Carbone IF, Kamel R, Gigli FMP
… +8 more, Romagnoli V, Yousef SS, Abdella RM, Ibrahim IF, Iurlaro E, Parodi V, Esposito G, Ferrazzi EM
J Matern Fetal Neonatal Med
· 2026 Dec · PMID 42036405
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OBJECTIVE: To evaluate maternal and fetal determinants of unplanned operative delivery in large-for-gestational-age fetuses. DESIGN: Prospective, non-randomized, multicenter study. SETTING: Hospital-based. POPULATION: Si...OBJECTIVE: To evaluate maternal and fetal determinants of unplanned operative delivery in large-for-gestational-age fetuses. DESIGN: Prospective, non-randomized, multicenter study. SETTING: Hospital-based. POPULATION: Singleton pregnancy, not affected by gestational diabetes, with an ultrasound diagnosis of large fetuses, but not within the ACOG criteria for macrosomia. METHODS: Per protocol, early induction of labor was scheduled when estimated fetal weight (EFW) and/or abdominal circumference (AC) >95 or when EFW and/or AC between 80 and 95 with unfavorable maternal indices, height < 155 cm and/or subpubic angle (SPA) < 100°. Expectant management was planned in cases without these maternal unfavorable indices. MAIN OUTCOME MEASURES: Unplanned operative delivery (vacuum-assisted or cesarean section). The proportion of unplanned operative delivery was compared between groups managed per protocol. The proportion of unplanned operative delivery of recruited women who were managed in violation of protocol was also analyzed and compared with that of those managed per protocol. The EFW to subpubic angle ratio (EFW/SPA) and the head circumference to subpubic angle ratios (HC/SPA) were evaluated by ROC analysis, and adjusted relative risks (RRs) for unplanned operative delivery were estimated using Poisson regression on the entire study population. RESULTS: Of the 223 patients included, 127 were managed per protocol (102 early induction, 25 expectant), while 96 were managed at clinicians discretion. Unplanned operative deliveries were more frequent among women induced per protocol than among those managed expectantly (52.9% vs. 12.0%; < 0.01). We also found that women who should have been induced per protocol, but underwent expectant management had a similar higher proportion of unplanned operative deliveries (59.6%). In multivariable analysis, EFW/SPA ratio ≥34.78 (RR = 1.71) and HC/SPA ratio ≥3.30 (RR = 1.39) - the optimal ROC-derived cutoffs - were associated with a higher risk of unplanned operative delivery. CONCLUSIONS: Unplanned operative delivery was associated with unfavorable fetal biometry/maternal-subpubic-angle ratios, which may help identify women at higher risk, providing a promising additional support for individualized delivery management.
Carbone IF, Gigli FMP, Romagnoli V
… +5 more, Gallicola B, Useli Bacchitta R, Parisi F, Esposito G, Cetin I
J Matern Fetal Neonatal Med
· 2026 Dec · PMID 42036403
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INTRODUCTION: Assisted vaginal birth (AVB) refers to the obstetric procedure commonly performed during the second stage of labor, aimed to expedite delivery after evaluating alternatives options of cesarean birth or expe...INTRODUCTION: Assisted vaginal birth (AVB) refers to the obstetric procedure commonly performed during the second stage of labor, aimed to expedite delivery after evaluating alternatives options of cesarean birth or expectant management. OBJECTIVE: To evaluate the risk factors for AVB and to compare perinatal factors and outcomes of vacuum extraction when applied to the mid/low cavity the perineum. STUDY DESIGN: Retrospective observational monocentric study conducted on the cohort of women with singleton pregnancies who delivered vaginally in 2023 at the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan. Multivariable logistic regression was used to identify factors independently associated with AVB. A secondary analysis compared maternal and neonatal outcomes between perineal and mid/low cavity vacuum applications. RESULTS: A total of 3455 vaginal births were included: 3090 spontaneous vaginal births and 365 AVB. After adjusting for all factors considered, maternal age (OR 1.04, 95% CI: 1.01-1.07), mode of conception (OR 1.58, 95% CI: 1.07-2.33), epidural analgesia (OR 6.25, 95% CI: 3.05-12.80), gestational age (OR 1.48, 95% CI: 1.31-1.67), and newborn male sex (OR 1.35, 95% CI: 1.06-1.73) were positively associated with AVB, whereas parity (OR 0.20, 95% CI: 0.14-0.29) was inversely associated. Compared to perineal applications, mid/low pelvic applications were associated with greater blood loss ( < 0.01), higher episiotomy rate (95.5% vs 88.2%, = 0.03), and increased ultrasound use (62.4% vs 23.5%, < 0.01). CONCLUSIONS: In this real-world cohort, AVB was mainly associated with well-established factors, confirming previous evidence. Mid/low cavity applications showed greater maternal morbidity than perineal applications, underscoring the importance of careful case selection and procedural planning.
Braga A, Araujo Júnior E, Werner H
… +11 more, Paiva G, Chagas M, Soares JP, Barboza É, Callado GY, Sun SY, Laurent JS, Amim Junior J, Rezende-Filho J, Berkowitz RS, Horowitz NS
J Matern Fetal Neonatal Med
· 2026 Dec · PMID 42036400
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BACKGROUND: Twin molar pregnancy (TMP) represents one of the most complex and high-risk entities within the spectrum of gestational trophoblastic disease. Characterized by the coexistence of a potentially viable fetus an...BACKGROUND: Twin molar pregnancy (TMP) represents one of the most complex and high-risk entities within the spectrum of gestational trophoblastic disease. Characterized by the coexistence of a potentially viable fetus and molar trophoblastic tissue, TMP poses significant diagnostic, obstetric, and oncologic challenges. OBJECTIVE: To provide a structured diagnostic and management framework for TMP, integrating clinical, biochemical, imaging, genetic, and pathological findings to support early recognition and informed clinical decision-making. METHODS: This narrative review synthesizes contemporary evidence from cohort studies and diagnostic guidelines, focusing on the clinical presentation, imaging characteristics, genetic evaluation, and outcomes associated with TMP. RESULTS: Early diagnosis is frequently hindered by overlapping features with partial hydatidiform mole and placental mesenchymal dysplasia, particularly as placental components merge with advancing gestation. Common clinical manifestations include vaginal bleeding, uterine enlargement disproportionate to gestational age, and systemic complications related to markedly elevated human chorionic gonadotropin levels, such as early-onset preeclampsia, hyperthyroidism, and theca lutein cysts. Ultrasonography remains the primary diagnostic modality, while magnetic resonance imaging provides additional value in complex cases. Genetic testing, including invasive fetal karyotyping and post-pregnancy molecular analysis, is essential for accurate classification and counseling. Management should be individualized, prioritizing maternal safety while recognizing the potential for favorable perinatal outcomes in selected cases. Current evidence suggests that continuation of pregnancy does not independently increase the risk of postmolar gestational trophoblastic neoplasia, which appears to be primarily driven by intrinsic trophoblastic biology. CONCLUSION: TMP remains a rare but clinically challenging condition requiring a high index of suspicion and a multidisciplinary approach. Early diagnosis, individualized management, and rigorous postmolar surveillance are essential to optimize maternal and perinatal outcomes.
Gutiérrez Alfonso LN, Bertolotto AM, Vargas Y
… +2 more, Granados C, Olaya-C M
J Matern Fetal Neonatal Med
· 2026 Dec · PMID 42036398
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OBJECTIVE: To characterize the pathological features of placentas from neonates with perinatal asphyxia and to compare them with those from neonates without asphyxia. METHODS: An observational case-control study was cond...OBJECTIVE: To characterize the pathological features of placentas from neonates with perinatal asphyxia and to compare them with those from neonates without asphyxia. METHODS: An observational case-control study was conducted, including a group of patients diagnosed with perinatal asphyxia and a comparison group without this condition. SETTING: A high-complexity neonatal unit. PARTICIPANTS: 83 neonates were included: 28 with perinatal asphyxia and 55 without asphyxia, all of whom had placental examination available. RESULTS: Umbilical cord abnormalities were significantly associated with perinatal asphyxia, particularly cervical entanglements-both tight and loose, and increased cord diameter; also, when comparing the presence of at least one anatomical abnormality of the umbilical cord. Among maternal complications, gestational diabetes showed a significant association; among fetal complications, major malformations and non-reassuring fetal status were significantly associated. CONCLUSION: Intrauterine factors are closely associated with perinatal asphyxia. We highlight the role of placental pathology-particularly anatomical alterations of the umbilical cord-in elucidating its underlying mechanisms. The evidence generated may contribute to enhancing early detection and informing the development of preventive strategies.
J Matern Fetal Neonatal Med
· 2026 Dec · PMID 42014324
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OBJECTIVE: To determine whether birth weight influences retinal development in children born preterm, we analyzed the thickness of the retinal nerve fiber layer (RNFL), fovea centralis, and choroid. METHODS: Participants...OBJECTIVE: To determine whether birth weight influences retinal development in children born preterm, we analyzed the thickness of the retinal nerve fiber layer (RNFL), fovea centralis, and choroid. METHODS: Participants born preterm were categorized as extremely low birth weight (ELBW, <1000 g), very low birth weight (VLBW, 1000-1500 g), and low birth weight (LBW, 1500-2500 g). RNFL thickness, fovea centralis thickness (macular center), and subfoveal choroidal thickness were measured using optical coherence tomography. Linear regression was used to evaluate associations between OCT parameters and birth weight. RESULTS: Of the 54 preterm-born children included, 34 were diagnosed with retinopathy of prematurity (ROP) (stage 1: 7; stage 2: 19; stage 3: 7), with 5 receiving laser treatment. Inferior and global mean RNFL thicknesses were lower in the ROP cohort than in the non-ROP cohort ( = 0.0012 and = 0.003, respectively). Fovea centralis thickness and choroidal thickness did not differ between the ROP and non-ROP cohorts ( = 0.16 and = 0.97, respectively). In adjusted regression models, birth weight was associated with inferior RNFL thickness (β 0.09; 95% CI 0.01-0.11; = 0.001), nasal RNFL thickness (β 0.06; 95% CI 0.01-0.10; = 0.001), and fovea centralis thickness (β 0.04; 95% CI 0.01-0.08; < 0.001). CONCLUSION: In children born preterm, lower birth weight is associated with thinner inferior and nasal RNFL. OCT-derived RNFL measurements may help inform long-term monitoring of retinal development in preterm-born children, particularly those with low birth weight and/or ROP history.
Kontopoulos E, Quintero LF, Quintero Kontopoulos A
… +3 more, Chmait RH, Steffensen T, Quintero R
J Matern Fetal Neonatal Med
· 2026 Dec · PMID 42010266
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OBJECTIVE: The CCAM (CPAM) volume ratio (CVR), an ultrasound index to predict hydrops or neonatal demise in fetuses affected with CPAM, is presumed to be independent of gestational age. A CVR of 1.6 has been proposed as...OBJECTIVE: The CCAM (CPAM) volume ratio (CVR), an ultrasound index to predict hydrops or neonatal demise in fetuses affected with CPAM, is presumed to be independent of gestational age. A CVR of 1.6 has been proposed as predictive of hydrops. The purpose of our study was to assess the fundamental mathematical concept of the CVR. STUDY DESIGN: Using published formulas, the right fetal lung volume was used as a surrogate of a theoretical CPAM involving the entire right lung. The head circumference was estimated using the previously published formula by Chitty et al. The ratio of right lung volume by the head circumference was assumed to be equivalent to the CVR, or CVR'. The relative increase in right lung volume necessary to produce a CVR' of 1.6 cm was assessed along gestational age. RESULTS: The CVR' increased with gestational age. The relative increase in lung volume necessary to produce a CVR' of 1.6 cm was smaller with advancing gestational age. CONCLUSIONS: The CVR increases with gestational age because it results from the division of two parameters of different dimensions, with a resulting quadratic equation. Thus, the size of the CPAM necessary to produce a CVR greater than 1.6 cm decreases with gestational age. Therefore, the use of a fixed value of the CVR, e.g. 1.6 cm, to predict fetal hydrops or neonatal demise, is inappropriate. A different ultrasound index that is independent of gestational age should be used in the counseling of patients with CPAM.
Zhang F, Wang H, Zhou Y
… +3 more, Gan Y, Tan X, Fan B
J Matern Fetal Neonatal Med
· 2026 Dec · PMID 42010240
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BACKGROUND: A Mendelian randomization (MR) study was carried out to investigate the causal relationship between sleep apnea syndrome (SAS) and the risk of obstetric disorders occurring, including postpartum depression, a...BACKGROUND: A Mendelian randomization (MR) study was carried out to investigate the causal relationship between sleep apnea syndrome (SAS) and the risk of obstetric disorders occurring, including postpartum depression, and to evaluate the potential mediating effect of an individual's body mass index (BMI). METHODS: Using genome-wide association study (GWAS) summary-level data, we utilized two-sample univariate MR analysis to examine the causal association between SAS and seven obstetric disorders. The causal effects of SAS on the selected disorders were primarily estimated using inverse variance weighting (IVW), supplemented by MR-Egger regression, and weighted median, simple mode, and weighted mode methods. Two-step MR mediation analysis was next conducted to assess whether the BMI mediated the identified associations. Sensitivity analyses were also performed, including MR-PRESSO, the MR-Egger intercept test, and leave-one-out analysis. Potential reverse causation was also evaluated using the MR-Steiger directionality test. RESULTS: Univariate MR analysis showed there was a significant positive causal association between SAS and the risk of postpartum depression (PPD) (OR = 1.13, 95% CI: 1.05-1.22, = 0.006; FDR-adjusted = 0.006). No significant causal associations were observed between SAS and the other six obstetric disorders investigated. The two-step MR mediation analysis indicated that an individual's BMI mediated a portion of the total effect of SAS on the risk of developing PPD, specifically 11.7% (indirect effect OR = 1.132, 95% CI: 1.053-1.217). CONCLUSION: This MR study provides evidence that there is a positive causal relationship between SAS and PPD, and suggests that an individual's BMI may partially mediate this link, highlighting the potential role of weight management in strategies to mitigate the risk of PPD in women with SAS, though this hypothesis requires validation in intervention trials.
Colacurci D, Sarno L, Fulgione C
… +16 more, Mazzarelli LL, Tagliaferri S, Saccone G, Mappa I, Derme M, Pajno C, Strina I, Martirani M, Alviggi C, D'Alessandro P, Sirico A, Di Girolamo R, Carbone L, Bifulco G, ARPO Working Group, Maruotti GM
J Matern Fetal Neonatal Med
· 2026 Dec · PMID 41968114
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BACKGROUND: fertilization (IVF) pregnancies are associated with an increased risk of maternal and perinatal complications. Advanced maternal age and multiple gestations are more common in IVF and may contribute to adver...BACKGROUND: fertilization (IVF) pregnancies are associated with an increased risk of maternal and perinatal complications. Advanced maternal age and multiple gestations are more common in IVF and may contribute to adverse outcomes. Evaluating the interaction between mode of conception and maternal age may help clarify risk profiles in IVF pregnancies. METHODS: This single-center, retrospective observational study included nulliparous women who delivered from 26 weeks' gestation onward. A total of 144 IVF and 106 spontaneously conceived pregnancies were analyzed. IVF pregnancies included cycles with fresh or frozen embryo transfer and homologous or heterologous fertilization. Maternal characteristics, pregnancy complications, fetal and neonatal outcomes were compared between groups. RESULTS: IVF pregnancies were associated with a significantly higher incidence of hypertensive disorders (17.9% vs 7.3%), and multiple pregnancies (25.9% vs 4.6%). Fetal complications, including fetal growth restriction (20% vs 7.3%), oligohydramnios (10.6% vs 2.8%), polyhydramnios (7.3% vs 0%), preterm premature rupture of membranes (6.4% vs 3%), and non-reassuring fetal heart rate patterns (17.1% vs 8%), were more frequent in IVF pregnancies. IVF pregnancies delivered at a lower gestational age (35.98 vs 37.99 weeks, < .001), with lower birth weight (2244 vs 3074 g, < .001), lower Apgar scores at 1 and 5 min, higher cesarean section rate (70.7% vs 52.8%), and higher NICU admission (38.8% vs 5.1%). CONCLUSION: IVF pregnancies were associated with increased maternal morbidity and adverse fetal and neonatal outcomes compared to spontaneous pregnancies, including hypertensive disorders, fetal growth restriction, preterm birth, cesarean delivery, and NICU admission.
J Matern Fetal Neonatal Med
· 2026 Dec · PMID 41956985
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BACKGROUND: miR-146a influences an individual's pain sensitivity through the regulation of inflammation-related pathways, and its genetic polymorphism may play a role in labor analgesia. OBJECTIVES: This study aimed to i...BACKGROUND: miR-146a influences an individual's pain sensitivity through the regulation of inflammation-related pathways, and its genetic polymorphism may play a role in labor analgesia. OBJECTIVES: This study aimed to investigate the impact of the miR-146a rs2910164 polymorphism on the efficacy of epidural fentanyl in labor analgesia. MATERIALS AND METHODS: In this study, a total of 142 primiparas who received epidural fentanyl analgesia were enrolled. Genotyping was conducted using the SNPscan Kit, and the miR-146a expression was measured by RT-qPCR. The 24-hour Visual Analogue Scale (VAS) score was utilized as an indicator to assess analgesic efficacy, and a logistic regression was employed to analyze the association between different genotypes and the effectiveness of pain relief. RESULTS: At the rs2910164 locus, the miR-146a expression in individuals with the CC genotype was significantly lower than that in those with the GG and GC genotypes, whereas no significant difference was observed between the GG and GC genotypes. Regarding clinical characteristics, the 24-hour VAS pain score was significantly higher in the CC genotype group compared to the GG and GC genotype groups. When the GG and GC genotypes were combined and compared against the CC genotype, the difference in VAS scores remained statistically significant. Logistic regression analysis revealed a significant association between the rs2910164 polymorphism and the 24-hour VAS score (OR = 3.189, 95% CI: 1.142-8.901, = 0.027). CONCLUSION: The CC genotype at the rs2910164 locus served as an independent risk factor associated with decreased efficacy of epidural fentanyl analgesia. However, further validation in larger multicenter studies is required before any clinical application can be considered.
Kajiwara K, Ogawa K, Reiko O
… +4 more, Umehara N, Hidenori A, Okamoto A, Wada S
J Matern Fetal Neonatal Med
· 2026 Dec · PMID 41956983
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OBJECTIVE: To assess the association between the cumulative duration of abnormal cardiotocography (CTG) findings, classified using the Japan Society of Obstetrics and Gynecology (JSOG) five-tier cardiotocography (CTG) cl...OBJECTIVE: To assess the association between the cumulative duration of abnormal cardiotocography (CTG) findings, classified using the Japan Society of Obstetrics and Gynecology (JSOG) five-tier cardiotocography (CTG) classification system, and fetal acidemia, with analyses performed separately for the first and second stages of labor. METHODS: We conducted a single-center retrospective cohort study at the National Center for Child Health and Development between 1 May 2015 and 1 May 1 2022, including women with planned vaginal delivery at ≥37 0/7 weeks of gestation. Cases with an umbilical artery blood pH <7.15 were categorized as the acidemia group; those with pH ≥7.15 served as controls. For each participant, all CTG tracings were reviewed and classified using the JSOG five-tier system (LEVELS 1-5). The cumulative duration of LEVELS 3-5 abnormalities and fetal tachycardia was calculated separately for the first and second stages of labor. Associations with acidemia were evaluated using multivariable logistic regression, adjusting for maternal body mass index, hypertensive disorders of pregnancy, gestational diabetes mellitus, fetal growth restriction, and chorioamnionitis. RESULTS: A total of 648 deliveries were analyzed (141 acidemia, 507 non-acidemia). During the first stage of labor, LEVELS 3 and 4 abnormalities showed a duration-related association with acidemia, whereas fetal tachycardia was significantly associated when lasting ≥30 min. During the second stage of labor, LEVEL 3 abnormalities showed no significant associations; however, LEVELS 4 and 5 abnormalities and fetal tachycardia lasting >60 min remained significantly associated with acidemia, demonstrating progressively higher odds with longer durations. CONCLUSION: Incorporating the cumulative duration of CTG abnormalities into the JSOG five-tier classification may improve the assessment of fetal acidemia risk. Our time-based analysis demonstrated that LEVEL-specific CTG abnormalities and fetal tachycardia showed duration-related associations with acidemia, particularly during the first stage of labor. LEVEL 3 abnormalities and fetal tachycardia during the first stage of labor were more associated, whereas LEVELS 4 and 5 abnormalities during the second stage were more associated with acidemia. These findings may facilitate more informed intrapartum decision-making by identifying fetuses at risk earlier in labor, potentially reducing unnecessary emergency cesarean deliveries and preventing severe acidemia.
J Matern Fetal Neonatal Med
· 2026 Dec · PMID 41942346
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PURPOSE: This study evaluates phase-specific antiviral efficacy of tenofovir disoproxil fumarate (TDF) in pregnant women with hepatitis B virus (HBV) infection, comparing immune-tolerant (IT), inactive carrier (IC), and...PURPOSE: This study evaluates phase-specific antiviral efficacy of tenofovir disoproxil fumarate (TDF) in pregnant women with hepatitis B virus (HBV) infection, comparing immune-tolerant (IT), inactive carrier (IC), and their corresponding gray zone (GZ-A, GZ-C). Perinatal outcomes and mother-to-child transmission (MTCT) risks were also assessed across these phases. METHODS: In this retrospective study, 717 pregnant women with HBV infection from Nanjing, China (2021-2023) were stratified into IT ( = 317), IC ( = 76), GZ-A ( = 98), and GZ-C ( = 226). Among them, 365 women received TDF antiviral therapy during mid-to-late pregnancy. Primary endpoints included complete virological response rate (CVR) and reductions in HBV DNA and HBsAg from baseline, measured at delivery and 6 months postpartum. RESULTS: TDF significantly reduced HBV DNA levels across all groups ( < .001), with the highest CVR rate observed in GZ-A (41.94% vs. 15.88% in IT at 6 months postpartum, = .002). Despite higher rates of transient liver dysfunction in GZ-A (22.45% vs. 12.62% in IT, = .007), no group exhibited increased MTCT or adverse pregnancy outcomes (APOs, > .05). HBsAg decline was most pronounced in GZ-C at 6 months postpartum (Δ = 0.69 log IU/mL vs Δ = 0.47 log IU/mL in IC, < .01). CONCLUSION: TDF effectively suppresses viral replication in pregnant women with HBV infection, including historically undertreated GZ subgroups, without compromising pregnancy safety. These findings provide a reference for phase-specific management strategies to optimize perinatal HBV care.