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Impact of Integrated Continuous Team Midwifery Care on Breastfeeding Success within the Iranian Health System: A Randomized Controlled Trial.

INTRODUCTION: Supporting women during the perinatal period helps build confidence, strengthens early bonding between mother and baby, and encourages successful breastfeeding. Continuous midwifery care models are one of the ways that support women in this periods. OBJECTIVE: This study aimed to evaluate the effect of integrated continuous team midwifery care (ICTMC) in enhancing breastfeeding success in the Iranian health system. METHODS: In this randomized controlled trial, 200 low-risk primiparous women with a gestational age of less than 12 weeks were recruited from public health centers. Participants were randomly assigned to either the intervention group, which received continuous midwifery care throughout pregnancy, childbirth, and postnatal follow-up, or the control group, which received routine care. The primary outcomes were early skin-to-skin contact and breastfeeding success at the time of discharge and at 4-6 weeks postpartum. Data were analyzed using Stata, employing descriptive statistics, Chi-square, independent t-test, Phi/Cramer's V, and Cohen's d. The p < 0.05 is significant. Data were analyzed with SPSS 26. RESULTS: ICTMC groups were significantly more likely to initiate skin-to-skin contactearly skin-to-skin contact immediately after birth (92% vs. 74%, p < 0.001) and achieve successful breastfeeding at the discharge time (88% vs. 70%, p = 0.002) compared to the control group. At 6 weeks postpartum, breastfeeding success remained higher in the intervention group (82% vs. 65%, p = 0.004). CONCLUSION: Women with ICTMC, effectively support skin-to-skin contactearly mother-infant bonding and enhance breastfeeding success among low-risk primiparous women. Integrating this model into routine maternal care may improve perinatal outcomes.

Humans

Exploring hormonal influences on nicotine craving and use across the perinatal period: A prospective longitudinal study.

INTRODUCTION: Perinatal nicotine use is common despite well-documented adverse consequences. We examined associations between reproductive-related hormones with nicotine craving and use during the perinatal period to identify potential novel intervention points. METHODS: All participants reported use of nicotine during the perinatal period. Participants were enrolled at gestational week &#x2265;&#x2009;36 and followed to postpartum week 12 via daily surveys (i.e., nicotine craving via 100-point scale, dichotomous use) and weekly hormone measurement in saliva (cortisol, oxytocin) or dried blood spots (progesterone, estradiol, testosterone, dehydroepiandrosterone sulfate). Bayesian mixed-effects models accounted for within-person correlation while estimating hormone effects. RESULTS: Participants (n&#x2009;=&#x2009;46) were 28.9&#x2009;&#xb1;&#x2009;4.9 years old. During follow-up, exclusive combustible cigarettes (n&#x2009;=&#x2009;20), electronic nicotine delivery systems (ENDS; n&#x2009;=&#x2009;13), or dual (n&#x2009;=&#x2009;2) use was observed, with variability in use and craving across participants and over time. During pregnancy, higher oxytocin was linked to greater craving (&#x3b2;=16.31, 95% CI: 3.71, 28.83). Greater peripartum declines in oxytocin were associated with more craving (&#x3b2;=8.71, 95% CI: 0.75, 16.93) and use (&#x3b2;=1.13, 95% CI: 0.05, 2.43). During postpartum, lower estradiol was linked to more craving (&#x3b2;=-1.17, 95% CI: -2.15, -0.18) and use (&#x3b2;=-0.40, 95% CI: -0.76, -0.03). In models simultaneously evaluating all postpartum hormones, the lone meaningful association was between estradiol and craving (&#x3b2;=-1.66, 95% CI: -2.84, -0.48). CONCLUSIONS: The results of this study suggest that oxytocin and estradiol may contribute to the risk of perinatal nicotine use. Additional research is needed to replicate our observations in more diverse study samples and explore implications for clinical intervention.

Bayesian

Effect of brewers' yeast or beta-glucan derived from Saccharomyces cerevisiae on breast milk supply following preterm birth: the BLOOM randomised controlled trial.

OBJECTIVE: Breast milk is the optimal source of nutrition for preterm infants; however, low breast milk production is common following a preterm birth. This study aimed to determine if taking brewers' yeast or beta-glucan improves daily expressed breast milk volume. DESIGN: Randomised, blinded, parallel, placebo-controlled trial. SETTING: Three Australian tertiary-level neonatal units. PATIENTS: Mothers with a singleton or twin pregnancy who gave birth at <34 weeks' gestation. INTERVENTIONS: Mothers were randomised within 72 hours of birth into three parallel groups in a 1:1:1 ratio to receive either brewers' yeast, beta-glucan or placebo capsules for 7&#x2009;days. MAIN OUTCOME MEASURE: Total expressed breast milk volume over a 24-hour period on day 7 of intervention. RESULTS: A total of 105 mothers underwent randomisation between August 2022 and April 2024 (36 brewers' yeast, 35 beta-glucan and 34 placebo). The adjusted mean difference in daily expressed breast milk volume was 94&#x2009;mL/day (95%&#x2009;CI -51 mL/day to 239&#x2009;mL/day) between the brewers' yeast and placebo groups and -25&#x2009;mL/day (95%&#x2009;CI -173 mL/day to 123&#x2009;mL/day) between the beta-glucan and placebo groups. Maternal side effects were similar across groups. CONCLUSION: We found no clear effect of short-term administration of brewers' yeast or beta-glucan on breast-milk production following preterm birth; both interventions were well tolerated. Given the small sample size, these findings do not rule out the possibility of a clinically meaningful benefit of brewers' yeast and suggest further research with a larger sample size may be warranted to clarify the potential clinical impact. TRIAL REGISTRATION NUMBER: ACTRN12622000968774.

Intensive Care Units, Neonatal

Less Invasive Surfactant Administration Using Video Laryngoscope to Decrease Pain in Neonates: A Randomized Controlled Trial.

OBJECTIVES: To assess whether the use of video laryngoscope, when compared to conventional laryngoscope decreases pain (assessed by Faceless Acute Neonatal Pain Scale) in preterm neonates while administering surfactant by LISA. METHODS: Preterm neonates <&#x2009;35 weeks requiring FiO2&#x2009;>&#x2009;0.3 on CPAP pressure of at least 6&#x2009;cm of H2O were administered surfactant by LISA technique either by video laryngoscope (Intervention) or conventional laryngoscope (Control). Faceless Acute Neonatal Pain Scale was used to determine pain 5&#x2009;min before the procedure, immediately, 5&#x2009;min, and 10&#x2009;min after the procedure. The primary outcome was severity of pain; secondary outcomes were time taken to complete the procedure, number of attempts, incidence of IVH, and adverse events during the procedure. RESULTS: In total, 42 neonates of <&#x2009;35 weeks gestation with comparable baseline demographics were randomized into 2 groups. The median (IQR) FANS score immediately post-procedure in the intervention arm was 2 (2-4) versus 2 (1-4) in the control arm, p&#x2009;=&#x2009;0.79. There was no statistical difference in the secondary outcomes studied. CONCLUSION: The two groups had no difference in the pain score. The pain experienced by neonates during the LISA procedure was moderate and of short duration and it did not depend on the type of laryngoscope used. Moderate pain during the procedure can be managed with nonpharmacological measures; thereby, the use of sedatives or analgesics can be avoided, which might be of concern. There was no difference in the number of attempts or in time taken to complete the procedure when performed by neonatologists experienced in using conventional laryngoscopes compared to video laryngoscopes. TRIAL REGISTRATION: Clinical Trial Registry of India: CTRI/2022/09/045204 on 05.09.2022.

Humans

Maternal obesity in rats results in male-specific increases in genome-wide DNA methylation in postnatal offspring liver.

Male-specific peripubertal DNA demethylation in the liver has been reported in mice. Here, we investigated whether it also occurs in rats, the influence of maternal obesity and whether DNA demethylation changes contribute to observed sex-specific effects of maternal obesity in offspring. Female rats were fed a high-fat, high-sugar 'cafeteria' (Caf) diet before mating with standard chow-fed males. The offspring liver methylome and transcriptome were examined. Body weight was higher in Caf-fed dams prior to mating, during gestation and at parturition. Male and female offspring from Caf-fed dams had lower birth weights but higher adult weights and adiposity than offspring from chow-fed dams. A comparison of DNA methylation in 3-week-old weaner males versus female siblings from chow-fed dams did not reveal the male-specific DNA demethylation that was previously reported in mice. However, strong maternal diet effects in male weaner offspring methylation were observed. A comparison of female weaners from chow- versus Caf-fed dams showed a range of differences, with 39% of differentially methylated regions (DMRs) having higher methylation in Caf offspring and 61% of DMRs having higher methylation in chow offspring. In stark contrast, 99% of maternal-diet-induced DMRs in male weaner offspring had higher methylation in offspring from Caf-fed dams. This suggests that maternal obesity induces widespread hypermethylation in the male offspring liver at weaning. However, a comparison with RNA sequencing data revealed limited transcriptional changes at this developmental stage or in adult offspring. While these data highlight how environmentally sensitive DNA methylation is in the male rodent perinatal period, these methylation changes may not be a major contributor to sex differences in developmentally programmed liver disease.

Animals

Prenatal exposure to indoor PM2.5 and children's cognitive performance at 4 years of age: an observational analysis from the UGAAR randomized controlled trial.

Outdoor fine particulate matter (PM2.5) concentrations during pregnancy are linked to reduced cognitive performance in children. We previously reported that portable HEPA filter air cleaners use during pregnancy improved children's mean full-scale IQ (FSIQ), but no previous studies have evaluated the relationship between indoor PM2.5 during pregnancy and FSIQ in childhood. We conducted an observational analysis using data from the Ulaanbaatar Gestation and Air Pollution Research (UGAAR) randomized controlled trial. Using a previously developed model of weekly indoor PM2.5 concentrations, we estimated the average concentrations in participants' homes over the full pregnancy and in each trimester. When the children were four years old, we measured FSIQ using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV). We used multiple linear regression to assess the adjusted relationships between interquartile range (IQR) contrasts in indoor PM2.5 during pregnancy and FSIQ among 475 mother-child dyads. An 8.8&#xa0;&#x3bc;g/m3 increase in indoor PM2.5 concentration over the full pregnancy was associated with a reduction of 1.4 points (95% CI: -3.4, 0.6) in mean FSIQ. The strongest association between PM2.5 concentrations and FSIQ was in the first trimester, when a 19.1&#xa0;&#x3bc;g/m3 contrast was associated with a 2.8-point reduction (95% CI: -5.7, 0.2) in mean FSIQ. Indoor PM2.5, particularly during early pregnancy, may impair brain development, leading to lower mean FSIQ scores in four-year old children. These results, combined with our previous analysis of HEPA filter air cleaners, indicate that reducing PM2.5 exposure during pregnancy has beneficial effects on children's cognitive performance.

Humans

Nipocalimab Phase 3 Dose Selection for Severe Hemolytic Disease of the Fetus and Newborn.

Nipocalimab, a neonatal Fc receptor (FcRn) blocker, is under evaluation for severe hemolytic disease of the fetus and newborn (HDFN). In the Phase 2 UNITY trial, weekly intravenous antenatal treatment with nipocalimab at dose regimens of 30 and 45 mg/kg prevented fetal anemia requiring intrauterine transfusion (IUT) in 54% of high-risk pregnancies and delayed the need for IUTs versus their previous pregnancies in the remaining 46% of pregnancies. This analysis aimed to select a weekly dose regimen of nipocalimab for the Phase 3 study in severe HDFN (NCT05912517) that maintains FcRn blockade throughout antenatal treatment, including with an unplanned dosing delay of up to 3 days. Observed pharmacokinetic/pharmacodynamic (PK/PD) data from UNITY (i.e., nipocalimab concentrations, FcRn occupancy, and serum IgG) were analyzed using a model-based approach. A PK/PD model originally developed in nonpregnant participants was updated to incorporate gestational weight gain. Nipocalimab PK and FcRn occupancy were described by a two-compartment model with nonlinear, dose-dependent PK, which captured longitudinal PK, FcRn occupancy, and IgG profiles during dosing and return toward baseline postpartum after discontinuation. Both 30 and 45 mg/kg achieved &#x223c;80%-85% reductions in maternal IgG; however, 30 mg/kg showed greater variability in predose trough concentrations, increasing the risk of falling below concentrations required for full FcRn occupancy across antenatal treatment. Simulations incorporating PK/PD variability indicated that 45 mg/kg weekly per current weight maintained full FcRn occupancy in >95% of pregnant individuals, even with dosing delays up to 3 days. Exploratory exposure-response analyses supported 45 mg/kg for the Phase 3 HDFN study.

Humans

Tuberculosis in children who are HIV-exposed uninfected.

OBJECTIVES: 1.3 million children are born each year to mothers with HIV but remain HIV-uninfected; more than 70% of these children live in settings with high tuberculosis (TB) burden. Whether children who are HIV-exposed uninfected (cHEU) are at increased risk of TB infection and disease is debated. DESIGN: We performed a systematic review and meta-analysis of TB infection and disease in cHEU versus children who are HIV-unexposed uninfected (cHUU) and children with HIV (CWH). METHODS: We searched PubMed, Embase, Web of Science, the Cumulative Index to Nursing and Allied Health Literature, and publication bibliographies through October 2025, using terms related to gestational HIV exposure and TB. We performed a qualitative synthesis and a meta-analysis of TST/IGRA positivity prevalence and disease cumulative incidence in cHEU versus cHUU, and cHEU versus CWH. RESULTS: : We included 26 studies in a systematic review and 18 studies in meta-analyses; 21/26 (81%) studies were restricted to children less than 2&#x200a;years of age. Prevalence of TST/IGRA positivity [RR 1.26; 95% confidence interval (CI) 0.92-1.72, I2 &#x200a;=&#x200a;0.0%] and cumulative disease incidence (RR 0.72; 95% CI 0.48-1.08, I2 &#x200a;=&#x200a;0.0%) were similar between cHEU and cHUU. Prevalence of TST/IGRA positivity (RR 0.24; 95% CI 0.02-3.91, I2 &#x200a;=&#x200a;93.2%) was not significantly different between cHEU and CWH. cHEU had lower risk of TB disease cumulative incidence than CWH (RR 0.29; 95% CI 0.16-0.51, I2 &#x200a;=&#x200a;71.5%). CONCLUSION: cHEU and cHUU experience similar risk of TB infection and disease, while cHEU experience lower risk of disease than CWH. Findings were limited by a lack of studies after infancy and a small number of studies.

Humans

Maternal disease control and pregnancy outcomes with anti-CD20 therapy versus natalizumab in multiple sclerosis: a systematic review.

BACKGROUND: Management of multiple sclerosis (MS) during pregnancy requires balancing maternal disease control with fetal safety. Among high-efficacy disease-modifying therapies, anti-CD20 monoclonal antibodies and natalizumab are commonly used in women with active disease, yet their comparative effectiveness and safety during pregnancy remain incompletely defined. This systematic review evaluated maternal disease activity and pregnancy-related outcomes associated with anti-CD20 exposure compared with natalizumab in pregnant women with MS. METHODS: PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library were searched from inception through February 2026. Eligible studies included pregnant women with MS exposed to anti-CD20 before or during pregnancy and reporting maternal disease activity compared to natalizumab. RESULTS: Seven studies were included, comprising six observational cohort studies and one pharmacovigilance disproportionality analysis. Across studies, anti-CD20 exposure was consistently associated with lower relapse activity than natalizumab, particularly in the postpartum period. Anti-CD20 strategies were also associated with markedly lower postpartum MRI activity and more favorable disability-related outcomes where reported. Meta-analysis of three studies demonstrated a significant reduction in postpartum MRI activity with anti-CD20 therapy compared with natalizumab (RR 0.06, 95% CI 0.02-0.24; I&#xb2; = 0%). No clear increase in major congenital anomalies was identified, although some data suggested higher odds of small for gestational age and maternal antibiotic use with anti-CD20 exposure. CONCLUSIONS: Anti-CD20 therapy was associated with lower maternal disease activity than natalizumab during pregnancy, especially for relapse prevention and postpartum MRI suppression. However, evidence regarding fetal and neonatal safety remains limited, warranting cautious individualized treatment decisions and further comparative research.

Humans

Associations Between Paternal Pre-Conceptional Body Mass Index and Lifestyle Factors and Offspring Weight Development.

BACKGROUND: Evidence suggests that pre-conceptional paternal factors, including BMI and diet, may influence offspring development. OBJECTIVES: We examined the associations between paternal BMI, dietary protein intake, glycemic index (GI), smoking and alcohol consumption and offspring development during the first 5&#x2009;years of life. METHODS: This secondary analysis of an RCT included 162 father-child pairs from pregnancies among women with pre-pregnancy overweight or obesity. Paternal characteristics were reported at gestational week 15, reflecting the preceding 3&#x2009;months. Offspring anthropometry was measured at birth, 6 and 18&#x2009;months, 3 and 5&#x2009;years. Associations were examined using linear mixed models and linear regression models. RESULTS: No consistent associations were found between paternal characteristics and offspring outcomes from birth to 3&#x2009;years. At age 5, higher paternal BMI was associated with higher offspring BMI z-score (&#x3b2;&#x2009;=&#x2009;0.07 (CI: 0.03; 0.10)), fat mass index (&#x3b2;&#x2009;=&#x2009;0.07&#x2009;kg/m2 (CI: 0.02; 0.12)) and fat-free mass index (&#x3b2;&#x2009;=&#x2009;0.05&#x2009;kg/m2 (CI: 0.01; 0.08)). Lower paternal protein intake was associated with higher offspring BMI z-score (&#x3b2;&#x2009;=&#x2009;0.54 (CI: 0.07; 1.01)) and fat-free mass index (&#x3b2;&#x2009;=&#x2009;0.60&#x2009;kg/m2 (CI: 0.13; 1.07)), while moderately higher protein intake was associated with higher waist-to-height ratio (&#x3b2;&#x2009;=&#x2009;0.03 (CI: 3.00&#x2009;&#xd7;&#x2009;10-3; 0.05)). Higher paternal GI was associated with lower offspring BMI z-score (&#x3b2;&#x2009;=&#x2009;-0.04 (CI: -0.08; -2.14-10-3)) at age 5. Smoking and alcohol were not associated with offspring outcomes. CONCLUSION: Paternal BMI was associated with offspring outcomes at age 5&#x2009;years, while findings for paternal dietary factors were less consistent.

Humans

Vesicoureteral reflux and anorectal malformations.

BACKGROUND: Renal and urinary tract anomalies are frequently associated with anorectal malformations (ARMs) and may adversely affect long-term renal outcomes, if not detected early. However, reliable clinical predictors for significant urologic abnormalities across different ARM phenotypes remain poorly defined. OBJECTIVE: To determine the prevalence and grade distribution of vesicoureteric reflux (VUR) in neonates with ARMs, and to explore its association with renal and urinary tract anomalies, the complexity of the ARM phenotype, and other factors are associated with high-grade VUR. METHODS: In this retrospective cross-sectional study, medical records of 64 neonates diagnosed with ARMs and managed at a tertiary children's hospital between 2018 and 2025 were reviewed. All patients underwent renal and urinary tract ultrasonography. Voiding cystourethrography (VCUG) was performed for all neonates according to our institutional protocol, regardless of ultrasound findings or ARM phenotype. Demographic characteristics, ARM phenotype (less-complex vs. complex), urologic findings, urinary tract infection (UTI) history, and associated anomalies were analyzed. Multivariable logistic regression models were used to identify independent predictors of complex ARM phenotype and high-grade VUR. RESULTS: The cohort consisted of 64 neonates (75% male) with a mean gestational age of 37.36 &#xb1; 1.83 weeks and a mean birth weight of 2940 &#xb1; 601 g. Renal and urinary tract anomalies were common, with hydronephrosis observed in 48.4%, VUR of any grade in 39.1% and hydroureter in 35.9%,of patients. High-grade VUR was identified in 21.9% of patients, and a documented history of UTI was present in 18.8% of the entire cohort. In multivariable analyses, birth weight, presence of VUR, and UTI history were not independently associated with complex ARM phenotype. Additionally, no demographic or clinical variables reliably predicted high-grade VUR. The predictive performance of the regression model for high-grade VUR was limited (AUC = 0.60). CONCLUSION: Renal and urinary tract anomalies are highly prevalent among neonates with ARMs, with VUR representing a prominent finding. The lack of robust clinical predictors for complex ARM phenotype or high-grade VUR underscores the limitations of selective screening strategies and supports the role of comprehensive urologic evaluation in neonates with ARM, regardless of anatomic subtype.

Humans

Gene-environment interaction between perinatal oxytocin exposure and Pten mutation shapes epigenetic reprogramming of oxytocin signaling and behavior in mice.

Synthetic oxytocin (Pitocin) is the most commonly used pharmacologic agent for induction and augmentation of labor. Beyond its uterotonic effects, oxytocin plays a critical role in neurodevelopment and social behavior. Dysregulated oxytocin signaling has been implicated in autism spectrum disorder (ASD), raising concern that perinatal exposure to exogenous oxytocin may have lasting neurodevelopmental consequences. This study aimed to determine whether offspring harboring a genetic predisposition for ASD are differentially impacted by perinatal oxytocin exposures, with a focus on long-term oxytocin signaling and autism-like behavior. Pregnant mice carrying offspring with heterozygous mutations in phosphatase and tensin homolog deleted on chromosome ten (Pten), a well-established monogenic risk factor for ASD, received continuous oxytocin versus phosphate-buffered saline (PBS) control via micro-osmotic pumps during late gestation. Wild-type (WT) offspring exposed to each treatment served as a secondary control. Adult offspring were assessed for oxytocin receptor (Oxtr) methylation in the frontal cortex and hippocampus, oxytocin expression in the hypothalamus, serum oxytocin levels, and were subject to a battery of social and anxiety-related behavior tests. Perinatal oxytocin exposure produced genotype-dependent effects in offspring. Epigenetic analyses revealed bidirectional remodeling of Oxtr methylation in the frontal cortex and hippocampus, with increased exon 1 methylation in WT mice and decreased methylation in Pten-mutant mice, resulting in significant genotype-treatment interactions. Hypothalamic oxytocin expression increased following treatment regardless of genotype, though baseline levels were higher in Pten-mutant mice. Neither oxytocin treatment nor genotype impacted long-term serum oxytocin levels. Behavioral outcomes were modest but context-specific: repetitive behaviors and cognition performance were unchanged, but oxytocin-treated Pten-mutant mice exhibited increased anxiety-like behavior alongside improved social memory. In contrast, oxytocin-treated WT mice showed reduced social novelty preference. Exploratory analyses suggested potential sex-dependent trends. Our findings support a model in which genetic susceptibility shapes the epigenetic encoding of early-life hormonal signals, thereby recalibrating oxytocin system function and downstream behavioral outcomes. Together, these data highlight the context-dependent effects of perinatal oxytocin exposure and argue against uniformly beneficial or detrimental effects, emphasizing the importance of gene-environment interactions in neurodevelopmental trajectories.

Animals

Exploring the dose-response relationship between prenatal exercise and postpartum depression: A systematic review and meta-analysis of randomized controlled trials.

IMPORTANCE: Postpartum depression (PPD) is a hidden and widespread global public health crisis affecting millions of mothers and infants annually. Prenatal exercise is a potentially accessible nonpharmacological strategy for PPD prevention, but its optimal dose remains uncertain. OBJECTIVE: To explore the dose-response relationship between prenatal exercise and the incidence of PPD through meta-analysis of randomized controlled trials (RCTs). DATA SOURCES: Systematic searches were conducted in PubMed, Embase, Web of Science, and Cochrane Library using MeSH terms and keywords related to "pregnant women," "prenatal exercise," and "postpartum depression," up to June 23, 2025. STUDY SELECTION: RCTs included examined prenatal exercise interventions in pregnant women without a history of depression, with PPD incidence reported using validated depression scales (such as EPDS, CES-D). Non-RCT studies, duplicate publications, and studies with insufficient data were excluded. DATA EXTRACTION AND SYNTHESIS: Two researchers independently extracted data according to the PRISMA guidelines. A random-effects model was used to pool odds ratios (OR) and their 95% confidence intervals (CI). Linear and nonlinear dose-response models were employed to analyze and evaluate the relationship between exercise dose (measured in METs-min/week) and the incidence of PPD. MAIN OUTCOME(S) AND MEASURE(S): The primary outcome is the incidence of PPD, analyzing its relationship with prenatal exercise dose. RESULTS: Eight RCTs involving 2231 pregnant women were included. The pooled analysis showed that prenatal exercise was associated with a potential reduction in PPD incidence, although the overall effect did not reach statistical significance (OR=0.58, 95% CI [0.33, 1.02]). In dose-stratified analysis, exercise doses &#x2265;500 METs-min/week were associated with significantly lower PPD incidence (OR=0.44, 95% CI [0.24, 0.78]). Subgroup analyses suggested trends toward greater benefits among women aged &#x2265;30 years and those initiating exercise between 14 and 28 weeks of gestation; however, subgroup differences did not reach statistical significance. The linear dose-response trend did not reach statistical significance (p = 0.0533), and neither the overall spline association (p = 0.1704) nor the test for nonlinearity (p = 0.6361) was statistically significant. CONCLUSIONS AND RELEVANCE: Prenatal exercise may be associated with a lower risk of PPD, but the overall pooled effect did not reach statistical significance. Findings concerning &#x2265;500 METs-min/week and the apparent flattening of the dose-response curve should be considered exploratory and require confirmation in larger trials.

Humans

[Pathogenicity analysis and prenatal genetic counseling for five Chinese pedigrees harboring a hemizygous c.-32C>G variant of FGF13 gene].

OBJECTIVE: To explore the pathogenicity and prenatal counseling strategies for five Chinese pedigrees harboring a hemizygous c.-32C>G (NM_001139500.2) variant of fibroblast growth factor 13 (FGF13) gene. METHODS: Five Chinese pedigrees found to carry a hemizygous c.-32C>G variant of the FGF13 gene at the Prenatal Diagnosis Center of Henan Provincial People's Hospital between January 2024 and January 2025 were selected as study subjects. The pedigrees had undergone prenatal diagnosis for a family history of genetic disorders, abnormal fetal ultrasound findings, or advanced maternal age. A retrospective analysis was carried out, wherein clinical data for all members of the pedigrees were obtained through the medical records system and outpatient visit system. Peripheral blood samples were collected from all pedigree members, and amniotic fluid samples were obtained from the probands. Following extraction of genomic DNA, prenatal diagnosis was performed using chromosomal microarray analysis (CMA) and trio whole-exome sequencing (trio-WES). Sanger sequencing was used to determine the carrier status for the candidate variant, and Mini-Mental State Examination (MMSE) was used to assess the cognitive function of hemizygous individuals carrying the FGF13 gene c.-32C>G variant. Pathogenicity of candidate variant was assessed based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2021-171). RESULTS: CMA and trio-WES revealed no pathogenic variants in all probands, whilst trio-WES and Sanger sequencing had identified 11 male individuals carrying a hemizygous c.-32C>G variant of the FGF13 gene from the five pedigrees, which included six adult males, a young boy, and four fetuses. One fetus had undergone termination of pregnancy due to hydrocephalus, one was born pre-term at 34+1 weeks of gestation owing to maternal hypertension, and other two were delivered at full term. Follow-up of the survived males revealed no phenotypic manifestations related to language or intellectual impairment. Among these, three adult males underwent the MMSE assessment, all of whom showed normal cognitive function. Search of the gnomAD database suggested the carrier frequency of FGF13 c.-32C>G variant in the East Asian population to be 0.125%, with 11 hemizygous males documented. Three male patients harboring the variant showed severe intellectual disability. Both in vitro and in vivo studies suggested that it could reduce the translation levels of FGF13 protein. Based on the ACMG guidelines, it was classified as variant of uncertain significance (BS4+PS3_Supporting). CONCLUSION: There is insufficient evidence to classify the FGF13 c.-32C>G as a pathogenic variant in clinical practice, and its presence should not be considered an indication for pregnancy termination due to major birth defects.

Adult

Lower urinary tract evaluation in children with cerebral palsy: A crossectional study.

INTRODUCTION: Cerebral palsy (CP) is a chronic, non-progressive motor disorder affecting voluntary movement and posture. Lower urinary tract (LUT) dysfunction is highly prevalent in children with CP. This study aims to evaluate LUT function in children with CP. MATERIAL AND METHODS: This cross-sectional study was conducted at a tertiary care hospital. Patients aged 5-18 years with established CP diagnosis were included. Evaluation included clinical history, physical examination, urinary ultrasonography with post-void residual (PVR) measurement, and urodynamic studies when indicated. Patients were categorized into three groups; group-1 (LUT dysfunction), group-2 (symptomatic), and group-3 (asymptomatic) for analysis. RESULTS: The study included 97 children with CP (41 girls, 56 boys; median age 8 years). Of the patients, 61.8% were ambulatory (GMFCS I-III) and 38.2% were non-ambulatory (GMFCS IV-V). At least one LUT symptom was detected in 75.3% of patients. Incontinence was the most common symptom at 69.1%. Incontinence prevalence was significantly higher in non-ambulatory patients (81.1% vs 61.7%, p = 0.044). Invasive urodynamics was performed in 19 patients, and LUT dysfunction was diagnosed in 89.5% of them (19.3% of the entire population). Prematurity rate was significantly higher in patients with LUT dysfunction (94.1% vs 64.8%, p = 0.017). Binary logistic regression analysis identified elevated PVR as the strongest independent risk factor for LUT dysfunction (OR = 108, p < 0.001). Abnormal urinary frequency (OR = 14.9, p = 0.022) and quadriplegia (OR = 10.3, p = 0.016) were other independent risk factors. ROC analysis determined the optimal cut-off value for PVR as 19 mL (sensitivity 58.82%, specificity 94.92%). In the intergroup analysis, multinomial logistic regression identified elevated PVR as the strongest predictor (Group-1 vs Group-2: OR = 101; Group-1 vs Group-3: OR = 24, both p < 0.003). Lower gestational age was also an independent risk factor in both comparisons (OR = 1.25-1.26, p < 0.020). DISCUSSION: This study demonstrates LUT dysfunction affects 19.3% of children with CP, strongly correlating with motor impairment severity. Elevated PVR emerged as the strongest independent predictor (OR = 108), offering a practical non-invasive screening tool. Our proposed urodynamic criteria achieved 94.7% diagnostic yield, enabling selective evaluation. Limitations include single-center design and cross-sectional methodology without longitudinal follow-up. These findings support integrating systematic urological assessment into standard CP care for early intervention. CONCLUSION: LUT dysfunction prevalence is high in children with CP, and symptom frequency increases with higher GMFCS levels. Elevated PVR is the strongest predictor, with a clinically applicable cut-off value of 19 mL. Particularly in quadriplegic, non-ambulatory, and premature patients, close follow-up and urodynamic evaluation when necessary should be performed with a multidisciplinary approach.

Humans

Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus.

BACKGROUND: Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral palsy for children) were shown in a 2009 Cochrane review. Internationally, use of magnesium sulphate for preterm cerebral palsy prevention is now recommended practice. As new randomised controlled trials (RCTs) and longer-term follow-up of prior RCTs have since been conducted, this review updates the previously published version. OBJECTIVES: To assess the effectiveness and safety of magnesium sulphate as a fetal neuroprotective agent when given to women considered to be at risk of preterm birth. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 17 March 2023, as well as reference lists of retrieved studies. SELECTION CRITERIA: We included RCTs and cluster-RCTs of women at risk of preterm birth that assessed prenatal magnesium sulphate for fetal neuroprotection compared with placebo or no treatment. All methods of administration (intravenous, intramuscular, and oral) were eligible. We did not include studies where magnesium sulphate was used with the primary aim of preterm labour tocolysis, or the prevention and/or treatment of eclampsia. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed RCTs for inclusion, extracted data, and assessed risk of bias and trustworthiness. Dichotomous data were presented as summary risk ratios (RR) with 95% confidence intervals (CI), and continuous data were presented as mean differences with 95% CI. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included six RCTs (5917 women and their 6759 fetuses alive at randomisation). All RCTs were conducted in high-income countries. The RCTs compared magnesium sulphate with placebo in women at risk of preterm birth at less than 34 weeks' gestation; however, treatment regimens and inclusion/exclusion criteria varied. Though the RCTs were at an overall low risk of bias, the certainty of evidence ranged from high to very low, due to concerns regarding study limitations, imprecision, and inconsistency. Primary outcomes for infants/children: Up to two years' corrected age, magnesium sulphate compared with placebo reduced cerebral palsy (RR 0.71, 95% CI 0.57 to 0.89; 6 RCTs, 6107 children; number needed to treat for additional beneficial outcome (NNTB) 60, 95% CI 41 to 158) and death or cerebral palsy (RR 0.87, 95% CI 0.77 to 0.98; 6 RCTs, 6481 children; NNTB 56, 95% CI 32 to 363) (both high-certainty evidence). Magnesium sulphate probably resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.96, 95% CI 0.82 to 1.13; 6 RCTs, 6759 children); major neurodevelopmental disability (RR 1.09, 95% CI 0.83 to 1.44; 1 RCT, 987 children); or death or major neurodevelopmental disability (RR 0.95, 95% CI 0.85 to 1.07; 3 RCTs, 4279 children) (all moderate-certainty evidence). At early school age, magnesium sulphate may have resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.82, 95% CI 0.66 to 1.02; 2 RCTs, 1758 children); cerebral palsy (RR 0.99, 95% CI 0.69 to 1.41; 2 RCTs, 1038 children); death or cerebral palsy (RR 0.90, 95% CI 0.67 to 1.20; 1 RCT, 503 children); and death or major neurodevelopmental disability (RR 0.81, 95% CI 0.59 to 1.12; 1 RCT, 503 children) (all low-certainty evidence). Magnesium sulphate may also have resulted in little to no difference in major neurodevelopmental disability, but the evidence is very uncertain (average RR 0.92, 95% CI 0.53 to 1.62; 2 RCTs, 940 children; very low-certainty evidence). Secondary outcomes for infants/children: Magnesium sulphate probably resulted in little to no difference in severe intraventricular haemorrhage (grade 3 or 4) (RR 0.81, 95% CI 0.64 to 1.04; 6 RCTs, 6542 infants; moderate-certainty evidence) and may have resulted in little to no difference in chronic lung disease/bronchopulmonary dysplasia (average RR 0.92, 95% CI 0.77 to 1.10; 5 RCTs, 6689 infants; low-certainty evidence). Primary outcomes for women: Magnesium sulphate may have resulted in little or no difference in severe maternal outcomes potentially related to treatment (death, cardiac arrest, respiratory arrest) (RR 0.32, 95% CI 0.01 to 7.92; 4 RCTs, 5300 women; low-certainty evidence). However, magnesium sulphate probably increased maternal adverse effects severe enough to stop treatment (average RR 3.21, 95% CI 1.88 to 5.48; 3 RCTs, 4736 women; moderate-certainty evidence). Secondary outcomes for women: Magnesium sulphate probably resulted in little to no difference in caesarean section (RR 0.96, 95% CI 0.91 to 1.02; 5 RCTs, 5861 women) and postpartum haemorrhage (RR 0.94, 95% CI 0.80 to 1.09; 2 RCTs, 2495 women) (both moderate-certainty evidence). Breastfeeding at hospital discharge and women's views of treatment were not reported. AUTHORS' CONCLUSIONS: The currently available evidence indicates that magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus, compared with placebo, reduces cerebral palsy, and death or cerebral palsy, in children up to two years' corrected age. Magnesium sulphate may result in little to no difference in outcomes in children at school age. While magnesium sulphate may result in little to no difference in severe maternal outcomes (death, cardiac arrest, respiratory arrest), it probably increases maternal adverse effects severe enough to stop treatment. Further research is needed on the longer-term benefits and harms for children, into adolescence and adulthood. Additional studies to determine variation in effects by characteristics of women treated and magnesium sulphate regimens used, along with the generalisability of findings to low- and middle-income countries, should be considered.

Humans