Early life vitamin D levels may be associated with autism spectrum disorder (ASD) and related traits, but causality is unknown. We examine whether higher-than-standard vitamin D 3 supplementation during the first 2 years, as well as higher pregnancy and childhood 25-hydroxyvitamin D (25(OH)D) levels and their trajectories, are associated with lower ASD trait scores at ages 6–8 years in a non-clinical cohort. This secondary analysis of the double-blind randomized clinical trial vitamin D intervention in infants (VIDI) comprised 366 Finnish children aged 6–8 years, 177 of whom were randomized to receive 400-IU and 189 to receive 1,200-IU daily oral vitamin D 3 supplementation between ages 2 weeks and 2 years. ASD-related traits were assessed at mean age 7.2 years (SD 0.4) using the parent-reported Autism Spectrum Screening Questionnaire (ASSQ). Predictor variables were supplementation group, 25(OH)D concentrations measured during pregnancy and at ages 1 and 2 years, as well as 25(OH)D trajectories (high vs. low) derived from these time points. None of the predictor variables of interest were associated with the outcome in the full sample. After sex stratification, among boys, 25(OH)D concentrations at 1 and 2 years were inversely associated with ASSQ scores (mean difference −0.2 of normalized SD score (95% CI −0.3 to −0.1, p  = .003) and −0.2 (95% CI −0.3 to −0.05, p  = .01) per 10 ng/mL 25(OH)D) after adjustment for age, breastfeeding, parental education, maternal depressive symptoms, and season of 25(OH)D assessment as was belonging to the higher 25(OH)D trajectory, −0.45 SD (95% CI −0.79 to −0.10, p  = .01). We found no indication that higher-than-normal vitamin D 3 supplementation between ages 0 and 2 years decreases ASD-related trait scores at ages 6–8 years. Sex-stratified analysis suggested an inverse association, among boys, between early life 25(OH)D concentrations and ASD-related traits, warranting further studies on potential causal direction and sex specificity of associations.

We aimed to investigate the impact of the delivery mode, comparing vaginal deliveries with elective Caesarean deliveries, on neonatal gene expression and immune system activation. By examining the differences in gene expression profiles and inflammatory markers in neonatal cord blood, the study sought to elucidate the biological processes influenced by the delivery mode. This study was conducted in Helsinki University Hospital, Finland, from 2018 to 2019. Study subjects were recruited at the hospital prior to delivery. Ribonucleic acid sequencing and the Olink Target 96 Inflammation panel were employed to analyze gene expression and protein levels in umbilical cord blood. The study involved 24 mothers and their newborn infants. The results revealed significant differences in gene expression between the Vaginal and Caesarean groups. In the Vaginal group, 95 genes were significantly upregulated, including those related to immune response and stress response. The Olink analysis indicated higher levels of interleukin 6, interleukin 8, and tumour necrosis factor superfamily member 14 in the Vaginal group. However, these differences lost significance after correction for multiple testing. This study demonstrates that the mode of delivery significantly influences neonatal gene expression and immune system activation.

BACKGROUND:Early life vitamin D levels may be associated with autism spectrum disorder (ASD) and related traits, but causality is unknown. We examine whether higher-than-standard vitamin D3 supplementation during the first 2 years, as well as higher pregnancy and childhood 25-hydroxyvitamin D (25(OH)D) levels and their trajectories, are associated with lower ASD trait scores at ages 6-8 years in a non-clinical cohort. METHODS:This secondary analysis of the double-blind randomized clinical trial vitamin D intervention in infants (VIDI) comprised 366 Finnish children aged 6-8 years, 177 of whom were randomized to receive 400-IU and 189 to receive 1,200-IU daily oral vitamin D3 supplementation between ages 2 weeks and 2 years. ASD-related traits were assessed at mean age 7.2 years (SD 0.4) using the parent-reported Autism Spectrum Screening Questionnaire (ASSQ). Predictor variables were supplementation group, 25(OH)D concentrations measured during pregnancy and at ages 1 and 2 years, as well as 25(OH)D trajectories (high vs. low) derived from these time points. RESULTS:None of the predictor variables of interest were associated with the outcome in the full sample. After sex stratification, among boys, 25(OH)D concentrations at 1 and 2 years were inversely associated with ASSQ scores (mean difference -0.2 of normalized SD score (95% CI -0.3 to -0.1, p = .003) and -0.2 (95% CI -0.3 to -0.05, p = .01) per 10 ng/mL 25(OH)D) after adjustment for age, breastfeeding, parental education, maternal depressive symptoms, and season of 25(OH)D assessment as was belonging to the higher 25(OH)D trajectory, -0.45 SD (95% CI -0.79 to -0.10, p = .01). CONCLUSIONS:We found no indication that higher-than-normal vitamin D3 supplementation between ages 0 and 2 years decreases ASD-related trait scores at ages 6-8 years. Sex-stratified analysis suggested an inverse association, among boys, between early life 25(OH)D concentrations and ASD-related traits, warranting further studies on potential causal direction and sex specificity of associations.

BACKGROUND:Animal experimental studies and human observational data suggest that fetal inflammatory response to chorioamnionitis is associated with increased risk of neonatal encephalopathy and attenuation of fetal responses to intrapartum hypoxia-ischemia, but the effects of clinical and/or histological chorioamnionitis and fetal inflammatory response on fetal heart rate patterns during labor in the term human fetus remain undefined. OBJECTIVE:To compare intrapartum fetal heart rate responses to hypoxia, assessed by fetal heart rate deceleration frequency and cumulative deceleration area, in acidemic fetuses in term labor to their peers with and without hypoxic-ischemic encephalopathy and clinical and/or histological chorioamnionitis. STUDY DESIGN:This retrospective cohort study included 317,126 term singleton deliveries from 7 hospitals in the Helsinki University Hospital district, Finland, between 2005 and 2024. Among these, 3487 newborns with umbilical artery acidemia, defined as pH<7.10, and continuous intrapartum cardiotocographic recordings were identified. Fetal heart rate data from the final 9 hours before birth were analyzed, with hourly median values calculated for deep deceleration (decreases of ≥60 beats per minute below baseline lasting >15 seconds) and shallow deceleration (decreases of 10-15 beats per minute lasting >15 seconds) frequencies, cumulative deceleration area (all decelerations of ≥10 beats per minute lasting >15 seconds), and uterine contraction frequency. Neonatal hypoxic-ischemic encephalopathy was diagnosed according to Sarnat staging, and chorioamnionitis based on clinical criteria and/or placental histology. Acidemic cases were categorized into 4 groups: acidemia with hypoxic-ischemic encephalopathy and clinical and/or histological chorioamnionitis (N=133), acidemia with hypoxic-ischemic encephalopathy without chorioamnionitis (N=181), acidemia with clinical and/or histological chorioamnionitis without hypoxic-ischemic encephalopathy (N=436), and acidemia without hypoxic-ischemic encephalopathy or chorioamnionitis (N=2737). RESULTS:Among 3487 term fetuses with umbilical artery acidemia, clinical and/or histological chorioamnionitis was associated with an increased risk of hypoxic-ischemic encephalopathy (adjusted odds ratio, 4.61; 95% confidence interval, 3.60-5.87; P<.001), despite a shift toward less severe umbilical artery acidemia, with a greater proportion of moderate (pH 7.09-7.00) and a lower proportion of severe (pH<7.00) acidemia (P=.026). Among histological chorioamnionitis cases, funisitis, a histopathologic manifestation of the fetal inflammatory response, remained independently associated with hypoxic-ischemic encephalopathy after adjustment for acidemia severity (adjusted odds ratio, 2.21; 95% confidence interval, 1.32-4.13; P<.001). Consistent with these findings, clinical and/or histological chorioamnionitis was associated with attenuated fetal heart rate responses to intrapartum hypoxic stress. Among fetuses who developed hypoxic-ischemic encephalopathy, those with clinical and/or histological chorioamnionitis exhibited fewer deep decelerations (adjusted ratio of medians, 0.62; 95% confidence interval, 0.49-0.76), a smaller cumulative deceleration area (adjusted ratio of medians, 0.70; 95% confidence interval, 0.59-0.82), and more shallow decelerations (adjusted ratio of medians, 2.45; 95% confidence interval, 2.33-2.63; all P<.001), despite similar uterine contraction frequency, with attenuation most pronounced among fetuses with funisitis. Clinical chorioamnionitis alone remained independently associated with hypoxic-ischemic encephalopathy (adjusted odds ratio, 1.44; 95% confidence interval, 1.02-2.05; P<.001), whereas histological chorioamnionitis was associated with a 2.5-fold higher risk than clinical chorioamnionitis alone (adjusted odds ratio, 2.54; 95% confidence interval, 1.68-3.86; P<.001). CONCLUSIONS:Clinical and histological chorioamnionitis, particularly when accompanied by funisitis, are associated with attenuated fetal heart rate responses to intrapartum hypoxic stress and reduced fetal tolerance to hypoxia, thereby increasing the risk of hypoxic-ischemic encephalopathy at milder degrees of acidemia.

OBJECTIVE:Low 25-hydroxyvitamin D concentration (25(OH)D) has been associated with sleep problems. There are no randomized trials on the association in childhood. We tested whether a high vs standard vitamin D3 dose has beneficial effects on sleep until 2 years of age and whether early life 25(OH)D is associated with sleep. METHODS:VIDI-study [Vitamin D Intervention in Infants] is a double-blind randomized clinical trial. Children received vitamin D3 supplementation of 400-IU (n = 421) or 1200-IU (n = 424) daily until 24 months of age. Blood 25(OH)D was analyzed and parents completed questionnaires at 11.7 (SD = 0.7) and at 26.0 (SD = 3.0) months (Brief Infant Sleep Questionnaire, Sleep Disturbance Scale for Children). Maternal 25(OH)D was analyzed at mean 11.3 (SD = 2.2) gestational weeks. We used regression models adjusted for season of birth, breastfeeding, gestational age, parental education, and mother's age, body-mass-index, smoking and sleep. RESULTS:High-dose versus standard-dose supplementation was not associated with child's sleep up to 24 months. Children with 25(OH)D ≥ 75 nmol/L at 12 months had less sleep disturbances at 24 months (adjusted for all covariates: B = -1.46 points 95 % CI: 2.89; -0.04, p = 0.05), especially disorders of arousal (B = -0.40, 95 % CI: 0.64;-0.15, p = 0.002). We also found associations between maternal 25(OH)D ≥ 75 nmol/L during pregnancy and child's more favorable sleep characteristics. CONCLUSION:We observed that high-dose versus standard-dose vitamin D3 provides no benefits for child's sleep, even if we found an association between child's higher 25(OH)D and less sleep disturbances. Higher maternal 25(OH)D during pregnancy was associated with child's better sleep, which should be studied further.

Amino-terminal propeptide of type 1 procollagen (P1NP) and carboxy-terminal crosslinked telopeptide of type 1 collagen (CTX-I) are markers of bone metabolism. We examined the effect of vitamin D3 supplementation on these markers and their relationship with growth and bone parameters in 12-month-old infants. In a randomized, double-blinded, vitamin D intervention in infants (VIDI) study, 987 infants received daily vitamin D3 supplementation of 10 μg (group-10) or 30 μg (group-30) from age 2 weeks to 24 months. We conducted a secondary analysis of the original VIDI trial. At 12 months of age, P1NP (n = 812) and CTX-I (n = 786) concentrations were analyzed, and anthropometrics and total bone mineral content, volumetric bone mineral density, cross-sectional area and polar moment of inertia of tibia were measured by peripheral quantitative computed tomography. The growth rate in weight and length was calculated from birth to 12 months. The vitamin D dose did not influence mean (SD) levels of CTX-I (group-10: 0.90 (0.31); group-30: 0.89 (0.31) (P > 0.53)). The mean difference of P1NP (CI 95%) comparing group-10 with group-30 was 35 (−103, 33) ng/mL (P = 0.31) in boys and −63 (−4, 130) ng/mL (P = 0.064) in girls. In group-10, girls had higher mean (SD) value of P1NP (1509 (362) ng/mL) than boys (1407 (297) ng/mL) (P = 0.003); no sex differences were observed in group-30 (girls: 1446 (359); boys: 1442 (359), P = 0.91) or CTX-I. P1NP associated positively with the growth rate in length (B (CI 95%) 0.0003 (0.0001, 0.001), P = 0.022) in the whole cohort but not in subgroups divided by the intervention group or sex, adjusted for birth size and parental heights and corrected for multiple testing. P1NP associated positively with the growth rate in weight (0.01 (0.0003, 0.01), P < 0.001). An inverse association was observed between CTX-I and length (cm) in the whole cohort (−0.90 (−1.40, −0.40), P = 0.005) and in group-30 (−1.05 (−1.72, −0.39), P = 0.011). Furthermore, CTX-I associated negatively with weight (SDS) in the whole cohort (−0.33 (−0.55, −0.12), P = 0.015) and the growth rate in weight (−0.43 (−0.66, −0.20), P = 0.005), persisting in group-30 and in boys but not in group-10 or in girls. Neither marker was associated with bone parameters. The observed sex difference in P1NP might suggest that a higher vitamin D dose resulted in a small decrease in bone collagen matrix formation in girls but not in boys. P1NP and CTX-I associate with growth and body size but not with bone mineralization in infancy.

Vitamin D is suggested to impact neurodevelopment, yet the current evidence is conflicting. We tested if vitamin D3 supplementation during the first two years of life, maternal 25-hydroxy-vitamin D (25(OH)D) concentration during pregnancy, and child’s 25(OH)D concentrations at 12 and 24 months are associated with neurocognitive abilities in 6.6-8.9-year-old children. Participants were from a Finnish vitamin D double-blind randomized clinical trial and classified themselves white. Children received either vitamin D3 400-IU (n = 189) or 1200-IU (n = 209) daily until 24 months of age. Serum 25(OH)D was analyzed from mothers at mean of 11.2 weeks of gestation, and from children at 12.0 and 23.9 months (25(OH)D, mean (SD) = 83.8 (21.7), 102.3 (30.1), 105.5 (28.6) nmol/L, respectively). Total Intelligence quotient (IQ) score was assessed with Wechsler Intelligence Scale for Children (WISC-IV) and executive functioning with A Developmental Neuropsychological Assessment (NEPSY-II) and parent-rated Behavior Rating Inventory of Executive Function (BRIEF) questionnaire. Neurocognitive abilities at age 6–8 years did not differ between the supplementation groups or according to 25(OH)D concentration at 12 or 24 months (total IQ: β = 1.14, 95

BACKGROUND:Young adults born preterm with very low birth weight (VLBW; <1500 g), especially those who had neonatal bronchopulmonary dysplasia (BPD), have reduced lung function compared with their term-born peers. We hypothesized that these impairments worsen between young and mid-adulthood. METHODS:We studied two birth cohorts: HeSVA (Finland) and NTNU LBW Life (Norway) with harmonized protocols. Lung function was assessed by spirometry in 115 VLBW (20 with BPD) and 142 controls at mean 36 years. The results were compared with young adulthood (22 years) spirometry in 198 VLBW (32 with BPD) and 225 control participants. RESULTS:In mid-adulthood, BPD-VLBW adults had lower z-scores in forced expiratory volume in 1 s (zFEV1; mean difference -1.49; 95%CI -1.94, -1.04) and in zFEV1/FVC (FVC: forced vital capacity; mean difference -0.84, 95%CI -1.23, -0.44) than controls. Corresponding differences for non-BPD-VLBW adults were -0.34 (95%CI -0.60, -0.08) and -0.30 (95%CI -0.53, -0.07). The differences in zFVC and zFEV1 between BPD-VLBW and control groups increased from young to mid-adulthood. CONCLUSION:In mid-adulthood, adults born preterm with VLBW had reduced airflow compared with term-born controls. These differences were more pronounced among those with a history of BPD, whose vital capacity also seems to decline faster. IMPACT:Impaired airflow and reduced vital capacity in VLBW adults do not improve with age. Among those with a history of BPD, vital capacity seems to reduce faster than among their term-born peers. Clinicians who see adults born preterm with VLBW should be vigilant for respiratory symptoms. We argue that a full medical history in all adults who present with respiratory symptoms should routinely include key birth characteristics such as preterm birth.

Cognitive functions emerge from dynamic functional interplay of cortical and subcortical areas that form networks. Preterm birth poses a risk for the formation and functionality of brain networks which may lead to severe brain dysfunctions. Infants born extremely preterm have the highest risk of developing neurocognitive impairments. However, it is still poorly understood how functional brain networks are organized and linked with the cognitive impairments in extremely prematurely born children and adolescents. We applied network-based statistics to study functional network connectivity during two brain-states, resting-state (Rest) and visuospatial working memory n-back tasks (Task), in a unique cohort of extremely preterm-born school-aged children and adolescents (n = 24, mean age 10.3 y, range 7.4-16.4 y) with normal general cognitive abilities and in their term-born peers (n = 22, mean age 9.5 y, range 7.4-13.7 y). We found significant group differences in functional connectivity strength in networks that support complex cognitive performance. The preterm group, compared with controls, modulated functional connectivity between Rest and Task differently within the dorsal attention (DAN, p = 0.016), default mode (DMN, p = 0.026) and visual (VN, p = 0.022) networks, and between DMN - DAN (p = 0.024), DMN - ventral attention network (VAN) (p = 0.035), and DMN - frontoparietal network (FPN) (p = 0.015). The groups also showed opposite age-related changes in connectivity strength within the DAN (Task, p = 0.005; Rest, p = 0.012), DMN (Task, p = 0.015) and FPN (Task, p = 0.002), and between the DAN - VAN (p = 0.047) and DAN - FPN (p = 0.009) during Rest, and FPN - VAN (p =0.028), DAN - FPN (p = 0.006), DMN - DAN (p = 0.042), DMN - VAN (p = 0.023), and DMN - FPN (p = 0.007) during Task. In controls, stronger within-network connectivity associated with better n-back task performance, whereas in the preterm group, stronger between-network connectivity associated with poorer performance. These results suggest that adjustment of functional connectivity to the cognitive demands supports successful performance in school-aged children and adolescents and that extremely preterm birth compromises the dynamics and developmental trajectories of brain networks.

BACKGROUND:Neonatal hypoxic-ischemic encephalopathy remains a leading cause of neonatal death and lifelong neurological impairment, imposing substantial economic burdens on affected families and healthcare system. While prior research has examined the cost-effectiveness of therapeutic hypothermia and hospital resource utilization, the economic impact of preventive strategies reflecting real-world variations in obstetric care has not been studied. OBJECTIVE:To compare the true cost of optimal vs substandard obstetric care in cases with and without neonatal hypoxic-ischemic encephalopathy. STUDY DESIGN:This retrospective economic analysis included a 20-year (2005-2024) cohort of 317,126 term singleton deliveries with 314 cases of hypoxic-ischemic encephalopathy across 7 hospitals within the Helsinki University Hospital district, Finland. Optimal care was defined as timely delivery in response to nonreassuring fetal status, while substandard care referred delayed or missed responses. The primary outcome was the direct neonatal healthcare cost from birth to hospital discharge. Secondary outcomes included the relative risk of hypoxic-ischemic encephalopathy and the incremental cost per disability-free life year gained by age 4. Costs across 4 groups (optimal or substandard care, with or without hypoxic-ischemic encephalopathy) were compared using generalized linear models. The study was powered at 90% to detect a ≥$1448 mean cost difference. RESULTS:The mean cost per newborn was lower in the optimal care group compared with the substandard care group, irrespective of hypoxic-ischemic encephalopathy occurrence ($1269 vs $2807; mean difference $1537 [+121%]; 95% confidence interval, $662-$2413; P<.001). The largest disparity was between neonatal hypoxic-ischemic encephalopathy cases after substandard care and cases without hypoxic-ischemic encephalopathy under optimal care ($28,315 vs $988; mean difference $27,327 [+2766%]; 95% confidence interval, $19,721-$34,779; P<.001). Optimal care yielded a 4-year disability-free life year gain of 0.06 per newborn (95% confidence interval, 0.05-0.07), with an incremental cost of $25,617 (95% confidence interval, $40,221 to $11,013; P<.001) per disability-free life year gained. The incidence of hypoxic-ischemic encephalopathy was 1.53% (95% confidence interval, 1.21-1.93) in the substandard care group, representing a 20-fold increase in risk (relative risk, 19.60; 95% confidence interval, 15.00-25.50) compared with the optimal care group (0.08%; 95% confidence interval, 0.07-0.09; P<.001). CONCLUSION:Optimal obstetric care was more cost-effective, less costly, and clinically more effective, lowering average healthcare costs per newborn while reducing the incidence of hypoxic-ischemic encephalopathy compared with substandard care.

Abstract Background Normal microbial colonization process from the mother to the newborn is disrupted by birth by caesarean section (CS). We assess, whether in CS-delivered infants, the intestinal microbiome could be successfully and safely normalized by postnatal oral transfer of maternal fecal microbiome (FMT). In this double-blinded randomized controlled trial started in autumn 2019, we assess the difference in heterogeneity of the intestinal microbiome between the two groups from birth to 24 months of age. The randomization code was opened in March 2024 when last transplanted child turned one year of age. Primary outcome measures are assessed from samples collected at 3 months of age. Methods 90 healthy pregnant women scheduled for elective CS were recruited. After screening and randomization, within two hours of delivery, 31 newborns were given 3.5 mg of the transplant from their own mothers or placebo mixed in mother’s milk. The children are followed for 24 months. Stool and blood samples from the child and mother are collected during the follow up and analyzed for changes in microbiome heterogeneity between the groups and to assess, for example, immunological changes associated with the transfer. Results All mothers were asymptomatic, no prescribed courses of antibiotics or travelling history outside the European Union region within three months of screening. 38 had positive findings in screening tests. 31 infants were included in the study of whom 15 received the transplant and 16 placebo. 3 adverse events were reported in the transplant group: one infant had thrombocytopenia at the age of two days, which normalized within one week. One infant was diagnosed with bilateral grade one intraventricular hemorrhage at the age of two weeks. One infant was treated for transient tachypnea of the newborn after receiving the transplant. None of the adverse events were considered related to the transplant. Conclusion In our proof-of-concept study we previously demonstrated the effectiveness and safety of our protocol. The immunology and microbiota samples (fecal and blood) of our first-of-a-kind randomized controlled trial are being analyzed and first results will be available in September 2024. Disclosures All Authors: No reported disclosures

Acute kidney injury (AKI) is common in very-low-birthweight (VLBW) infants. Both fluid overload and dehydration can lead to AKI. Our aim was to examine the associations between early fluid and sodium intake and AKI. This retrospective cohort study comprised 421 VLBW infants born at < 32 weeks. Detailed data on fluid management during the first 24 h of life, diuresis and weight changes during the first postnatal week and plasma creatinine measurements during the first 2 postnatal weeks were acquired from an electronic patient information system. AKI was defined according to the KDIGO definition modified for neonates. The incidence of AKI was 8.6

To determine the basis for perinatal nutritional mismatch causing metabolic dysfunction-associated steatotic liver disease and diabetes mellitus, we examined adult phenotype, hepatic transcriptome, and pancreatic β-islet function. In prenatal caloric-restricted rats with intrauterine growth restriction (IUGR) and postnatal exposure to high fat with fructose (HFhf) or high carbohydrate, we investigated male and female IUGR-HFhf and IUGR-high carbohydrate, vs HFhf and control offspring. Males more than females displayed adiposity, glucose intolerance, insulin resistance, hyperlipidemia, and hepatomegaly with hepatic steatosis. Male hepatic triglyceride synthesis, de novo lipogenesis genes increased, while female lipolysis, β-oxidation, fatty acid efflux, and FGF21 genes increased. IUGR-HFhf males demonstrated reduced β-islet insulin and humanin, and type 1 diabetes mellitus human amniotic fluid increased humanin. Humanin suppression disabled glucose stimulated insulin, ATP production, with apoptotic diminished β-islet viability. Humanin and FGF21 may reverse perinatal nutritional mismatched phenotype by restoring functional β islets and preventing metabolic dysfunction-associated steatotic liver disease and diabetes mellitus.

Objectives To evaluate the effect of delivery hospital busyness on the postnatal condition and the perinatal mortality among small preterm infants born at ≤32+0 gestational weeks.Design The daily delivery volume distribution is defined as lowest 10% (‘quiet’) and highest 10% (‘busy’) delivery-volume days, and days between (80%) as optimal delivery-volume days. We analysed differences in the incidence of selected adverse outcomes between quiet and busy days compared with optimal delivery-volume days by logistic regression followed by crude (ORs) and adjusted ORs (aORs) with 99% CIs.Setting A population-based cohort study based on prospectively collected real-world data from five university hospitals and 21 non-tertiary-level delivery hospitals in Finland, 2006‒2016.Participants 4323 small preterm infants.Primary outcome measures Umbilical cord pH ≤7.05, Apgar score 0–3 points at the age of 1 min, Apgar score 0–3 points at age 5 min, birth asphyxia (International Classification of Diseases-10 code), resuscitation with intubation.Secondary outcome measures Perinatal mortality comprising stillbirths and early neonatal deaths (<7 days).Results Busy days (busy vs optimal) showed no correlation with the primary birth-related outcomes. However, in the university hospitals, quiet days were associated with 80% lower odds of asphyxia (aOR 0.20, 99% CI 0.08 to 0.48) and 47% lower odds of resuscitation (aOR 0.53, 99% CI 0.39 to 0.72) compared with their incidence on optimal days.In university hospitals, the odds of early neonatal mortality among small preterm infants on busy days were twofold (aOR 2.08, 99% CI 1.26 to 3.45) than on optimal days. In the non-tertiary hospitals, however, this difference was statistically non-significant (aOR 0.68, 99% CI 0.19 to 2.45).Conclusions In the tertiary university delivery hospitals, busyness was associated with a twofold increase in early neonatal mortality among small preterm infants, whereas infants’ condition at birth on busy days was comparable to their condition on optimal days. Neonatal capacity in tertiary units during busy days may be critical under stress.

Abstract Background Exclusive enteral nutrition (EEN, oral or enteral liquid feeds only) is an established first-line therapy to induce remission in Crohn’s disease (CD) in children, but not in adults where low tolerance has been reported. Recently, smaller studies have suggested advantages of EEN in preoperative optimisation in adults. We hypothesise that in this setting, EEN is feasible and is associated with improved inflammatory and nutritional markers. Methods Consecutive patients with small bowel or ileocolic Crohns disease, who started preoperative EEN at two large IBD centres 2020-2023 were retrospectively studied. EEN was part of a 4-6week preoperative optimisation pathway. Outcomes were compliance and serum albumin, c-reactive protein and body weight, respectively. Medians (range) & Wilcoxon tests used. Results Thirty-two patients started EEN for stricturing (n=10) or penetrating disease (n=14). Six patients (19%) did not tolerate EEN and received parenteral nutrition (n=2) or reverted to normal diet (n=4), while 26 patients (81%) completed EEN until surgery. This group received EEN during 38 (17-70) days. C-reactive protein concentrations decreased from 8.5 (1-157) to 3 (1-96) mg/L (p = 0.0051), and albumin levels increased from 33.5 (27-44) to 38 (26-42) g/L (p< 0.001), while body weight did not change, from 67 (48.5-107) to 66.6 (48.5-105.7) kg (p = 0.25). 21 (81%) EEN patients underwent minimally invasive surgery, 22 (85%) had a primary anastomosis and 4 a stoma. Median postoperative length of stay was 4 (2-11) days. One patient with a severe complication, no one with an anastomotic leakage. Conclusion EEN was well tolerated in this cohort of patients undergoing surgery for complicated CD. EEN was associated with improved systemic inflammation, a maintained nutritional status, and favourable postoperative outcomes despite the complexity of disease in this group of patients. These results align with previous studies that have shown the effectiveness of EEN in reducing disease activity and promoting mucosal healing in CD patients.By reducing inflammation and uphold nutritional status, EEN might help to create a more favourable surgical environment, potentially leading to better outcomes and decreased postoperative complications.

Microbial colonization of the neonatal gut involves maternal seeding, which is partially disrupted in cesareanborn infants and after intrapartum antibiotic prophylaxis. However, other physically close individuals could complement such seeding. To assess the role of both parents and of induced seeding, we analyzed two longitudinal metagenomic datasets (health and early life microbiota [HELMi]: N = 74 infants, 398 samples, and SECFLOR: N = 7 infants, 35 samples) with cesarean -born infants who received maternal fecal microbiota transplantation (FMT). We found that the father constitutes a stable source of strains for the infant independently of the delivery mode, with the cumulative contribution becoming comparable to that of the mother after 1 year. Maternal FMT increased mother -infant strain sharing in cesarean -born infants, raising the average bacterial empirical growth rate while reducing pathogen colonization. Overall, our results indicate that maternal seeding is partly complemented by that of the father and support the potential of induced seeding to restore potential deviations in this process.

To describe sodium and potassium intake, their sources and plasma concentrations, and the association between intake and morbidity in very-low-birthweight (VLBW, <1500 g) infants during the first week of life. This retrospective cohort study comprised 951 VLBW infants born at <32 weeks. Infants were divided into three groups according to gestational age: 23–26 ( n  = 275), 27–29 ( n  = 433) and 30–31 ( n  = 243) weeks. Data on fluid management and laboratory findings were acquired from an electronic patient information system. The median sodium intake was highest in the 23–26 week group, peaking at 6.4 mmol/kg/day. A significant proportion of sodium derived from intravascular flushes; it reached 27% on day 1 in the 23–26 week group. High cumulative sodium intake in the first postnatal week was associated with weight gain from birth to day 8 in the 23–26 week group. High intake of sodium associated with an increased risk of surgically ligated patent ductus arteriosus (PDA), bronchopulmonary dysplasia and intraventricular haemorrhage, whereas low intake of potassium associated with an increased risk of PDA. Sodium intake in the most premature infants exceeded recommendations during the first postnatal week. Saline flushes accounted for a significant proportion of the sodium load.