papers
Pregnancy and perinatal outcomes stratified by soluble fms-like tyrosine kinase-1 and placental growth factor gestation-specific thresholds in women with suspected preeclampsia.
Creswell L, Christodoulou M, Chang K … +7 more , Pentecost L, Sun B, Zaikin A, Napolitano R, Hillman SL, Stott D, Nzelu D
Am J Obstet Gynecol · 2026 Jul · PMID 41740916 · Publisher ↗
OBJECTIVE: To evaluate gestational age appropriate soluble fms-like tyrosine kinase-1 and placental growth factor concentrations in determining abnormal outcomes in women with suspected preeclampsia. STUDY DESIGN: Retros...
OBJECTIVE: To evaluate gestational age appropriate soluble fms-like tyrosine kinase-1 and placental growth factor concentrations in determining abnormal outcomes in women with suspected preeclampsia. STUDY DESIGN: Retrospective single-center study of 457 singleton pregnancies from a tertiary referral center in the United Kingdom. Four subgroups were defined using gestational age-adjusted thresholds for soluble fms-like tyrosine kinase-1 (>95th centile) and placental growth factor (<fifth centile). Continuous variables were assessed for normality; non-normally distributed data were analyzed using the Kruskal-Wallis test with Bonferroni-adjusted pairwise comparisons. Log-transformed biochemical, angiogenic, and ultrasound variables were analyzed using one-way analysis of variance (df=3) with Dunnett post hoc comparisons versus controls (df=1). Categorical variables were compared using chi-square or Fisher's exact tests with post hoc comparisons where appropriate. A two-tailed P value <0.05 was considered statistically significant. RESULTS: Amongst singleton pregnancies with available soluble fms-like tyrosine kinase-1/placental growth factor ratios, angiogenic profiling classified women into 4 groups. Group 1 (soluble fms-like tyrosine kinase-1>95th, PlGF <fifth; n=100), Group 2 (soluble fms-like tyrosine kinase-1>95th, placental growth factor >fifth; n=58), Group 3 (soluble fms-like tyrosine kinase-1<95th, placental growth factor <fifth; n=31), and controls (Group 4) (soluble fms-like tyrosine kinase-1<95th, placental growth factor >fifth; n=268). Distinct angiogenic and ultrasonographic profiles were observed between groups (one-way analysis of variance, F (3,453), P<0.001). On post hoc Dunnett's, when compared to controls, Groups 1 and 3 with low placental growth factor (<fifth centile) had a significantly lower mean first trimester pregnancy associated plasma protein-A (0.6, [95% CI 0.6-0.7] and 0.5, [0.4-7.0] vs 0.9 [0.8-1.0]; df=1, P<0.001) and higher second trimester combined uterine artery Doppler pulsatility index (1.47 [1.35-1.59] and 1.31 [1.13-1.51] vs 0.98 [0.93-1.02]; df=1, P<0.001). Markers of maternal end-organ involvement also demonstrated strong group-level differences (one-way analysis of variance, F(3,453), P<0.001). On post hoc Dunnett's, when compared to controls, Groups 1 and 2 (sFlt-1>95th centile) had a significantly lower mean platelet count (182.8 [168-198.8] and 176.7 [160.4-194.6] vs 212.5 [204.9-220.4]; df=1, P<0.01), higher mean creatinine levels (70.1 [65.2-75.4] and 70.1 [63.3-78.3] vs 59.4 [57.7-61.2]; df=1, P<0.01) and higher mean urine protein: creatinine ratios (93 [68.7-126.1] and 58.9 [38.9-89.0] vs 25.8 [22.2-29.9]; df=1, P<0.01). The incidence of preeclampsia occurring before 37 weeks was higher in Groups 1 to 3 when compared to the controls, occurring in 78.0%, 39.7%, 31.3%, and 6.7% of pregnancies, respectively (P<0.001). Adverse neonatal outcomes were clustered particularly in Group 1 which had the lowest median gestational age at birth (median 33.4 [29.2-35.7] and lowest birthweight centile (0.26 [0.00-2.71]. The incidence of small for gestational age infants and need for neonatal intensive care unit admission was significantly higher across Groups 1 to 3 when each of the groups was individually compared to the controls (P<0.001 for all). Stillbirths occurred only in Groups 1 (5.3%, n=5) and 3 (6.9%, n=2) which had low placental growth factor levels <fifth centile. CONCLUSION: Stratification of women with suspected preeclampsia using gestational age-specific thresholds for soluble fms-like tyrosine kinase-1 and placental growth factor can identify distinct maternal and fetal phenotypes with significantly different clinical outcomes. Elevated soluble fms-like tyrosine kinase-1 concentrations appear to be strongly associated with severe maternal disease, whilst low placental growth factor appears to correlate with adverse fetal and neonatal outcomes including growth restriction, stillbirth, and prolonged neonatal intensive care stay.
Artificial cycle frozen embryo transfer improves uterine perfusion during later pregnancy but is associated with higher preeclampsia incidence.
Donno V, Prats P, Plancha M … +3 more , Rodriguez I, Nicolaides KH, Polyzos NP
Am J Obstet Gynecol · 2026 Jul · PMID 41730489 · Publisher ↗
BACKGROUND: Uterine artery pulsatility index is a key biomarker for preeclampsia screening and the most reliable indicator of uterine perfusion across all pregnancy trimesters. Although recent findings reveal a significa...
BACKGROUND: Uterine artery pulsatility index is a key biomarker for preeclampsia screening and the most reliable indicator of uterine perfusion across all pregnancy trimesters. Although recent findings reveal a significant decrease in uterine artery pulsatility index during first trimester in artificial cycle frozen embryo transfer pregnancies, no previous study evaluated whether this decrease persists throughout the second and third trimesters, when hormonal treatment is discontinued. Considering the crucial role of uterine artery pulsatility index during the second half of pregnancy risk assessment, recommended by international guidelines to ensure early preeclampsia detection and proper pregnancy monitoring, we set out to perform a large retrospective study to evaluate the impact of endometrial preparation on second and third trimesters uterine artery pulsatility index. OBJECTIVE: The study aims to evaluate the possible impact of endometrial preparation for frozen embryo transfer on uterine vascular resistance during the second and third trimesters. STUDY DESIGN: This retrospective single-center study analyzed 27,495 singleton pregnancies that underwent Uterine Artery Pulsatility Index evaluation during the second trimester (20-22 weeks) of pregnancy at our University Hospital between January 2010 and November 2024. Among them, 23,547 were naturally conceived and 3948 resulted from Assisted Reproductive Technology (385 ovulation induction and intrauterine insemination, 864 in vitro fertilization frozen embryo transfer, and 2699 after frozen embryo transfer) (356 natural cycle frozen embryo transfer and 2343 artificial cycle frozen embryo transfer). Additionally, third trimester (35-37 weeks) Uterine Artery Pulsatility Index evaluations were available for 11,096 pregnancies. Pregnancies with fetal congenital abnormalities, aneuploidies, and twin pregnancies were excluded. The primary aim of the study was to investigate Uterine Artery Pulsatility Index values throughout pregnancy based on different types of conception. Analysis of covariance and linear mixed model (including potential confounders such as smoking, diabetes, race, chronic hypertension, aspirin administration, thrombophilia, age, weight, and oocyte donation) were used to analyze the association between mode of conception and log10-transformed multiple of the median values of Uterine Artery Pulsatility Index. RESULTS: The use of hormonal treatment in artificial cycle frozen embryo transfer cycles was associated with a significantly lower second-trimester Uterine Artery Pulsatility Index values 0.73 (artificial cycle frozen embryo transfer) as compared with all other modes of conception vs 0.89 (naturally conceived), 0.92 (ovulation induction and intrauterine insemination), 0.94 (fresh embryo transfer), and 0.89 (natural cycle frozen embryo transfer) (P<.001). Differences persisted during the third trimester with Uterine Artery Pulsatility Index values 0.95 for artificial cycle frozen embryo transfer vs 1.00 (naturally conceived), 1.03 (ovulation induction and intrauterine insemination), 1.00 (in vitro fertilization frozen embryo transfer), and 1.02 (natural cycle frozen embryo transfer) (P<.001). The results were confirmed after applying the multivariable regression analysis. Despite the improved uterine perfusion, artificial cycle frozen embryo transfer was associated with a 4-fold higher incidence of preeclampsia (5.2%) compared to natural cycle frozen embryo transfer (1.1%), naturally conceived (1.4%), ovulation induction and intrauterine insemination (1%), and fresh embryo transfer (2.2%) (P<.001). CONCLUSION: The present study demonstrates that artificial cycle frozen embryo transfer is associated with reduced uterine vascular resistance across all pregnancy trimesters. This finding strongly supports the urgent need to revise the current second and third trimester preeclampsia risk assessment algorithm to ensure accurate early detection and proper management of high-risk pregnancies.
Higher long-term healthcare utilization in children conceived through medically assisted reproduction: findings from a 16-year cohort study.
van Heusden A, Yuan W, Dalziel K … +1 more , Hua X
Am J Obstet Gynecol · 2026 Jul · PMID 41730488 · Publisher ↗
BACKGROUND: The use of medically assisted reproduction is increasing over time, and there are limited data on the long-term health services use associated with medically assisted reproduction. OBJECTIVE: This study aimed...
BACKGROUND: The use of medically assisted reproduction is increasing over time, and there are limited data on the long-term health services use associated with medically assisted reproduction. OBJECTIVE: This study aimed to examine the long-term healthcare service use and prescription medication use in children who were conceived through medically assisted reproduction and to compare it with that of naturally conceived children. STUDY DESIGN: Data from Growing up in Australia: Longitudinal Study of Australian Children, a population-based longitudinal cohort study, linked with Australian Medicare administrative records, were used for this study. Out-of-hospital healthcare service use and costs, including prescription medication use, were compared between children who conceived with and those who were conceived without medically assisted reproduction. Generalized linear models and logistic models were applied to investigate the association of medically assisted reproduction with total healthcare costs and the use of prescription medications with adjustment for a wide range of birth, pregnancy, and socioeconomic characteristics. RESULTS: The study included 4789 singleton children who were followed from birth to the age 16 years with 246 of them conceived through medically assisted reproduction. Higher healthcare use and costs were seen for children who were conceived through medically assisted reproduction when compared with naturally conceived children across all age bands, except for ages 10 to 11 years, and the differences were statistically significant for ages 2 to 3 years (mean difference, $87.53; 95% confidence interval, $8.87-$166.19) and for ages 4 to 5 years (mean difference, $117.53; 95% confidence interval, $30.95-$204.11) after controlling for birth, pregnancy conditions, and socioeconomic characteristics. Among all available age bands, children aged 6 to 15 years who were conceived through medically assisted reproduction were found to have 2.41 (95% confidence interval, 1.15-5.08) to 3.20 (95% confidence interval, 1.54-6.64) times the odds of being prescribed attention-deficit/hyperactivity disorder medications than naturally conceived children after controlling for birth, pregnancy, and socioeconomic characteristics. In terms of mental health medications, children who were conceived through medically assisted reproduction had 5.24 (95% confidence interval, 2.02-13.58) and 2.96 (95% confidence interval, 1.23-7.13) times the odds of being prescribed these medications than naturally conceived children for the age bands 4 to 5 and 6 to 7 years, respectively, after adjusting for covariates. Little to no differences were observed in the use of prescriptions for adrenaline autoinjectors, asthma medications, eczema medications, anti-infectives medications (antiviral, antibacterial, antifungal), or other medications between children conceived through medically assisted reproduction and those conceived naturally. CONCLUSION: This study highlights a higher need for long-term healthcare services and associated resources for children who were conceived through medically assisted reproduction, which cannot be explained by socioeconomic-related parental health-seeking behaviors and perinatal factors, like multiple births and birth weight. This study helps to anticipate the downstream financial impact on the health system associated with the increasing use of medically assisted reproduction and emphasizes an opportunity for early screening and detection of relevant health conditions among children conceived through medically assisted reproduction.
Abnormal soluble fms-like tyrosine kinase to placental growth factor ratio during pregnancy and subjective memory impairment 3 to 6 years postpartum.
Platero J, Garcia-Manau P, Costa N … +12 more , Garcia Z, Garrido-Giménez C, Pellicer C, Ullmo J, Jordi M, Nan M, Mora J, Garcia-Osuna A, Sánchez-Garcia O, Choliz M, Cruz-Lemini M, Llurba E
Am J Obstet Gynecol · 2026 Jul · PMID 41724313 · Publisher ↗
BACKGROUND: Preeclampsia is a pregnancy-related disorder characterized by systemic endothelial dysfunction and angiogenic imbalance, most notably elevated levels of soluble fms-like tyrosine kinase-1 and decreased placen...
BACKGROUND: Preeclampsia is a pregnancy-related disorder characterized by systemic endothelial dysfunction and angiogenic imbalance, most notably elevated levels of soluble fms-like tyrosine kinase-1 and decreased placental growth factor. While preeclampsia has been associated with long-term cardiovascular and cognitive risks, the specific role of angiogenic imbalance in predicting postpartum memory impairment remains unclear. Identifying biomarkers that can anticipate future neurocognitive outcomes may offer opportunities for early intervention and monitoring. OBJECTIVE: To evaluate whether preeclampsia and angiogenic imbalance during pregnancy, defined by a soluble fms-like tyrosine kinase-1/placental growth factor ratio ≥38, are associated with subjective memory impairment 3 to 6 years postpartum. STUDY DESIGN: Cross-sectional study at a tertiary hospital in Barcelona, Spain. Individuals were prospectively recruited during pregnancy and reevaluated 3 to 6 years postpartum. Preeclampsia was defined per American College of Obstetricians and Gynecologists criteria. Angiogenic imbalance during pregnancy was defined as soluble fms-like tyrosine kinase-1/placental growth factor ≥38 (determined between 28 and 40 weeks of gestation). Subjective memory performance was assessed using the validated Memory Failures of Everyday Life questionnaire. Memory impairment was defined as a total Memory Failures of Everyday Life score ≥36. Logistic and linear regression models were used to examine associations, adjusting for relevant confounders. RESULTS: A total of 266 individuals were reevaluated between August 2023 and February 2025. 81 of them (30.45%) had a documented history of preeclampsia. Participants with an elevated soluble fms-like tyrosine kinase-1/placental growth factor ratio during pregnancy showed a higher prevalence of memory impairment (30.0% vs 16.2%, P=.03). In multivariable analysis, angiogenic imbalance remained significantly associated with increased odds of memory impairment (odds ratio=2.18, 95% confidence interval [1.02-4.65], P=.04). In contrast, preeclampsia diagnosis alone was not significantly associated with memory outcomes (odds ratio=1.35, 95% confidence interval [0.70-2.60], P=.37). CONCLUSION: An elevated soluble fms-like tyrosine kinase-1/placental growth factor ratio during pregnancy is associated with an increased risk of subjective memory impairment 3 to 6 years postpartum. These findings highlight the potential utility of angiogenic biomarkers as early indicators of long-term cognitive vulnerability, supporting the need for longitudinal follow-up and targeted preventive strategies in women exposed to angiogenic imbalance during pregnancy.
Posttraumatic stress disorder after second-trimester medical termination of pregnancy.
Anselem O, Vivanti AJ, Bouchghoul H … +12 more , Quibel T, Winer N, Jouannic JM, Castaigne V, Perdriolle-Galet E, Massardier J, Rousseau J, Radjack R, Tsatsaris V, Ancel PY, Goffinet F, DILATOP Study Group
Am J Obstet Gynecol · 2026 Jul · PMID 41724312 · Publisher ↗
OBJECTIVE: To evaluate the risk of posttraumatic stress disorder after indicated second-trimester termination of pregnancy and to identify factors associated with a probable diagnosis of severe posttraumatic stress disor...
OBJECTIVE: To evaluate the risk of posttraumatic stress disorder after indicated second-trimester termination of pregnancy and to identify factors associated with a probable diagnosis of severe posttraumatic stress disorder. STUDY DESIGN: Secondary analysis of a multicenter randomized controlled trial comparing the efficacy of cervical dilators inserted concurrently with misoprostol with that of misoprostol alone for women undergoing termination of pregnancy between 15 and 27 weeks of gestation. Posttraumatic stress disorder was evaluated by the Impact of Event Scale-Revised questionnaire, self-administered 1 to 4 months after termination of pregnancy. This 22-item scale is designed to assess subjective distress caused by traumatic events and has been validated in perinatal care. The literature suggests that a score ≥33 indicates a probable diagnosis of posttraumatic stress disorder and a score ≥37 a probable diagnosis of severe posttraumatic stress disorder. Maternal and obstetric characteristics associated with a score ≥37 were studied with mixed models. We present results after multiple imputation to take selective dropouts and missing information at follow-up into account and for complete cases. RESULTS: Among the 347 women enrolled, 247 (71.2%) Impact of Event Scale-Revised questionnaires were available. Median time between termination of pregnancy and completion of the questionnaire was 7 weeks (interquartile range, 4.9-13.3). The mean Impact of Event Scale-Revised score was 32.1 (standard deviation, 15.4). The Impact of Event Scale-Revised score was ≥33 for 44.9% (95% confidence interval, 38.4-51.4) of women and ≥37 for 35.8% (95% confidence interval, 29.7-41.8). After multivariate analysis, obstetric or labor-related characteristics such as parity, gestational age over 22 weeks, use of cervical dilators, labor >12 hours, and pain or complications during delivery or postpartum were not associated with an Impact of Event Scale-Revised score ≥37. The results were similar in complete cases. CONCLUSION: Nearly half of women undergoing medically indicated second-trimester termination of pregnancy were at risk of posttraumatic stress disorder and more than one-third of severe posttraumatic stress disorder. The absence of risk factors underlines the potential benefits of systematic psychological evaluation after termination of pregnancy for all women.
Prevention of recurrent spontaneous preterm delivery using probiotics: results from a prospective, single-arm, multicenter trial.
Yoneda S, Akamata N, Nakamura M … +15 more , Kumazawa K, Sakura M, Fukuhara K, Kuribayashi M, Nagasaki S, Kodama Y, Matsui H, Suzuki T, Kirihara N, Iwamoto S, Kobayashi T, Otsuki K, Nakai A, Saito S, PPP trial Collaborators
Am J Obstet Gynecol · 2026 Jul · PMID 41722754 · Publisher ↗
BACKGROUND: The rate of recurrent spontaneous preterm delivery is 30% (95% confidence interval, 27%-34%) globally and 22.3% in Japan. Probiotics containing Clostridium species may reduce spontaneous preterm delivery by i...
BACKGROUND: The rate of recurrent spontaneous preterm delivery is 30% (95% confidence interval, 27%-34%) globally and 22.3% in Japan. Probiotics containing Clostridium species may reduce spontaneous preterm delivery by inducing regulatory T cells, which play an important role in maintaining pregnancy. OBJECTIVE: We investigated whether the administration of probiotics including Clostridium butyricum prevented recurrent spontaneous preterm delivery in high-risk pregnant women. STUDY DESIGN: We conducted a prospective, single-arm, nonblinded, multicenter trial across 31 hospitals in Japan between May 2021 and October 2024. Pregnant women (aged 18-43 years) with a history of spontaneous preterm delivery received oral probiotics (Clostridium butyricum [10 mg/tablet], Enterococcus faecium [2 mg/tablet], and Bacillus subtilis [10 mg/tablet]) from 10 to 14 weeks to 36 weeks 6 days of gestation. The primary endpoint was the rate of recurrent spontaneous preterm delivery at <37 weeks, compared against the historical rate of 22.3% from Japan's national perinatal database. The rate of spontaneous preterm delivery before 34 weeks and neonatal outcomes among spontaneous preterm delivery were evaluated as secondary outcomes. Recurrent spontaneous preterm delivery before 28 weeks was evaluated among women with a history of spontaneous preterm delivery before 28 weeks. RESULTS: Among 343 enrolled patients, 315 (91.8%) were included in the analysis. The recurrence rate of spontaneous preterm delivery at <37 weeks was 14.9% (47/315; 95% confidence interval, 11.2%-19.3%), which was significantly lower than the historical rate (P=.0013). The secondary endpoint analysis showed that the rate of spontaneous preterm delivery before 34 weeks was 3.5% (11/315; 95% confidence interval, 1.8%-6.2%). Among women with a history of extreme preterm delivery (<28 weeks), the rate of recurrent spontaneous preterm delivery before 28 weeks was 1.5% (1/65; 95% confidence interval, 0.0%-8.3%). There were no stillbirths, defined as fetal death at or after 22 weeks of gestation. No serious adverse events, defined as events resulting in death or persistent disability, were reported, and the incidence of nonserious adverse events was consistent with expectations. CONCLUSION: In this prospective study, oral administration of probiotics was associated with a lower recurrence rate of spontaneous preterm delivery compared with nationally reported historical rate. These findings suggest that this approach may be a potential strategy to reduce recurrent spontaneous preterm delivery and should be further evaluated in a controlled trial.
The impact of a previous cesarean delivery on in vitro fertilization outcomes: a registry-based cohort study.
Létourneau I, Walker M, Gale J
Am J Obstet Gynecol · 2026 Jun · PMID 41722753 · Publisher ↗
BACKGROUND: Cesarean delivery rates have climbed over the past few decades. We sought to evaluate whether a previous cesarean delivery is associated with reduced live birth rates following a subsequent embryo transfer wh...
BACKGROUND: Cesarean delivery rates have climbed over the past few decades. We sought to evaluate whether a previous cesarean delivery is associated with reduced live birth rates following a subsequent embryo transfer when compared with patients with a history of vaginal delivery. OBJECTIVE: This study aimed to evaluate the impact of a previous cesarean delivery by reporting the live birth rate following the first embryo transfer and comparing it with the rates among patients with a previous vaginal delivery. STUDY DESIGN: We performed a retrospective, registry-based cohort study of all patients in Ontario, Canada, with a previous delivery, either vaginal or cesarean delivery, who subsequently had an embryo transfer between January 1, 2013, and December 31, 2020. A total of 7460 patients were included of which 4587 patients were in the vaginal delivery group and 2873 patients were in the cesarean delivery group. Data from the provincial birth register, Better Outcomes Registry & Network Ontario, and from the fertility registry, Canadian Assisted Reproductive Technology Register Plus were used for this study. A modified Poisson regression model was used to estimate the relative risk with 95% confidence intervals. Models were adjusted for age at oocyte retrieval, age at embryo transfer, number of previous deliveries, number of embryos transferred, type of embryo transfer (fresh vs frozen-thawed), and embryo stage at transfer. Crude risk differences with 95% confidence intervals were calculated. RESULTS: Patients with a previous cesarean delivery had a statistically significant lower live birth rate (adjusted risk ratio, 0.84; 95% confidence interval, 0.80-0.90; risk difference, -4.6 per 100; 95% confidence interval, -6.8 to -2.4), positive human chorionic gonadotropin rate (adjusted risk ratio, 0.92; 95% confidence interval, 0.88-0.96), implantation rate (adjusted risk ratio, 0.91; 95% confidence interval, 0.86-0.96), clinical pregnancy rate (adjusted risk ratio, 0.90; 95% confidence interval, 0.85-0.95), ongoing pregnancy rate (adjusted risk ratio, 0.87; 95% confidence interval, 0.82-0.92), and live birth rate with good perinatal outcome (adjusted risk ratio, 0.82; 95% confidence interval, 0.76-0.88) when compared with patients with a previous vaginal delivery. CONCLUSION: A previous cesarean delivery was associated with lower live birth rates and other fertility-related pregnancy outcomes after the first subsequent embryo transfer when compared with a previous vaginal delivery. Because residual confounding cannot be excluded in this retrospective, registry-based study, these findings should be interpreted as associations. The results of this study emphasize the importance of further research to investigate possible etiologies that underlie this association.
Placental histopathology and early childhood neurodevelopment in the Environmental influences on Child Health Outcomes cohort.
Fisher SA, Xun X, Gemmill A … +17 more , Yee LM, Mithal LB, Hamvas A, Regnier RA, Aschner JL, Maitre NL, O'Connor TG, Cowell W, Kahn LG, Newman RB, Miller RK, Salafia C, Elliott AJ, Singh AM, Baumann-Blackmore N, Goldstein JA, ECHO Cohort Consortium
Am J Obstet Gynecol · 2026 Jul · PMID 41722752 · Full text
BACKGROUND: Prenatal exposures influence childhood neurodevelopment. Placental histopathology has been associated with abnormal early childhood neurodevelopment, albeit often confounded by prematurity and/or fetal growth...
BACKGROUND: Prenatal exposures influence childhood neurodevelopment. Placental histopathology has been associated with abnormal early childhood neurodevelopment, albeit often confounded by prematurity and/or fetal growth restriction. Most pregnant people, however, have term births, and some of these children have abnormal neurodevelopment despite the absence of adverse birth outcomes. Leveraging placental histopathology may help distinguish infants at a higher risk of subsequent neurodevelopmental impairment following a term birth. OBJECTIVE: To investigate the association of placental histopathology with a high-risk screen for abnormal early childhood neurodevelopment following a term birth. STUDY DESIGN: The sample included singleton births at ≥37 weeks 0 days between 2020 and 2023 in the prospective, longitudinal multisite Environmental Influences on Child Health Outcomes cohort. Children with available placental histopathologic data and whose birthing parent had completed at least one Ages & Stages Questionnaire-Third Edition between 2 and 18 months of life were eligible for inclusion. Children diagnosed with hypoxic-ischemic encephalopathy after birth were excluded. Exposures were chronic placental inflammation, maternal or fetal acute inflammatory response, and maternal or fetal vascular perfusion. The primary outcome was a high-risk composite Ages & Stages Questionnaire-Third Edition screen, defined as a high-risk score (≥2 standard deviations below the mean) on at least one of the 5 individual domains (communication, gross motor, fine motor, personal-social, and problem-solving) on any Ages & Stages Questionnaire-Third Edition questionnaire performed between 2 and 18 months of life. Individual Ages & Stages Questionnaire-Third Edition domains were secondarily assessed. Generalized estimating equation models were used to calculate the odds of a high-risk screen for each outcome in children exposed vs unexposed to each placental histopathologic finding, adjusted for maternal age, education, insurance, depression, parity, child sex, and birthweight. RESULTS: At Environmental Influences on Child Health Outcomes sites performing placental collection and histopathologic evaluation, assessment of at least one Ages & Stages Questionnaire-Third Edition domain was performed in 7353 children aged 2 to 18 months during the study period. Of these, 486 (13%) were born at term and met additional eligibility criteria. Pregnant participants self-identified predominately as non-Hispanic White (57%), exceeded a high school education (78%), and were multiparous (70%). The frequency of each placental histopathologic exposure ranged from 16.5% to 59.5%, and the primary outcome of a high-risk composite Ages & Stages Questionnaire-Third Edition screen was present in 26% of children. In multivariable analyses, none of the placental exposures were associated with a high-risk composite Ages & Stages Questionnaire-Third Edition screen (adjusted odds ratio, 1.43; 95% confidence interval, 0.95-2.15) at 2 to 18 months. However, chronic placental inflammation was associated with high-risk communication (adjusted odds ratio, 2.84; 95% confidence interval, 1.09-7.40) and fine motor (adjusted odds ratio, 2.26; 95% confidence interval, 1.02-5.04) domain scores at 2 to 18 months and with a high-risk screen for the composite Ages & Stages Questionnaire-Third Edition score (adjusted odds ratio, 2.07; 95% confidence interval, 1.05-4.07) and gross motor domains (adjusted odds ratio, 3.89; 95% confidence interval, 1.25-12.10) at 12 to 18 months. In post-hoc sensitivity analyses, associations between chronic placental inflammation and high-risk Ages & Stages Questionnaire-Third Edition screens varied by child sex and were not present in individuals without obesity (body mass index <30 kg/m). CONCLUSION: After a term birth, placental histopathology was not associated with a high-risk composite Ages & Stages Questionnaire-Third Edition screen in children assessed at 2 to 18 months. However, chronic placental inflammation was positively associated with a high-risk composite score in children aged 12 to 18 months. This population may warrant enhanced surveillance, screening, and diagnostic follow-up for neurodevelopmental impairment in early childhood.
Cross-border use of assisted reproductive technology in the United States, 2014 to 2022.
Albright NL, Gaskins AJ, Hipp HS … +1 more , Kawwass JF
Am J Obstet Gynecol · 2026 Jul · PMID 41722751 · Publisher ↗
BACKGROUND: The United States has become a major destination for cross-border reproductive care, yet limited national data exist on international assisted reproductive technology users and their outcomes. OBJECTIVE: To c...
BACKGROUND: The United States has become a major destination for cross-border reproductive care, yet limited national data exist on international assisted reproductive technology users and their outcomes. OBJECTIVE: To characterize cross-border reproductive care in the United States and compare assisted reproductive technology utilization patterns and outcomes between US and non-US residents. STUDY DESIGN: Retrospective cohort study using data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System characterizing temporal trends, treatment characteristics, and live birth outcomes among 2,275,167 assisted reproductive technology cycles from 2014 to 2022, including 59,246 (2.6%) cycles from non-US residents representing 182 countries. Outcomes were stratified by oocyte source and plurality (for preterm birth) and analyzed using multivariable log-binomial regression with generalized estimating equations. RESULTS: The number and percentage of assisted reproductive technology cycles among non-US residents rose steadily from 2014 to 2019 (2.8% to 3.4%) before declining in 2020. China accounted for the highest volume of international patients (19,718 cycles), nearly 3-fold higher than the next closest country, Canada (6990 cycles). Compared to US residents, non-US patients were more likely to use intracytoplasmic sperm injection (93% vs 84%), preimplantation genetic testing (68% vs 43%), donor oocytes (52% vs 9%), and gestational carriers (45% vs 2%). Live birth rate was slightly higher among non-US residents for autologous (48.3% vs 44.2%; adjusted risk ratio, 1.02; 95% confidence interval, 1.00-1.04) and donor oocyte cycles (55.5% vs 48.4%; adjusted risk ratio, 1.10; 95% confidence interval, 1.09-1.13). CONCLUSION: Cross-border reproductive care accounts for a growing proportion of assisted reproductive technology cycles in the United States, with non-US residents more frequently using advanced and third-party reproductive technologies. Despite differences in assisted reproductive technology treatments, non-US residents experienced slightly better outcomes. These findings highlight persistent global disparities in assisted reproductive technology access and underscore the United States's role as a key destination for complex fertility care.
Prenatal wildfire smoke exposure and adverse neonatal outcomes in a high-risk cohort of pregnant women with asthma.
Brew BK, Gibson PG, Collison A … +11 more , Karmaus W, Szwec S, Holliday E, Morgan G, Gopi K, Zosky G, Jensen ME, McDonald VM, Robinson PD, Mattes J, Murphy VE
Am J Obstet Gynecol · 2026 Jul · PMID 41720420 · Publisher ↗
BACKGROUND: Climate change is contributing to more frequent wildfires. Exposure to wildfire smoke during pregnancy increases the risk of adverse neonatal outcomes. Pregnant women with asthma and their newborns are partic...
BACKGROUND: Climate change is contributing to more frequent wildfires. Exposure to wildfire smoke during pregnancy increases the risk of adverse neonatal outcomes. Pregnant women with asthma and their newborns are particularly at risk of negative effects from wildfire smoke exposure and remain understudied. Determining critical windows of exposure during pregnancy could help inform mitigation strategies for this high-risk group. OBJECTIVE: This study aimed to assess the association of prenatal wildfire smoke exposure with adverse neonatal outcomes in mothers with asthma and to determine which period of pregnancy is most critical. STUDY DESIGN: This was a multicenter cohort study (Breathing for Life Trial) including mothers and newborns from 6 antenatal clinics across 4 cities in Australia (Sydney, Brisbane, Newcastle, Canberra). Pregnant women (n=1275) with asthma were recruited at 12 to 23 weeks of gestation. Chronic lung disease (other than asthma), miscarriages, and perinatal deaths were excluded. Prenatal wildfire smoke exposure days and daily wildfire-related particulate matter ≤2.5 μm concentrations were determined by residence. Exposure over pregnancy was assessed in 3 ways: (1) cumulative days of wildfire smoke (0, 1-4, 5-9, ≥10 days); (2) wildfire smoke-affected days and wildfire-related particulate matter ≤2.5 μm as continuous variables for each gestational month; and (3) a natural experiment comparing exposure during the 2019-2020 summer extreme wildfire period with historical controls. Neonatal outcomes included birthweight, low birthweight (<2500 g), gestational length, preterm birth (<37 weeks), neonatal intensive care unit admission, and cesarean delivery. RESULTS: The mean age of women was 30.7 years (SD, 5.5), 85% were White, 15% were smokers, and 69% were overweight or obese. The prenatal mean daily particulate matter ≤2.5 μm concentration (all sources) was 7.6 μg/m (SD, 1.42); the median daily wildfire-related particulate matter ≤2.5 μm concentration was 0.1 μg/m (range, 0-7.7 μg/m); and the median number of prenatal cumulative days of wildfire smoke exposure was 3 (range, 0-71 days). Prenatal exposure to ≥10 cumulative wildfire smoke days was associated with low birthweight (adjusted odds ratio, 4.2; 95% confidence interval, 1.2-13.9), preterm birth (adjusted odds ratio, 2.8; 95% confidence interval, 1.1-7.2), and neonatal intensive care unit admission (adjusted odds ratio, 5.0; 95% confidence interval, 1.4-17.8). Exposure to wildfire-related particulate matter ≤2.5 μm in the second and third gestational months was associated with preterm birth, small for gestational age, and neonatal intensive care unit admission. In the natural experiment, prenatal exposure was associated with low birthweight (adjusted odds ratio, 2.6; 95% confidence interval, 1.1-6.2), preterm birth (adjusted odds ratio, 2.5; 95% confidence interval, 1.2-5.2), and neonatal intensive care unit admission (adjusted odds ratio, 4.8; 95% confidence interval, 2.0-11.2). CONCLUSION: In pregnant women with asthma, prenatal exposure to wildfire smoke early in pregnancy increases the risk of adverse neonatal outcomes. Measures to reduce wildfire smoke exposure early in pregnancy could be beneficial.
Altered microbial colonization of the urogenital tract in female overactive bladder syndrome.
Koch M, Umek W, Makristathis A … +8 more , Hausmann B, Bodner-Adler B, Krögler-Halpern K, Dibon A, Loimer R, Bauer R, Heinzl F, Carlin GL
Am J Obstet Gynecol · 2026 Jun · PMID 41713718 · Publisher ↗
BACKGROUND: The discovery of a resident urinary microbiome has challenged the long-standing view of the bladder as sterile. Overactive bladder, a common and burdensome condition, has been linked to urinary dysbiosis, yet...
BACKGROUND: The discovery of a resident urinary microbiome has challenged the long-standing view of the bladder as sterile. Overactive bladder, a common and burdensome condition, has been linked to urinary dysbiosis, yet the origins of bladder colonization and its relationship to adjacent microbiomes remain unclear. OBJECTIVE: To compare the urinary microbiome profiles of women with overactive bladder to those of healthy controls, to assess intraindividual relationships between the urinary and other urogenital or mucosal microbiomes-including the vaginal, urethral, buccal sites, and stool-and to identify potential colonization pathways by analyzing microbial overlap within and between individuals. STUDY DESIGN: In a cross-sectional study, we profiled the microbiomes of 50 women with overactive bladder and 49 healthy controls across urine, urethra, vagina, oral cavity, and stool. DNA was extracted using standardized protocols and the V3 to V4 region of the 16S rRNA gene was sequenced on the Illumina MiSeq platform. Reads were processed with Divisive Amplicon Denoising Algorithm 2 and taxonomically classified using the SILVA ribosomal RNA database. Diversity metrics (alpha and beta diversity), differential abundance testing (DESeq2), and cross-site microbial overlap analyses were performed in R using established packages (phyloseq, vegan, mia, and microViz). Subgroup analyses accounted for menopausal status. RESULTS: Overactive bladder cases exhibited higher alpha diversity in urethral and vaginal samples and significantly different beta diversity across all sites compared with controls (P<.004). The urethra of overactive bladder cases contained reduced Lactobacillus but was enriched with Bacteroides, Bifidobacterium, Gardnerella, Hydrotalea, Streptococcus, and other genera. Six taxa (Alistipes, Bacteroides, Bifidobacterium, Bradyrhizobium, Hydrotalea, and Neisseria) consistently met thresholds for abundance and prevalence in urethra and were also elevated in overactive bladder urine, vagina, and oral cavity, but not stool. Intraindividual analyses showed greater urethra-urine and urethra-vagina divergence in overactive bladder than in controls, indicating disruption of the normal microbial continuum. Subgroup analyses confirmed between-group differences irrespective of menopausal status. Notably, dysbiosis in overactive bladder over-rode the premenopausal/postmenopausal contrasts observed in controls. CONCLUSION: Women with overactive bladder seem to have a distinct multisite dysbiosis, most pronounced in the urogenital tract, characterized by the loss of Lactobacillus and enrichment of selected taxa across urethra, urine, vagina, and oral cavity. The observed microbial overlap across urogenital sites, compared with stool, is consistent with predominant urogenital microbial relatedness in this cross-sectional cohort. These findings provide insight into microbiome alterations in overactive bladder and highlight the need for longitudinal studies to clarify mechanisms and evaluate potential microbiome-targeted strategies. Given the cross-sectional design, these findings describe associations and cannot establish causality or the directionality of microbial transmission between compartments.
Pelvic floor symptoms 1 year postpartum following forceps and vacuum deliveries: impact of levator ani muscle avulsion.
Grindheim S, Siafarikas F, Volløyhaug I … +2 more , Kessler J, Baghestan E
Am J Obstet Gynecol · 2026 Jun · PMID 41707898 · Publisher ↗
BACKGROUND: Pelvic floor symptoms, such as vaginal bulge and stress urinary incontinence, are closely linked to vaginal delivery, especially assisted vaginal delivery. In addition, levator ani muscle avulsion, which may...
BACKGROUND: Pelvic floor symptoms, such as vaginal bulge and stress urinary incontinence, are closely linked to vaginal delivery, especially assisted vaginal delivery. In addition, levator ani muscle avulsion, which may occur during vaginal delivery, increases the risk of pelvic floor dysfunction. However, the isolated effect of forceps or vacuum delivery in women with and without avulsion remains unclear. OBJECTIVE: This study aimed to determine whether the presence of vaginal bulge symptoms and urinary incontinence 1 year after delivery differed between different vaginal delivery modes, accounting for levator ani muscle avulsion. In addition, this study aimed to assess the overall presence and bother of pelvic floor dysfunction across different delivery modes. STUDY DESIGN: This was a cross-sectional analysis of the Bergen Birth Study, a prospective observational cohort study comparing maternal and neonatal outcomes after forceps, vacuum, and spontaneous vaginal deliveries. Primiparous women with a singleton vaginal delivery at term between June 2021 and April 2023 were eligible. Exposure was defined as the delivery mode (spontaneous vaginal, vacuum, or forceps delivery). The women later underwent a transperineal ultrasound examination to assess levator ani muscle avulsion and answered the Pelvic Floor Distress Inventory-20 for grading of pelvic floor symptoms 9 to 12 months after delivery. The primary outcomes were the presence of vaginal bulge symptoms, stress urinary incontinence, and urge urinary incontinence on the Pelvic Floor Distress Inventory-20 questionnaire, with the degree of bother graded as "somewhat" or higher. Multiple logistic regression analysis was performed to compare the odds of vaginal bulge symptoms, stress urinary incontinence, and urge urinary incontinence between different modes of delivery. Age, body mass index, and self-reported prepregnancy urinary dysfunction were adjusted for as potential confounders. Nonparametric tests were used to compare the Pelvic Floor Distress Inventory-20 sum score between different delivery modes. RESULTS: In this study, 699 women were available for analysis, 238 had forceps delivery, 238 had vacuum delivery, and 223 had spontaneous vaginal delivery. Moreover, 142 of 699 women (20.3%) had levator ani muscle avulsion. Vaginal bulge symptoms were present in 10 (4.5%), 19 (8.0%), and 37 (15.6%) women after spontaneous, vacuum-assisted, and forceps-assisted deliveries, respectively. Women who underwent forceps delivery had an adjusted odds ratio of 3.21 (95% confidence interval, 1.56-7.14) of reporting bulge symptoms 1 year after delivery compared with those who underwent spontaneous delivery and an adjusted odds ratio of 1.87 (95% confidence interval, 1.02-3.49) compared with those who underwent vacuum delivery. In contrast, vacuum delivery was not associated with bulge symptoms compared with spontaneous delivery (adjusted odds ratio, 1.74 [95% confidence interval, 0.80-4.02]). In the subgroup analysis of women with intact levator ani muscle, the difference between forceps delivery and vacuum delivery was not significant (adjusted odds ratio, 1.59 [95% confidence interval, 0.74-3.47]). No association was found between mode of delivery and stress or urge urinary incontinence. Levator ani muscle avulsion was associated with more bulge symptoms (adjusted odds ratio, 3.58 [95% confidence interval, 2.06-6.18]) and urge urinary incontinence (adjusted odds ratio, 2.00 [95% confidence interval, 1.11-3.51]). The median Pelvic Floor Distress Inventory-20 score was statistically higher in the forceps delivery group than in the vacuum delivery and spontaneous vaginal delivery groups (25.0 in the forceps delivery group vs 18.2 in the vacuum delivery group [P=.03] and 25.0 in the forceps delivery group vs 16.7 in the spontaneous vaginal delivery group [P=.02]). CONCLUSION: Forceps delivery increased the odds of vaginal bulge symptoms 1 year after delivery compared with both vacuum and spontaneous vaginal deliveries. In women with no levator ani muscle avulsion, no difference was observed between the instruments. A higher Pelvic Floor Distress Inventory-20 score indicates greater symptom burden after forceps delivery, which seems to be mediated by the presence of levator ani muscle avulsion.
Endometrial pathology and surgical extent in ovarian adult granulosa cell tumor: associations with stage and survival.
Karstensen S, Brink GJ, Jochumsen K … +5 more , Groeneweg JW, Gort EH, Witteveen PO, Lauszus F, Zweemer RP
Am J Obstet Gynecol · 2026 Jun · PMID 41707897 · Publisher ↗
BACKGROUND: Adult granulosa cell tumor is a rare ovarian cancer with less aggressive behavior than epithelial ovarian cancer. However, recurrence occurs in up to 30% of patients and is challenging to manage, as treatment...
BACKGROUND: Adult granulosa cell tumor is a rare ovarian cancer with less aggressive behavior than epithelial ovarian cancer. However, recurrence occurs in up to 30% of patients and is challenging to manage, as treatment options are limited. Additionally, adult granulosa cell tumor has been linked to synchronous endometrial pathology, including endometrial hyperplasia and cancer, but the impact of these abnormalities on surgical decision-making and survival outcomes remains unclear. OBJECTIVE: To evaluate how coexisting endometrial abnormalities influence surgical management and overall survival, and to examine the association between surgical extent (conservative vs complete staging) and recurrence in patients with adult granulosa cell tumor. STUDY DESIGN: This retrospective cohort study included all patients diagnosed with histologically confirmed ovarian adult granulosa cell tumor in Denmark between January 2007 and December 2021. Analyses were first conducted in the comprehensive nationwide Danish cohort, and results were subsequently compared in a combined analysis including data from a Dutch adult granulosa cell tumor cohort (January 2000-December 2021). Surgical procedures were categorized as complete staging (including hysterectomy, bilateral salpingo-oophorectomy, omental and peritoneal biopsies, and peritoneal washings) or less extensive surgery with clinical staging. Abnormal uterine bleeding and endometrial pathology were identified, and their associations with surgical extent and International Federation of Gynecology and Obstetrics stage were assessed. Progression-free survival was compared with surgical extent and International Federation of Gynecology and Obstetrics stage. RESULTS: A total of 252 Danish and 195 Dutch patients (n=447) were included, with median follow-up times of 7.2 and 3.2 years, and recurrence rates of 18% and 42%, respectively. In the Danish cohort, abnormal uterine bleeding and endometrial hyperplasia were associated with receiving less extensive surgery (odds ratio=0.35, 95% confidence interval: 0.18-0.66 and odds ratio=0.39, 95% confidence interval: 0.19-0.76). Furthermore, abnormal uterine bleeding, endometrial hyperplasia, and endometrial cancer were each associated with lower International Federation of Gynecology and Obstetrics stage at diagnosis of adult granulosa cell tumor (odds ratio=0.32, 95% confidence interval: 0.15-0.64; odds ratio=0.28, 95% confidence interval: 0.12-0.6; and odds ratio=0.16, 95% confidence interval: 0.01-0.94, respectively). In the Danish cohort, overall survival was not affected by endometrial cancer (hazard ratio=0.8, 95% confidence interval: 0.21-3.16). No difference in progression-free survival was observed between patients undergoing complete staging and those managed conservatively (hazard ratio=1.37, 95% confidence interval: 0.65-2.88). International Federation of Gynecology and Obstetrics stage IC (hazard ratio=9.4, 95% confidence interval: 4.0-22.29) and stage II-III (hazard ratio=8.4, 95% confidence interval: 2.9-24.17) had higher rates of recurrences compared with those with International Federation of Gynecology and Obstetrics stage IA or IB. Analyses of the combined Danish and Dutch cohorts demonstrated estimates consistent with those observed in the Danish cohort. CONCLUSION: The presence of abnormal uterine bleeding, endometrial hyperplasia, and endometrial cancer was associated lower International Federation of Gynecology and Obstetrics stage, suggesting that these factors facilitate earlier detection of adult granulosa cell tumor without adversely affecting overall survival. Complete surgical staging is not associated with improved progression-free survival in patients with adult granulosa cell tumor. Higher International Federation of Gynecology and Obstetrics stage (IC or higher) was, as expected, associated with an increased rate of recurrence compared to stage IA and IB.
Combined impact of first-trimester risk and aspirin adherence on preterm preeclampsia prevention.
Rolnik DL, Tan MY, Syngelaki A … +4 more , Wright D, Poon LC, Nicolaides KH, ASPRE and SPREE Collaborators
Am J Obstet Gynecol · 2026 Jun · PMID 41707896 · Publisher ↗
BACKGROUND: Aspirin prevents preterm preeclampsia in high-risk pregnancies, but the extent to which its effectiveness depends on adherence and baseline risk remains uncertain. OBJECTIVE: To evaluate how first-trimester p...
BACKGROUND: Aspirin prevents preterm preeclampsia in high-risk pregnancies, but the extent to which its effectiveness depends on adherence and baseline risk remains uncertain. OBJECTIVE: To evaluate how first-trimester preeclampsia risk and aspirin adherence jointly influence aspirin's preventive effect, and to assess the potential benefits and harms of targeted versus universal prophylaxis. STUDY DESIGN: We combined data from the Aspirin for Evidence-based Preeclampsia Prevention and the Screening Program for Preeclampsia cohorts, including singleton pregnancies delivering at ≥24 weeks. All pregnancies were screened for preterm preeclampsia at 11 to 13 weeks using the Fetal Medicine Foundation competing risks model, which combines maternal characteristics, mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor. Aspirin adherence and baseline risk distributions were modeled using Monte Carlo simulations to estimate relative risk, absolute risk reduction, and number needed to treat under 4 adherence scenarios: full (100%), trial-based (intention-to-treat), 50%, and variable adherence positively correlated with predicted risk (ρ=0.4). Decision-curve analysis assessed net benefit across risk thresholds. RESULTS: Simulations informed by 51,024 pregnancies indicated that aspirin's preventive effect varied substantially with adherence. In fixed-adherence scenarios, the strongest effect occurred with full adherence (relative risk 0.25, 95% confidence interval 0.09-0.66) and the weakest with 50% adherence (relative risk 0.70, 95% confidence interval 0.58-0.98). Under variable adherence, relative risk decreased nonlinearly with baseline risk, approaching the per-protocol effect in high-risk women but near null in low-risk women. Absolute risk reduction and number needed to treat were highly dependent on predicted risk: at 1 in 50 to 1 in 100 risks, number needed to treat ranged from 73 to 146 with high adherence and 161 to 321 with 50% adherence, whereas at lower risks, numbers needed to treat exceeded several thousand even with high adherence. Decision-curve analysis indicated that targeted prophylaxis using the Fetal Medicine Foundation model provided greater net benefit than universal treatment, primarily by avoiding unnecessary interventions. CONCLUSION: Aspirin is highly effective for preventing preterm preeclampsia in women at increased risk, but its effect depends on predicted risk and adherence. The absolute benefit of treatment is negligible in low-risk populations. A targeted screen-and-treat strategy using the Fetal Medicine Foundation model maximizes clinical benefit while minimizing unnecessary treatment.
Survival outcomes after inadvertent surgery in low-risk early-stage cervical cancer.
Agusti N, Viveros-Carreño D, Wu CF … +8 more , Iniesta MD, Kanbergs A, Wilke RN, Bercow A, Barajas K, Pareja R, Melamed A, Rauh-Hain JA
Am J Obstet Gynecol · 2026 Jun · PMID 41707895 · Publisher ↗
BACKGROUND: Recent randomized de-escalation trials have shown that planned simple hysterectomy with lymph node assessment provides outcomes comparable to radical hysterectomy in selected patients with early-stage cervica...
BACKGROUND: Recent randomized de-escalation trials have shown that planned simple hysterectomy with lymph node assessment provides outcomes comparable to radical hysterectomy in selected patients with early-stage cervical cancer (tumors ≤2 cm, limited stromal invasion). However, whether these favorable outcomes extend to patients who undergo inadvertent simple hysterectomy-performed without oncologic surgical planning due to diagnostic or treatment pathway failures-remains unknown. OBJECTIVE: To evaluate whether patients with early-stage cervical cancer (tumors ≤2 cm) who underwent inadvertent surgery have similar overall survival compared with those treated with planned oncologic surgery. We also assessed whether salvage adjuvant therapy in this setting shows a survival benefit over observation. STUDY DESIGN: This cohort study used data from the U.S. National Cancer Database (2010-2020) to identify patients with early-stage cervical cancer (≤2 cm) who underwent either planned oncologic surgery or inadvertent surgery (simple hysterectomy without nodal staging), including women with an inadvertent diagnosis or those inadequately treated for previously known in situ or microinvasive disease. Missing data were handled through multiple imputations. Inverse probability of treatment weighting balanced covariates across groups. Overall survival was analyzed using inverse probability of treatment weighting-adjusted Kaplan-Meier curves and Cox proportional hazards models. Subgroup analyses assessed effect modification. Inverse probability of treatment weighting was reapplied within the inadvertent surgery cohort to compare overall survival by salvage adjuvant therapy receipt. RESULTS: Among 5608 eligible patients, 688 (12.3%) underwent inadvertent surgery, including 258 with an inadvertent diagnosis and 430 with a known diagnosis but inadequate surgical treatment, while 4920 (87.7%) received planned oncologic surgery. After inverse probability of treatment weighting adjustment, patients in the inadvertent surgery cohort had significantly lower 5-year overall survival (91.5% vs 96.2%; HR, 1.89; 95% CI, 1.42 to 2.52; P<.001). Adjuvant (chemo) radiotherapy was more common after inadvertent surgery (29.1% vs 11.3%, P=0.035). Among these patients, salvage adjuvant (chemo) radiotherapy did not significantly improve overall survival when compared with observation (HR, 1.33; 95% CI, 0.59-3.00; P=.5). CONCLUSION: In patients with low-risk, early-stage cervical cancer, inadvertent surgery was associated with a survival disadvantage. Salvage adjuvant (chemo) radiotherapy failed to overcome this disadvantage, underscoring the importance of appropriate oncologic surgical planning and referral.
Risk of ovarian cancer in women with a pathogenic or likely pathogenic variant in NBN: a systematic review and meta-analysis.
Ganesan S, Mansour L, Dibden A … +14 more , Sideris M, Malan A, Oxley S, Kalra A, Sia J, Wei X, Deshmukh P, Mohamed H, Morgan RD, Flaum N, Brentnall A, Fierheller CT, Evans DG, Manchanda R
Am J Obstet Gynecol · 2026 Feb · PMID 41707894 · Publisher ↗
OBJECTIVE: NBN is a putative ovarian cancer susceptibility gene. The association between a pathogenic variant in NBN and ovarian cancer is not well established. We aimed to estimate the ovarian cancer risk in unselected...
OBJECTIVE: NBN is a putative ovarian cancer susceptibility gene. The association between a pathogenic variant in NBN and ovarian cancer is not well established. We aimed to estimate the ovarian cancer risk in unselected women with an NBN pathogenic variant. DATA SOURCES: PubMed and Embase searched from inception to January 2026. ELIGIBILITY CRITERIA: Population: Women diagnosed with ovarian cancer undergoing germline sequencing of NBN (intervention). STUDY APPRAISAL AND SYNTHESIS METHODS: We followed a prospective protocol as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42024567791). The number of NBN pathogenic variants in ovarian cancer cases in included studies was pooled and an estimated odds calculated. This was compared to the odds of an NBN loss-of-function variant in Genome Aggregation Database v4.1 controls of matched ethnicities to obtain the odds ratio of ovarian cancer with an NBN pathogenic variant. We performed prespecified subgroup analyses for high-grade serous carcinoma and non-high-grade serous carcinoma, and those with a family history of ovarian cancer. RESULTS: Searches yielded 9025 studies; 57 studies (n=40,537) were included in our initial analysis: 36 in majority White cohorts (n=33,822) and 21 in non-White cohorts (n=6715). In the White cohorts, the odds ratio of ovarian cancer with an NBN pathogenic variant was 1.68 (95% confidence interval, 1.37-2.07; P<.001), and the derived relative risk and lifetime risk of ovarian cancer 1.66% and 3.32%, respectively. For the most common pathogenic variant c.657_661del, the odds ratio was 2.69 (95% confidence interval, 1.58-4.57; P<.001), and the relative risk and lifetime risk of ovarian cancer 2.60% and 5.2%, respectively. The odds ratio of high-grade serous carcinoma and non-high-grade serous carcinoma is 1.58 (95% confidence interval, 1.02-2.45; P=.039) and 2.43 (95% confidence interval, 1.56-3.81; P<.001), respectively. Data in non-White cohorts and in ovarian cancer cases with family history were insufficient for any meaningful inference. CONCLUSION: There is a clear association between an NBN pathogenic variant and ovarian cancer in the White population, and this may be stronger with non-high-grade serous carcinoma compared to high-grade serous carcinoma. Further data are required to confirm the association with family history or establish any association in the non-White population. NBN pathogenic variants could be combined with other nongenetic and genetic (polygenic risk score) ovarian cancer risk factors using complex ovarian cancer risk-prediction models going forward, to identify several NBN-positive women at an ovarian cancer risk level for offering surgical prevention.
Severe maternal morbidity is associated with increased risk of cerebral palsy in offspring.
Ahmed AM, Driollet B, Buajitti E … +3 more , Hutcheon JA, Rosella L, Yang S
Am J Obstet Gynecol · 2026 Jun · PMID 41707893 · Publisher ↗
BACKGROUND: Severe maternal morbidity has been linked to maternal mortality and several perinatal complications, but the evidence on associations with children's neurodevelopmental disorders is still unclear. OBJECTIVE:...
BACKGROUND: Severe maternal morbidity has been linked to maternal mortality and several perinatal complications, but the evidence on associations with children's neurodevelopmental disorders is still unclear. OBJECTIVE: To assess associations between severe maternal morbidity and cerebral palsy in children, overall and by major severe maternal morbidity subtypes. STUDY DESIGN: Longitudinal cohort study of all live births in the province of Ontario, Canada, between 2003 and 2019 followed up through 2020 (n=2,136,816), under a single-payer healthcare system. Severe maternal morbidity (n=41,396) was identified from inpatient or emergency department diagnoses during the index pregnancy or postpartum (20 weeks gestation to 42 days postpartum) based on validated algorithms according to diagnostic and procedure codes. Severe maternal morbidity was categorized into severe hypertensive disorders of pregnancy (severe preeclampsia, Hemolysis, Elevated Liver enzymes, and Low Platelets syndrome, and eclampsia combined), severe hemorrhage (eg, antepartum or postpartum hemorrhage with coagulation defect, red cell transfusion, procedures to the uterus, or hysterectomy), sepsis (puerperal sepsis or septicemia during labor), and other severe maternal morbidities (eg, admission to intensive care, shock). Cerebral palsy in offspring was defined as a single inpatient or 2 or more outpatient diagnoses at least 2 weeks apart between birth and the end of follow-up (age, 1-17 years). Associations were estimated using Poisson regression models. RESULTS: Of 2,136,816 children included in this study (mean [standard deviation] gestational age, 38.9 [1.8] weeks; 1,074,548 males [51.3%]), 41,396 (2.0%) were exposed to severe maternal morbidity. In a median follow-up of 9.5 years (interquartile range, 5.2-13.7), 5352 children were diagnosed with cerebral palsy (0.3%), of which 272 cerebral palsy cases (0.7%) were exposed to severe maternal morbidity. The average annual cerebral palsy incidence rate was 7.5 per 10,000 child-years in those exposed to severe maternal morbidity and 2.5 per 10,000 in those unexposed. Children of mothers with severe maternal morbidity had an increased risk of cerebral palsy (rate ratio, 2.71; 95% confidence interval, 2.39-3.06) after adjusting for maternal sociodemographic and clinical characteristics. All severe maternal morbidity subtypes considered were associated with increased risks of cerebral palsy, with the strongest associations observed for severe hypertension disorders (adjusted rate ratio, 3.29 [2.44-4.33]). Other severe maternal morbidity subtypes also showed similarly increased risks (adjusted rate ratio for sepsis, 2.45 [1.86, 3.15]), severe hemorrhage 2.44 (1.89, 3.09), and other severe maternal morbidity subtypes (2.81 [2.30-3.39]). CONCLUSION: In this population-based study of more than 2 million births, severe maternal morbidity was associated with an increased risk of cerebral palsy. This risk was observed across major severe morbidity subtypes, including hypertensive disorders, hemorrhage, and sepsis. These findings highlight the potential benefits of optimizing maternal health and illustrate potential long-term adverse consequences of severe maternal morbidity in offspring. Children of mothers who experience severe or life-threatening events during the perinatal period may benefit from enhanced surveillance for early cerebral palsy symptoms.
Identification of preterm growth-restricted fetuses requiring delivery within 7 days from the TRUFFLE studies.
Dall'Asta A, Stampalija T, Wolf H … +1 more , Lees C
Am J Obstet Gynecol · 2026 Jul · PMID 41698520 · Publisher ↗
Abstract loading — click title to view on PubMed.
Azithromycin in preterm premature rupture of membranes: population pharmacokinetics and dose optimization.
Boelig RC, Lam K, Soni V … +5 more , Rochani A, Kaushal G, Hoffman M, Roman A, Kraft WK
Am J Obstet Gynecol · 2026 Mar · PMID 41692622 · Publisher ↗
BACKGROUND: Various empirically selected azithromycin dosing regimens are used as part of an antibiotic regimen to prolong latency in the setting of preterm premature rupture of membranes with limited prospective clinica...
BACKGROUND: Various empirically selected azithromycin dosing regimens are used as part of an antibiotic regimen to prolong latency in the setting of preterm premature rupture of membranes with limited prospective clinical or pharmacologic data to guide dose selection. Azithromycin clears from plasma quickly to concentrate in tissue, thus dosing is based on optimal local concentrations rather than plasma concentration which is the focus of the current study. OBJECTIVE: Compare pharmacokinetic parameters of 1 g once vs 500 mg daily dosing of azithromycin in the setting of preterm premature rupture of membranes and simulate various dosing regimens to identify the optimal regimen that maintains amniotic fluid concentration of azithromycin over the minimum inhibitory concentration of common genitourinary pathogens associated with intraamniotic infection or inflammation. STUDY DESIGN: This is a prospective study of singleton gestations with preterm premature rupture of membranes who received either 1 g once or 500 mg daily x 7 days of azithromycin. Maternal plasma samples were collected predose, 1 to 4 and 12 to 24 hours postdose, and every 24 hours thereafter. Participants in the 500 mg once daily group had plasma samples collected prior to their next dose. Amniotic fluid samples were collected opportunistically in a noninvasive manner by extracting amniotic fluid from sanitary pads. Population pharmacokinetic analysis was performed with Monolix version 2024R1. Because azithromycin efficacy is both time and concentration dependent, various parameters were compared including concentration at 168 hours, area under the curve over time, and percentage of time above the minimum inhibitory concentration of common genitourinary pathogens. Finally, multiple oral dosing regimens were simulated to estimate amniotic fluid exposure over a 7-day period. Data are presented as median and interquartile range. RESULTS: Eighteen participants with 101 plasma and 223 amniotic fluid samples were included in the analysis. A two-compartment model with first-order absorption best described the plasma data. In examining the amniotic fluid data, only vaginal progesterone supplementation in the pregnancy was associated with decreased distribution into amniotic fluid, no other covariate impacted the model. Azithromycin exposure in the first 24 hours was greater with 1 g once (area under the amniotic fluid curve from time 0-24 hours/minimum inhibitory concentration 27.84 [9.01, 71.77] for 1 g once vs 13.84 [4.52, 36.44] for 500 mg daily, P<0.01). Azithromycin concentration by day 7 (27.46 [10.42, 97.85] vs 5.92 [2.07, 21.86] ng/ml, P<0.01) as well as time over minimum inhibitory concentration of common genitourinary pathogens, even at the lowest desired concentration of >20 ng/ml (86.14 [27.87, 98.23] vs 64.66 [0, 99.28] hrs, P<0.01) were greater with daily dosing compared to 1 g once. Simulated dosing regimens suggest that a loading dose followed by daily dosing (1 g once then 500 mg daily for 6 days) or alternate day dosing (2 g once, 1 g days 2 and 4) most rapidly and consistently maintain amniotic azithromycin concentration>60 ng/ml over a 7-day period. CONCLUSION: Administration of 500-mg azithromycin daily x 7 days is superior to 1 g once at maintaining amniotic fluid azithromycin concentrations over the minimum inhibitory concentration of common genitourinary pathogens. The optimal simulated dosing regimen is a loading dose followed by daily dosing or alternate day dosing. Our findings can inform current clinical care and dose selection in future clinical trials.
Ampicillin-gentamicin versus ampicillin alone for prolonged prelabor rupture of membranes at term in group B streptococcus-negative patients: a randomized controlled trial.
Abu Shqara R, Glikman D, Goldinfeld G … +5 more , Hassan D, Orabi A, Ganem N, Lowenstein L, Frank Wolf M
Am J Obstet Gynecol · 2026 Jun · PMID 41692621 · Publisher ↗
BACKGROUND: Prolonged prelabor rupture of membranes at term increases the risk of maternal and neonatal infections, yet the optimal prophylactic antibiotic regimen in patients with confirmed negative group B Streptococcu...
BACKGROUND: Prolonged prelabor rupture of membranes at term increases the risk of maternal and neonatal infections, yet the optimal prophylactic antibiotic regimen in patients with confirmed negative group B Streptococcus colonization remains unclear. OBJECTIVE: We compared maternal and neonatal outcomes between 2 prophylactic antibiotic regimens, ampicillin plus gentamicin vs ampicillin alone, in patients with term prelabor rupture of membranes and confirmed negative group B Streptococcus colonization. STUDY DESIGN: This single-center, randomized controlled trial was conducted at a tertiary university-affiliated hospital between November 2022 and July 2025. Eligible participants were women with singleton term pregnancies, prelabor rupture of membranes ≥18 hours, and negative group B Streptococcus colonization. Patients were randomized 1:1 to receive intravenous ampicillin (2 g every 6 hours) plus gentamicin (5 mg/kg every 24 hours) or ampicillin alone, initiated 18 hours after prelabor rupture of membranes. The co-primary outcomes were the incidences of clinical chorioamnionitis and endometritis. Secondary outcomes included intrapartum fever, postpartum maternal infections, postpartum stay ≥5 days, and neonatal morbidity. Chorioamniotic cultures were obtained postpartum. Analyses were performed on an intention-to-treat basis. RESULTS: A total of 207 women were randomized (103 to ampicillin-gentamicin; 104 to ampicillin alone).Clinical chorioamnionitis occurred less frequently in the ampicillin-gentamicin group than in the ampicillin-alone group (1.9% vs 10.6%; P=.019; number needed to treat, 11.5; 95% confidence interval, 7-45). The endometritis rates were similar between the groups. Postpartum infectious morbidity was also lower in the combined-treatment group (1.9% vs 9.6%; P=.033), as was the rate of postpartum hospitalization ≥5 days (3.9% vs 13.5%; P=.024). In the ampicillin-gentamicin group, admission to the neonatal intensive care unit due to suspected early-onset sepsis was lower (2.9% vs 8.7%, P=.031) and positive chorioamniotic cultures were less frequent (20.9% vs 36.7%; P=.029). The prevalence of Enterobacteriaceae spp. was lower (12.1% vs 25.6%; P=.033). CONCLUSION: Among patients with confirmed negative group B Streptococcus colonization and with prolonged term prelabor rupture of membranes, clinical chorioamnionitis and postpartum maternal infectious morbidity were lower following prophylactic administration of ampicillin plus gentamicin compared to ampicillin monotherapy. Broader Gram-negative coverage may improve maternal outcomes and warrants further evaluation.
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