Previous studies have suggested that human papillomavirus (HPV) and HPV-related disease may be associated with increased risk of adverse pregnancy outcomes, e.g., hypertensive disorders of pregnancy, small for gestational age (SGA), and gestational diabetes mellitus (GDM). As active surveillance for cervical intraepithelial neoplasia grade 2 (CIN2) leaves the lesion and underlying infection untreated, we aimed to investigate whether the risk of adverse pregnancy outcomes differs between women who undergo active surveillance for CIN2 compared to women having an immediate large loop excision of the transformation zone (LLETZ). We conducted a nationwide register-based cohort study in Denmark. Individual-level data was collected from Danish healthcare registers. We included women aged 18-40 with a first-time diagnosis of CIN2 between January 1, 1998, and December 31, 2018, and a subsequent singleton birth. We estimated the risk of hypertensive disorder of pregnancy, SGA, and/or GDM in a subsequent pregnancy. We calculated crude and adjusted relative risks (aRR) adjusting for potential confounders using modified Poisson regression. We included 10 537 women with CIN2 and a subsequent singleton birth; 4430 women (42%) underwent active surveillance, and 6107 women (58%) had a LLETZ. We identified 548 (5.2%) cases of hypertensive disorders of pregnancy, 379 cases of SGA (3.6%), and 315 cases of GDM (3.0%). For all three outcomes, the adjusted relative risk was comparable between active surveillance and immediate LLETZ (aRR 1.08 (95% CI 0.91-1.29), aRR 0.94 (95% CI 0.74-1.19), aRR 0.92 (95% CI 0.73-1.16), respectively). Stratified analyses revealed insignificant differences in the risk of hypertensive disorders of pregnancy, SGA, and GDM. No association was found between CIN2 management and risks of hypertensive disorders, SGA, or GDM in later pregnancy. These findings suggest that untreated HPV-related lesions do not increase adverse pregnancy risks and may help reassure women during clinical counseling about future pregnancies after CIN2 treatment.

Fetal fat accretion follows a spatiotemporal pattern. Fetuses who are small-for-gestational-age (SGA) demonstrate reduced fat accumulation, but whether specific body regions are disproportionately affected remains unclear. To characterize regional fat differences between SGA and appropriate-for-gestational-age (AGA), assess the modifying effects of SGA-onset timing and cerebroplacental ratio (CPR), and evaluate associations with neonatal morbidity. SGA pregnancies were prospectively recruited, and AGA controls retrospectively identified. SGA was defined as estimated fetal weight <10th centile and classified as early-onset (< 32weeks) or late-onset (≥ 32weeks), with CPR categorized as normal (≥ 5th centile) or abnormal (< 5th centile). Fetal Magnetic resonance imaging was performed at 3-T using T1-weighted two-point Dixon. Subcutaneous fat was segmented and subdivided into cheeks, trunk, upper and lower limbs. Fat signal fraction and fat mass were computed, with regional fat mass adjusted to global fat mass. Linear mixed models compared groups, and univariate logistic regression assessed associations with adverse outcomes. Sixty-four participants (35 SGA, 29 AGA) were included. Fat signal fraction was significantly lower in SGA across all regions (P<0.001). Upper limb adjusted fat mass was reduced in SGA (P=0.043), while other regions showed no differences (P≥0.08). Fat signal fraction and adjusted fat mass did not differ by SGA onset or CPR status. Lower fat signal fraction in all regions was associated with higher morbidity rates, whereas adjusted fat mass was not. SGA fetuses exhibit globally reduced lipid content with a disproportionate upper limb fat mass deficit, suggesting selective vulnerability of peripheral fat depots.

To evaluate the efficacy of oral Lactobacillus rhamnosus GG (LGG) in reducing neonatal enterocolitis (NEC), sepsis and mortality in very low birth weight (VLBW) infants. This open-label randomized controlled trial included enterally-fed VLBW infants with gestational age ≤ 32weeks; those with gastrointestinal anomalies, severe birth asphyxia (APGAR score < 3 at 5min), cyanotic congenital heart disease, and those not started on feeds by 14days of life were excluded. Participants were randomized to receive either no probiotic (control) group, or probiotic (LGG; intervention) group. The intervention group received the first dose of LGG (probiotic) at feed initiation and was continued till 35weeks of corrected gestational age. The control group received only breast milk. Clinical outcomes (mortality, NEC, sepsis) were compared in both groups during hospital stay. A total of 236 infants were enrolled. The primary composite outcome of sepsis, NEC or mortality was seen in 35 (30.4%) and 33 (27.2%) infants, respectively in the LGG and control groups (RR 0.85; 95%CI 0.48-1.50, P = 0.592). The mean (SD) time to reach full feeds was 11.9 (4.2) and 12.0 (5.5) days in the LGG and control groups, respectively; P = 0.561. The mean (SD) time to regain birth weight was 13.5 (3.9) and 13.6 (3.9) days in the LGG and control groups, respectively (P = 0.982). There was no significant difference in duration of hospital stay, duration of mechanical ventilation, or duration of antimicrobial therapy between the two groups (P > 0.05). Use of LGG as single component probiotic in VLBW infants did not confer any significant benefit on the composite outcome of mortality, sepsis or NEC. Clinical Trial Registry of India; Ref. No. CTRI/2021/03/031724 dated Mar 03, 2021.

The weekly insulin-like growth factor I (IGF-I) profile for children and adolescents treated with long-acting growth hormone differs from that of daily growth hormone (GH). The objective of this study is to provide guidance on the use of once-weekly somapacitan and IGF-I monitoring in prepubertal short children and adolescents born small for gestational age (SGA) or with idiopathic short stature (ISS), Noonan syndrome (NS), or Turner syndrome (TS). Modeling, including population pharmacokinetic/pharmacodynamic (PK/PD) modeling, were utilized, analyzing IGF-I data from 4 clinical studies, including 2 phase 3 trials (REAL8: NCT05330325; REAL9: NCT05723835) involving children and adolescents born SGA (N = 80), ISS (N = 69), NS (N = 62), and TS (N = 79), along with additional data from phase 2 (REAL5: NCT03878446, N = 59) and phase 1 trials (NCT01973244, N = 24). Relationships between somapacitan dose, exposure, baseline IGF-I SD score (SDS), and height velocity (HV) were established in children born SGA, with similar responses anticipated for those with ISS, NS, or TS. A linear model enabled the estimation of average weekly IGF-I exposure from a single sample collected during the somapacitan dosing interval. IGF-I SDS simulations support flexible dosing changes while maintaining a minimum of 4 days between doses. Somapacitan 0.24 mg/kg/week produced similar IGF-I SDS changes and height velocity increases as daily GH in prepubertal short children and adolescents born SGA or with ISS, NS, or TS. The results support that the guidance already established for GHD regarding somapacitan initiation, dosing flexibility, and IGF-I monitoring remain appropriate for prepubertal short children and adolescents born SGA or with ISS, NS, or TS.

ObjectivesThis study aims to investigate the correlation of Doppler ultrasound indices of umbilical artery (UA), middle cerebral artery (MCA), cerebro-placental ratio (CPR), length of umbilical cord (UC) coiling, and birthweight, as well as the predictors of these parameters for small for gestational age (SGA).MethodsThis cross-sectional study was conducted between June 2022 and June 2024 at Hue University of Medicine and Pharmacy Hospital, Vietnam. The study enrolled 337 full-term primigravida with uncomplicated singleton pregnancies who underwent Doppler transabdominal ultrasound between 37+0 and 41+0 weeks of gestation to assess fetal Doppler indices and length of UC coiling. Birthweight was collected at delivery.ResultsThe study found significant differences relating birthweight and resistance index of umbilical artery (RI-UA) between abnormal and normal coiling groups (3028.83 ± 469.81 vs 3129.52 ± 378.82 and 0.604 ± 0.087 vs 0.579 ± 0.073). There was a significantly weak negative correlation between RI of umbilical artery Doppler and birth weight (r = -0.178). Additionally, a significantly weak positive correlation coefficient between CPR and birth weight (r = 0.111) was found. Length of umbilical cord coiling had a weak positive correlation with pulsatility index of uterine artery (PI-UA). RI of umbilical artery Doppler helps in predicting the small gestational age at birth with AUC: 0.72 (0.57-0.87).ConclusionRI-UA and birthweight were significantly different between abnormal and normal coiling pregnancies. The higher RI-UA is more related to lower birthweight. RI-UA helps in predicting the small gestational age at birth better than other parameters.

To study the cognitive outcome of Chinese very-low-birth-weight (VLBW) infants and its relationship to brain magnetic resonance imaging (MRI), we conducted a prospective cohort design including 104 VLBW and 110 full-term (FT) infants born in 2020. The mean Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) scores of VLBW infants were significantly lower than those of FT infants (all P < .001). The MDI and PDI scores of VLBW infants with MRI abnormalities were significantly lower than those of infants with normal MRI and FT infants (all P < .01). The brain MRI findings were correlated with the incidence of neurodevelopmental impairments (NDI) (OR = 5.05, 95% CI = 1.378-18.478; P = .015). In conclusion, VLBW infants are at high risk for neonatal brain MRI abnormalities and NDI at 24 months, and neonatal MRI abnormality is a strong predictor for later NDI.

To investigate if providing additional parenteral amino acids to extremely low birthweight (ELBW) infants improves neurocognitive function, lean mass, and muscle strength at early school age, without adverse effects on blood pressure and general health. Multicenter, 2-arm parallel, double-blinded randomized trial of an additional 1 g/d of parenteral amino acids for 5days after birth or placebo (1:1 ratio), with follow-up at 6 to 7years old' corrected age. The primary outcome was survival free of neurocognitive impairment, defined as a standard score more than 1 SD below the age-corrected mean in 1 or more National Institutes of Health Toolbox cognitive and motor tests. Fifteen secondary outcomes included measures of motion perception, numeracy, body size and composition, blood pressure, and emotional-behavioral and psychosocial health. Of 309 eligible children, 280 (153 [55%] girls) were assessed at school age. The proportion surviving without neurocognitive impairment was similar between the amino acid and placebo groups (21% vs 23%; adjusted risk difference [aRD], -5.0; 95% CI, -12.8 to 2.7; P = .21). Children in the amino acid group had lower muscle strength than placebo group (relative handgrip strength z-score: mean, -0.73 [SD, 1.01] vs mean, -0.33 [SD, 1.17]; adjusted mean difference, -0.39; 95% CI, -0.65 to -0.13) and may have had increased risk of low psychosocial functioning (26% vs 18%; aRD, 10.7; 95% CI, -1.3 to 22.6). Other secondary outcomes were similar between groups. In ELBW infants, providing an additional 1 g/d of parenteral amino acids for 5days after birth has little to no effect on survival without neurocognitive impairment at school age and may have adverse effects on strength and psychosocial functioning.

Antenatal, pregnancy and delivery risk factors for infant cerebral palsy: an umbrella review of meta-analyses and systematic reviews.

Independent and combined effects of first-trimester elevated fasting blood glucose and high-normal blood pressure on pregnancy outcomes.

Gestational diabetes mellitus (GDM) is one of the most frequent pregnancy complications. Investigating clinical risk factors for adverse pregnancy outcomes in women with GDM would help predict and prevent neonatal complications. We developed a machine learning model to discover risk factors for adverse pregnancy outcomes. Women with GDM from tertiary hospitals in Korea were included (n = 305, discovery cohort; n = 911, validation cohort). Supervised machine learning classification models, including ExtraTree, RandomForest, GradientBoosting, AdaBoost, Bagging, XGBoost, and Light Gradient Boosting Machine (LGBM), were developed to predict adverse pregnancy outcomes. Outcomes included large for gestational age (LGA), small for gestational age (SGA), low Apgar score, and preterm delivery. The top-ranked risk factors identified through feature importance were further validated using binary logistic regression analysis. In predicting LGA, the RandomForest model achieved the highest AUROC of 0.726 on the validation cohort. For SGA, the RandomForest model achieved the highest AUROC of 0.628. For low Apgar score and preterm delivery, the ExtraTree model showed the best performance with AUROCs of 0.689 and 0.616, respectively. This study presents machine learning models as a foundational tool for identifying factors associated with adverse pregnancy outcomes in women with GDM. These models may serve as a foundation for future development of clinical decision support tools.

Do race and ethnicity modify the association between pre-pregnancy and prenatal stressful life events and adverse birth outcomes among a population-based sample of at-risk women?

Underlying placental lesions in small for gestational age (SGA) subgroups: mild SGA, severe SGA, and stillbirth SGA: a cross-sectional data linkage study.

Late-onset sepsis (LOS) remains a leading cause of morbidity and mortality in preterm infants, with decreasing incidence in high-income countries but persistent challenges in low- and middle-income countries. This study aimed to evaluate the epidemiology, microbiological profile, and short-term outcomes of LOS in very low birth weight (VLBW) preterm infants in Brazil. A multicenter cohort study across 18 level 3 neonatal units of the Brazilian Network on Neonatal Research included 13,439 VLBW infants (400-1499 g birth weight, 22-36 weeks gestation) admitted between 2010 and 2020, excluding those with major malformations, congenital infections or death before 72 hours. Main outcomes included incidence of proven and clinical LOS, in-hospital mortality, and associated short-term morbidities. The cohort had a mean gestational age of 29 ± 3 weeks and birth weight of 1079 ± 275 g. The incidence of proven LOS was 24.6%, and clinical LOS was 19.2%. Gram-positive bacteria predominated (64.1%, with 49.4% coagulase-negative staphylococci), followed by Gram-negative bacteria (27.2%) and fungi (8.8%). Over the decade, fungal infections decreased, while Gram-negative bacterial infections and proven LOS incidence increased. In-hospital mortality was 24.8%, showing no reduction. LOS was associated with an increased risk of death and severe morbidities. This comprehensive 10-year cohort in Brazil reveals a concerning epidemiological shift, characterized by a significant increase in Gram-negative infections and a persistent, high LOS incidence and mortality among VLBW infants. These findings, particularly the lack of improvement in prognosis, underscore the urgent need for targeted and effective preventive and control interventions tailored for resource-limited settings.

Comparison of Size Determination using Fenton and World Health Organization Growth Charts in Term Infants.

To evaluate whether progesterone-induced changes in endometrial thickness (EMT) affect singleton infant outcomes during frozen-thawed embryo transfer (FET) cycles. This retrospective study analyzed 6,331 singleton live births following frozen-thawed Day 3 embryo transfers. EMT was measured via transvaginal ultrasound one day before progesterone initiation and on the day of FET. Participants were grouped by EMT change: increase, decrease, or stable. Primary outcomes included mean birthweight, low birthweight (LBW), and small-for-gestational-age (SGA) status. Associations between EMT changes and neonatal outcomes were evaluated using multivariable linear and logistic regression. No significant differences in mean birthweight were observed among the three groups (3,355.30 ± 502.69g vs. 3,351.30 ± 474.79g vs. 3,344.26 ± 514.54g; p = 0.753). Compared with the EMT stable group, the EMT decreased group showed no significant increase in LBW (1.1%; aOR 1.645, 95% CI 0.818-3.307) or SGA (2.7%; aOR 1.141, 95% CI 0.783-1.662). Similarly, the EMT increased group showed no significant association with LBW (aOR 1.310, 95% CI 0.723-2.375) or SGA (aOR 0.912, 95% CI 0.660-1.261). Multiple linear regression confirmed that gestational age and infant gender significantly influenced birthweight, while EMT change did not. EMT may increase, decrease, or remain stable after progesterone administration in FET cycles. However, these changes do not demonstrate an independent association with adverse perinatal outcomes in term singleton infants.

To assess adverse pregnancy and birth outcomes after bivalent prefusion F subunit-based respiratory syncytial virus vaccine (RSVpreF) vaccination during the first season of availability. This was a target trial emulation study including eight health systems across eight states (California, Oregon, Washington, Colorado, Maryland, Virginia, Minnesota, and Wisconsin) and Washington, DC, in the Vaccine Safety Datalink (VSD). We included pregnant patients aged 16-49 years who had enrolled at a VSD site between September 22, 2023, and February 29, 2024. Exposure was defined as receipt of RSVpreF vaccination between 32 and less than 37 weeks of gestation. Outcomes included preterm birth (PTB), stillbirth, small-for-gestational-age (SGA) birth weight, and hypertensive disorders of pregnancy (HDP) assessed with electronic health record data. Stillbirth cases were confirmed through chart review. Pregnant patients exposed to RSVpreF vaccines were matched 1:1 to unexposed pregnant patients at the gestational week of vaccination by propensity to be vaccinated and VSD site. Unexposed pregnant patients were assigned an index date equivalent to the gestational day of vaccination for their vaccinated match. If the unvaccinated match was subsequently vaccinated, the pair was censored. We report adverse event risks and adjusted risk ratios (aRRs) with corresponding 95% CIs adjusted for nulliparity using a log binomial model with robust variance. We identified 13,966 pregnant patients who received the RSVpreF vaccine. A higher percentage of nulliparous patients were in the vaccinated group (46.4%) compared with the unvaccinated group (38.7%). Comparing RSVpreF vaccinated pregnant patients and their unvaccinated matches, rates of PTB (4.0% vs 4.5%, respectively; aRR 0.90, 95% CI, 0.80-1.00), stillbirth (0.79/1,000 and 0.72/1,000; aRR 0.99, 95% CI, 0.41-2.36), and SGA birth weight (6.8% and 6.5%; aRR 1.02, 95% CI, 0.92-1.12) did not significantly differ. The rate of any HDP among RSVpreF vaccinated patients was 17.3% vs 15.0% among their unvaccinated matches (aRR 1.13, 95% CI, 1.07-1.19). Initial prenatal RSVpreF safety surveillance shows a largely favorable safety profile. Although we identified a small but statistically significant increased risk for HDP after RSVpreF vaccination, there was no increased risk for PTB, SGA birth weight, or stillbirth.

Gestational environmental chemical exposures are widespread. Some chemicals are known to adversely affect birth outcomes, but many remain understudied. To evaluate associations of gestational exposure to a priori identified chemicals in 10 classes with birth outcomes in a large, diverse US cohort. In the prospective Environmental influences on Child Health Outcomes Cohort study, 5318 mother-child pairs were enrolled from January 1, 2000, to December 31, 2021, with data on gestational urinary chemical concentrations, gestational age at birth, and birth weight. Statistical analysis was performed from January 2024 to February 2026. In single, midgestation (median, 25 weeks [IQR, 21-30 weeks]) urine samples, concentrations of 113 analytes (chemicals or their metabolites) from 10 chemical classes were simultaneously measured: fungicides and herbicides (n = 11), insecticides (n = 20), halogenated phenols (n = 5), organophosphate esters (n = 10), benzophenones (n = 6), bisphenols (n = 14), parabens (n = 6), antimicrobials (n = 2), phthalates or alternative plasticizers (n = 32), and polycyclic aromatic hydrocarbons (PAHs) (n = 7). Linear mixed-effects regression models with a random effect for site were used to estimate covariate-adjusted differences in gestational age at birth (days) and birth weight-for-gestational age (BW-GA) z scores per IQR increase in urinary analyte concentrations. In secondary analyses, odds ratios (ORs) for preterm birth and small for gestational age (SGA) were estimated. In the sample of 5318 mother-child pairs, most infants (2667 female [50%]; median gestational age at birth, 39.0 weeks [IQR, 38.0-40.0 weeks]) were born to college-educated (67% [3218 of 4785]), parous (56% [2815 of 5007]) mothers (median age at delivery, 30.7 years [IQR, 26.1-34.3 years]). A total of 43 of 113 analytes (38%) were detected in 50% or more of samples. Multiple phthalates or alternative plasticizers were associated with younger gestational age at birth or lower BW-GA z scores; for example, summed diisononyl phthalate metabolites were associated with a 0.6-day (95% CI, -1.0 to -0.1 days) younger gestational age (preterm birth OR, 1.16 [95% CI, 1.01-1.34]), and summed phthalate or alternative plasticizers were associated with a 0.06 (95% CI, -0.11 to -0.02) lower BW-GA z score (SGA OR, 1.09 [95% CI, 0.93-1.27]). Two halogenated phenols, benzophenone 8, bisphenol F, and several PAHs were associated with lower BW-GA z scores; for example, 1- and 9-hydroxphenanthrene were associated with a 0.04 (95% CI, -0.08 to -0.01) lower BW-GA z score (SGA OR, 1.13 [95% CI, 1.01-1.27]). This large cohort study of diverse US pregnancies found widespread exposure to 10 classes of environmental chemicals, many of which were associated with differences in gestational age at birth or lower BW-GA z scores. These findings indicate that reducing gestational exposure to chemicals, particularly phthalates or alternative plasticizers and PAHs, could promote healthy deliveries and better child outcomes.

Prenatal exposure to wildfire-related PM2.5 and birth outcomes: A population-based California statewide study.

Fetal growth restriction (FGR) subjects exhibit altered metabolism, with higher metabolic rate due to their small body mass, and by adopting strategies to minimise energy expenditure. We investigated how these metabolic differences develop, or manifest in growth trajectories, after FGR, small for gestational age (SGA) with no evidence of FGR, and normal pregnancies. We curated a unique composite dataset of subjects between 14 weeks of gestation and six years of age. First, we assessed fetal and infant heart rate to assess whether higher metabolic rate persisted postnatally after FGR. Next, as the largest energy expenditure is brain synaptic maintenance, we tested whether FGR infants had lower white matter volume (proxy for synapse number). Finally, we modelled longitudinal body weight into childhood in FGR, SGA, and control groups, and tested for associations with neurodevelopmental scores at 1–2 years. Heart rate at rest was 3.2 beats per minute higher in FGR fetuses and infants (710 subjects), and FGR infants exhibited only 52% the increase in heart rate to a nociceptive procedure (i.e. a physiological challenge) observed in controls. FGR infants had 7 cm3 smaller white matter volume (270 subjects). Finally, for every − 100 g an individual’s weight deviated below their group’s average (1660 subjects), their motor score was 0.4 points lower (1030 subjects). FGR subjects continue to exhibit metabolic differences long after birth, which may further disadvantage them beyond the initial antenatal insult. Growth trajectories encode information about how FGR is transmitted into suboptimal neurodevelopment, and could identify intervention opportunities.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-026-53713-y.

Purpose: The increase in the number of premature births in the Kyrgyz Republic was accompanied by the growth of the proportion of newborns with very low (VLBW) and extremely low birth weight (ELBW), which required a systematic analysis of the survival. The study aimed to determine the dynamics of survival among newborns in these groups for 2019-2024, accounting for regional differences. Material and Methods: Kaplan-Meier curves and the log-rank test were used to assess statistical significance. Data, including medical records, reports from perinatal centres, and official statistics from the National Statistical Committee of the Kyrgyz Republic, were collected from all regions of the country, with an emphasis on regional differences in neonatal care infrastructure. Results: The survival of newborns weighing 1,000 to 1,499 grams increased from 23.4% to 51.8%, accompanied by a reduction in early neonatal mortality from 48% to 26%. Among children weighing less than 1,000 grams, survival increased from 2.2% to 8.6%, at remained low. It was established that the most pronounced improvement was observed in the southern regions of the country, whereas in the northern and mountainous areas, the lag remained. The main factors driving positive dynamics were the expansion of antenatal care, the equipping of hospitals with intensive care equipment, and improvements in staff qualifications. Conclusion: The practical significance of the study lies in the justification for further development of neonatal care infrastructure to reduce infant mortality and balance regional differences in Kyrgyzstan.