Search Results (1,166)

Background: Prenatal stress affects fetal neurodevelopment and may increase the risk of seizures. This study aimed to analyze the impact of maternal restraint stress during pregnancy on neonatal status epilepticus (SE) in rats. Methods: Pregnant Wistar rats were subjected to restraint stress from gestation days 12 to 20. Offspring were assessed for body weight, size, and corticosterone levels. SE was induced in postnatal day 7 rats using the lithium–pilocarpine model. Neurodegeneration was analyzed using Fluoro-Jade C staining. Results: Maternal restraint stress resulted in reduced weight gain for the mothers and lower body weight and size for their offspring. Stressed neonates exhibited higher levels of serum corticosterone. Male neonates exhibited shorter latency to stage 1 seizures and increased hippocampal neurodegeneration compared with control males, whereas female neonates were largely unaffected. Conclusions: Maternal restraint stress produced only mild, sex-dependent effects on neonatal seizure susceptibility, affecting males but not females, suggesting a limited yet selective influence of prenatal stress on early brain vulnerability. Full article

Background/Objectives: Intermittent fasting (IF), such as Ramadan fasting, is common among pregnant women despite religious exemptions. The possible impact of fasting on pregnancy outcome and, in particular, on birthweight is uncertain and was documented with conflicting evidence. Methods: The aim of this meta-analysis and systematic review was to investigate the association between intermittent fasting during pregnancy and neonatal birthweight, along with low birthweight (LBW, <2500 g) risk. Studies evaluating fasting during pregnancy with reported neonatal outcomes were included. We searched (PubMed, Scopus, Web of Science) from 2004 through June 2025. All contributing studies were observational in design; no randomized trials were identified. The risk of bias was assessed using the Newcastle-Ottawa Scale. The pooled relative risks (RR) and mean differences (MD) were calculated according to random-effects models (DerSimonian–Laird method) and heterogeneity was quantified with the I² statistic. Results: Nineteen studies, all observational in design, were included for qualitative synthesis, and six studies yielded quantitative data to conduct meta-analyses. No randomized controlled trials were identified. Intermittent fasting during pregnancy, encompassing more than 1.3 million pregnancies, was associated with a small but statistically significant reduction in neonatal birth weight. The pooled mean difference was −94 g (95% CI: −176 to −12 g; p = 0.03; I² = 70%), indicating a minor but statistically significant effect that is unlikely to be clinically meaningful. The pooled RR for LBW was 0.96 (95% CI: 0.88–1.05; p = 0.38; I² < 10%), showing no association between fasting and low birthweight risk. Sensitivity analyses reduced heterogeneity (I² ≈ 55%) and confirmed the robustness of these findings. According to the GRADE approach, the certainty of evidence was moderate for birthweight and high for LBW. Conclusions: Intermittent fasting during pregnancy, including Ramadan fasting, was associated with a minor but statistically significant reduction in neonatal birthweight without increasing the risk of low birthweight. This difference was small and clinically negligible. Further prospective studies are needed to clarify trimester-specific effects and long-term developmental outcomes. Full article

Background/Objectives: Systemic hydrocortisone (HCS) in very low birth weight (VLBW) infants is commonly used to treat early hypotension or prevent bronchopulmonary dysplasia. This study evaluated the associations between postnatal HCS exposure and neurodevelopment in VLBW infants by comparing regional brain volume at term-equivalent age (TEA) with neurodevelopmental outcomes in early infancy. Methods: This retrospective cohort study included VLBW infants admitted to a neonatal intensive care unit (NICU) between 2013 and 2019. The cumulative HCS dose during hospitalization was recorded, and regional brain volumes were analyzed using magnetic resonance imaging at TEA. Neurodevelopmental outcomes were assessed at a corrected age for prematurity of 18–24 months. Results: Among 146 infants, 57 were classified in the high HCS group (>90 mg/kg) and 89 in the low HCS group (≤90 mg/kg HCS). Bronchopulmonary dysplasia, periventricular leukomalacia, and sepsis were more frequent in the high HCS group. Ninety-five infants underwent magnetic resonance imaging, which revealed reduced brain volumes in the high HCS group. At follow-up, cerebral palsy (35.9% vs. 9.1%, p = 0.003), neurodevelopmental impairment (54.0% vs. 23.6%, p = 0.002), and head circumference <10th percentile (64.3% vs. 19.5%, p < 0.001) were more common in the high HCS group. After adjustment, HCS > 90 mg/kg remained independently associated with cerebral palsy (adjusted odds ratio [aOR] 5.44, p = 0.016) and reduced head circumference (aOR 4.45, p = 0.016). Conclusions: High cumulative HC exposure correlated with reduced brain volume at TEA and adverse neurodevelopmental outcomes at 24 months of age. Careful monitoring of dose and treatment duration is essential to balance therapeutic benefits against potential risks. Full article

Background: We aimed to compare the perinatal outcomes of dichorionic/diamniotic twin (DC/DA) pregnancies resulting from in vitro fertilization (IVF) with those resulting from spontaneous DC/DA pregnancies. Methods: The study group included 99 women with DC/DA pregnancies resulting from IVF, and the control group included 92 women with spontaneous DC/DA pregnancies. Maternal demographic characteristics (age, parity, and gravidity), pre-existing conditions (chronic hypertension and pregestational diabetes mellitus), and obstetric history were recorded. Pregnancy outcomes included gestational age at delivery, number of fetuses, and mode of delivery. The antepartum complications that we evaluated include first- and second-trimester bleeding, placenta previa, preterm birth, fetal growth restriction (FGR), oligohydramnios, and tocolytic use. The obstetric complications that we assessed include prematurity, twin-to-twin transfusion syndrome (TTTS), and hydrops fetalis. Additionally, neonatal data such as 1st minute and 5th minute Apgar scores, birth weight, neonatal intensive care unit (NICU) admission, presence of congenital anomalies, and neonatal death were recorded, and comparisons were made between the groups. Results: Women in the IVF group were older (34.7 ± 6.9 vs. 32.3 ± 6.1 years, p = 0.03) and more frequently primiparous (73.7% vs. 37.0%, p < 0.001). The mean gestational age at delivery was slightly lower in the IVF group, though this was not statistically significant (34.3 ± 3.5 vs. 35.1 ± 2.5 weeks, p = 0.101). Cesarean delivery was common in both groups, with comparable overall rates (90.9% vs. 94.6%, p = 0.411), but emergency cesarean section occurred more frequently in IVF pregnancies (81.8% vs. 55.8%, p = 0.001). No significant differences were found regarding chronic hypertension or pregestational diabetes. However, several differences were demonstrated in terms of obstetric complications. For example, preterm births and fetal growth restriction (FGR) were significantly more frequent in IVF pregnancies (59.8% vs. 30.4%, p < 0.001), and tocolytic use was also more frequent (56.6% vs. 29.7%, p < 0.001). No significant differences were observed in terms of placenta previa, oligohydramnios, TTTS, hydrops fetalis, and neonatal outcomes. The logistic regression analysis revealed that IVF pregnancies were associated with an increased risk of preterm birth: OR 3.45, 95% CI 1.85–6.78 (p < 0.001); the risk of FGR was also higher in IVF pregnancies: OR 2.11, 95% CI 1.02–4.37 (p = 0.015). However, tocolytic use was not significantly associated with IVF: OR 1.49, 95% CI 0.50–4.44 (p = 0.471). Conclusions: Although DC/DA pregnancies conceived through IVF have a higher risk of preterm birth, fetal growth restriction, and greater use of tocolytic agents than spontaneous DC/DA pregnancies, their neonatal outcomes are similar. Full article

Background and Objectives: Neonates and children are at high risk of medication errors (ME) with intravenous (IV) infusion therapies, particularly when strategies such as the “rule of six” with individualized, weight-based concentrations are used. Standard concentrations (SCs) have been proposed to reduce variability, improve safety, and facilitate the use of electronic prescribing and smart infusion technologies. The impact of SCs for continuous IV infusions on ME rates in neonatal and pediatric settings was systematically evaluated. Methods: A systematic review was conducted in MEDLINE, Embase and CINAHL (database inception-August 2025) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies implementing SCs for neonatal or pediatric IV infusions and measuring outcomes referring to ME rates were included. The relative risk reduction/increase in MEs was calculated. Results: Five uncontrolled before-after studies published between 2005 and 2020 were included. The relative risk reductions ranged from 41.2% to 95.1% for overall ME and from 49.7% to 100% for selected error types. In two studies, the relative risk for two error types (paper-generated prescriptions, administration) increased after implementing SCs. Reviewed benefits included decreased calculation and preparation errors, reduced medication process times, improved workflow efficiency and high staff satisfaction. Conclusions: SCs may contribute to safer IV infusion practice in the neonatal and pediatric setting, especially combined with smart technologies and training. However, current evidence is limited and heterogeneous. Larger, prospective experimental studies are needed to confirm their long-term impact on pediatric ME rates. Full article

Background and Objectives: Necrotizing enterocolitis (NEC) represents a severe gastrointestinal emergency in preterm infants. The aim of this study was to identify risk factors and predictive parameters for NEC requiring surgery and to evaluate associated short-term outcomes. Materials and Methods: We conducted a retrospective study in preterm neonates diagnosed with NEC admitted to a tertiary neonatal intensive care unit (NICU) between January 2015 and May 2025. Demographic data, perinatal events, risk factors, clinical signs, imaging findings, and outcomes were analyzed, with a particular focus on surgically managed cases. Descriptive and inferential statistical methods were applied. Results: Forty-four infants met the inclusion criterion. The mean gestational age (GA) was 29.34 ± 4.3 weeks, and the mean birth weight was 1100 ± 563 g. According to Bell’s severity index, 45.5% had Bell Stage I, 36.4% Stage II, and 18.2% Stage III. Eleven patients (25%) required surgery. All surgical patients had abdominal distension, and 63.6% had bilious gastric residue. Abdominal X-ray showed pneumoperitoneum in 72.7% and pneumatosis intestinalis in 27.3% of cases. Laboratory abnormalities, including thrombocytopenia, elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and hyponatremia (45.5%; 133 ± 6.95 mmol/L), were frequently associated with surgical NEC. A lower GA and birth weight correlated with a higher Bell stage (p = 0.0085 and p = 0.0291). Overall mortality was 29.5% (13/44); surgical mortality was 9.1% (1/11). Conclusions: In this single-center lot, low gestational age and birth weight, abdominal distension with bilious residuals, systemic inflammation, and hyponatremia were frequent among infants who required surgery. Selected infants may benefit from early surgery even without perforation, but inferences are limited by this study’s sample size and retrospective design. Prospective multi-center studies are needed to validate predictors and refine surgical timing. Full article

(1) Background: Preterm infants are deprived of crucial growth and development that occurs during the last trimester of pregnancy. Optimal nutrition after birth, including sufficient intakes of protein and energy, have been emphasized to improve postnatal growth and development of preterm infants. This study investigated the impact of routine nutritional strategies as used in a Neonatal Intensive Care Unit in South Africa and in the Netherlands, respectively, on the preterm infant’s postnatal growth; (2) Methods: This retrospective observational study included 100 preterm infants from a South African cohort and 86 preterm infants from a Dutch cohort. Over the first four postnatal weeks, total intravenous (IV) fluid volume (i.e., IV. glucose and/or parenteral nutrition (PN) and enteral nutrition (EN) were recorded, and total energy and protein intakes were calculated. Anthropometric measurements were taken and expressed as Z-scores per week; (3) Results: At birth, the South African cohort had a higher gestational age compared to the Dutch cohort; however, weight, length and head circumference Z-scores were lower. During the first four postnatal weeks, the Dutch cohort had a significant higher total energy and protein intakes by the combination of PN and EN than the South African cohort, that mostly received EN only. In addition, the South African cohort showed a more pronounced decline in Z-scores compared to the Dutch cohort; (4) Discussion: Over the 4-week study period, the South African cohort showed more pronounced growth faltering compared to the Dutch cohort preceded by lower total energy and protein intakes; (5) Conclusions: The use of PN, while EN is incremented daily, should be considered in the South African cohort to diminish postnatal growth faltering in preterm infants. Full article

Objectives: Gestational diabetes mellitus (GDM), particularly when combined with overweight or obesity, is associated with adverse neonatal outcomes such as high birth weight and increased adiposity. We determined the effect of a preconception lifestyle intervention initiated before and continued throughout pregnancy on neonatal, birth-related, and body composition outcomes at birth and 6–8 weeks of age in children of participants in the BEFORE THE BEGINNING randomized controlled trial. Methods: People (N = 167) at increased risk of GDM and planning pregnancy were randomly allocated 1:1 to intervention or control. The intervention included time-restricted eating and exercise training. Time-restricted eating involved consuming all energy within ≤10 h/day, ≥5 days per week, and the amount of exercise was set using a heart rate-based physical activity metric (Personal Activity Intelligence, PAI), with the goal of ≥100 weekly PAI points. The main outcome of interest in this report was the proportion of infants with birth weight > 4.0 kg. Results: Among 106 live births, 21% (11/53) of infants in the intervention group and 28% (15/53) in the control group had birth weight > 4 kg (p = 0.367). Mean birth weight did not differ significantly between groups (mean difference −159.3 g, 95% confidence interval −375.7 to 57.2, p = 0.148). No significant between-group differences were found for additional neonatal, birth-related, or early postnatal body composition outcomes. Conclusions: In this secondary analysis, we found no evidence of effects of a preconception lifestyle intervention on the risk of macrosomia or neonatal body composition. Full article

Background/Objectives: Histological chorioamnionitis (HCAM) is a risk factor of chronic lung disease (CLD) in preterm neonates. Funisitis, an indicator of fetal inflammatory response, has been linked to adverse neonatal outcomes, but its impact on respiratory outcomes in extremely preterm neonates remains uncertain. In this study, we investigated whether HCAM with funisitis is associated with poorer respiratory outcomes when compared with HCAM alone in preterm (gestational age 22–36 weeks) neonates. Methods: This was a retrospective cohort study. We divided very low-birth weight (VLBW) preterm neonates with placenta histopathology examinations into three groups—normal, isolated HCAM, and HCAM with funisitis. Perinatal characteristics, radiographic findings, morbidities, and respiratory outcomes were compared. Results: Among 244 VLBW neonates, 25 (10.2%) had HCAM with funisitis, 88 (36.1%) had isolated HCAM, and the remaining 131 were in the normal group. Neonates with HCAM and funisitis had a significantly lower gestational age (26.44 ± 2.1 weeks) but a higher incidence of clinical chorioamnionitis (40.0%) than those with isolated HCAM (12.5%) or normal placentas (6.9%). Moreover, the incidence of cystic–interstitial lung changes before 2 weeks of postnatal age was higher in the HCAM with funisitis group (56.5%) than in the isolated HCAM group (25.0%), and the normal group (4.4%). CLD occurred in 66.7%, 37.7%, and 1.3% of these groups, respectively, and the need for home oxygen at follow-up was 26.1%, 13.7%, and 6.4%. Both isolated HCAM and HCAM with funisitis protected against severe respiratory distress syndrome. However, extremely preterm birth and funisitis had a more adverse impact on CLD development than HCAM alone (adjusted odds ratio 15.259 vs. 3.841). Conclusions: Funisitis independently predicts poor respiratory outcomes in extremely preterm infants. The long-term clinical impacts of funisitis in preterm infants should be further investigated. Full article

Background/Objectives: Prolonged hospitalization of clinically stable preterm infants may lead to nosocomial infections, interfere with breastfeeding, and hinder parent-infant bonding. We evaluated the impact of an early discharge program with hospital-at-home (HaH) on hospital stay and clinical outcomes among preterm infants. Methods: A retrospective case–control study was conducted in a tertiary neonatal unit (Spain). Fifty infants managed with HaH (2016–2020) were compared with ninety-six controls receiving conventional in-hospital care. Baseline characteristics, growth, and clinical events up to 12 months were collected. Analyses included bivariate comparisons and multiple linear regression for length of stay, adjusted for gestational age, birth weight, sex, and parental factors. Results: Baseline characteristics were comparable between groups. Discharge weight was lower in HaH infants (1865 vs. 2130 g; p < 0.001), but no differences were observed at 6 or 12 months. Length of stay was shorter in HaH infants (26.3 vs. 33.8 days; p = 0.081), and the multivariable model showed an independent 5.5-day reduction (β −5.53; 95% CI −10.96 to −0.11; p = 0.046). Exclusive breastfeeding was more frequent (74% vs. 59%; p = 0.08) and significantly longer in HaH infants (141.9 vs. 81.1 days; p = 0.024). No increases were found in complications at discharge, emergency visits (28% vs. 32%; p = 0.7), or readmissions (18% vs. 31%; p = 0.2). Conclusions: Among clinically stable preterm infants, early discharge with HaH was associated with a shorter hospital stay and longer exclusive breastfeeding duration, without evidence of increased morbidity or healthcare use; however, causal inference cannot be established due to the observational design. These findings support the implementation of nurse-led HaH programs as a safe, family-centered strategy for neonatal care. Full article

Background: Medication safety in pregnancy, puerperium, and perinatal periods is underexplored because these populations are excluded from clinical trials. EudraVigilance offers post-marketing evidence, but disproportionality analyses focus on isolated drug event pairs and may miss syndromic patterns. We applied a network- and cluster-based framework to EudraVigilance reports on antiviral use in pregnancy to improve surveillance and identify meaningful constellations. Methods: We retrieved all individual case safety reports (ICSRs) from January 2015 to June 2025, including pregnancy, puerperium, or perinatal terms, focusing on suspect antivirals. After parsing terms, disproportionality metrics were computed as a benchmark. A bipartite drug–event network was built and projected to event–event co-occurrence networks; Louvain community detection identified clusters. Clusters were characterized by size, drug mix, seriousness, overlap with disproportionality signals, and stratification across periods. Results: The dataset comprised 106,924 ICSRs and 232,067 unique pairs. Disproportionality yielded 6142 signals, mainly involving antiretrovirals (ritonavir, lamivudine, zidovudine, emtricitabine/tenofovir). Network analysis revealed clusters grouping maternal and fetal/neonatal outcomes (e.g., fetal death, low birth weight), and transplacental transfer, highlighting structures not visible in pairwise analyses. Several clusters combined high-frequency exposures with clinically relevant outcomes, suggesting early-warning potential. Conclusions: Combining disproportionality with network- and cluster-based pharmacovigilance adds value for monitoring pregnancy medication safety. Beyond individual signals, this approach reveals meaningful clusters and “bridge” reactions connecting adverse-event domains, offering a richer framework for perinatal surveillance. Despite spontaneous-reporting limits, findings generate hypotheses for mechanistic and pharmacoepidemiologic follow-up and support network methods as complements to traditional pharmacovigilance. Full article

Hyperbilirubinemia, commonly known as jaundice, is a prevalent condition in newborns, primarily arising from alterations in red blood cell metabolism during the first week of life. While conventional diagnostic methods, such as serum analysis and transcutaneous bilirubinometry, are effective, there remains a critical need for robust, non-invasive, image-based diagnostic tools. In this study, we propose a custom-designed convolutional neural network for classifying jaundice in neonatal images. Image preprocessing and segmentation techniques were systematically evaluated. The optimal workflow, which incorporated contrast enhancement and the extraction of regular skin patches of 144 × 144 pixels from regions of interest segmented using the Segment Anything Model, achieved a testing F1-score of 0.80. Beyond performance, this study addresses numerous shortcomings in the existing literature in this area relating to trust, replicability, and transparency. To this end, we employ fair performance metrics that are more robust to class imbalance, a transparent workflow, share source code, and use Gradient-weighted Class Activation Mapping to visualise and quantify the image regions that influence the classifier’s predictions in pursuit of epistemic justification. Full article

Background/Objectives: Melatonin, produced by the placenta and pineal gland, regulates circadian timing and has antioxidant and immunomodulatory actions. After birth, neonatal secretion is low and its circadian pattern matures over months; evidence in preterm neonates is mixed. We longitudinally monitored morning blood melatonin from birth to 38 weeks’ postmenstrual age (PMA) in breast milk-fed preterm neonates, assessing differences by time of birth (day vs. night), PMA, and weight-for-gestational-age (WfGA). Methods: A prospective NICU cohort, conducted within the ProMote study. In total, 132 preterm neonates were recruited from 112 mothers. For infants ≥33 weeks’ GA, three samples were obtained: umbilical cord (available in 94; otherwise at the first NICU admission), day of life (DOL) 4–7, and DOL 10–14; for infants <33 weeks’ GA, an additional sample at 35–36 weeks’ PMA. Melatonin was measured by ELISA. Primary analyses used raw melatonin concentrations in linear mixed-effects models; sensitivity analyses checked robustness. Results: A final sample comprised 122 neonates. Concentrations were low to modest with wide between-neonate variation and no monotonic change across PMA. Mixed models showed no consistent differences by time of birth and no stable WfGA effect; occasional PMA-specific contrasts did not recur at adjacent time points. Umbilical cord concentrations were low, and gestational age at birth did not materially influence levels at a given PMA. Sensitivity analyses led to the same inference. Conclusions: In breast milk-fed preterm neonates, morning serum melatonin from 26–38 weeks’ PMA shows substantial individual variability without consistent differences by time of birth, PMA, or WfGA. Full article

Hypoxia-ischemia is a serious perinatal complication affecting neonates globally. Animal models have increased the understanding of its pathophysiology and have been used to investigate potential therapies. Exenatide, clinically used for the treatment of type 2 diabetes mellitus, also protects the rodent brain from hypoxia-ischemia. The rabbit brain has an earlier neurodevelopmental maturation than rodents, as well as similar postnatal maturation to humans. We hereby introduce a new, reproducible hypoxia-ischemia model in rabbit kits at postnatal day (P) 3–4. Following hypoxia-ischemia, rabbit kits received different exenatide concentrations: 170 μg/g (2-dose) or 500 μg/g (1- or 2-dose), or vehicle. The brains were collected seven days later for histological assessment showing that 500 μg/g exenatide, either as a 1- or 2-dose regimen, reduced brain tissue loss by 90% in hypoxia-ischemia experiments both at P3 and P4. A second cohort received a 1-dose 500 μg/g of exenatide or vehicle, and were sacrificed at different early time-points for glucose, ketone bodies, body weight, and temperature measurements. Our results showed a transient 2-fold increase in ketone bodies (0.6 to 1.3 mmol/L) at 6 h. Exenatide did not affect glucose, body temperature or weight gain and appears to be safe and well tolerated in the rabbit model of hypoxia-ischemia. Full article

Background/Objectives: Postnatal growth restriction and duration of hospital stay have been identified as risk factors for adverse neurodevelopment in preterm infants. Implementation of a family-centered care (FCC) program in our institution reduced length of stay in preterm infants. This study evaluates the effect of more early discharge on growth up to three months postmenstrual age (PMA). Methods: We conducted a prospective, single-center cohort study in a German level III neonatal unit (October 2020–November 2023) including six consecutive cohorts (n = 184) with progressive FCC implementation. This secondary analysis examined growth at discharge, term-equivalent age (TEA), and three months PMA. Results: PMA at discharge significantly decreased from the baseline to intervention cohort 5 (37.8 ± 2.1 vs. 35.7 ± 0.91 weeks PMA; p = 0.03). Compared to the baseline cohort, infants in intervention cohort 5 had significantly lower weight, length, and head circumference at discharge. However corresponding Z-Scores did not differ significantly between the cohorts. No significant differences in growth outcomes were observed at TEA or at three months PMA. Furthermore, there were no significant differences in the change in Z-Score for weight, length, and HC from birth to three months PMA. Conclusions: Early discharge under FCC did not impair growth to three months PMA, suggesting that early discharge is a safe practice with respect to growth outcomes in preterm infants. Further randomized multicenter studies are needed to confirm these results. Full article