Journal of Maternal-Fetal & Neonatal Medicine最新文献

Aims: Cervical insufficiency (CI) is the inability of the cervix to retain the pregnancy leading to a high risk of second-trimester fetal loss or extremely preterm birth. There is no current evidence of any association between CI and maternal abnormal glucose tolerance (AGT). The aim of this study was to investigate a potential association between CI and maternal AGT.

Material and methods: This retrospective case-control study was conducted by recruiting all women referred to the Department of Women and Child Health of the Research Hospital Gemelli IRCCS of Rome, from 2016 to 2023 for CI. Cases were chosen among patients with an ultrasound finding of short cervical length (<25 mm) before 24 weeks of gestation, with at least one second trimester fetal loss for CI. Healthy women admitted for delivery at term with at least one previous normal pregnancy and no previous fetal losses or preterm deliveries were enrolled as controls. All women enrolled in this study, both cases and controls, were monthly evaluated for fasting glucose levels in pregnancy and underwent oral glucose tolerance test (OGTT) for gestational diabetes mellitus (GDM) screening at 24-28 weeks of gestation. Prevalence of AGT was compared among cases and controls and the finding of AGT was associated with maternal-neonatal outcomes among the study population. Cases and controls were compared using parametric or non-parametric tests, as appropriate. Multivariable logistic regression analyses were performed to account for potential confounders, such as maternal age and BMI.

Results: Women with CI showed a significantly higher prevalence of diabetes mellitus type 2 (DM2) (11/96 vs. 1/96, p < 0.01), vaginal/cervical infections (45/96 vs. 22/96, p < 0.001), and chorioamnionitis (28/96 vs. 0/96, p < 0.0001) compared to controls.

Conclusions: Pregnant women with DM2 were eightfold more likely to have CI compared to pregnant women with normal glucose tolerance.

Objectives: To explore the genetic value and clinical management strategies for subsequent pregnancies in women with a history of adverse obstetric outcomes.

Methods: 204 pregnant women with a history of adverse obstetric outcomes, including spontaneous abortions and/or offspring with developmental anomalies, were retrospectively enrolled. The subjects were categorized into four groups based on the adverse characteristics of previous obstetric histories: inborn developmental anomalies group (IDAG, n = 53), genetic anomalies group (GAG, n = 35), composite group (CG, n = 52), and unknown etiology group (UEG, n = 64). In the subsequent pregnancy, the following strategies were conducted: ① All the fetuses underwent standardized ultrasound screening; ② Invasive fetal prenatal diagnosis were performed, including karyotyping (n = 204), copy number variation sequencing (CNV-seq, n = 161) and whole exome sequencing (WES, n = 11); ③ Dynamic ultrasound assessments and clinical follow-ups of pregnancy outcomes ranging from six months to six years were carried; ④ Fetal outcomes and maternal clinical characteristics among the different groups were further compared.

Results: ① Mean maternal age was not significant among four groups, however, the median gravidity and the median number of spontaneous abortion in UEG were the highest (p < 0.05). ② 8.33% (17/204) fetal genetic anomalies in subsequent pregnancy were found with abnormal chromosomes and 13.04% (21/161) anomalies were found by CNV-seq, among which 12 were investigated additionally. However, no significant difference was in the detection rate (DR) of karyotypes or CNVs among four groups. ③ 13 (6.37%, 13/204) fetuses presented abnormal ultrasonic manifestations accompanied with CNVs or pathogenic genes, and the DR of 9.38% (6/64) in abnormal manifestations of UEG was the highest. ④ 17 (8.33%, 17/204) chose termination and the survivors' growth and development were normal in the follow-ups from six months to six years.

Conclusion: Prenatal genetic diagnosis should be recommended for all subsequent pregnancies of families with adverse obstetric history. In addition, dynamic ultrasound and follow-up management are essential for clinicians to optimize neonatal outcomes.

Objective: To evaluate the contribution of the Causes of Death and Associated Condition (CODAC) classification system in reducing the proportion of nonspecific and unspecified causes of stillbirths compared to the ICD-10 system and to assess maternal and pregnancy-related factors associated with stillbirth in Brazil.

Methods: A retrospective cross-sectional study was conducted in ten tertiary obstetric care facilities in Brazil, including cases of stillbirths 2009 to 2018. Data were obtained from medical records, death certificates, and postmortem investigations. The CODAC system was applied to identify specific causes of death, and maternal and pregnancy characteristics were evaluated to find associations with stillbirth. Agreement between the two systems was assessed using the kappa coefficient, and McNemar's test was used to evaluate differences in the prevalence of unspecified causes.

Results: Of the 3390 initially assessed cases, 2545 were included in the final analysis. The CODAC system reduced the proportion of unspecified stillbirths from 40.79% (ICD-10) to 22.00%. Regional disparities were evident. Cases with unspecified causes (ICD-10 P20/P95) were more prevalent in the northeast (56.4%), whereas other specific ICD-10 causes were predominant in the southeast (47.9%). Maternal conditions such as preeclampsia (24.0% vs. 18.6%, p = 0.004) and placental abruption (20.6% vs. 10.0%, p < 0.001) were significantly associated with cases in which a specific cause of stillbirth was assigned. The agreement between the classification systems was low (kappa = 0.376), and McNemar's test showed a significant difference (p < 0.001).

Conclusion: The CODAC improves the understanding of causes of death over the ICD-10 classification system currently used in Brazil. The CODAC was able to decrease the proportion of unexplained cases, which could potentially contribute to better informing maternal and perinatal health policies.

Background: Acute Kidney Injury (AKI) is common in neonates admitted to the Neonatal Intensive Care Unit (NICU). Neonatal AKI is associated with multiple comorbid conditions of greater clinical severity, which also increase the neonate's risk of mortality. Understanding the risk of mortality, in addition to the severity of AKI, may be useful in determining alternative treatment options for neonates with AKI.

Methods: Two independent datasets containing neonatal patient data from eleven healthcare centers were filtered, cleaned, and combined to produce a dataset fit for training and testing with seven Machine Learning algorithms. After initial modeling with 34 training features, feature elimination was utilized to isolate the most contributing features and create streamlined models. The models were fine-tuned using Bayesian search before being compared to select the most accurate and interpretable architecture.

Results: A patient cohort of 245 patients included 189 alive and 56 deceased neonates with incidence of AKI. Of the 245 patients included in this study, 73.5% were male and 26.5% were female, alongside a median age at entry of 12 h and interquartile range of 35 h. Three tree-based models, Random Forest, XGBoost, and LightGBM, were found to be the most accurate and interpretable of the seven models tested. Support Vector Machine produced similar results, albeit with less interpretability. The RAMA (Raina, Arnav, Max, Aadi) model followed results of the XGBoost algorithm, with Area under the Receiver Operating Characteristic Curve (AUC-ROC) of 0.882 ± 0.132, Accuracy of 0.878 ± 0.052, and F1 Score of 0.923 ± 0.029.

Conclusion: RAMA utilizes a tree-based decision-making algorithm, allowing it to determine the risk of mortality in neonates susceptible to AKI.

Objective: To investigate non-linear associations between pre-pregnancy BMI and new-onset hypertensive disorders of pregnancy (HDP), and the relationship between gestational weight gain (GWG) trajectories and HDP.

Methods: Using data from the Ningbo Birth Cohort of Population Undergoing ART (NBart) cohort (June 2018-June 2024), we included women with singleton ART pregnancies. Restricted cubic splines, latent class mixed models, and logistic regression were applied.

Results: Of 4219 eligible pregnancies, 255 (6.0%) developed HDP. Risk increased when pre-pregnancy BMI exceeded 21.5 kg/m² (∼6% higher per 0.5 kg/m² gain). In stratified analyses, risk also increased below 16.6 kg/m²; the J-shaped relationship was evident in normal-weight women; a significant non-linear association was not detected within the overweight and obese subgroups alone. Advanced maternal age, nulliparity, primary infertility, and frozen embryo cycle amplified BMI-related risk. Exceeding recommended GWG guidelines at various pregnancy stages increased HDP risk; refined GWG thresholds were proposed for ART pregnancies. Two GWG patterns-concave negative (0-20 ± 1 weeks; aOR = 0.540, 95% CI: 0.290-0.944) and delayed acceleration (entire gestation period; aOR = 0.627, 95% CI: 0.380-0.996)-were inversely associated with HDP. Both featured minimal or negative early-pregnancy weight change followed by steady gain, occurred predominantly in overweight and obese women, and total GWG was lower compared with other patterns.

Conclusions: Maintaining optimal pre-pregnancy BMI and adhering to the proposed, more conservative GWG thresholds for ART pregnancies may reduce HDP risk. Distinct GWG trajectories may further modulate this risk.

Background: The early postpartum period (first 42 days after delivery) is a high-risk window for severe maternal morbidity (SMM), yet clinical predictors are not well characterized. We examined rates and clinical factors that associate with early postpartum SMM by infant birthweight category to inform future intervention strategies.

Methods: We constructed a retrospective, population-based cohort of 542,702 live births in Georgia (2016-2020) using linked birth certificate and hospital discharge records. Infant birthweight was categorized as normal or above (NBW+, ≥2500 g), moderately low (LBW, 1500-2499 g), or very low (VLBW, <1500 g). We estimated early postpartum SMM rates, adjusted risk ratios (RRs), and population attributable risk percentages (PARs) for medical, obstetric, and delivery-related factors using multivariable modeling.

Results: Among 542,702 livebirths (492,190 NBW+; 41,337 LBW; 9,172 VLBW), early postpartum SMM rates were highest among VLBW (153 per 10,000) compared with LBW (76 per 10,000) and NBW+ (41 per 10,000) deliveries. Cesarean delivery was associated with the largest observed PAR for all birthweight categories (VLBW: 56.8%; LBW: 25.6%; NBW+: 26.8%) followed by SMM at delivery (VLBW: 15.0%; LBW: 11.4%; 4.2% for NBW+). Chronic and perinatal health conditions each accounted for ≤6% PAR.

Conclusions: Women delivering VLBW and LBW infants experienced nearly four-fold and two-fold higher risks of early postpartum SMM, respectively, compared with NBW+ births. Delivery events, particularly cesarean and SMM at delivery, were associated with the greatest PAR of early postpartum SMM. Findings underscore the need for postpartum monitoring protocols, especially after complicated deliveries, and integrated models of maternal-infant care.

Background: Cesarean scar pregnancy (CSP) is a form of abnormal implantation in which the gestational sac embeds within the myometrial defect of a previous cesarean incision. Its incidence is rising in parallel with increasing cesarean delivery rates. Emerging evidence indicates that CSP and placenta accreta spectrum (PAS) share common histopathological and sonographic characteristics, supporting the concept that CSP represents an early phenotype within the PAS.

Objective: To synthesize current evidence on the diagnosis, classification and management of CSP and to clarify the biological and clinical continuum linking CSP with PAS, with emphasis on early prediction and reproductive implications.

Results: Early first-trimester targeted transvaginal ultrasonography, including assessment of residual myometrial thickness, implantation site, vascularity and standardized classification systems, remains central to diagnosis and risk stratification. Surgical approaches that incorporate scar resection via laparoscopy, laparotomy or transvaginal techniques demonstrate the highest success and lowest recurrence rates, as excision of scar tissue restores myometrial integrity. Other modalities such as suction curettage, hysteroscopy, local methotrexate, uterine artery embolization, balloon tamponade and high-intensity focused ultrasound show variable effectiveness depending on gestational age and CSP subtype. Expectant management may result in live birth, but it carries substantial risk because PAS develops in up to 80% of ongoing pregnancies and severe hemorrhage and hysterectomy are common. Shared pathological findings such as deficient decidualization, myometrial disruption and abnormal uteroplacental vascular remodeling support the concept that CSP and PAS represent a unified pathological spectrum rather than distinct entities.

Conclusion: CSP may represent an early phenotype within the PAS. Standardized terminology, early first-trimester screening and risk-based management strategies are essential to reduce maternal morbidity and optimize reproductive outcomes. Multicenter prospective studies are needed to guide evidence-based prevention and treatment strategies.

Background: Kabuki syndrome (KS) is a rare, multiple congenital anomaly syndrome, characterized by dysmorphic facial features, skeletal anomalies, dermatoglyphic abnormalities, developmental delay, mild-to-moderate intellectual disability, and postnatal growth restriction. KS type 1 (KS1, OMIM 147920) is caused by autosomal dominant pathogenic mutations in KMT2D, and KS type 2 (KS2, OMIM 300867) is caused by X-linked dominant pathogenic mutations in KDM6A.

Objectives: To identify the genetic etiologies in a fetus with increased nuchal translucency (NT) observed by ultrasound at 11⁺⁶weeks of gestation.

Methods: Chromosomal microarray analysis (CMA) and trio-exome sequencing (trio-ES) were performed on amniotic fluid sample to investigate the potential genetic causes. Sanger sequencing was utilized for validation of the candidate variant.

Results: A 28-year-old Chinese pregnant woman was referred for prenatal evaluation due to fetal increased NT (NT = 6.7 mm). CMA yielded a normal result, with no pathogenic or likely pathogenic copy number variants, or mosaicism detected. However, trio-ES identified a novel de novo frameshift mutation (NM_021140.4: c.2429dup (p.Thr811Aspfs*2)) in the KDM6A gene. This variant was classified as pathogenic (PVS1 + PS2_Supporting + PM2_Supporting) based on the American College of Medical Genetics and Genomics guidelines.

Conclusions: The fetus was diagnosed with X-linked dominant KS2. The identification of this novel frameshift variant, together with the first report of increased NT as a prenatal feature, enriched both the mutation spectrum and prenatal phenotypic spectrum of KS2. These findings underscore the diagnostic utility of ES for fetuses with increased NT, especially when CMA yields normal results.