Am. J. Obstet. Gynecol. [JOURNAL]
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200 papers
The role of misclassification in progression of cervical intraepithelial neoplasia grade 2 during active surveillance: results from a historical cohort.
Brønd M, Christensen T, Randrup TH … +6 more , Tarpø CL, Sand C, Stoler M, Jenkins D, Bønløkke S, Hammer A
Am J Obstet Gynecol · 2026 Apr · PMID 42061781 · Publisher ↗
BACKGROUND: Many countries have recently implemented active surveillance for cervical intraepithelial neoplasia grade 2 as an option in younger women due to high regression rates and because excisional treatment is assoc...
BACKGROUND: Many countries have recently implemented active surveillance for cervical intraepithelial neoplasia grade 2 as an option in younger women due to high regression rates and because excisional treatment is associated with an increased risk of preterm birth. However, the known low reproducibility of the cervical intraepithelial neoplasia grade 2 diagnosis poses a major challenge for active surveillance, suggesting that the observed risk of progression in prior studies may be due to initial misclassification of the cervical intraepithelial neoplasia grade 2 diagnosis. OBJECTIVE: This study aimed to assess the association between expert-verified histological diagnoses of cervical biopsies in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2 and the subsequent risk of cervical intraepithelial neoplasia grade 3 or worse. STUDY DESIGN: We conducted a historical cohort study on women undergoing active surveillance for cervical intraepithelial neoplasia grade 2, diagnosed at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank and were eligible for inclusion if they were aged 23 to 40 years at the time of cervical intraepithelial neoplasia grade 2 diagnosis. Women with a prior history of cervical intraepithelial neoplasia grade 2 or worse, loop electrosurgical excision procedure, or hysterectomy were excluded. Three expert pathologists independently graded cervical lesions by reviewing hematoxylin and eosin and p16-stained tissue slides from the time of cervical intraepithelial neoplasia grade 2 diagnosis. Women were followed for 28 months, from the date of the cervical intraepithelial neoplasia grade 2 diagnosis until a record of progression, loop electrosurgical excision procedure, hysterectomy, or end of follow-up, whichever occurred first. Using modified Poisson regression analysis, we estimated the crude and adjusted relative risks of cervical intraepithelial neoplasia grade 3 or worse, including corresponding 95% confidence intervals. We adjusted for age, index cytology, and human papillomavirus genotype as potential confounders. RESULTS: A total of 437 women were included with a median age of 27 years. Upon expert review, 56 (12.8%) were upgraded to cervical intraepithelial neoplasia grade 3, 261 (59.7%) had cervical intraepithelial neoplasia grade 2 confirmed, and 120 (27.5%) were downgraded to cervical intraepithelial neoplasia grade 1/normal. Overall, 173 (39.6%) women had a subsequent record of cervical intraepithelial neoplasia grade 3 or worse, ranging from 22.5% in women with expert cervical intraepithelial neoplasia grade 1/normal, to 42.2% in women with expert cervical intraepithelial neoplasia grade 2, and 64.3% in women with expert cervical intraepithelial neoplasia grade 3. Thus, women with an expert-verified cervical intraepithelial neoplasia grade 3 diagnosis were more likely to have a subsequent record of cervical intraepithelial neoplasia grade 3 or worse during follow-up (adjusted relative risk, 1.37 [1.07; 1.75]) compared to those who had expert cervical intraepithelial neoplasia grade 2. This association remained significant in stratified analyses for women aged 31 to 40 years (adjusted relative risk, 1.85 [1.25; 2.76]), in women with high-grade index cytology (adjusted relative risk, 1.43 [1.04; 1.97]), and women with a nonhuman papillomavirus16 lesion (adjusted relative risk, 1.66 [1.09; 2.52]). The risk of cervical intraepithelial neoplasia grade 3 or worse remained high for women presenting with a high-grade cytology or human papillomavirus 16 positivity at baseline, irrespective of expert diagnosis. CONCLUSION: Our findings demonstrate substantial interobserver variability in the diagnosis of community-detected cervical intraepithelial neoplasia grade 2, with nearly half of the cases being reclassified upon expert review. This underscores the heterogeneity of this diagnosis and the importance of accurate diagnosis to minimize both undertreatment and overtreatment. These results highlight the need for individualized, risk-based management strategies for cervical intraepithelial neoplasia grade 2 that integrate virological and cytological factors rather than relying solely on histopathology.
Late-onset diagnosis of gestational diabetes after normal mid-pregnancy screening in women with large for gestational age or polyhydramnios: a systematic review and meta-analysis.
Dominsky O, Berkovitz-Shperling R, Rosenberg-Fridman M … +3 more , Gabbai D, Ram S, Yogev Y
Am J Obstet Gynecol · 2026 Apr · PMID 42055184 · Publisher ↗
OBJECTIVE: To determine the detection rate of late-onset gestational diabetes mellitus and associated perinatal outcomes in women with normal mid-pregnancy glucose screening who undergo repeat oral glucose tolerance test...
OBJECTIVE: To determine the detection rate of late-onset gestational diabetes mellitus and associated perinatal outcomes in women with normal mid-pregnancy glucose screening who undergo repeat oral glucose tolerance test due to suspected large-for-gestational-age fetuses or polyhydramnios. DATA SOURCES: We systematically searched PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library for studies published from January 2010 to November 2024. STUDY ELIGIBILITY CRITERIA: We included cohort studies reporting late gestational diabetes mellitus detection rates in women with documented normal mid-pregnancy glucose testing (negative glucose challenge test or normal 75 g oral glucose tolerance test at 24-28 weeks) who underwent repeat oral glucose tolerance test after 28 weeks due to sonographic findings of suspected large for gestational age or polyhydramnios. We excluded studies of women with preexisting diabetes, those lacking documented normal mid-pregnancy screening, and those examining routine late testing without specific clinical indication. STUDY APPRAISAL AND SYNTHESIS METHODS: Study quality was assessed using the Newcastle-Ottawa Scale. Pooled detection rates with 95% confidence intervals were calculated using random-effects meta-analysis. Subgroup analyses were performed by clinical indication, timing of testing, initial screening method (2-step vs 1-step), and maternal body mass index. Perinatal outcomes were compared using pooled odds ratios calculated with the Mantel-Haenszel method. RESULTS: Six cohort studies including 2166 women met inclusion criteria. The pooled detection rate was 15.0% (95% confidence interval, 9.9%-21.0%; I=91%). Detection rates varied significantly by indication: suspected large for gestational age 20.8% (95% confidence interval, 17.4%-24.6%) vs isolated polyhydramnios 4.8% (95% confidence interval, 2.0%-10.8%). Women with late-onset gestational diabetes mellitus had significantly higher rates of neonatal hypoglycemia (odds ratio, 1.82; 95% confidence interval, 1.18-2.81), overall cesarean delivery (odds ratio, 2.00; 95% confidence interval, 1.47-2.72), elective cesarean for large for gestational age/macrosomia (odds ratio, 3.37; 95% confidence interval, 2.01-5.64), emergent cesarean (odds ratio, 1.64; 95% confidence interval, 1.05-2.57), and induction of labor (odds ratio, 2.27; 95% confidence interval, 1.32-3.89). Macrosomia by birthweight and large for gestational age at delivery were not significantly elevated. CONCLUSION: Late oral glucose tolerance test detects gestational diabetes mellitus in approximately one in 6 women with normal mid-pregnancy screening who develop large for gestational age or polyhydramnios. Late-onset gestational diabetes mellitus is associated with significantly increased neonatal hypoglycemia and cesarean delivery, with the largest effect for elective cesarean for suspected large for gestational age/macrosomia. These findings may inform clinical decision-making regarding repeat glucose testing in the third trimester.
Levonorgestrel intrauterine system versus hysteroscopic niche resection: addressing concerns on study design and interpretation (reply to letter to the editor).
Zhang J, Zhu Q, Yan L
Am J Obstet Gynecol · 2026 Apr · PMID 42055183 · Publisher ↗
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Is it niche healing or just amenorrhea? Reinterpreting the superiority of the levonorgestrel intrauterine system (letter to the editor).
Lee KY, Chiang YC, Sheu BC
Am J Obstet Gynecol · 2026 Apr · PMID 42044710 · Publisher ↗
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Evaluation of weight change during ovarian stimulation treatment.
Elder S, Flannagan K, Romanski P … +2 more , Zalles L, Roeca C
Am J Obstet Gynecol · 2026 Apr · PMID 42035819 · Publisher ↗
BACKGROUND: The number of women undergoing ovarian stimulation for either in vitro fertilization or planned oocyte cryopreservation for conception or fertility preservation has remarkably increased over the past decade....
BACKGROUND: The number of women undergoing ovarian stimulation for either in vitro fertilization or planned oocyte cryopreservation for conception or fertility preservation has remarkably increased over the past decade. Prior to undergoing ovarian stimulation, patients are typically counseled about risks, including medication reactions, surgical risks, and anticipated number of oocytes from each cycle based on ovarian reserve testing. One possible side effect that is a common concern among patients is what amount of weight change might be expected during the treatment cycle. However, there are very limited data on how much weight can change during modern ovarian stimulation treatment cycles. OBJECTIVE: To determine the mean weight change for patients undergoing ovarian stimulation and to evaluate whether this differed in patients diagnosed with ovarian hyperstimulation syndrome and/or those undergoing multiple cycles. STUDY DESIGN: Retrospective cohort study of 22,106 antagonist ovarian stimulation cycles with weight collected prior to stimulation and on the day of retrieval (n=8332) or postretrieval (n=13,774) from January 1, 2017 to December 31, 2023. Main outcome was mean weight fluctuation (kg) from baseline weight during ovarian stimulation. P values were obtained from linear regression models fitted with generalized estimating equations. RESULTS: Mean weight gain for the entire cohort was 0.64±1.64 kg, ranging from 2.3 to 6.8 kg. Smaller initial body mass index and higher oocytes retrieved were associated with greater weight gain. Weight gain among patients diagnosed with ovarian hyperstimulation was 47% higher than patients who did not develop ovarian hyperstimulation syndrome (0.94 kg vs 0.64 kg), but this difference was not statistically significant (P=.08). There was no difference in time of return to baseline weight in patients with ovarian hyperstimulation syndrome vs those without ovarian hyperstimulation syndrome after retrieval. There was no difference in return to baseline weight in those with higher number of oocytes retrieved (≥10) vs those with lower number of oocytes retrieved (<10). For patients who underwent multiple cycles, there was no difference in the weight gained in each subsequent cycle compared to the first cycle. CONCLUSION: Our study is the first large cohort to report weight changes during antagonist ovarian stimulation cycles, which was on average modest and temporary. Patients of low body mass index, recipients of dual trigger, and ≥10 oocytes retrieved exhibited higher weight gain.
Early pregnancy oxylipin markers of inflammation and oxidative stress are associated with small-for-gestational-age birth and specific phenotypes of fetal growth restriction.
Ferguson KK, Welch BM, Stevens DR … +7 more , Bommarito PA, Milne GL, Meeker JD, Edin ML, Zeldin DC, Cantonwine DE, McElrath TF
Am J Obstet Gynecol · 2026 Apr · PMID 42035818 · Full text
BACKGROUND: Fetal growth restriction places the fetus at risk for stillbirth, perinatal mortality, and severe morbidity, yet the disease remains difficult to diagnose, predict, and treat. Homeostasis of inflammation and...
BACKGROUND: Fetal growth restriction places the fetus at risk for stillbirth, perinatal mortality, and severe morbidity, yet the disease remains difficult to diagnose, predict, and treat. Homeostasis of inflammation and oxidative stress is critical to the establishment of a healthy pregnancy, and biomarkers of these processes could contribute to these goals. Oxylipins are derived from polyunsaturated fatty acids and act as key mediators of this homeostasis and thus may be promising tools for understanding the etiology of fetal growth restriction and possible therapeutic targets. OBJECTIVE: Examine the association between early-pregnancy oxylipin biomarkers of inflammation and oxidative stress and small-for-gestational-age anfd large-for-gestational-age birth as well as ultrasound-based phenotypes of fetal growth restriction. STUDY DESIGN: In a case-cohort study of small-for-gestational-age and large-for-gestational-age births (N=901), we measured 24 oxylipins in plasma and urine collected at ∼10 weeks' gestation. We examined associations between oxylipins and small-for-gestational-age (n=248) and large-for-gestational-age birth (n=241) as our primary endpoints. As a secondary approach, we explored associations between oxylipins and phenotypes of small-for-gestational-age and large-for-gestational-age births that were characterized based on longitudinal fetal growth measures. RESULTS: A primary urinary metabolite of the proinflammatory thromboxane-A was associated with small-for-gestational-age birth (odds ratio, 1.43; 95% confidence interval, 1.20-1.72). In secondary analyses, the thromboxane metabolite was most strongly associated with a phenotype of late-pregnancy growth restriction. Additionally, the urinary isoprostanes were associated with increased odds of an early-pregnancy growth restriction phenotype. For example, a 5-series isoprostane was associated with higher odds (odds ratio, 2.22; 95% confidence interval, 1.34-3.69) of early-pregnancy growth restriction compared to appropriate for gestational age. For large-for-gestational-age births, associations were not significant after false discovery rate correction. CONCLUSION: Associations between circulating oxylipins in early pregnancy and small-for-gestational-age birth may reflect disturbances in the balance of inflammation and oxidative stress, processes that are critical to the establishment of pregnancy and healthy fetal growth. These associations differed based on small-for-gestational-age phenotype, that is, early-pregnancy vs late-pregnancy growth restriction, providing possible insights into distinct etiologies. Oxylipins may be useful targets for early prediction and/or intervention on fetal growth restriction.
Fetal Medicine Foundation preeclampsia screening at population level (reply to letter to the editor).
Mans-Gallart N, Axelsson D, Lilliecreutz C
Am J Obstet Gynecol · 2026 Apr · PMID 42031354 · Publisher ↗
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Grandmaternal smoking during pregnancy and grandoffspring stillbirth risk: clarifying residual confounding (reply to letter to the editor).
Villamor E, Miglin AK, Cnattingius S
Am J Obstet Gynecol · 2026 Apr · PMID 42031353 · Publisher ↗
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The Fetal Medicine Foundation preeclampsia screening at the population level (letter to the editor).
Bujold E, Rolnik DL, Nicolaides KH
Am J Obstet Gynecol · 2026 Apr · PMID 42031352 · Publisher ↗
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Beyond direct exposure: rethinking multigenerational risk transmission in stillbirth (letter to the editor).
Küçük Z
Am J Obstet Gynecol · 2026 Apr · PMID 42031351 · Publisher ↗
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Vacuum-induced tamponade using urological catheters for postpartum hemorrhage.
Ranieri E, Kalimeris S, Ochsenbein N … +1 more , Haslinger C
Am J Obstet Gynecol · 2026 Apr · PMID 42025716 · Publisher ↗
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A randomized controlled trial comparing remote blood pressure monitoring with office-based blood pressure monitoring for women at high risk of preeclampsia.
Rajkumar T, Hennessy A, Shanmugalingam R … +7 more , You W, Canty A, Pickup W, Potter D, Butten K, Varnfield M, Makris A
Am J Obstet Gynecol · 2026 Apr · PMID 42025715 · Publisher ↗
BACKGROUND: Women at a high risk of developing preeclampsia are recommended to have additional blood pressure surveillance, but frequent outpatient attendances are demanding for patients and the healthcare system. It is...
BACKGROUND: Women at a high risk of developing preeclampsia are recommended to have additional blood pressure surveillance, but frequent outpatient attendances are demanding for patients and the healthcare system. It is unclear whether remote blood pressure monitoring can replace conventional office-based monitoring and improve healthcare utilization without increasing the signal for harm. OBJECTIVE: To evaluate the effects of substituting clinic blood pressure monitoring with remote blood pressure monitoring on fetal and maternal outcomes, and healthcare utilization, in pregnant women at a high risk of developing preeclampsia. STUDY DESIGN: Unblinded, noninferiority, multicenter randomized controlled trial, with recruitment between July 2022 and February 2024 from 3 metropolitan hospitals in Australia. Participants were pregnant women at a high risk of developing preeclampsia based on clinical risk factors or combined first-trimester screening tests, who are routinely referred to a specialist hypertension service for extra blood pressure surveillance, in addition to standard antenatal care. Women randomized to usual care attended these specialist hypertension clinics in-person, with frequency of appointments dictated by clinical need. Women randomized to remote blood pressure monitoring, in addition to receiving routine antenatal care, measured their own blood pressure using an automated blood pressure machine with data transmitted via a smartphone application for specialist review. The primary outcome was a perinatal composite of adverse events of at least one of perinatal loss, high-level neonatal care for more than 48 hours, or a small-for-gestational age baby (<10th centile for fetal weight). The primary outcome was assessed in the intention-to-treat population. The trial was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12620001049965p). RESULTS: 270 women were included in the final analysis (intervention n=132, usual care n=138; mean age 34 years, 60.4% from a self-reported non-Caucasian ethnic group). There was no difference in the primary outcome (hazard ratio, 1.0; 95% confidence interval, 0.57-1.76; P=.99). There was also no difference in secondary fetal and maternal outcomes. The intervention group had less total antenatal attendances (median [interquartile range], 14 [10-17]) compared to usual care (16 [13-20]; P<.01) and less planned outpatient appointments (median [interquartile range], 10 [8-12] vs 13 [10-16]; P<.01), without an associated increase in unscheduled hospital presentations. Women undertaking remote blood pressure monitoring were less likely to be admitted to hospital for any cause (hazard ratio, 0.54; 95% confidence interval, 0.30-0.97; P=.04) and specifically for hypertension (hazard ratio, 0.41; 95% confidence interval, 0.19-0.88; P=.02). More antihypertensive prescriptions filled per patient in the intervention arm compared to usual care (median [interquartile range], 5 [3-9] vs 3 [2-5]; P<.01). CONCLUSION: Compared to usual care, remote blood pressure monitoring reduced antenatal outpatient appointments and the likelihood of inpatient admissions, without increasing adverse fetal and maternal outcomes. Women undertaking remote monitoring were also more likely to fill antihypertensive medication scripts.
Reducing the long-term impact of cesarean scar defects: a focus on prevention.
Walker SP, Bartels HC, Jurkovic D … +1 more , Jauniaux E
Am J Obstet Gynecol · 2026 Apr · PMID 42019565 · Publisher ↗
As cesarean delivery rates continue to rise worldwide, the long-term obstetric and gynecological complications associated with cesarean scar defects are becoming increasingly prevalent. These include cesarean scar ectopi...
As cesarean delivery rates continue to rise worldwide, the long-term obstetric and gynecological complications associated with cesarean scar defects are becoming increasingly prevalent. These include cesarean scar ectopic pregnancies, placenta previa accreta, secondary subfertility, chronic pelvic pain, and intermenstrual bleeding. The objective of this review is to evaluate how the optimization of the hysterotomy location in relation to myometrial thickness and uterine vascularity, together with an appropriate uterine closure technique, could reduce the long-term impact of cesarean scar defects. A wide range of closure techniques has been described, with substantial heterogeneity in study design, outcome measures, and follow-up intervals, limiting definitive conclusions. Emerging evidence suggests that unlocked, interrupted, purse-string, and endometrium-free sutures, along with the use of monofilament or barbed sutures, may reduce cesarean scar formation and thus the risks of scar placentation in subsequent pregnancies. These approaches may promote better healing by reducing tissue compression and ischemia, unlike continuous, locked, endometrium-inclusive sutures, which may impair perfusion. Increasing attention to endometrium-free closure and precise anatomical realignment highlights the importance of meticulous surgical technique in contemporary obstetrics. Surgical repair of cesarean scar defects improves outcomes in patients with chronic gynecological symptoms and subfertility. However, evidence supporting its role in preventing obstetric complications in subsequent pregnancies remains limited, in part because such complications are rare. Moreover, cesarean scar defect repair requires removing the scar tissue and reconstruction using healthy myometrium, which may theoretically increase the risk of dehiscence or uterine rupture in subsequent pregnancies. A key knowledge gap in much of the existing literature is its focus on imaging-defined cesarean scar defects rather than on patient-centered long-term gynecological symptoms. Well-designed, multiarm studies that incorporate standardized postpartum imaging to characterize uterine remodeling over time are essential for identifying best practices. While resource-intensive, advancing this field could improve long-term patient outcomes and reduce healthcare costs.
The role of language barriers in medical professional liability cases in obstetrics and gynecology.
Schaffer AC, Einbinder JS, Zawi T … +1 more , Sato L
Am J Obstet Gynecol · 2026 Apr · PMID 42002250 · Publisher ↗
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Improving communication in pregnancy: a neurodivergent-responsive approach.
Grünebaum A, Coverdale JH, Gordon MR … +4 more , Mcleod-Sordjan R, Pollet SL, Kirby A, Chervenak FA
Am J Obstet Gynecol · 2026 Apr · PMID 42002249 · Publisher ↗
Communication, informed consent, and patient cooperation in obstetrics often occur under significant time pressure, particularly on labor and delivery units where delays can directly affect maternal and fetal outcomes. S...
Communication, informed consent, and patient cooperation in obstetrics often occur under significant time pressure, particularly on labor and delivery units where delays can directly affect maternal and fetal outcomes. Standard communication approaches assume uniform information processing, which may not apply to patients with neurodivergence, including autism spectrum disorder, attention-deficit/hyperactivity disorder, and related sensory processing differences. These differences are common, frequently unrecognized in pregnant women, and can become clinically consequential during key transitions in care. This Clinical Opinion presents a neurodivergent responsive framework for obstetric practice that emphasizes early identification of communication and sensory processing differences during prenatal care and translation of these needs into actionable intrapartum strategies. The approach is grounded in qualitative evidence and established communication principles, recognizing the current absence of robust outcome-based data. Practical adaptations include the use of plain and concrete language, stepwise information delivery, written reinforcement, teach-back, advance warning before physical contact, and structured involvement of support persons. A central component is the development of a brief communication care plan, distinct from a birth preference document, designed to ensure that communication needs are visible and actionable across care transitions. These adaptations are applied across prenatal counseling, admission, intrapartum decision-making, and postpartum discharge, where failures in communication may lead to delayed consent, reduced tolerance of monitoring or procedures, and misunderstanding of discharge instructions. Because these strategies align with established patient safety principles and benefit a broad range of patients, their implementation represents an extension of standard obstetric care. This framework offers a pragmatic approach to improving communication, consent, and patient experience in contemporary obstetric practice.
Neurodevelopmental disorders following fetal reduction of triplet pregnancies: a nationwide cohort study.
Larsen ML, Kristensen SE, Rasmussen MK … +2 more , Hoei-Hansen CE, Petersen OB
Am J Obstet Gynecol · 2026 Apr · PMID 42000097 · Publisher ↗
BACKGROUND: Triplet pregnancies carry high risks of prematurity and subsequent neurodevelopmental disorders. Fetal reduction from triplets to twins improves short-term obstetric outcomes, but long-term neurodevelopmental...
BACKGROUND: Triplet pregnancies carry high risks of prematurity and subsequent neurodevelopmental disorders. Fetal reduction from triplets to twins improves short-term obstetric outcomes, but long-term neurodevelopmental outcomes among surviving children remain uncertain. OBJECTIVE: To compare the long-term risk of neurodevelopmental disorders among liveborn children from trichorionic triamniotic triplet pregnancies managed with fetal reduction from 3 to 2 fetuses vs no reduction. STUDY DESIGN: We conducted a nationwide, population-based cohort study using the Danish Fetal Medicine Database, linked to national health registries and local prenatal records. We included all trichorionic triamniotic triplet pregnancies diagnosed at the routine first-trimester scan (11-14 weeks' gestation) with estimated due dates from January 1, 2008, through December 31, 2018. Liveborn children were then followed from birth until an outcome of interest, death, emigration, or the end of the study period (December 31, 2022). The outcomes of interest were neurodevelopmental disorders, defined by diagnoses of epilepsy, cerebral palsy, or intellectual disability, combined into a primary composite outcome of any of these disorders. Cumulative incidence through age 15 years was estimated in each group, with death as a competing risk. Moreover, cause-specific hazard ratios (HRs) were estimated using multivariable Cox regression with robust variance to account for clustering within pregnancies, adjusted for maternal age, educational level, and assisted reproduction. RESULTS: Among 313 eligible trichorionic triamniotic pregnancies, 219 (70%) underwent 3-2 fetal reduction at a median gestational age of 11+6 weeks (IQR 11+5-12+1), and 87 (28%) did not. Overall, 625 liveborn children were included (399 (64%) from reduced pregnancies and 226 (36%) from nonreduced pregnancies). Over a median follow-up of 9.3 years (IQR 6.5-12.5), 34 children were diagnosed with at least one neurodevelopmental disorder (cumulative incidence at 15 years, 6.6% (95% CI 4.4%% to 9.5%)). Neurodevelopmental disorders were diagnosed in 13 children after reduction and in 21 without. Thus, the cumulative incidence of neurodevelopmental disorders by age 15 was 4.2% (95% CI 2.1-7.5) after 3-2 fetal reduction and 10.7% (95% CI 6.5%% to 16.2%) with no reduction (Gray test, P<0.001). Furthermore, fetal reduction was associated with a lower hazard of neurodevelopmental disorders (adjusted HR, 0.33 (95% CI 0.15-0.71)). For individual disorders, estimates were directionally similar but imprecise due to small numbers; for epilepsy, the adjusted HR was 0.37 (0.14-0.98) following fetal reduction. Among all pregnancies with at least one surviving child, the absolute risk of minimum one child being diagnosed with a neurodevelopmental disorder was 5.9% (12/202) following fetal reduction; however, 19,8% (17/86) without. CONCLUSION: Among liveborn children from trichorionic triamniotic triplet pregnancies, fetal reduction from 3 to 2 fetuses was associated with a substantially lower long-term risk of severe neurodevelopmental disorders compared with no reduction.
Biallelic mutations in ANAPC13 cause female infertility characterized by oocyte maturation arrest both in humans and mice.
Wang Y, Ding Z, Liu X … +10 more , Liu X, Tan H, Zheng N, Yu K, Chen B, Wang F, Cao Y, Huang L, Sang Q, Zhu F
Am J Obstet Gynecol · 2026 Apr · PMID 41997520 · Publisher ↗
BACKGROUND: Oocyte maturation arrest is an intractable clinical problem, resulting in recurrent failure of assisted reproductive treatments. The anaphase-promoting complex or cyclosome orchestrates a series of proteolyti...
BACKGROUND: Oocyte maturation arrest is an intractable clinical problem, resulting in recurrent failure of assisted reproductive treatments. The anaphase-promoting complex or cyclosome orchestrates a series of proteolytic events to ensure proper cell cycle progression of mitosis in somatic cell proliferation and meiosis during oocyte maturation. Defects in anaphase-promoting complex or cyclosome subunits, such as ANAPC8 and ANAPC12, have been demonstrated linked to oocyte maturation arrest. However, the roles of other anaphase-promoting complex or cyclosome subunits in oocyte maturation remain unclear. OBJECTIVE: This study aimed to reveal the causal relationship between ANAPC13 mutations and oocyte maturation arrest, while elucidating the pathogenic mechanism to provide a theoretical basis for clinical diagnosis and treatment. STUDY DESIGN: Patients diagnosed with oocyte maturation arrest by morphologic assessment during assisted reproductive treatments were recruited and underwent whole-exome sequencing. Mutations in ANAPC13 were identified in 3 patients and screened out as the candidate. The recurrent mutation c.6C>A was recapitulated in a knock-in mouse model (Anapc13 mice) to clarify its association with oocyte maturation arrest, with wild-type mice (Anapc13 mice) serving as controls. Further phenotyping experiments with mouse oocytes, proteomic analysis of human oocytes, and molecular experiments with cell lines and plasmids were conducted to determine the role of ANAPC13 in oocyte maturation. Anapc13 mRNA microinjection was performed as an exploratory rescue treatment. RESULTS: We identified 2 biallelic ANAPC13 mutations (NM_001242374.1: c.6C>A; p.D2E and c.71T>G; p.L24R) in 3 infertile females with oocyte maturation arrest at metaphase I. Oocytes from the Anapc13 female mice similarly displayed an extremely low proportion of mature oocytes, whether obtained after superovulation (Anapc13: 96.63% ± 3.40% vs Anapc13: 1.66% ± 3.34%, P<0.001) or in vitro maturation (Anapc13: 70.30% ± 1.10% vs Anapc13: 0.83% ± 1.66%, P<0.001). An in-depth study of oocytes demonstrated that mutant ANAPC13 disrupts the protein composition of oocytes during metaphase I-to-anaphase I transition by impairing anaphase-promoting complex or cyclosome function, without changing the spindle assembly checkpoint dynamics. Furthermore, a molecular mechanistic study revealed that anaphase-promoting complex or cyclosome dysfunction resulted from abnormal subunit interaction. Moreover, Anapc13-mutant oocytes can be partially (49.20% ± 3.60%) rescued to extrude the first polar body by microinjection of Anapc13 mRNA. CONCLUSION: Our study demonstrated the critical role of ANAPC13 in human and mouse oocyte maturation, established a causal relationship between ANAPC13 mutations and oocyte maturation arrest, and further provided preliminary evidence that microinjection may serve as a potential treatment for these patients with ANAPC13 mutations.
In women with chronic hypertension, does fetal growth restriction increase progression to maternal preeclampsia?
Magee LA, Chatzakis C, Syngelaki A … +3 more , Akolekar R, von Dadelszen P, Nicolaides KH
Am J Obstet Gynecol · 2026 Apr · PMID 41997519 · Publisher ↗
BACKGROUND: Among women with chronic hypertension, it is unclear whether uteroplacental dysfunction should be classified as indicating superimposed preeclampsia or be considered a direct complication of chronic hypertens...
BACKGROUND: Among women with chronic hypertension, it is unclear whether uteroplacental dysfunction should be classified as indicating superimposed preeclampsia or be considered a direct complication of chronic hypertension. OBJECTIVE: To evaluate whether fetal growth concerns at a routine fetal ultrasound at 35+0 to 36+6 weeks of gestation were related to progression to preeclampsia. STUDY DESIGN: We undertook a secondary analysis of a prospectively evaluated cohort of women with chronic hypertension and singleton pregnancies who underwent routine fetal ultrasound at 35-36 weeks' gestation. We compared the incidence of preeclampsia and other adverse pregnancy outcomes between cases and propensity score-matched controls; cases had an estimated fetal weight <10th percentile, with and without fetal growth restriction, defined as abnormal fetal Dopplers (uterine artery pulsatility index >95th percentile, umbilical artery pulsatility index >95th percentile, or middle cerebral artery pulsatility index <5th percentile), and controls had estimated fetal weight ≥10th percentile. Superimposed preeclampsia was defined by maternal criteria, either traditionally by the development of new-onset proteinuria at ≥20 weeks or by additional maternal criteria according to the 2019 American College of Obstetricians and Gynecologists or 2021 International Society for the Study of Hypertension in Pregnancy guidance. Covariates included in propensity score-matched were maternal race/ethnicity, mode of conception, smoking status, systemic lupus erythematosus, parity, history of preeclampsia, history of a baby with birthweight <10th percentile, maternal age, body mass index, and gestational weight gain in kilograms. Matching was conducted using a nearest-neighbor algorithm without replacement, a ratio of 1 case to 2 controls, and a caliper width of 0.2 standard deviation of the logit of the propensity score. Balance between groups after matching was assessed using standardized mean differences, with values <0.1 considered indicative of adequate balance. RESULTS: Of the 1258 included pregnancies with chronic hypertension, there were 167 (13.3%) cases (64, 38.3% of which were designated as fetal growth restriction cases with abnormal fetal Dopplers), and 1091 (86.7%) controls. Of 1258 women, 234 (18.6%) went on to develop preeclampsia. After propensity score matching analysis, there were no differences between the 167 cases and 334 propensity score-matched controls in baseline maternal or 35-36 weeks' characteristics. Cases with fetal growth restriction (vs propensity score-matched controls) more often developed preeclampsia (regardless of definition), underwent labor induction, had a cesarean delivery, and had a shorter ultrasound-to-birth interval by 1.8 weeks; they also delivered 1.7 weeks earlier and more often had babies with birthweight <10th percentile for gestational age or those admitted to the neonatal unit. There was no difference between groups in the composite neonatal outcome. Cases without fetal growth restriction (vs propensity score-matched controls) did not differ with regard to the development of preeclampsia, but they did have a shorter ultrasound-to-birth interval (by 0.8 weeks), delivered 0.7 weeks earlier, and more often had babies with birthweight <10th percentile. CONCLUSION: Our findings suggest that women with chronic hypertension who have evidence of fetal growth restriction at 35-36 weeks' gestation (but not those with only an estimated fetal weight <10th percentile) more frequently develop maternal manifestations of superimposed preeclampsia and should be considered for enhanced maternal and fetal surveillance. These findings should be replicated at earlier gestational ages.
Transcriptomic evidence of remodeling in postpartum levator ani muscle associated with maternal age and recovery time after first vaginal delivery.
Swenson CW, Pouladi N, Zabriskie HA … +5 more , Bourrant PE, Li J, Wilson LS, Drummond MJ, Lussier YA
Am J Obstet Gynecol · 2026 Apr · PMID 41997518 · Full text
BACKGROUND: Older maternal age at first vaginal delivery, defined in some studies as ≥30 years old, confers a substantial increased risk of pelvic organ prolapse. Age-related impairment of postpartum recovery of levator...
BACKGROUND: Older maternal age at first vaginal delivery, defined in some studies as ≥30 years old, confers a substantial increased risk of pelvic organ prolapse. Age-related impairment of postpartum recovery of levator ani muscles may help explain this association; yet, little is known about the biomolecular changes that occur in the levator ani after vaginal delivery, or with aging. OBJECTIVE: To evaluate the transcriptional signature of the levator ani immediately after vaginal delivery and 6 to 8 weeks postpartum among young primiparas (18-25 years) and older primiparas (≥35 years). STUDY DESIGN: This study is a prospective study in which nulliparous women were recruited in the third trimester of pregnancy. Levator ani muscle biopsies were obtained immediately after vaginal delivery and at 6 to 8 weeks postpartum. Clinical measures of pelvic floor support and levator ani muscle function were obtained at the 6 to 8-week postpartum visit. Biopsies were analyzed using RNA sequencing methods and differentially expressed genes were compared with those reported in prior studies of pelvic organ prolapse patients. We used a moderated t test (false discovery rate <5%) to identify differentially expressed genes associated with postpartum delivery, maternal age, and the interaction between the 2. Principal component analysis confirmed segregation of clinical phenotype variables based on gene expression. RESULTS: Eight women (3 young and 5 older) underwent levator ani biopsies at both time points and had sufficient tissue for analyses. A total of 58 differentially expressed genes were identified when evaluating the interaction of age and recovery interval, including TP53BP1 (upregulated), PRR12 (upregulated), ZNF316 (upregulated), and PLK3 (downregulated). Between age groups, 309 differentially expressed genes were identified, while 159 were identified between time points. Both age groups were enriched for core tissue repair and homeostatic programs. Twenty of the differentially expressed genes identified in the separate analyses of age and time were previously identified in 4 case-control studies of pelvic organ prolapse. The correlation between the transcriptomic signature (principal component 3) and the overall clinical phenotype profile (principal component 1) was significant (ρ=0.88, false discovery rate <0.05), while the correlation observed with maternal age alone was not (ρ=-0.72). CONCLUSION: In agreement with clinical evidence, the effects of maternal age on levator ani muscle recovery can be seen at the transcriptional level. Age and recovery time share similar biological processes that, when disrupted, may predispose the levator ani to altered recovery and long-term susceptibility to pelvic organ prolapse. Specifically, elevated TP53BP1 combined with reduced PLK3 suggests a pattern of disrupted p53-regulated checkpoint and elevated cellular senescence which would impair healing. Results from the principal component analysis indicate that the transcriptomic signature captures clinical features beyond chronological age alone. Together, this study suggests a mechanistic pathway whereby aged levator ani may be at an increased risk of further dysfunction and disease and opens the possibility of targeted therapies to prevent pelvic organ prolapse.
Association between hypertensive disorders of pregnancy and severe maternal morbidity.
Granger Howard ME, Campbell BA, Boghossian NS
Am J Obstet Gynecol · 2026 Apr · PMID 41997517 · Publisher ↗
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