We aimed to investigate whether maternal and fetal genetic predispositions to insulin deficiency and resistance affect offspring fetal growth through distinct pathways in multi-ethnic populations. In 5065 multi-ethnic mother-infant pairs, we examined the conditional associations of maternal and fetal partitioned polygenic risk scores (pPRSs) for type 2 diabetes-related pathways with fetal growth outcomes, including birthweight, sum of skinfold thicknesses (SSF), large-for-gestational-age (LGA) births and small-for-gestational-age (SGA) births. Two-sample Mendelian randomisation (2SMR) in Europeans was performed for triangulation. Exposures were eight type 2 diabetes-related pathways (n=1,812,017), eight beta cell function indices (n=26,356) and two insulin sensitivity indices (n=53,657). Outcomes were maternal and fetal genetically determined birthweight (n=406,063). Mediation analysis was used to assess the mediation effects of maternal glucose levels and BMI on maternal genetic effects and of cord blood C-peptide on fetal genetic effects. Co-localisation analyses were performed to test for shared causal variants. Fetal type 2 diabetes polygenic risk score (PRS) and pPRSs for lipodystrophy-related insulin resistance and impaired fasting glucose (IFG)-related insulin deficiency were associated with lower birthweight and SSF, while maternal type 2 diabetes PRS and pPRSs for IFG-related insulin deficiency and obesity-related insulin resistance were associated with higher offspring birthweight, SSF and LGA. These associations were consistent across five ethnic groups. Maternal post-load hyperglycaemia mediated 44.2% and 34.2% of the effects of type 2 diabetes PRS and IFG pPRS, respectively, while maternal BMI mediated 43.4% of the effect of Obesity pPRS. 2SMR found consistent results in Europeans and further revealed that fetal insulin sensitivity index and corrected insulin response were associated with higher birthweight. Some loci with shared causal variants acted through multiple pathways, including CDKAL1, TCF7L2, ADCY5 and MACF1. Reduced fetal growth may be driven by lipodystrophy-related insulin resistance and IFG-related insulin deficiency pathways. Targeting pregnant women with high type 2 diabetes PRS/pPRS and prescribing interventions to reduce their post-load hyperglycaemia and BMI may help reduce offspring risk of LGA.

Gestational exposure to metals and small vulnerable newborns: a systematic review and meta-analysis.

Gestational intestinal parasitosis and anaemia: A double-hit for pregnancy outcomes.

Background: Very low birth weight (VLBW) neonates are especially susceptible to environmental stressors such as excessive noise, which can disturb physiological stability. Despite the American Academy of Pediatrics (AAP) recommendations to maintain neonatal intensive care unit (NICU) sound levels below 45 decibels (dB), these levels often exceed these limits, potentially affecting neonatal outcomes. Aims and Objectives: This study aimed to evaluate the impact of ambient noise on key physiological parameters – heart rate, respiratory rate, and oxygen saturation (SpO2) – in VLBW neonates and to highlight the importance of optimizing auditory environments in NICUs. Materials and Methods: A prospective observational study was conducted over 1 year in the NICU of Gauhati Medical College and Hospital. Hemodynamically stable VLBW neonates (<1500 g) were enrolled. Ambient sound levels were measured during the morning, afternoon, and night shifts using the iNVH Android application. Simultaneously, physiological parameters including heart rate, respiratory rate, and SpO2 were recorded. Data from the NICU were compared with values obtained from the Kangaroo Mother Care (KMC) unit. Results: Noise levels in the NICU frequently surpassed the AAP-recommended thresholds, with peak recordings reaching up to 105.4 dB. A statistically significant increase in heart rate and respiratory rate was observed during higher noise exposure compared to the quieter KMC setting. However, SpO2 did not show any significant variation across settings. Conclusion: The study underscores a clear association between elevated ambient noise and altered physiological responses in VLBW neonates. While SpO2 remained unaffected, increased heart and respiratory rates suggest a stress response to excessive noise. Implementing effective noise-reduction strategies in NICUs is critical to improving care and outcomes of VLBW infants.

Assessing adherence to TRIPOD+AI guidelines in machine learning models for predicting small for gestational age and fetal growth restriction: a systematic review.

Perinatal and maternal morbidity in the setting of preterm birth may differ by delivery indication. We compared perinatal and maternal outcomes of second trimester (24 0/7 - 27 6/7 weeks' gestation) deliveries indicated for preeclampsia with severe features (PE-SF) with those following preterm premature rupture of membranes (PPROM). Secondary analysis of an observational cohort study of singleton and twin preterm deliveries before 35 weeks' gestation at 33 hospitals across the United States. Singletons without congenital anomalies who were delivered due to PE-SF or PPROM from 24 0/7 - 27 6/7 weeks gestation were included. The primary outcome was a composite of perinatal morbidity or death, defined as fetal or neonatal death, severe bronchopulmonary dysplasia grade III, intraventricular hemorrhage grade III-IV, necrotizing enterocolitis stage IIA or greater, periventricular leukomalacia, retinopathy of prematurity stage III-IV, or culture-proven sepsis. Secondary outcomes included components of the primary outcome, small-for-gestational-age (SGA) birth, and a composite of maternal morbidity. Among 7515 in the original cohort, 164 deliveries for PE-SF and 119 deliveries following PPROM were included. Individuals with PE-SF were more likely to have BMI ≥ 30 kg/m2, hypertensive disorder of pregnancy in a prior pregnancy, chronic hypertension, and cesarean birth (p <0.05) compared with those who delivered following PPROM. Composite perinatal morbidity or death did not differ between groups (aOR 1.60, 95% CI 0.89, 2.85, p=0.11), but fetal death was significantly higher in the PE-SF group (aOR 6.04, 95% CI 1.42, 25.71). Neonates delivered for PE-SF were more likely to be SGA (aOR 13.45, 95% CI 2.92, 61.94). Composite maternal morbidity did not differ between groups (aOR 1.18, 95% CI 0.62, 2.26). Second-trimester preterm birth indicated for PE-SF was associated with a higher rate of fetal death than birth for PPROM. Composite neonatal and maternal morbidity did not differ by indication.

Birth outcomes after in vitro fertilization among cancer survivors.

Our objectives were to evaluate the association between fetal growth abnormalities and adverse perinatal outcomes in term pregnancies using four different fetal growth references: the recently published Swedish references by Lindström etal., the currently used Swedish references by Maršál etal., and the international standards by the WHO and INTERGROWTH-21st (IG21st). The study aimed to evaluate the performance of each reference and determine which reference most accurately identifies small for gestational age (SGA) infants at risk of perinatal mortality and morbidity. This population-based cohort study included 1 126 059 singleton term births in Sweden from 2010 to 2020. Data were obtained from national registers, including the Swedish Medical Birth Register and the Swedish Neonatal Quality Register. Birthweight centiles were calculated using each growth reference. Adverse perinatal outcomes were categorized by severity and included stillbirth, neonatal death, and serious neonatal morbidity. Logistic regression models were used to assess predictive performance, and sensitivity and false positive rates (FPR) were calculated for SGA thresholds (<3rd and <10th centiles). The distribution of birthweight centiles varied significantly across references. For SGA <3rd centile, the rate ranged from 9.6% for Lindström, 2.5% for Maršál, 1.9% for WHO, to 0.7% for IG21st. All references showed similar overall predictive performance (C-index ≈ 0.67) but with different discriminatory ability. The predicted risk of perinatal death increased at lower centiles for the Lindström reference than for the Maršál and WHO references, and at higher centiles for the IG21st reference. The Lindström reference identified the highest proportion of infants as SGA and had the highest sensitivity but also the highest FPR for detecting adverse outcomes. TheIG21st reference classified the smallest proportion as SGA, resulting in the lowest sensitivity and FPR. While all fetal growth references showed comparable predictive ability for adverse perinatal outcomes, they differed substantially in sensitivity and FPR. When the top priority is to identify as many at-risk fetuses as possible, Lindström etal.'s reference seems to be the best choice. However, when the top priority is a balanced sensitivity versus FPR, the WHO reference seems most suitable for clinical practice in this population of term births.

Objective: To investigate the relationship between maternal pre-pregnancy body mass index (BMI) and clinical pregnancy outcomes and singleton live birth outcomes in frozen-thawed embryo transfer (FET) cycles. Methods: A total of 45 856 patients who underwent FET in Henan Provincial People's Hospital and the Second Affiliated Hospital of Zhengzhou University from January 2013 to December 2023 were retrospectively analyzed, including 15 960 singleton live births. Based on the female's BMI, they were divided into the underweight group (BMI<18.5 kg/m2), the normal weight group (BMI 18.5-<25.0 kg/m2), the overweight group (BMI 25.0-<30.0 kg/m2), and the obese group (BMI≥30.0 kg/m2). Multivariate linear models and logistic regression models were used to evaluate the effects of maternal pre-pregnancy BMI on clinical pregnancy outcomes and singleton live birth outcomes. Generalized additive model was used to fit the curve between maternal pre-pregnancy BMI and perinatal outcomes and to determine the threshold. Results: (1) Among 45 856 FET patients, there were 2 390 cases (5.21%) in the underweight group, 30 177 cases (65.81%) in the normal weight group, 10 835 cases (23.63%) in the overweight group, and 2 454 cases (5.35%) in the obesity group. The early abortion rate of overweight and obesity group, the clinical pregnancy rate and live birth rate of underweight group, the clinical pregnancy rate of obesity group were higher than those of normal weight group, and the live birth rate of overweight group was lower than that of normal weight group, and the differences were statistically significant (all P<0.01). (2) Among the 15 960 singleton live birth FET patients, 926 (5.80%) were in underweight group, 10 620 (66.54%) were in normal weight group, 3 561 (22.31%) were in overweight group, and 853 (5.34%) were in obesity group. The incidences of preterm birth, extremely preterm birth, macrosomia and large for gestational age (LGA) in the overweight and obese groups were significantly higher than those in the normal weight group (all P<0.05). The incidence of small for gestational age (SGA) infants in the underweight group was significantly higher than that in the normal weight group, while the incidences of preterm birth, macrosomia and LGA infants were all significantly lower than those in the normal weight group (all P<0.05). (3) Maternal pre-pregnancy overweight and obesity were associated with early miscarriage (aOR=1.20, 1.37), preterm birth (aOR=1.49, 1.70), very preterm birth (aOR=1.64, 2.09), macrosomia (aOR=1.87, 2.57), and LGA (aOR=1.55, 1.95), and the risks of live birth (aOR=0.87, 0.80) and low birth weight infant (aOR=0.65, 0.51) were significantly decreased (all P<0.01). Maternal pre-pregnancy underweight had no significant effect on early miscarriage, clinical pregnancy and live birth (all P>0.05), but the risks of preterm birth (aOR=0.69), macrosomia (aOR=0.34) and large for gestational age (aOR=0.54) were significantly reduced; the risk of SGA (aOR=1.52) was significantly increased (all P<0.05). (4) The results of curve fitting and threshold effect analysis showed that the risk of very preterm birth (aOR=1.09, 95%CI: 1.05-1.13; P<0.001) increased with the increase of maternal pre-pregnancy BMI, and the risk of low birth weight infants (aOR=0.93, 95%CI: 0.90-0.96; P<0.001) decreased with the increase of maternal pre-pregnancy BMI, and the curve fitting was linear. The relationship between preterm birth, macrosomia, SGA, LGA and maternal pre-pregnancy BMI were nonlinear, and the thresholds were all 25.0 kg/m2. Conclusions: Maternal overweight and obesity before pregnancy could increase the early abortion rate, decrease the live birth rate, and increase the risk of preterm birth, very preterm birth, macrosomia and LGA of single live birth infants in FET. Women with pre-pregnancy BMI≤25.0 kg/m2 could obtain better perinatal outcomes.

Mortality in very-low birth-weight (VLBW) infants accounts for up to 50%-70% of the neonatal mortality and up to 25%-30% of infant mortality. Despite the global increase in survival rates, this population remains at heightened risk for developing long-term neurodevelopmental delays, chronic lung disease, malnutrition, and visual and hearing disabilities. The gut microbial composition of VLBW differs from full-term infants and is typically dominated by pathobionts. In this study, we characterized the bacterial composition of the VLBW infant microbiota born at Pereira Rossell Children's Hospital (academic, tertiary referral center) in Montevideo, Uruguay by sequencing the full-length 16S rRNA gene using Oxford Nanopore Technologies. We describe a high predominance of Klebsiella pneumoniae and Escherichia coli in these infants. By sequencing stool samples from two time points, we show that the microbial community diversity increases over time with a higher relative abundance of Bacteroides and Veillonella. Moreover, we describe the effect on the microbial composition of long antibiotic exposure. Different species of the Klebsiella genus, along with Escherichia coli, Enterobacter cloacae, Citrobacter freundii, and Veillonella parvula were observed at a higher relative abundance in patients with more than 5 days of antibiotic treatment. Taken together, our findings shed light on the development and establishment of microbial communities in early-life microbial communities in South America. Our results point to postnatal antibiotics as a major factor orchestrating this process. The integration of microbial community health considerations into preterm clinical care is crucial for improving long-term infant development.

Bronchopulmonary dysplasia (BPD) is the most prevalent chronic lung disease in very preterm infants; however, conventional classifications have limited ability to predict severity before 36 weeks' postmenstrual age (PMA). A new Japanese classification, based on small for gestational age (SGA), bubbly/cystic chest radiographic findings, and chorioamnionitis (CAM), was proposed to enable earlier risk stratification. However, its validation in homogeneous cohorts is warranted. This study aimed to examine the association between this new Japanese classification and severe BPD development at 36 weeks' PMA in a secondary analysis of a randomized controlled trial (RCT). A retrospective secondary analysis of a multicenter, double-blind RCT of inhaled corticosteroids in 12 tertiary neonatal intensive care units in Japan (2006-2009) was performed. Infants with a birth weight (BW)<1,000 g and requiring mechanical ventilation were enrolled. Of those 211 infants, 194 survivors were analyzed. Severe BPD was defined by National Institute of Child Health and Human Development criteria as requiring supplemental oxygen (fraction of inspired O2 >0.30) or positive pressure ventilation at 36 weeks' PMA. Logistic regression analyses were adjusted for gestational age, BW, sex, Apgar score, maternal steroid use, respiratory distress syndrome, and patent ductus arteriosus. Among the 194 infants, 25 were SGA, 45 had bubbly/cystic findings, and 86 had CAM. Severe BPD occurred in 80 infants. A multivariate analysis identified SGA (adjusted odds ratio [aOR], 3.32; 95% confidence interval [CI], 1.16-9.48; P=0.032) and bubbly/cystic findings (aOR, 10.88; 95% CI, 4.43-26.72; P<0.01) as independent risk factors. Compared with type II (non-CAM, no bubbly/cystic findings), type I (bubbly/cystic only: aOR, 6.21; 95% CI, 1.93-14.36) and type III (CAM plus bubbly/cystic: aOR, 15.32; 95% CI, 2.48-46.32) were significantly associated with severe BPD. The new Japanese classification demonstrated that SGA and bubbly/cystic findings at day 28 independently predicted severe BPD. Early stratification using this classification may facilitate the early identification of high-risk infants for targeted interventions.

Fetal growth restriction (FGR) affects cardiac function and increases the risk of cardiac pathologies. We describe the relationship between cardiac contractility and cardiac size and shape in FGR and small-for-gestational age (SGA) fetuses to determine if ultrasound measurements can indicate functional cardiac sequelae. This prospective cohort study included fetuses with gestational ages of 23.0-39.0 weeks (FGR: n=55, SGA: n=40, appropriate for gestational age/AGA: n= 22). FGR was defined as fetuses with EFW <10th centile and abnormal arterial doppler studies; SGA was defined as fetuses with EFW <10th centile with normal doppler studies. Two-dimensional cardiac video clips of the 4-chamber view (4CV) were obtained for all fetuses and measurements of its size and shape were made. Speckle tracing measures of contractility were obtained as previously described. Individual size, shape, and speckle tracing measurements were compared by ANOVA between FGR, SGA, and appropriate for gestational age (AGA) groups. Comparisons by Mann Whitney U were used to compare a combined FGR+SGA group with the AGA group for all measurements. Abnormality was determined by simple count of values >95th centile or <5th centile based on predicted effect of FGR/SGA on each measurement. Frequency was binary, with a fetus assigned a 1 if they had any abnormal measurement, and 0 if not. Severity was determined by summing the abnormal measurements. Frequency and severity were determined independently for contractility versus size and shape and compared across groups using chi-squared and ANOVA respectively.

Claims data are a valuable source to study neonatal outcomes across a wide range of clinical questions. Infants' delayed enrollment in infant insurance poses challenges in capture of neonatal outcomes, which may be charged to the maternal health plan, posing misclassification risks. We evaluated outcome ascertainment across three infant enrollment scenarios. We used Merative MarketScan databases (2012-2018) in the United States to construct a mother-infant linked cohort and assess the outcome ascertaiment precision with varying infant enrollment requirement. We found that allowing delayed infant enrollment in their own insurance within the first 4 weeks of life retained sample size, nearly doubled case numbers and yielded outcome prevalences similar to those of cohorts with full enrollment since birth. Use of maternal claims in addition to infant claims in this cohort made minor contributions to case capture for neonatal-specific outcomes, while significantly decreasing specificity of more general outcomes. Longer delays in enrollment yielded lower outcome prevalences with higher contributions of maternal claims even for neonatal-specific outcomes. For small for gestational age (SGA), both maternal and infant claims contributed similar proportions of cases. These findings inform strategies for outcome ascertainment in claims-based perinatal research and emphasize outcome-specific case ascertainment strategies to balance sensitivity and specificity.

A single umbilical artery (SUA) is associated with a risk of adverse perinatal outcome. Around 11% of fetuses with SUA present with an associated major anomaly, including those of the central nervous system. However, studies on the associations between SUA and childhood neurodevelopmental disorders (NDD), such as intellectual disability (ID), attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, epilepsy, impaired hearing and impaired vision, are limited. We aimed to evaluate the risk of NDD in children presenting with an isolated SUA (iSUA) at birth and the possible impact of sex, and to examine the extent to which gestational age at birth and birth weight mediate the effect of iSUA on NDD. This was a historical national cohort study linking data from the Medical Birth Registry of Norway with other mandatory national registries. We included all singleton live births in Norway between 1 January 1999 and 31 December 2013, and follow-up of the study cohort was concluded on 31 December 2019. We included all newborns diagnosed with iSUA. Data regarding NDD diagnosis were obtained from the Norwegian National Insurance Scheme and the Norwegian Patient Registry. We used multilevel logistic regression to calculate odds ratios (ORs) with 95% CIs, and performed sex-stratified analyses. A causal mediation analysis of the relationship between iSUA and NDD with preterm birth (live birth < 37 weeks' gestation) and small-for-gestational age (SGA) (birth weight < 5th percentile) was performed. The cohort of 858 397 singleton live births included 3532 cases diagnosed with iSUA (0.41%), of which 1802 (51.3%) were male, 253 (7.2%) were born preterm and 249 (7.0%) were SGA. iSUA was associated with increased odds of subsequent ID (OR, 1.56 (95% CI, 1.09-2.23)) and ADHD (OR, 1.22 (95% CI, 1.02-1.47)), but there was no observed association with other NDD. In sex-stratified analyses, the associations with iSUA were observed in females but not in males. Preterm birth and SGA were each found to mediate < 10% of the total effect of iSUA on ID. iSUA was weakly associated with ID and ADHD, but not with other NDD. These associations were influenced by sex and were mediated by < 10% by preterm birth or SGA. The absence of associations of iSUA with other NDD is reassuring, and this finding is useful in the counseling of expectant parents of fetuses with iSUA. © 2026 International Society of Ultrasound in Obstetrics and Gynecology.

Preeclampsia is a severe pregnancy complication that threatens maternal and neonatal health and well-being. Previous studies on epigenome-wide association analysis (EWAS) of preeclampsia produced inconsistent results in cord blood tissues, and one possible explanation is their failure to rigorously adjust for cell proportions, gestational age, or other necessary variables. Here, we calculated the DNA methylation change in cord blood from newborns affected by preeclampsia, using a multi-ethnic cohort from the Hawaii population (24 cases, 38 controls). We comprehensively adjusted for variables such as maternal age, body mass index (BMI), parity, and estimated the cell proportions. We also re-analyzed two previous datasets with adjustments to estimated cell proportions and conducted a pooled analysis by merging all three datasets together to increase the statistical power (58 cases, 71 controls). Lastly, we include idiopathic preterm (preterm delivery with no known reasons) cord blood samples (n=11) to disentangle the effect of severe preeclampsia and small gestational age. We showed that after adjusting cell type proportions and patient clinical characteristics, most of the so-called statistically significant CpG methylation changes associated with severe preeclampsia disappeared in our own data, two public datasets, and the pooled analysis combining all three datasets. This result still holds after including idiopathic preterm samples in the control group. Rather, we found that gestation progression is accompanied by statistically significant proportion changes in several cell types, such as granulocytes, nRBCs, CD8Ts, and B cells, which contribute to most DNA methylation differences between case and control groups. Preeclampsia has interactions on cell proportion changes in granulocytes, monocytes, and nRBCs. In summary, our study shows that the previously reported differentially methylated patterns in cord blood are actually artifacts due to not properly adjusting for cell type heterogeneity, gestational age, and clinical covariates. Severe preeclampsia is not associated with statistically significant DNA methylation changes but changes in cell proportion. This finding alerts to the scientific rigor needed in EWAS.

Small for gestational age (SGA) neonates have an increased risk of obesity, diabetes mellitus, and glucose intolerance in adult life. Understanding the factors that can increase the risk of SGA and complications might help with management. Hence, we quantified the cellular parameters, random blood sugar (RBS), and insulin-like growth factor (IGF)-axis proteins in appropriate for gestational age (AGA) ( n = 40) and SGA ( n = 20) neonates cord blood samples. Cord blood cell parameters and RBS were measured using an automated analyzer; insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 2 (IGFBP2) proteins were measured using enzyme-linked immunosorbent assay (ELISA). Mean % hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), red blood cell distribution width (RDW), packed cell volume (PCV), MCH concentration (MCHC), white blood cells (WBC), basophils, neutrophils, monocytes, lymphocytes, and RBS did not alter between AGA and SGA, except an increased red blood cells (RBC) ( P = .034) and platelet ( P = .025), and decreased eosinophils ( P = .037). The cord blood plasma IGF1 did not differ ( P = .79), and insulin-like growth factor binding protein 2 (IGFBP2) was significantly higher ( P = .04) in SGA. Overall, the RBC, platelets and IGFBP2 proteins were increased, and eosinophils were reduced in SGA neonates.

Background. Prenatal exposure to fine particulate matter (PM₂.₅), composed of airborne particles smaller than 2.5 micrometers, is a significant environmental risk that can adversely affect pregnancy. Exposure to PM₂.₅ during pregnancy has been associated with a number of adverse birth outcomes, including small for gestational age (SGA), low birth weight (LBW), and preterm birth (PTB). This literature review summarizes evidence published between 2020 and 2025 regarding the relationship between prenatal PM₂.₅ exposure during different pregnancy trimesters and the risk of PTB, LBW, and SGA.Aim of the review. This review gathers and evaluates epidemiological studies from 2020 to 2025 examining the connection between prenatal exposure to PM₂.₅ and adverse perinatal outcomes such as SGA, LBW, and PTBMethods. In our review, we included case-control and cohort primary epidemiological studies that were published between 2020 and 2025. Maternal exposure to ambient PM₂.₅ in connection with PTB, LBW, or SGA was evaluated in eligible studies. Results. Across the reviewed studies, prenatal exposure to PM₂.₅ was linked to an increased risk of LBW and SGA, with heightened susceptibility in the first and second trimesters. Associations with PTB were also noted but more variable. Many large population-based studies found small but statistically significant effects, especially those using thorough exposure assessment methods.Conclusions. The current evidence suggests that maternal exposure to ambient PM₂.₅ during pregnancy is associated with an increased risk of adverse birth outcomes, especially indicators of restricted fetal growth. These findings highlight the need for further study to clarify critical exposure windows, underlying biological processes, and effective strategies to reduce exposure during pregnancy. They also support the importance of air quality as a controllable environmental factor for maternal and offspring health.

IntroductionExtremely premature infants (EPIs) are at significant risk for early mortality and severe intraventricular hemorrhage. This study aimed to investigate the risk factors associated with early mortality and severe intraventricular hemorrhage in EPIs with a gestational age of less than 28 weeks and to evaluate the predictive value of these risk factors in determining adverse outcomes.MethodsA retrospective analysis was conducted on clinical data from EPIs admitted to the Neonatal Intensive Care Unit at Maternal and Child Health Hospital of Hubei Province between January 2019 and December 2024. Infants were categorized into two groups based on their early outcomes: an adverse outcome group (n = 110) and a favorable outcome group (n = 183). Binary logistic regression analysis was used to identify high-risk factors for adverse outcomes in EPIs, and receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of these factors.ResultsThis study revealed that the maximum vasoactive-inotropic score (Max VIS) (OR: 1.136, 95% CI: 1.070, 1.216) and middle cerebral artery resistance index (MCA-RI) (OR: 450.489, 95%CI: 36.163, 5,611.780) and vaginal delivery (OR: 3.684, 95%CI: 2.005, 6.768) were independent risk factors for adverse outcomes in EPIs, while gestational age was a protective factor (OR: 0.568, 95% CI: 0.415, 0.778). ROC curve analysis indicated that Max VIS > 9.5, MCA-RI > 0.81, vaginal delivery, and small gestational age had predictive value for adverse outcomes in EPIs (P < 0.05), with area under the curves (AUC) of 0.680 (95% CI: 0.615, 0.745), 0.693 (95%CI: 0.628, 0.758), 0.653 (95% CI: 0.588, 0.718), and 0.660 (95% CI: 0.275, 0.404), respectively. The combination of all four factors yielded the highest predictive performance, with an AUC of 0.833 (95%CI: 0.783, 0.883), sensitivity of 72.7%, and specificity of 81.4%.ConclusionElevated Max VIS, increased MCA-RI, vaginal delivery, and small gestational age are independent risk factors for early mortality and severe intraventricular hemorrhage in EPIs. Each is a valuable predictor of adverse outcomes, and their combination demonstrates the highest predictive value, providing significant clinical reference for the early management of these high-risk neonates.

Total parenteral nutrition (TPN) is essential for growth in very-low-birthweight (VLBW) infants. The worldwide variation in TPN dosing strategies warrants investigation. This study compared clinical outcomes of aggressive, rapid-increase, and standard TPN dosing strategies in VLBW infants. A systematic review and network meta-analysis were conducted following the PRISMA NMA guideline. Searches were performed in PubMed, Scopus, Web of Science, CINAHL, CENTRAL, and ProQuest. Dosing strategies were classified as aggressive (higher starting dose), rapid-increase (standard start with rapid escalation), and standard (NICE-based). Outcomes were analyzed using a Frequentist model in RStudio v4.4.1. Nine randomized controlled trials were included. Compared with aggressive and standard strategies, the rapid-increase strategy was associated with a shorter time to regain birth weight (MD = -1.43 days; 95% CI -2.82 to -0.05; P-score = 0.80). The rapid-increase strategy was also associated with a shorter length of hospitalization (MD = -0.38 days; 95% CI -6.56 to 5.80; P-score = 0.54). Regarding safety outcomes, the rapid-increase strategy had the lowest proportions of mortality (Prop = 0.043), retinopathy (Prop = 0.124), and sepsis (Prop = 0.141), but a higher proportion of patent ductus arteriosus (PDA) (Prop = 0.508). The rapid-increase approach demonstrated the most favorable balance between efficacy and safety outcomes among the included trials, although the small number of studies is a limitation. Rapid-increase TPN, using the recommended starting dose but achieving maintenance more quickly, may offer clinical advantages for VLBW infants. Further long-term studies are needed to confirm developmental and metabolic impacts.

BackgroundObservational studies link high blood pressure in pregnancy to numerous adverse pregnancy and perinatal outcomes; however, findings may be affected by residual confounding or reverse causation. This study aimed to assess the causal effect of blood pressure during pregnancy on a range of pregnancy and perinatal outcomes.MethodsWe performed two-sample Mendelian randomization (MR) to assess the effect of systolic and diastolic blood pressure (SBP/DBP) during pregnancy on 16 primary and eight secondary adverse pregnancy and perinatal outcomes. We obtained genetic association data from large-scale meta-analyses of genome-wide association studies involving predominantly European ancestry individuals for SBP/DBP (N = 1,028,980), and pregnancy and perinatal outcomes (N = 74,368–714,899). We used inverse-variance weighted (IVW) MR for main analyses and MR-Egger, weighted median, weighted mode, multivariable MR, and IVW adjusted for fetal genetic effects for sensitivity analyses.ResultsA 10 mmHg higher genetically predicted maternal SBP increased the odds of gestational diabetes, induction of labour, low birth weight (LBW), small-for-gestational age (SGA), preterm birth (PTB), and neonatal intensive care unit (NICU) admission (OR ranging from 1.11 [95% CI 1.02 to 1.20] for NICU admission to 1.33 [1.26 to 1.41] for LBW); while decreasing the odds of high birth weight (HBW), large-for-gestational age (LGA), and post-term birth [OR ranging from 0.76 (0.69 to 0.83) for HBW to 0.94 (0.90 to 0.99) for post-term birth]. We did not find evidence that genetically predicted higher maternal SBP was related to miscarriage or stillbirth. The results for maternal DBP were similar to the results for SBP. Overall, the main results were consistent across sensitivity analyses accounting for pleiotropic instruments and fetal genetic effects.ConclusionsHigher maternal blood pressure reduces gestation duration and fetal growth and increases the risks of induction of labour, gestational diabetes, and neonatal intensive care unit admission. This and other emerging evidence highlight the value of interventions aimed at controlling blood pressure in the population to reduce the burden of adverse pregnancy outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12916-025-04548-3.