Perslev K, Klarskov N, Bergholt T
… +1 more, Jangö H
Am J Obstet Gynecol
· 2026 May · PMID 42173186
·
Publisher ↗
BACKGROUND: Prophylactic antibiotics reduce the risk of wound complications after second-degree perineal tears and episiotomy. However, the long-term consequences of experiencing a wound complication remain poorly studie...BACKGROUND: Prophylactic antibiotics reduce the risk of wound complications after second-degree perineal tears and episiotomy. However, the long-term consequences of experiencing a wound complication remain poorly studied. OBJECTIVE: (1) To evaluate the frequency of pelvic floor symptoms after second-degree tear and episiotomy and (2) to evaluate whether women who developed a wound complication had more pelvic floor symptoms 9 to 12 months postpartum compared to women without wound complications. STUDY DESIGN: This study is a long-term follow-up of participants enrolled in the REPAIR study, a single-center, placebo-controlled, randomized trial conducted at a university hospital in Denmark. The original trial enrolled 442 women with a second-degree perineal tear or episiotomy to assess the effect of prophylactic antibiotics on wound complications. Long-term outcomes were assessed using 2 data sources: a pelvic floor questionnaire and a late postpartum follow-up clinical examination. Analyses of questionnaire-based outcomes included all women who completed the pelvic floor questionnaire regardless of attendance to the clinical examination. Analyses of outcomes from the clinical examination were restricted to women who attended the late postpartum follow-up visit. RESULTS: Of the 442 women included in the REPAIR study, 433 had information on wound healing status, of whom 51 (12%) experienced a clinically relevant complication. A total of 378 women completed the pelvic floor questionnaire and 362 attended the late postpartum follow-up. Pelvic floor symptoms were common across incontinence, prolapse, and sexual domains. Women with wound complications reported higher prevalences of symptoms, particularly related to sexual function, prolapse, and lower body image scores. This remained stable after adjustment for obstetric factors associated with wound complications. In the clinical examination, diagnostic prolapse was more frequent among women with wound complications, while anatomical prolapse and pelvic floor measurements were similar between groups. CONCLUSION: Pelvic floor symptoms were common 9 to 12 months after second-degree tears or episiotomy. Women with postpartum wound complications reported more symptoms, particularly related to sexual function, prolapse, and body image. These findings suggest that wound healing is associated with long-term pelvic floor health and support attention to prevention and follow-up.
Li J, Huang J, Zhang Z
… +5 more, Liu Y, Zhang Q, Chen H, Guo Y, Li Y
Am J Obstet Gynecol
· 2026 May · PMID 42173184
·
Publisher ↗
BACKGROUND: In vitro fertilization has transformed reproductive medicine, yet offspring conceived through in vitro fertilization display elevated risks for diverse long-term health conditions, with underlying mechanisms...BACKGROUND: In vitro fertilization has transformed reproductive medicine, yet offspring conceived through in vitro fertilization display elevated risks for diverse long-term health conditions, with underlying mechanisms unclear. Long Interspersed Nuclear Elements-1, a mobile genetic element responsive to environmental stress, represents a potential mediator. OBJECTIVE: This study aimed to test the hypothesis that in vitro fertilization procedures may act as an embryonic stressor that alters Long Interspersed Nuclear Elements-1 dynamics, potentially contributing to genomic instability associated with long-term disease susceptibility. STUDY DESIGN: Umbilical cord blood or peripheral blood from 33 in vitro fertilization and 42 naturally conceived neonates were collected for whole-genome sequencing. Total Long Interspersed Nuclear Elements-1 proportion in individual genome was counted with Bowtie2 software. De novo Long Interspersed Nuclear Elements-1 insertion and Long Interspersed Nuclear Elements-1 deletion were detected with Mobile Element Locator Tool. Three parent-matched in vitro fertilization-naturally conceived sibling pairs were included to control for genetic background. Disease association analysis was performed for genes within 500 kb of differential Long Interspersed Nuclear Elements-1 sites in The Database for Annotation, Visualization and Integrated Discovery (DAVID). Statistical analysis was performed using the R language. RESULTS: In vitro fertilization offspring demonstrate elevated global Long Interspersed Nuclear Elements-1 content compared to naturally conceived controls (P=.04). This finding was corroborated in 3 sibling pairs from identical genetic backgrounds, where in vitro fertilization-conceived children consistently exhibited higher Long Interspersed Nuclear Elements-1 levels than their naturally conceived siblings. Eleven genomic loci with differential Long Interspersed Nuclear Elements-1 insertion frequencies and 14 loci with differential Long Interspersed Nuclear Elements-1 deletion frequencies between in vitro fertilization offspring and naturally conceived controls were identified. Notably, these differential Long Interspersed Nuclear Elements-1 sites demonstrated significant enrichment near genes implicated in metabolic, cardiovascular, neuropsychiatric, and neoplastic diseases, conditions associated with in vitro fertilization conception. CONCLUSION: These findings provide preliminary evidence that in vitro fertilization conception is associated with increased Long Interspersed Nuclear Elements-1 content and altered genomic distribution of Long Interspersed Nuclear Elements-1 elements. The proximity of these differential Long Interspersed Nuclear Elements-1 sites to disease-associated genes suggests a plausible genomic mechanism linking in vitro fertilization-associated embryonic stress to elevated disease risk. This work provides valuable molecular insights that may inform the ongoing discussion about assisted reproductive technology safety and suggests that continued attention to genomic integrity in in vitro fertilization-conceived individuals would be beneficial.
Ginsberg Y, Bang S, Khatib N
… +4 more, Ross MG, Zipori Y, Weinr Z, Beloosesky R
Am J Obstet Gynecol
· 2026 May · PMID 42173182
·
Publisher ↗
BACKGROUND: Antenatal magnesium sulfate (Mg) is recommended for fetal neuroprotection in preterm birth, yet optimal dosing remains uncertain. The American College of Obstetricians and Gynecologists (ACOG), jointly with t...BACKGROUND: Antenatal magnesium sulfate (Mg) is recommended for fetal neuroprotection in preterm birth, yet optimal dosing remains uncertain. The American College of Obstetricians and Gynecologists (ACOG), jointly with the Society for Maternal-Fetal Medicine (SMFM), endorses three dosing regimens with up to sevenfold variation in cumulative dose (i.e., 4g, 10.5g, or 31.5g). Maternal-fetal inflammation has been associated with fetal brain injury and adverse neurodevelopmental outcomes. Emerging evidence suggests a dose-dependent Mg effect, where low doses support neuronal survival, while higher doses may adversely induce neuronal apoptosis and neurodegeneration. This study aimed to compare the effects of low- and high-dose maternal MgSO on fetal neuroinflammation in an established animal model of maternal inflammation. METHODS: Pregnant Sprague-Dawley rats (n = 30) on gestational day 20 received intraperitoneal injections of lipopolysaccharide (LPS, 500 μg/kg) a component of gram-negative bacterial membranes used to model intrauterine infection or saline. Dams were then randomized to receive subcutaneous treatment with saline, low-dose Mg (150 mg/kg loading dose), or a high-dose protocol (150 mg/kg loading dose followed by 15 mg/kg every 20 minutes for 2 hours before and after the injection). The primary endpoint was fetal brain pro-inflammatory cytokine expression (IL-6 and TNF-α). Fetal brains and placentas were collected and assigned to one of six treatment groups. Tissues were analyzed for inflammatory cytokines (Western blot), and maternal/fetal serum was analyzed for Mg levels and cytokine concentrations (ELISA). RESULTS: Maternal and fetal serum Mg levels were lowest in the saline control groups, increased with low-dose Mg, and were highest with high-dose Mg, confirming dose-dependent transplacental transfer. Fetal brain inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), were significantly elevated following maternal inflammation compared to saline controls (IL-6: 2.06±0.05 vs. 0.75±0.12U; TNF-α: 2.11±0.04 vs. 0.76±0.12U; P < 0.05). Both low- and high-dose Mg significantly reduced fetal brain cytokine levels to near baseline (Low Mg: IL-6 0.71±0.04U, TNF-α 0.75±0.13U; High Mg: IL-6 0.73±0.26U, TNF-α 0.74±0.33U; P < 0.05), with no significant difference between the two Mg groups. Comparable cytokine reduction was observed in placental tissue. CONCLUSION: In this experimental model, low-dose maternal Mg was as effective as a higher-dose regimen in attenuating fetal brain and placental pro-inflammatory cytokine expression following LPS-induced maternal inflammation. These findings suggest that a reduced Mg exposure, equivalent to a 4g loading dose in clinical practice, may be sufficient for fetal neuroprotection, and support the need for prospective clinical studies comparing reduced-duration Mg protocols.
Shaw CJ, Rivens I, Symonds-Tayler R
… +7 more, Townson J, Owen-Jones E, Strange H, Playle R, Giussani DA, Haar GT, Lees CC
Am J Obstet Gynecol
· 2026 May · PMID 42167394
·
Publisher ↗
BACKGROUND: Twin-twin transfusion syndrome is a complication unique to monochorionic pregnancy, where shared placental vascular connections can lead to a circulatory imbalance, resulting in preterm delivery and attendant...BACKGROUND: Twin-twin transfusion syndrome is a complication unique to monochorionic pregnancy, where shared placental vascular connections can lead to a circulatory imbalance, resulting in preterm delivery and attendant in utero or neonatal mortality. The only disease-modifying treatment is fetoscopic laser ablation of blood vessels, which has attendant risks of invasive intrauterine therapy. OBJECTIVE: In this first-in-human technical feasibility and safety study, we investigated noninvasive, ultrasound-guided high-intensity focused ultrasound to occlude placental vascular targets as identified by color Doppler. The 2 outcomes were (1) safety: number/rate of patients experiencing significant iatrogenic harm, for first 14 days after high-intensity focused ultrasound and (2) efficacy: number/rate of targeted placental vessels which appear occluded at the end of a high-intensity focused ultrasound treatment cycle, assessed using comparison of color Doppler imaging of target anastomoses prehigh-intensity focused ultrasound and posthigh-intensity focused ultrasound exposure. STUDY DESIGN: Participants with anterior placenta and early-onset twin-twin transfusion syndrome were recruited to a Phase 1a clinical trial with co-primary endpoints of safety and efficacy of vessel occlusion at 12 to 17 weeks of gestational age. RESULTS: Ten participants underwent targeted ultrasound-guided high-intensity focused ultrasound occlusion of placental blood vessels that connected the 2 circulations, verified by color Doppler imaging, in whom 27 of 30 (90%) targeted placental vessels were successfully occluded by ultrasound-guided high-intensity focused ultrasound. No treatment-related significant maternal or fetal adverse events were recorded, and 18 of 20 fetuses were alive 14 days post-treatment. Participants expressed positive attitudes toward ultrasound-guided high-intensity focused ultrasound, valuing clear and consistent communication and sufficient time to consider participation in the study. CONCLUSION: In this Phase 1 study, ultrasound-guided high-intensity focused ultrasound showed a high rate of successful occlusion of placental vascular targets and no adverse side effects were observed within 14 days of treatment in women with early-onset twin-twin transfusion. While clinical efficacy of the technique could not be formally evaluated, 5 participants required fetoscopic laser and of the pregnancies treated, 12 of 20 neonates were alive at discharge.
Vural M, Pohle-Rüffer MC, Rauh M
… +2 more, Kappelmeyer M, Köninger A
Am J Obstet Gynecol
· 2026 May · PMID 42162710
·
Publisher ↗
OBJECTIVE: To evaluate the feasibility, safety, and outcomes of a modified uterus-preserving focal excision technique for Placenta Accreta Spectrum Disorder, including placenta percreta, based on pathoanatomical defects...OBJECTIVE: To evaluate the feasibility, safety, and outcomes of a modified uterus-preserving focal excision technique for Placenta Accreta Spectrum Disorder, including placenta percreta, based on pathoanatomical defects and neovascularization rather than tissue invasiveness. STUDY DESIGN: We retrospectively reviewed 15 consecutive cases of Placenta Accreta Spectrum Disorder (International Federation of Gynecology and Obstetrics stages 2-3b) treated between 2020 and 2025 at a tertiary referral center using a standardized focal resection technique. Diagnosis was established by abdominal and transvaginal sonography. Preoperative planning included detailed patient counseling, multidisciplinary team coordination, and preparation of blood products. The surgical procedure involved meticulous bladder dissection, stepwise ligation of vessels, and targeted excision of placenta percreta areas. RESULTS: Uterus-preserving surgery was achieved in 14 of 15 patients (93%). One (7%) patient required emergency supracervical hysterectomy due to uncontrolled hemorrhage. Median blood loss was 2000 mL (interquartile range, 1500-2500 mL), and 4 patients required no transfusion. Bladder injury occurred in 6 patients (40%), all of which were managed successfully without long-term sequelae at ≥1 year of follow-up. No maternal deaths were reported. Focal resection was feasible even in emergency situations and in cases of high-grade Placenta Accreta Spectrum Disorder (up to International Federation of Gynecology and Obstetrics 3b). Histopathological confirmation and intraoperative video documentation supported the reproducibility and accuracy of the diagnosis and technique. CONCLUSION: This study reports a series of cases with focal excision of Placenta Accreta Spectrum Disorder, allowing preservation of the uterus and associated with limited maternal morbidity, which compares favorably with the commonly used cesarean hysterectomy.
Zhang E, Huang Y, Seaman SJ
… +2 more, Wright JD, Friedman AM
Am J Obstet Gynecol
· 2026 May · PMID 42134736
·
Publisher ↗
BACKGROUND: It is unknown to what extent the surgical management of endometriosis occurs in the outpatient settings and which factors are associated with ambulatory vs inpatient surgical care. OBJECTIVE: The objective of...BACKGROUND: It is unknown to what extent the surgical management of endometriosis occurs in the outpatient settings and which factors are associated with ambulatory vs inpatient surgical care. OBJECTIVE: The objective of this study was to perform a nationwide analysis comparing trends, clinical factors, disease manifestations, surgical approaches, and hospital charges between ambulatory and inpatient surgical cases for endometriosis. STUDY DESIGN: This serial cross-sectional study analyzed inpatient and ambulatory surgeries from 2016 to 2022 with a primary diagnosis of endometriosis. Inpatient surgeries were analyzed using the National Inpatient Sample, a nationally representative inpatient database. Ambulatory surgeries were analyzed using the Nationwide Ambulatory Surgery Sample, a nationally representative ambulatory surgical database. Surgical trends were analyzed using joinpoint regression and presented as the average annual percent change. Demographic and clinical characteristics associated with inpatient vs ambulatory surgery were reported. Surgical procedures, endometriosis involvement sites, and surgical complications were also compared between inpatient and ambulatory surgeries. RESULTS: A nationwide total of 70,535 weighted inpatient and 561,894 weighted ambulatory surgical encounters for endometriosis were identified between 2016 and 2022. Over the study period, inpatient surgical volume decreased by 49% from 14,080 cases in 2016 to 7110 cases in 2022 (average annual percent change, -11.5% [95% confidence interval, -14.4% to -8.7%]), whereas outpatient surgical volume increased by 17% from 73,270 cases in 2016 to 85,896 cases in 2022 (average annual percent change, 2.8% [95% confidence interval, 0.2%-5.4%]). Inpatient surgical cases were more likely to occur among patients who were older (median age, 40 vs 37 years), who had a higher Elixhauser comorbidity index, who were more likely to be enrolled in Medicaid insurance (20% vs 16%), and who lived in the lowest median income ZIP code quartile (26% vs 21%). Ovarian involvement (37% vs 26%), bowel involvement (10% vs 3%), multiorgan involvement (40% vs 30%), concurrent pelvic infection (3.0% vs 1.4%), and intraoperative complications were all more common among patients undergoing inpatient compared with ambulatory surgery. Hysterectomy with salpingo-oophorectomy was most frequent in the inpatient setting but also accounted for a large proportion of ambulatory procedures (61% vs 47%), with a significant shift of this operation from inpatient to ambulatory care over the study period. CONCLUSION: An increasing proportion of surgeries for endometriosis, including hysterectomy, is now being performed in the outpatient setting. Inpatient surgical cases are more common among medically complex patients and those with distinct socioeconomic characteristics.
Eide-Djavit B, Eggebø TM, Dalen I
… +4 more, von Brandis P, Kessler J, Tappert C, Sande RK
Am J Obstet Gynecol
· 2026 May · PMID 42107846
·
Publisher ↗
BACKGROUND: Friedman found in 1955 that most nulliparous women without epidural analgesia delivered within 2 hours in the second stage of labor. Estimating the probability of spontaneous delivery and assessing relevant p...BACKGROUND: Friedman found in 1955 that most nulliparous women without epidural analgesia delivered within 2 hours in the second stage of labor. Estimating the probability of spontaneous delivery and assessing relevant predictors in a contemporary obstetrical population is essential for clinical decision-making. OBJECTIVE: The aim of this study was to estimate the probability distribution of spontaneous delivery in occiput anterior and occiput posterior positions during the pushing phase, stratified by parity and epidural analgesia. STUDY DESIGN: The study was a retrospective cohort study at 3 Norwegian University hospitals from 2012 to 2024. Women without a uterine scar who reached the active second stage of labor and delivered a single fetus in cephalic presentation at term were eligible. The primary outcome was the estimated duration from the start of the pushing phase to spontaneous delivery. Fetal position was classified as occiput anterior or occiput posterior at time of delivery. Secondary outcomes were adverse maternal outcomes (obstetrical anal sphincter injuries and postpartum hemorrhage >1000 mL) and neonatal outcomes (5-minute Apgar score <7 and umbilical cord pH <7.0). The data were analyzed with survival methods. RESULTS: The final study population comprised 120,218 births. Among nulliparous women, there were 50,972 (94.8%) births in the occiput anterior position and 2798 (5.2%) in the occiput posterior position. Corresponding values among parous women were 63,153 (95.0%) and 3295 (5.0%), respectively. The estimated probability of spontaneous delivery within 120 minutes in nulliparous women with occiput anterior delivery was 98.4% (95% confidence interval [95% CI], 98.1-98.6) in women without epidural analgesia and 84.3% (95% CI, 83.1-85.4) in women with epidural analgesia. The benefit of pushing for >120 minutes in women without epidural analgesia was marginal, whereas an additional 30 minutes of pushing increased the probability to 90.1% (95% CI, 86.3-92.8) in women with epidural analgesia. In nulliparous women with occiput posterior deliveries, the corresponding probabilities after 120 minutes were 78.6% (95% CI, 73.4-82.8) in women without epidural analgesia and 44.9% (95% CI, 40.5-49.0) in women with epidural analgesia. Few spontaneous deliveries occurred after 120 minutes, and the benefit of pushing beyond 120 minutes for nulliparous women with a persistent occiput posterior position was low. In parous women with occiput anterior deliveries, the probability of spontaneous delivery after 60 minutes of pushing was 99.0% (95% CI, 98.9-99.1) in women without epidural analgesia and 94.5% (95% CI, 94.1-94.9) in women with epidural analgesia. Women without epidural analgesia did not benefit from pushing for >60 minutes, whereas the probability increased to 97.4% (95% CI, 97.0-97.7) after 90 minutes in women with epidural. The probabilities after 60 minutes of pushing in women with occiput posterior deliveries were 92.5% (95% CI, 91.2-93.6) and 72.9% (95% CI, 69.5-75.9), respectively, and increased to 97.4% (95% CI, 96.3-98.2) and 82.6% (95% CI, 78.3-86.1) with pushing until 90 minutes but did not increase beyond these time limits. Active pushing for >30 minutes was associated with higher rates of adverse maternal outcomes and with lower Apgar scores in all women and with higher rates of pH<7.0 in parous women. CONCLUSION: The estimated probability of a spontaneous delivery varied with parity, the use of epidural analgesia, and fetal position. The time limits of the pushing phase should be individualized accordingly.
Shrestha KS, Jensen C, Boggess K
… +2 more, Ramos GA, Battarbee AN
Am J Obstet Gynecol
· 2026 May · PMID 42105800
·
Publisher ↗
BACKGROUND: Metformin works by increasing insulin sensitivity, which may aid in the management of insulin-treated type 2 diabetes in pregnancy. However, large trials have found that adjunctive metformin did not reduce co...BACKGROUND: Metformin works by increasing insulin sensitivity, which may aid in the management of insulin-treated type 2 diabetes in pregnancy. However, large trials have found that adjunctive metformin did not reduce composite adverse neonatal outcomes in this population. OBJECTIVE: Our objective was to determine if baseline insulin requirements modified the effect of metformin on adverse neonatal and maternal outcomes. STUDY DESIGN: We performed a secondary analysis of the Medical Optimization and Management of Pregnancies with Overt Type 2 Diabetes (MOMPOD) trial, a randomized controlled trial of metformin versus placebo in insulin-treated type 2 diabetes (T2D) or diabetes diagnosed in early pregnancy. We included participants who took ≥1 dose of study drug and had baseline insulin data available. Our primary outcome was a composite of adverse neonatal outcomes, as defined by the parent trial. Secondary outcomes included cesarean delivery, maternal gestational weight gain, and change in insulin requirements during pregnancy, among others. Total daily dose (TDD) of insulin at randomization was evaluated as an effect modifier of the relationship between metformin and the primary outcome using a likelihood ratio test with p<0.10 as significant. To illustrate effect modification, we subsequently evaluated the association between metformin and outcomes among subgroups with TDD <30 units (U), >60U, and >90U using multivariable Poisson regression with robust error variance and ordinary least squares regression. RESULTS: Of the 794 participants included in the parent trial analysis, 785 (99%) met criteria for our study. The median TDD at randomization was 62U (IQR 35, 88) with 155 (20%) using <30U, 225 (29%) using 30-60U, 222 (28%) using 60-90U, 100 (13%) using 91-120U, and 83 (10%) using >120U. There was a significant interaction between metformin and TDD of insulin in relation to the primary composite adverse neonatal outcome (p=0.089). For participants with TDD of insulin <30U, adjunctive metformin was associated with a lower risk of the composite adverse neonatal outcome, compared with placebo (44% vs 55%, adjusted relative risk 0.76, 95% CI [0.59-0.98]). There were no differences in the composite adverse neonatal outcome among participants with TDD of insulin >60U or >90U. However, for participants with TDD of insulin >60U and >90U, adjunctive metformin was associated with a smaller increase in insulin requirements during pregnancy, compared with placebo (TDD >60U: mean difference -13 units, 95% CI -26 to -1; TDD>90U: mean difference -27 units, 95% CI -50 to -5). CONCLUSION: The effect of metformin on maternal and neonatal outcomes in the MOMPOD trial cohort differed by baseline insulin requirements. In pregnant women with pregestational type 2 diabetes or diabetes diagnosed early in pregnancy, adjunctive metformin was associated with a lower risk of the composite adverse neonatal outcome, preterm birth, LGA, NICU admission, and less neonatal fat mass among participants with low baseline insulin requirements, when compared with placebo. Conversely, metformin may help mitigate increases in insulin requirements during pregnancy for those with high baseline insulin requirements. Further studies are needed to confirm our findings and investigate the mechanisms underlying the differential effects of metformin based on baseline insulin requirements in pregnancy.
Leruez-Ville M, Grevent D, Bourgon N
… +9 more, Chatzakis C, Parodi M, Fourgeaud J, Veyrenche N, Bahi-Buisson N, Pichon C, Magny JF, Boddaert N, Ville Y
Am J Obstet Gynecol
· 2026 May · PMID 42092723
·
Publisher ↗
BACKGROUND: Congenital cytomegalovirus infection is the leading nongenetic cause of sensorineural hearing loss and is associated with a broad spectrum of neurodevelopmental outcomes. A possible association between congen...BACKGROUND: Congenital cytomegalovirus infection is the leading nongenetic cause of sensorineural hearing loss and is associated with a broad spectrum of neurodevelopmental outcomes. A possible association between congenital cytomegalovirus and autism spectrum disorder has been hypothesized for several decades, based on case reports and small retrospective studies. OBJECTIVE: The objective was to estimate the strength of the association between congenital cytomegalovirus and neurodevelopmental abnormalities including autism spectrum disorder, their dependence on the timing of maternal infection, and their potential neuroanatomical correlates. STUDY DESIGN: We conducted a prospective observational cohort study including children with confirmed congenital cytomegalovirus infection followed at a single tertiary referral center in France between 2001 and 2024. Maternal cytomegalovirus infections were classified and dated using centralized serological assessment. Children underwent standardized longitudinal follow-up, including audiological, neurological, behavioral, and neuroimaging evaluations, up to 48 months of age. Fetal brain magnetic resonance imaging was available for cases diagnosed antenatally. Outcomes of interest included hearing loss, neurodevelopmental impairment, and autism spectrum disorder. RESULTS: Among 642 children with confirmed congenital cytomegalovirus infection, 504 (78.5%) were exposed to a maternal primary infection with known timing. Of these, 288 (57.1%) followed first-trimester infection, 144 (28.6%) second-trimester infection, and 72 (14.3%) third-trimester infection. Long-term congenital cytomegalovirus-related sequelae, including hearing loss and neurodevelopmental impairment, were observed exclusively in children exposed to first-trimester maternal primary infection. Autism spectrum disorder was diagnosed in 11 children (1.7%), all of whom were symptomatic at birth; all cases following maternal primary infection occurred after first-trimester exposure. Compared with estimates from the general French population, prevalence in children with congenital cytomegalovirus was 4-fold higher (odds ratio, 4.25; 95% confidence interval, 1.63-21.33). In all children diagnosed with autism spectrum disorder, temporal lobe white matter abnormalities, especially in the temporal poles, were identified on postnatal magnetic resonance imaging and were present on antenatal imaging in fetuses who underwent prenatal magnetic resonance imaging. The review of all fetal magnetic resonance imagings from the prenatally diagnosed subgroup revealed that temporal lobe white matter abnormalities were present in a minority of cases and no child without temporal lobe abnormality developed autism spectrum disorder. CONCLUSION: In this large prospective cohort, adverse long-term outcomes following maternal primary infection were observed only after first-trimester exposure. Autism spectrum disorder occurred exclusively in this group and was consistently associated with temporal lobe white matter abnormalities. These findings support a time-restricted window of fetal vulnerability to cytomegalovirus-related brain injury and suggest that neuroimaging findings may contribute to prenatal and neonatal risk stratification and help inform prenatal and postnatal counseling.
BACKGROUND: Maternal iron deficiency anemia is a persistent global health challenge associated with an increased risk of adverse perinatal outcomes. A recent multicenter clinical trial found reduced rates of low-birthwei...BACKGROUND: Maternal iron deficiency anemia is a persistent global health challenge associated with an increased risk of adverse perinatal outcomes. A recent multicenter clinical trial found reduced rates of low-birthweight infants in mothers treated initially (early second trimester of pregnancy) with intravenous ferric carboxymaltose infusion compared with those treated with oral iron supplement. The secondary findings included improved hematologic indices 4 weeks after treatment and reduced rate of stillbirth with single-dose intravenous iron infusion. OBJECTIVE: This study aimed to determine whether initial response to iron therapy is associated with the risk of stillbirth and other adverse perinatal outcomes in pregnant patients with singleton pregnancies and moderate iron deficiency anemia. STUDY DESIGN: This was a secondary analysis of a multicenter randomized controlled trial in India that compared single-dose intravenous iron infusion with oral iron supplement for the initial management of moderate iron deficiency anemia (hemoglobin level of 7.0-9.9g/dL) at 14 to 17 weeks of gestation. The primary outcome for this secondary analysis was stillbirth. The secondary outcomes were early preterm birth at <34 weeks of gestation and small-for-gestational-age infants (<10th percentile). The predictors of interest were maternal hemoglobin, ferritin, and transferrin saturation levels, measured at 20 to 24 weeks of gestation. In addition, longitudinal hematologic and iron indices throughout pregnancy and their association with outcomes were assessed. The relative risk of each outcome based on posttreatment hemoglobin, ferritin, and transferrin saturation levels was assessed using Poisson regression, adjusting for maternal age, body mass index, parity, treatment modality, baseline hemoglobin level, and study site. A 2-sided alpha level of .05 was used for all analyses. Given that most nutrients exhibit U-shaped or threshold risk curves, we also fit models, allowing for a quadratic function for the relationship between hematologic parameters at all times and the risk of each event. RESULTS: A total of 4252 participants were included in this analysis, of whom 1421, 1424, and 1407 received intravenous ferric derisomaltose infusion, intravenous ferric carboxymaltose infusion, and oral iron supplement, respectively. In evaluating the linear relationship, each unit increase in hemoglobin response at 20 to 24 weeks of gestation was significantly associated with a reduced risk of stillbirth (relative risk, 0.74 [95% confidence interval, 0.56-0.98]). In evaluating the quadratic relationship, a significantly progressive increase in the risk of stillbirth (P<.0001) and early preterm birth at <34 weeks of gestation (P=.01) was determined with decreasing Hb <10.5. Although a significant quadratic relationship was identified between small-for-gestational-age infant and hemoglobin level (P=.008), the relative risk of small for gestational age and lower hemoglobin level was not statistically significant. CONCLUSION: Inadequate improvement in hemoglobin level at 20 to 24 weeks of gestation after iron therapy in pregnancies complicated by moderate iron deficiency anemia was associated with an increased risk of stillbirth and early preterm birth. Our findings highlight the potential importance of early screening and treatment of maternal anemia. Given the association between persistent anemia at 20 to 24 weeks of gestation and adverse outcomes, prospective trials should focus on whether early pregnancy, or even preconception, improvement in hemoglobin level is an effective intervention to prevent adverse perinatal outcomes, such as stillbirth and early preterm birth.
OBJECTIVE: To evaluate the association between periconceptional exposure to glucagon-like peptide-1 receptor agonists and fetal, pregnancy-related, obstetric, and delivery outcomes. DATA SOURCES: PubMed, Embase, and Web...OBJECTIVE: To evaluate the association between periconceptional exposure to glucagon-like peptide-1 receptor agonists and fetal, pregnancy-related, obstetric, and delivery outcomes. DATA SOURCES: PubMed, Embase, and Web of Science were searched from database inception through November 2025 to identify relevant studies. STUDY ELIGIBILITY CRITERIA: Cohort and observational studies comparing human pregnancies with periconceptional glucagon-like peptide-1 receptor agonist exposure to unexposed comparator groups were included. Case reports and case series were also included for narrative synthesis. Studies involving nonhuman animals were excluded from the primary meta-analysis but referenced in the background synthesis. STUDY APPRAISAL AND SYNTHESIS METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Random-effects meta-analyses were performed using odds ratios or mean differences with 95% confidence intervals. Heterogeneity was assessed using the I-squared statistic. Sensitivity analyses were conducted using comparator-specific control groups to account for maternal disease. RESULTS: Twenty-two studies, comprising 49,395 human pregnancies with periconceptional glucagon-like peptide-1 receptor agonist exposure, were included. Meta-analysis of 10 cohort and observational studies showed no statistically significant association between exposure and major congenital malformations, cardiac malformations, gestational age and weight, preterm delivery, live birth, spontaneous pregnancy loss, hypertensive disorders of pregnancy, or cesarean delivery. A small but statistically significant association with renal malformations was detected (odds ratio, 1.23; 95% confidence interval, 1.09-1.39); however, this was largely driven by a single large cohort with substantial baseline imbalances. Heterogeneity was moderate to high for several outcomes. Narrative synthesis of case reports and series identified no consistent pattern of adverse outcomes. CONCLUSION: Current human evidence does not demonstrate a consistent association between periconceptional glucagon-like peptide-1 receptor agonist exposure and major adverse fetal, pregnancy, obstetric, or labor outcomes. The observed risk for renal malformations should be interpreted with caution as it likely reflects residual confounding by maternal disease severity. These findings provide cautious reassurance following inadvertent exposure but do not support routine use during pregnancy, highlighting the need for robust studies with long-term follow-up.