Effects of Total Parenteral Nutrition on Serum Osmolality and Patent Ductus Arteriosus.

BACKGROUND: The persistence of high serum osmolality in the early postnatal period is a risk for developing patent ductus arteriosus (PDA). Early aggressive nutrition (EAN), involving total parenteral nutrition (TPN), by which enough concentrations of glucose and amino acids are administered intravenously, is recommended postnatally to improve the neurological prognosis in preterm infants. However, the effects of EAN involving TPN on serum osmolality and the development of a PDA have not been adequately studied. OBJECTIVES: Thus, in this study, we aimed to investigate the impact of TPN on serum osmolality and determine whether increased serum osmolality could be associated with a higher incidence of PDA in preterm infants. METHODS: In this single-center retrospective observational study, preterm infants born at <28 weeks of gestation who had been admitted to our neonatal intensive care unit (NICU) before (pre-TPN period) and after the introduction of TPN (post-TPN) were included. We reviewed the medical records of these patients, compared the changes in serum osmolality from birth to five days after birth, the clinical background, and the incidence of PDA between these two periods, and analyzed the risk factors. Additionally, the factors affecting the serum osmolality in very preterm infants were examined. The patients who met the intervention criteria of our NICU and received a cyclooxygenase (COX) inhibitor, Indacin® (Nobelpharma, Tokyo, Japan), within seven days after birth were classified as PDA+; those who could not be identified to have PDA flow by echo and did not receive a COX inhibitor were classified as PDA-. RESULTS: The postnatal day and serum sodium (Na+) were statistically significantly correlated with a higher serum osmolality. Serum osmolality remained statistically significantly higher in the PDA+ cohort compared with the PDA- cohort after the first day of life. However, no statistically significant differences were observed in serum osmolality after 24 hours of age, weeks of gestational age, birth weight, or incidence of PDA between the pre- and post-TPN periods. The results of the multiple logistic regression analyses revealed that the increased serum osmolality correlated with PDA development. CONCLUSIONS: In this study, the serum Na+ statistically significantly correlated with a higher serum osmolality. Moreover, the increased serum osmolality correlated with PDA development. Thus, the prevention of hypernatremia might reduce the incidence of PDA. Nonetheless, the findings in this study revealed that no statistically significant differences in serum osmolality were observed between the pre-and post-TPN periods, indicating that TPN had little effect on serum osmolality.

Is an Exclusive Human Milk Diet at the Time of Neonatal Intensive Care Unit Discharge Adequate to Maintain Growth and Neurodevelopment among Very Preterm Infants?

Background: An exclusive human milk (EHM) diet has numerous benefits. Formula supplementation may be recommended for former preterm infants at the time of neonatal intensive care unit (NICU) discharge to meet perceived metabolic demands and caloric goals. Recommendations addressing postdischarge nutrition for very preterm infants (VPTIs) are controversial, as the benefits of human milk supplementation regarding long-term growth, neurodevelopment, and chronic conditions are mixed. Objective: To compare growth and neurodevelopment of former VPTI fed an EHM diet to a supplemented/formula diet at NICU discharge. Materials and Methods: A retrospective cohort study of VPTI was followed at the Regional Neonatal Follow-up Program. Patients were categorized by diet at NICU discharge: EHM diet; mixed diet (EHM and formula); and exclusive formula diet. Growth percentile ranks at the first neonatal follow-up visit and 3 years of age were compared by diet type at NICU discharge. Neurodevelopmental outcomes as measured by the Bayley Scales of Infant Development 3rd Edition at 3 years of age were also compared. Results: Among 835 VPTIs, weight percentiles at the first neonatal follow-up visit were similar between the three NICU discharge diet types. One hundred fifty-eight subjects received neurodevelopmental evaluations at 3 years of age; anthropometrics and neurodevelopment were similar irrespective of diet at NICU discharge. Conclusion: An EHM diet at NICU discharge is appropriate to support growth in infancy as well as growth and neurodevelopment through 3 years of age. Thus, this raises the question of whether routine nutritional supplementation is necessary for VPTIs at NICU discharge.

Prospective, non-blinded, randomized controlled trial on early administration of pulmonary surfactant guided by lung ultrasound scores in very preterm infants: study protocol.

Background: Bedside lung ultrasonography has been widely used in neonatal intensive care units (NICUs). Lung ultrasound scores (LUS) may predict the need for pulmonary surfactant (PS) application. PS replacement therapy is the key intervention for managing moderate to severe neonatal respiratory distress syndrome (NRDS), with early PS administration playing a positive role in improving patient outcomes. Lung ultrasonography aids in the prompt diagnosis of NRDS, while LUS offers a semi-quantitative assessment of lung health. However, the specific methodologies for utilizing LUS in clinical practice remain controversial. This study hypothesizes that, in very preterm infants [<32 weeks gestational age (GA)] exhibiting respiratory distress symptoms, determining PS application through early postnatal LUS combined with clinical indicators, as opposed to relying solely on clinical signs and chest x-rays, can lead to more timely PS administration, reduce mechanical ventilation duration, improve patient outcomes, and lower the occurrence of bronchopulmonary dysplasia (BPD). Methods and design: This is a protocol for a prospective, non-blinded, randomized controlled trial that will be conducted in the NICU of a hospital in China. Eligible participants will include very preterm infants (< 32 weeks GA) exhibiting signs of respiratory distress. Infants will be randomly assigned in a 1:1 ratio to either the ultrasound or control group. In the ultrasonography group, the decision regarding PS administration will be based on a combination of lung ultrasonography and clinical manifestations, whereas in the control group, it will be determined solely by clinical signs and chest x-rays. The primary outcome measure will be the mechanical ventilation duration. Statistical analysis will employ independent sample t-tests with a significance level set at α = 0.05 and a power of 80%. The study requires 30 infants per group (in total 60 infants). Results: This study aims to demonstrate that determining PS application based on a combination of LUS and clinical indicators is superior to traditional approaches. Conclusions: This approach may enhance the accuracy of NRDS diagnosis and facilitate early prediction of PS requirements, thereby reducing the duration of mechanical ventilation. The findings of this research may contribute valuable insights into the use of LUS to guide PS administration.

Gestational age at birth, birth weight, and gestational age when intrauterine brain sparing occurs determines the neonatal outcome in growth-restricted infants born before 32 weeks of gestation: a retrospective cohort analysis.

Background: Preterm birth and fetal growth restriction are the main determinants of perinatal mortality. In the absence of therapeutic interventions, management is restricted to the observation of fetal growth and fetoplacental perfusion to determine the timing of delivery. Fetal circulatory redistribution, known as "brain sparing," represents a sign of fetal hypoxia and has been implemented in algorithms for when to deliver. In the absence of any other option, the nitric oxide donor pentaerythrityl tetranitrate (PETN), which has been shown to improve fetoplacental flow and reduce preterm birth in high-risk patients, is offered to patients as a personal therapy attempt. The aim of this study was to evaluate determinants related to pregnancy, including PETN intake during pregnancy, on immediate neonatal outcomes in a cohort of growth-restricted infants born before 32 completed weeks of gestation. Methods: We performed a retrospective cohort study of 98 infants born with a birth weight below the 10th percentile before 32 completed weeks of gestation at our tertiary care center between 2010 and 2019. PETN was offered to all mothers with a history of severe adverse pregnancy outcomes who were at high risk of developing fetal growth restriction as an individual therapy attempt. Results: The mean gestational age at birth was 188.5 days, and the mean birth weight was 549 g, corresponding to a median percentile of three. In 73 (79.3%) cases, brain sparing occurred during pregnancy. A total of 22 (22.4%) neonates were stillborn, 20 died postnatally, and 37.3% developed a severe complication. Multivariable analysis revealed birth weight percentile, gestational age at birth, and gestational age when brain sparing first occurred to be robust predictors of mortality or severe neonatal morbidity. In 39 neonates of mothers taking PETN, this impact of brain sparing was not observed. Conclusion: Our study is the first to demonstrate a significant association between the early occurrence of brain-sparing and severe neonatal outcomes in a cohort of very early preterm, growth-restricted newborns. The data suggest that PETN intake may ameliorate the effect of brain sparing in the affected neonates.

Gut Dysbiosis in the First-Passed Meconium Microbiomes of Korean Preterm Infants Compared to Full-Term Neonates.

Since gestational age (GA) is an important factor influencing the presence of specific microbiomes, we aimed to characterize the core microbiomes of preterm infants compared to full-term (FT) infants. This study investigated the differences in microbiota composition between very preterm (VP), moderate-to-late preterm (MLP), and FT neonates by examining the core microbiomes of a large cohort of Korean neonates. Meconium samples from 310 neonates with a GA range of 22-40 weeks were collected, and 16S rRNA analyses were performed; 97 samples were obtained from the FT, 59 from the VP, and 154 from the MLP group. Firmicutes, Bacteroidetes, and Proteobacteria were the phylum-level core microbiomes. Infants born before 37 weeks showed a disruption in the core microbiomes. At the phylum level, the relative abundance of Bacteroidetes was positively (r = 0.177, p = 0.002) correlated with GA, while that of Proteobacteria was negatively (r = -0.116, p = 0.040) correlated with GA. At the genus level, the relative abundances of Bacteroides and Prevotella were positively correlated with GA (r = 0.157, p = 0.006; r = 0.160, p = 0.005). The meconium of preterm infants exhibited significantly lower α-diversities than that of FT infants. ß-diversities did not appear to differ between the groups. Overall, these findings underscore the importance of GA in shaping the early gut microbiome.

Mortality and extrauterine growth restriction of necrotizing enterocolitis in very preterm infants with heart disease: a multi-center cohort study.

Congenital heart disease (CHD) and patent ductus arteriosus (PDA) are risk factors of necrotizing enterocolitis (NEC) in infants. However, it is unclear whether the prognosis of NEC is different between very preterm infants (VPIs) with and without heart diseases. This was an observational cohort study that enrolled VPIs (born between 24+0 and 31+6 weeks) admitted to 79 tertiary neonatal intensive care units (NICU) in the Chinese Neonatal Network (CHNN) between 2019 and 2021. The exposure was CHD or isolated PDA, and VPIs with NEC were divided into three groups: complicated with CHD, with isolated PDA, and without heart diseases. The primary outcomes were NEC-related adverse outcomes (death or extrauterine growth restriction (EUGR)). Logistic regression models were used to adjust potential confounders and calculate the odds ratios (ORs) and 95% confidential intervals (CIs) for each outcome. A total of 1335 VPIs with NEC were enrolled in this study, including 65 VPIs with CHD and 406 VPIs with isolated PDA. The VPIs with heart diseases had smaller gestational ages and lower body weights at birth, more antenatal steroids use, and requiring inotrope prior to the onset of NEC. While suffering from NEC, there was no significant increased risks in NEC-related death in VPIs with either CHD (adjusted OR [aOR]: 1.10; 95% CI: 0.41-2.50) or isolated PDA (aOR: 1.25; 95% CI 0.82-1.87), and increased risks in EUGR were identified in either survival VPIs with CHD (aOR: 2.35; 95% CI: 1.31-4.20) or isolated PDA (aOR: 1.53; 95% CI: 1.16-2.01) in survivors. The composite outcome (death or EUGR) was also more often observed in VPIs with either CHD (aOR: 2.07; 95% confidence interval [CI]: 1.20-3.60) or isolated PDA (aOR: 1.51; 95% CI: 1.17-1.94) than that without heart diseases. VPIs with either CHD or isolated PDA were associated with significantly prolonged duration of fasting, extended time to achieve full enteral feeding, and longer ventilation duration and hospitalization duration. Similar characteristics were also seen in VPIs with isolated PDA, with the exception that VPIs with CHD are more likely to undergo surgical intervention and maintain a prolonged fast after NEC.     Conclusion: In VPIs with NEC, CHD and isolated PDA are associated with an increased risk in worse outcomes. We recommend that VPIs with cardiac NEC be managed with aggressive treatment and nutrition strategies to prevent EUGR. What is Known: • CHD and PDA are risk factors for NEC in infants, which can lead to adverse outcomes such as death and EUGR. • NEC in infants with heart disease differs clinically from that in infants without heart disease and should be recognized as a separate disease process. What is New: • CHD and isolated PDA are associated with increased risks of EUGR in VPIs with NEC. • Risk factors associated with VPIs with cardiac NEC suggested these patients should be managed with aggressive treatment and nutrition strategies to adverse outcomes.

Real-time predictive model of extrauterine growth retardation in preterm infants with gestational age less than 32 weeks.

The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0-95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

Perinatal Outcomes of Immigrant Mothers and Their Infants Born Very Preterm across Germany.

BACKGROUND: In Germany, more than 40% of infants are born to immigrant parents. Increased survival rates of very preterm (below 32 weeks gestation at birth; VP) infants have not resulted in equally improved life chances and quality of life. More information on perinatal variations in outcomes according to social inequalities, migration background, and language barriers is needed. We tested whether mothers' immigrant status and language barriers are associated with perinatal health and short-term neonatal outcomes. METHODS: The data are from the national multi-centre German Neonatal Network (GNN) cohort, including VP births from 2009 onwards. In total, 3606 (n = 1738 female) children were assessed, and 919 (n = 449 female) of these children had immigrant backgrounds. Immigrant status was operationalised as a binary variable based on the children's mothers' countries of birth (born in Germany vs. foreign-born). Self-reported home language (L1) was used to calculate the average linguistic distance to German as one continuous variable. RESULTS: Mixed-effects models showed that two out of fourteen effects of interest survived the adjustment for known confounders and accounting for the nestedness of data within birth hospitals. Linguistic distance from mothers' L1s to German was independently associated with diagnoses of preeclampsia (OR = 1.01, 95% CI = [1.00, 1.01]). Infants of foreign-born mothers had higher odds for amniotic infection syndrome (AIS; OR = 1.45 [1.13, 1.86]) than infants of German mothers. CONCLUSIONS: Our findings from this large multi-centre longitudinal cohort of VP-born children indicate that maternal immigrant status and language barriers have limited impact on perinatal health and severe neonatal outcomes. This suggests that, regardless of background or language skills, there may be few inequalities in the perinatal health of pregnant women and their newborn preterm infants.

Cesarean delivery is associated with lower neonatal mortality among breech pregnancies: a systematic review and meta-analysis of preterm deliveries ≤32 weeks of gestation.

OBJECTIVE: To investigate the association between actual and planned modes of delivery, neonatal mortality, and short-term outcomes among preterm pregnancies ≤32 weeks of gestation. DATA SOURCES: A systematic literature search was conducted in 3 main databases (PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to November 16, 2022. The protocol was registered in advance in the International Prospective Register of Systematic Reviews (CRD42022377870). STUDY ELIGIBILITY CRITERIA: Eligible studies examined pregnancies ≤32nd gestational week. All infants received active care, and the outcomes were reported separately by different modes of delivery. Singleton and twin pregnancies at vertex and breech presentations were included. Studies that included pregnancies complicated with preeclampsia and abruptio placentae were excluded. Primary outcomes were neonatal mortality and intraventricular hemorrhage. STUDY APPRAISAL AND SYNTHESIS METHODS: Articles were selected by title, abstract, and full text, and disagreements were resolved by consensus. Random effects model-based odds ratios with corresponding 95% confidence intervals were calculated for dichotomous outcomes. Risk Of Bias In Non-randomized Studies - of Interventions-I was used to assess the risk of bias. RESULTS: A total of 19 observational studies were included involving a total of 16,042 preterm infants in this systematic review and meta-analysis. Actual cesarean delivery improves survival (odds ratio, 0.62; 95% confidence interval, 0.42-0.9) and decreases the incidence of intraventricular hemorrhage (odds ratio, 0.70; confidence interval, 0.57-0.85) compared to vaginal delivery. Planned cesarean delivery does not improve the survival of very and extremely preterm infants compared to vaginal delivery (odds ratio, 0.87; 95% confidence interval, 0.53-1.44). Subset analysis found significantly lower odds of death for singleton breech preterm deliveries born by both planned (odds ratio, 0.56; 95% confidence interval, 0.32-0.98) and actual (odds ratio, 0.34; 95% confidence interval, 0.13-0.88) cesarean delivery. CONCLUSION: Cesarean delivery should be the mode of delivery for preterm ≤32 weeks of gestation breech births due to the higher mortality in preterm infants born via vaginal delivery.

Spontaneous intestinal perforation among very preterm infants in China: a multicenter cohort study.

Background: Spontaneous intestinal perforation (SIP) is one of the most serious surgical bowel conditions affecting preterm infants. There are limited data on the mortality and morbidities of very preterm infants [VPIs, <32 weeks' gestational age (GA)] with SIP in China. The study aimed to describe the prevalence, treatment, and outcomes of SIP among VPIs in China. Methods: This retrospective cohort study included all infants born at 24+0-31+6 weeks GA from January 1, 2019, to December 31, 2020, and admitted within seven days after birth to the neonatal intensive care units in the Chinese Neonatal Network. The primary outcome was survival without major morbidities. The association between SIP and neonatal outcomes was evaluated using multivariate logistic regression controlling for possible confounders. Results: Out of the 15,814 enrolled infants, 150 (1.0%) developed SIP with a median onset age of four (IQR 2-6) days. Infants with GA 24+0-25+6 weeks had the highest incidence of SIP (13/532, 2.4%), followed by those with GA 26+0-27+6 weeks (22/2,005, 1.1%), 28+0-29+6 weeks (44/5,269, 0.8%) and 30+0-31+6 weeks (71/8,008, 0.9%). Ten SIP cases were lost to follow-up with unknown survival status and 41 (29.3%) of the remaining 140 infants with SIP died during hospitalization. Only 29.3% of infants with SIP survived without major morbidities, significantly lower than those without SIP (59.2%; P<0.01). Multivariate analysis revealed SIP was associated with a higher risk of overall death (adjusted OR 3.36; 95% CI: 1.85 to 6.08), late-onset sepsis (adjusted OR 2.10; 95% CI: 1.02 to 4.31), and bronchopulmonary dysplasia (adjusted OR 2.49; 95% CI: 1.44 to 4.30). Among all infants with SIP, 28 (18.7%) did not receive any surgical intervention. Laparotomy was provided to 113 (92.6%) of the remaining 122 infants, solely (84/122, 68.9%) or following peritoneal drainage (29/122, 23.8%), while nine (7.4%) infants underwent peritoneal drainage only. Conclusions: Around 1% of VPIs in China developed SIP, associated with increased risk of mortality and morbidities. Over 90% of VPIs with SIP underwent laparotomy as initial or subsequent surgical treatment. Effective and evidence-based strategies are needed for the prevention and management of SIP.

Feeding intolerance scoring system in very preterm and very low birth weight infants using clinical and ultrasound findings.

Very preterm infants are at a high risk of developing feeding intolerance; however, there are no widely accepted definitions of feeding intolerance. This study aimed to develop a scoring system for feeding intolerance in very preterm infants by combining clinical symptoms and ultrasonography (US) findings. This prospective cohort study included very preterm and/or very low birth weight infants. We defined feeding intolerance as the inability to achieve full feeding (150 ml/kg/day) by 14 days of life. The clinical findings included vomiting, abdominal distention, and gastric fluid color. US findings included intestinal peristaltic frequency, gastric residual volume, peak systolic velocity, and the resistive index of the superior mesenteric artery. We conducted multivariate analyses to evaluate the potential predictors and developed a scoring system to predict feeding intolerance. A total of 156 infants fulfilled the eligibility criteria; however, 16 dropped out due to death. The proportion of patients with feeding intolerance was 60 (42.8%). Based on the predictive ability, predictors of feeding intolerance were determined using data from the US at 5-7 days of age. According to multivariate analysis, the final model consisted of 5 predictors: abdominal distention (score 1), hemorrhagic gastric fluid (score 2), intestinal peristaltic movement ≤18x/2 min (score 2), gastric fluid residue >25% (score 2), and resistive index >0.785 (score 2). A score equal to or above 5 indicated an increased risk of feeding intolerance with a positive predictive value of 84.4% (95% confidence interval:73.9-95.0) and a negative predictive value of 76.8% (95% confidence interval:68.4-85.3). The scoring system had good discrimination (area under the receiver operating characteristic curve:0.90) and calibration (p = 0.530) abilities. This study developed an objective, accurate, easy, and safe scoring system for predicting feeding intolerance based on clinical findings, 2D US, and color Doppler US.

Association between risk of preterm birth and long-term and short-term exposure to ambient carbon monoxide during pregnancy in chongqing, China: a study from 2016-2020.

BACKGROUND: Preterm birth (PTB) is an important predictor of perinatal morbidity and mortality. Previous researches have reported a correlation between air pollution and an increased risk of preterm birth. However, the specific relationship between short-term and long-term exposure to carbon monoxide (CO) and preterm birth remains less explored. METHODS: A population-based study was conducted among 515,498 pregnant women in Chongqing, China, to assess short-term and long-term effects of CO on preterm and very preterm births. Generalized additive models (GAM) were applied to evaluate short-term effects, and exposure-response correlation curves were plotted after adjusting for confounding factors. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using COX proportional hazard models to estimate the long-term effect. RESULTS: The daily incidence of preterm and very preterm birth was 5.99% and 0.41%, respectively. A positive association between a 100 µg/m³ increase in CO and PTB was observed at lag 0-3 days and 12-21 days, with a maximum relative risk (RR) of 1.021(95%CI: 1.001-1.043). The exposure-response curves (lag 0 day) revealed a rapid increase in PTB due to CO. Regarding long-term exposure, positive associations were found between a 100 µg/m3 CO increase for each trimester(Model 2 for trimester 1: HR = 1.054, 95%CI: 1.048-1.060; Model 2 for trimester 2: HR = 1.066, 95%CI: 1.060-1.073; Model 2 for trimester 3: HR = 1.007, 95%CI: 1.001-1.013; Model 2 for entire pregnancy: HR = 1.080, 95%CI: 1.073-1.088) and higher HRs of very preterm birth. Multiplicative interactions between air pollution and CO on the risk of preterm and very preterm birth were detected (P- interaction<0.05). CONCLUSIONS: Our findings suggest that short-term exposure to low levels of CO may have protective effects against preterm birth, while long-term exposure to low concentrations of CO may reduce the risk of both preterm and very preterm birth. Moreover, our study indicated that very preterm birth is more susceptible to the influence of long-term exposure to CO during pregnancy, with acute CO exposure exhibiting a greater impact on preterm birth. It is imperative for pregnant women to minimize exposure to ambient air pollutants.

The early educational environment at five years of age in a European cohort of children born very preterm: challenges and opportunities for research.

BACKGROUND: Early childhood education offers opportunities for stimulation in multiple developmental domains and its positive impact on long-term outcomes and wellbeing for children is well documented. Few studies have explored early education in children born very preterm (VPT; <32 weeks of gestation) who are at higher risk of neurodevelopmental disorders and poor educational outcomes than their term-born peers. The purpose of the study is to describe and compare the educational environment of children born VPT in European countries at 5 years of age according to the degree of perinatal risk. METHODS: Data originated from the population-based Screening to Improve Health In very Preterm infants (SHIPS) cohort of children born VPT in 2011/2012 in 19 regions from 11 European countries. Perinatal data were collected from medical records and the 5-year follow-up was conducted using parental questionnaires. Outcomes at 5 years were participation in early education (any, type, intensity of participation) and receipt of special educational support, which were harmonized across countries. RESULTS: Out of 6,759 eligible children, 3,687 (54.6%) were followed up at 5 years (mean gestational age 29.3 weeks). At 5 years, almost all children (98.6%) were in an educational program, but type (preschool/primary), attendance (full-time/part-time) and use and type of school support/services differed by country. In some countries, children with high perinatal risk were more likely to be in full-time education than those with low risk (e.g. Estonia: 97.9% vs. 87.1%), while the inverse pattern was observed elsewhere (e.g. Poland: 78.5% vs. 92.8%). Overall, 22.8% of children received special educational support (country range: 12.4-34.4%) with more support received by children with higher perinatal risk. Large variations between countries remained after adjustment for socio-demographic characteristics. CONCLUSIONS: There are marked variations in approaches to early education for children born VPT in Europe, raising opportunities to explore its impact on their neurodevelopment and well-being.

No differences were observed in the prevention of necrotizing enterocolitis and late-onset sepsis among preterm infants who received either single-species or multi-species probiotics.

BACKGROUND: Probiotic prophylaxis has been suggested to reduce the incidence of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in very preterm newborns. However, choosing the optimal probiotic is difficult due to variations in strain-specific effects and interactions facilitated by the use of combination species. AIMS: To compare clinical outcomes of very preterm infants receiving multi or single-species probiotics. STUDY DESIGN: Retrospective, single-center, cohort study. SUBJECTS: Very preterm infants (<32 weeks' gestation) born between 2019 and 2022 at a tertiary perinatal center received either a multi-species (Lactobacillus rhamnosus 45 %, Lactobacillus casei 15 %, Lactobacillus acidophilus 15 %, Bifidobacterium infantis 15 %, Bifidobacterium bifidum 10 %; n = 228) or a single-species (Bifidobacterium breve BR03 and B632; n = 227) probiotic formulation. MAIN OUTCOME MEASURES: NEC, LOS, and mortality. RESULTS: The overall incidence of NEC and LOS was 3.1 % and 13.8 %, respectively. There were no differences between the multi-species and single-species probiotic groups in the rate of NEC (3.5 % vs 2.6 %; p = 0.787), LOS (15.4 % vs 12.3 %; p = 0.416), mortality (0.9 % vs 1.8 %; p = 0.449), or composite outcome (NEC, LOS and/or death; 16.7 % vs 12.8 %; p = 0.290). CONCLUSION: The clinical outcomes of very preterm newborns receiving multi vs. single-species probiotic formulations were similar in our study. In view of the sample size and low baseline rate of NEC in our unit, further trials are warranted to investigate the effects of specific probiotics for prevention of serious neonatal morbidities.

Metabolomic Analysis Reveals the Association of Severe Bronchopulmonary Dysplasia with Gut Microbiota and Oxidative Response in Extremely Preterm Infants.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease mainly affecting premature infants needing ventilation or oxygen for respiratory distress. This study aimed to evaluate the molecular linkages for BPD in very and extremely preterm infants using a metabolomics-based approach. A case-control study of enrolling preterm infants born before 32 weeks gestational age (GA) was prospectively performed. These preterm infants were subsequently stratified into the following two groups for further analysis: no or mild BPD, and moderate or severe BPD based on the 2019 NICHD criteria. Urinary metabolomic profiling was performed using 1H-Nuclear magnetic resonance (NMR) spectroscopy coupled with partial least squares discriminant analysis (PLS-DA) at a corrected age of 6 months. Metabolites significantly differentially related to GA and BPD severity were performed between groups, and their roles in functional metabolic pathways were also assessed. A total of 89 preterm infants born before 32 weeks gestation and 50 infants born at term age (above 37 completed weeks' gestation) served as controls and were enrolled into the study. There were 21 and 24 urinary metabolites identified to be significantly associated with GA and BPD severity, respectively (p < 0.05). Among them, N-phenylacetylglycine, hippurate, acetylsalicylate, gluconate, and indoxyl sulfate were five metabolites that were significantly higher, with the highest importance in both infants with GA < 28 weeks and those with moderate to severe BPD, whereas betaine and N,N-dimethylglycine were significantly lower (p < 0.05). Furthermore, ribose and a gluconate related pentose phosphate pathway were strongly associated with these infants (p < 0.01). In conclusion, urinary metabolomic analysis highlights the crucial role of gut microbiota dysbiosis in the pathogenesis of BPD in preterm infants, accompanied by metabolites related to diminished antioxidative capacity, prompting an aggressive antioxidation response in extremely preterm infants with severe BPD.

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OBJECTIVES: To investigate the current status of delivery room transitional care management for very/extremely preterm infants in Shenzhen City. METHODS: A cross-sectional survey was conducted in November 2022, involving 24 tertiary hospitals participating in the Shenzhen Neonatal Data Network. The survey assessed the implementation of transitional care management in the delivery room, including prenatal preparation, delivery room resuscitation, and post-resuscitation management in the neonatal intensive care unit. Very/extremely preterm infants were divided into four groups based on gestational age: <26 weeks, 26-28+6 weeks, 29-30+6 weeks, and 31-31+6 weeks. Descriptive analysis was performed on the results. RESULTS: A total of 140 very/extremely preterm infants were included, with 10 cases in the <26 weeks group, 45 cases in the 26-28+6 weeks group, 49 cases in the 29-30+6 weeks group, and 36 cases in the 31-31+6 weeks group. Among these infants, 99 (70.7%) received prenatal counseling, predominantly provided by obstetricians (79.8%). The main personnel involved in resuscitation during delivery were midwives (96.4%) and neonatal resident physicians (62.1%). Delayed cord clamping was performed in 52 cases (37.1%), with an average delay time of (45±17) seconds. Postnatal radiant warmer was used in 137 cases (97.9%) for thermoregulation. Positive pressure ventilation was required in 110 cases (78.6%), with 67 cases (60.9%) using T-piece resuscitators and 42 cases (38.2%) using a blended oxygen device. Blood oxygen saturation was monitored during resuscitation in 119 cases (85.0%). The median time from initiating transitional care measures to closing the incubator door was 87 minutes. CONCLUSIONS: The implementation of delivery room transitional care management for very/extremely preterm infants in the hospitals participating in the Shenzhen Neonatal Data Network shows varying degrees of deviation from the corresponding expert consensus in China. It is necessary to bridge the gap through continuous quality improvement and multicenter collaboration to improve the quality of the transitional care management and outcomes in very/extremely preterm infants.

The impact of general anesthesia on the outcomes of preterm infants with gestational age less than 32 weeks delivered via cesarean section.

Background: Recent advancements in China's perinatal and neonatal intensive care have significantly reduced neonatal mortality, yet preterm births before 32 weeks remain the primary cause of neonatal fatalities and contribute to long-term disabilities. The prognosis of very preterm infants (VPIs) is significantly affected by factors including the intrauterine environment, delivery method and neonatal intensive care. Cesarean section which often used for preterm births has implications that are not fully understood, particularly concerning the type of anesthesia used. This study examines the impact of general anesthesia (GA) during cesarean delivery on VPI outcomes, aiming to identify strategies for mitigating GA-associated risks. Methods: This cohort study analyzed 1,029 VPIs born via cesarean section under 32 weeks' gestation at our single-center from 1 January 2018, to 31 December 2022. Detailed medical records, encompassing perioperative information, maternal data and neonatal outcomes were meticulously examined. The primary aim of this investigation was to compare maternal characteristics and neonatal outcomes between VPIs delivered under GA and neuraxial anesthesia (NA). A significance level of p < 0.05 was established. Results: Of the 1,029 VPIs analyzed, 87.95% (n = 905) were delivered via NA and 12.05% (n = 124) via GA. Mothers with hypertensive pregnancy diseases and emergency operations were more inclined to choose GA. VPIs delivered under GA showed a lower Apgar score at one and 5 minutes (p < 0.01), increased need for tracheal intubation resuscitation (32.2% vs. 12.2%, p < 0.01) and a greater incidence of severe neurological injury (SNI) (14.5% vs. 5%, p < 0.01). Multivariable analysis revealed GA was significantly associated with lower Apgar scores at one (OR 6.321, 95% CI 3.729-10.714; p < 0.01) and 5 minutes (OR 4.535, 95% CI 2.975-6.913; p < 0.01), higher risk of tracheal intubation resuscitation (OR = 3.133, 95% CI = 1.939-5.061; p < 0.01) and SNI (OR = 3.019, 95% CI = 1.615-5.643; p < 0.01). Furthermore, for VPIs delivered under GA, a prolonged interval from skin incision to fetus delivery was associated with a lower 5-min Apgar score (p < 0.01). Conclusion: This study revealed the significant impact of GA on adverse outcomes among VPIs. In cases when GA is required, proactive measures should be instituted for the care of VPIs such as expediting the interval from skin incision to fetal delivery.

Psycho-emotional intervention with parents of very preterm babies during the first year: A single-arm pilot study.

Studies of intervention programs that aim to improve the emotional state of parents of children admitted to the neonatal intensive care units (NICU) are scarce in Spain. The aims of this single-arm pilot study are to get to know the emotional profile of parents of high-risk preterm newborns, and to explore parents' patterns of emotional well-being before and after a psychological program called the Parental Empowerment Program, to increase parental readiness levels. The sample was made up of 100 parents (50 couples) who participated in the program. Measurements were taken of post-traumatic stress, depression, and resilience at 1 month and 12 months. Repeated measurements and dyadic data analyses were performed. One month after the birth of the baby and prior to the start of the program, mothers show more symptoms of stress and depression than fathers. After the intervention, both parents experienced improvements in their mood levels. The evidence obtained seems to show that high resilience levels and low post-traumatic stress symptoms are associated with reduced depression levels after implementing the program. However, the heterogeneity of the responses obtained, the observed associations between stress, resilience, and maternal depression, along with the reciprocal influence between maternal and paternal depression 1 year after the intervention, highlight the need for a more in-depth exploration of the interplay between risk and protective factors in this population. Despite the identified potential threats to validity, further work in this direction is recommended, including the implementation of clinical trials to demonstrate intervention efficacy. The adaptation of the parents' mutual emotional adjustment at each stage would allow them to participate more actively in the baby's care.

Association of Growth During Infancy with Neurodevelopment and Obesity in Children Born Very Preterm: The Environmental Influences on Child Health Outcomes Cohort.

OBJECTIVE: To evaluate associations between change in weight z score after neonatal intensive care unit (NICU) discharge and neurodevelopmental outcomes and obesity at 12-48 months of age among individuals born very preterm. STUDY DESIGN: This secondary analysis used data from infants born very preterm participating in the Environmental influences on Child Health Outcomes cohort (n = 1400). Growth during infancy was calculated as change in weight z score between NICU discharge and follow-up at a mean of 27 months of age. Very low weight gain was defined as a change in weight z score <-1.67; very high weight gain was a change in weight z score >1.67. Neurodevelopmental outcomes included the Bayley Scales of Infant and Toddler Development, Child Behavior Checklist 1.5-5 years, and Modified Checklist for Autism in Toddlers. Multivariable linear regression was used to estimate associations between increase in weight z score and neurodevelopmental outcomes. RESULTS: Very low weight gain between NICU discharge and follow-up (experienced by 6.4% of participants) was associated with lower scores on cognitive (adjusted mean difference: -4.26; 95% CI: -8.55, -0.04) and language (adjusted mean difference: -4.80; 95% CI: -9.70, -0.11) assessments. Very high weight gain (experienced by 13.6% of participants) was associated with an increased obesity risk (adjusted relative risk: 6.20; 95% CI: 3.99, 9.66) but not with neurodevelopmental outcomes. CONCLUSIONS: Very high weight gain in the first 12-48 months after NICU discharge was associated with a higher risk of obesity at follow-up; very low weight gain was associated with lower scores on cognitive and language assessments.