Neonatal Age Research Articles

Increased prevalence of negative pregnancy and fetal outcomes in women with primary adrenal insufficiency. A systematic review and meta-analysis.

Maternal primary adrenal insufficiency (PAI) during pregnancy, due to either Addison disease (AD) or congenital adrenal hyperplasia (CAH), is rare. Only few studies have examined the subsequent important outcomes of maternal glucocorticoid and mineralocorticoid deficiencies during pregnancy upon the fetus and the neonate. Therefore, this systematic review and meta-analysis evaluated the impact of these deficiencies, with data from PubMed/Medline, Cochrane/CENTRAL, and Google Scholar. A total of 31 studies were included for qualitative analysis and 11 for quantitative analysis. Studies examining the prevalence of spontaneous abortion, preterm birth, the occurrence of small for gestational age (SGA) neonates, as well as the neonatal birth weight were included. The systematic review revealed a substantial number of spontaneous abortions, preterm births and SGA neonates in pregnant women with PAI. The meta-analysis showed a mean spontaneous abortion prevalence of 18%, 18% and 17% in women with PAI, AD or CAH, respectively. The mean preterm birth prevalence was 11% when women with AD or CAH were analyzed together, and 13% and 9% in women with AD or CAH, respectively, when these women were analyzed separately. The mean prevalence of SGA neonates was 8% when women with AD or CAH were analyzed together, and 5% and 10% in women with AD or CAH, respectively, when these women were analyzed separately. The mean fetal birth weight was within normalcy in all women with PAI, as well as in women with AD or CAH. In conclusion the executed systematic review of 31 studies followed by a meta-analysis of 11 studies in pregnant women with PAI has shown a greater prevalence of pregnancies with negative outcome (spontaneous abortion, preterm birth) and of negative fetal outcome (SGA) in women with either AD or CAH, as compared to control pregnant women.

The Robust Negative Binomial Regression Model on Under-five Mortality due to Pneumonia in the Province of East Java

Robust Negative Binomial regression model (RNBR) is a modelling method to overcome a problem if there are outliers and overdispersion in the data. Outliers are data points that are significantly different from other data. Outliers have a significant effect on modelling to the resulting model. Furthermore, overdispersion is indicated by the presence of too large values of Pearson statistics. In this study, the RNBR model was used to determine the factors of the toddler immune variable at post neonatal age that significantly influenced the number of under-five deaths caused by pneumonia in East Java Province. Based on the modelling obtained, it shows that the RNBR model provides more robust results in handling outlier and overdispersion problems. This can be seen from the AIC value of the RNBR model is smaller than the AIC of the Poisson regression model. In addition, and which are measures of the influence of outliers on the model, decreased from 1 for the Poisson regression model to around 0.42 for the RNBR model.

Practical Way to Use Supraglottic Airway Device.

We read a review of case reports published on Current Pediatric Reviews 2024 about the use of I-gel® in neonatal complicated intubation, and we decided to write a commentary on the benefits and limitations of using supraglottic airways in neonatal age, with a specific focus on Igel [1]. The use of supraglottic airway devices in neonatal ages is limited to particular conditions, but further research is showing the utility of these devices as the first choice in neonatal resuscitation or airway stabilization. Our commentary highlights the broader practical applications of I-gel and reinforces its role as a valuable tool in neonatal resuscitation.

First trimester maternal serum PAPP-A and free β-hCG levels and risk of SGA or LGA in women with and without GDM

BackgroundMaternal gestational diabetes (GDM), small (SGA) and large (LGA) for gestational age neonates are associated with increased morbidity in both mother and child. We studied how different levels of first trimester pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fβ-hCG) were associated with SGA and LGA in GDM pregnancies and controls.MethodsAltogether 23 482 women with singleton pregnancies participated in first trimester combined screening and delivered between 2014 and 2018 in Northern Finland and were included in this retrospective case-control study. Women with GDM (n = 4697) and controls without GDM (n = 18 492) were divided into groups below 5th and 10th or above 90th and 95th percentile (pc) PAPP-A and fβ-hCG MoM levels. SGA was defined as a birthweight more than two standard deviations (SD) below and LGA more than two SDs above the sex-specific and gestational age-specific reference mean. Odds ratios were adjusted (aOR) for maternal age, BMI, ethnicity, IVF/ICSI, parity and smoking.ResultsIn pregnancies with GDM the proportion of SGA was 2.6% and LGA 4.5%, compared to 3.3% (p = 0.011) and 1.8% (p < 0.001) in the control group, respectively. In ≤ 5th and ≤ 10th pc PAPP-A groups, aORs for SGA were 2.7 (95% CI 1.5–4.7) and 2.2 (95% CI 1.4–3.5) in the GDM group and 3.8 (95% CI 3.0–4.9) and 2.8 (95% CI 2.3–3.5) in the reference group, respectively. When considering LGA, there was no difference in aORs in any high PAPP-A groups. In the low ≤ 5 percentile fβ-hCG MoM group, aORs for SGA was 2.3 (95% CI 1.8–3.1) in the control group. In fβ-hCG groups with GDM there was no association with SGA and the only significant difference was ≥ 90 percentile group, aOR 1.6 (95% CI 1.1–2.5) for LGA.ConclusionAssociation with low PAPP-A and SGA seems to be present despite GDM status. High PAPP-A levels are not associated with increased LGA risk in women with or without GDM. Low fβ-hCG levels are associated with SGA only in non-GDM pregnancies.

Influencing factors for postpartum depression in women with gestational diabetes mellitus.

It remains undefined about the association between gestational diabetes mellitus (GDM) and postpartum depression (PPD). Hence, a cross-sectional study was conducted to evaluate the association between GDM and PPD among pregnant women and to investigate the influencing factors for PPD. From June 2021 to June 2022, 205 parturients with GDM and 201 without GDM were included in the study as the GDM group and the control group, respectively. The collected data from the general information questionnaire and Self Rating Depression Scale (SDS) were statistically analyzed based on binomial logistic regression analyses and generalized linear mixed models (GLMMs). Age at delivery, gestational age, glycosylated hemoglobin, triglyceride, SDS, and proportions of women who had a history of induced abortion or GDM were significantly different between the GDM group and control group (P<0.05). The incidence of PPD in the GDM group was significantly higher than that in the control group. The neonatal body weight and triglyceride in GDM women with PPD were significantly lower than those in GDM women without PPD (P<0.001). The univariate logistic regression analysis demonstrated that educational age was a protective factor, while glycosylated hemoglobin and GDM were risk factors for PPD. The multiple linear regression analysis revealed that neonatal body weight (OR=-0.904, 95%CI: -1.657 to -0.152, P=0.019) and educational age (OR=-0.166, 95%CI: -0.306 to -0.025, P=0.021) were protective factor, while GDM (OR=1.854, 95%CI: 1.027-2.681, P<0.0001) was a risk factor for PPD. GDM may be associated with PPD. Neonatal body weight and educational age were protective factors for PPD, and GDM was a risk factor for PPD. Therefore, more attention should be paid to the mental health status of women with GDM, especially those with lesser educational age and lower neonatal body weight.

The development and implementation of a specialised care plan for late preterm and small for gestational age neonates admitted in maternity settings

IntroductionWhile there is recognition that Late preterm (LP) and small for gestational age (SGA) neonates have complex needs, reports on pragmatic approaches to optimise the care of these infants in practice are limited. AimTo implement and evaluate a specialised care plan to support the provision of optimal care to LP and SGA neonates admitted on maternity wards. MethodsA specialised care plan was implemented in a pre-post interventional study. Data were collected on neonates’ characteristics, hypoglycaemic incidents, and hypoglycaemia that led to a Neonatal Intensive Care admission. ResultsApproximately 10% of neonates born in the pre and post intervention periods were LP or SGA. Neonatal hypoglycaemic events reduced from six pre-intervention to three events post-intervention. Instances of neonatal hypoglycaemia that led to Neonatal Intensive Care admission reduced from three pre-intervention to one post-intervention. ConclusionThe specialised care plan was effective in optimising care for LP and SGA neonates.

The landscape of congenital heart disease treated with the Ross procedure

BackgroundThe Ross procedure has excellent outcomes in the pediatric population. Some series have reported age- and anatomy-dependent outcomes, but a comprehensive analysis stratified by these variables has not been reported to date. We sought to describe the landscape of congenital heart disease (CHD) treated with the Ross procedure and identify the patients best served by this operation. MethodsOver a total of 30 years, 317 pediatric patients underwent the Ross procedure. These patients were stratified into 4 age groups—neonates (age <31 days; n = 21), infants (age 31 days to 1 year; n = 40), children (age 1-12 years; n = 165), and adolescents (age 13-18 years; n = 91)—and 3 anatomic groups—isolated aortic valve (AV) disease (n = 221), Shone complex or multilevel left ventricular outflow tract (LVOT) obstruction (n = 61), and complex CHD (n = 35). The groups were compared across outcomes. ResultsNeonates and infants had the highest rates of Shone syndrome (P < .001), complex CHD (P < .001), concomitant root enlargement (P < .001), and arch procedures (P < .001). Operative mortality and morbidity were 4.4% (n = 14/317) and 14% (n = 44/317), respectively. Both were higher in neonates and infants (P < .001 for both) but lower for patients with isolated AV disease (P < .001 for both). Ten-year survival and freedom from LVOT reintervention were 92% and 81%, respectively, and were significantly better in patients with isolated AV disease compared to those with complex CHD (P < .001 and P = .005, respectively). In neonates and infants with isolated AV disease, operative mortality was 4% (n = 1/23), morbidity was 9% (n = 2/23), 10-year survival was 85.6%, and 10-year freedom from LVOT reintervention was 88.4%. ConclusionsAmong pediatric patients, those with isolated AV disease are best served with the Ross procedure, regardless of age. Complex CHD is associated with lower survival and increased risk of LVOT reintervention.

Maternal autoimmune disease and offspring risk of haematological malignancies: a case–control study

Autoimmune diseases are known to be associated with an increased risk of cancer. Whether maternal immune dysregulation can have an impact on the development of haematological malignancies in offspring remains uncertain. Therefore, we explored the association between offspring risk of haematological malignancies and maternal autoimmune disease using a real-world nationwide population-based study. In this case-control study, we identified 2172 children with haematological malignancies between 2004 and 2019 from Taiwan's National Health Insurance program and compared them with population-based controls without haematologic malignancies, who were matched with each individual at a ratio of 1:4. The medical information of the autoimmune mothers were obtained from the Taiwan Maternal and Child Health Database. Conditional logistic regression was used to estimate the odds ratio for haematologic malignancy in offspring. Furthermore, subgroup and stratified analyses were conducted. Among the rheumatologic diseases in our study, Crohn's disease was the most common disease both in the haematological malignancy group (1.1%) and the control group (0.9%). In multivariable analysis, the odds ratio for haematological malignancy in offspring with maternal autoimmune diseases was 1.2 (95% confidence interval [CI] 0.91-1.58). The overall risk of haematologic malignancy was not significantly higher when adjusted for specific risk factors, including neonatal age, maternal age, family income, urbanization, maternal occupation, birth weight, or maternal comorbidity, except for prematurity. When comparing different autoimmune diseases among haematological malignancies and the control group, maternal psoriatic arthritis/psoriasis had the highest adjusted overall risk for haematological malignancies (adjusted OR 2.11, CI 0.89-5), followed by ankylosing spondylitis (adjusted OR 1.45, CI 0.7-3), autoimmune thyroiditis (OR 1.26, CI 0.57-2.81), systemic lupus erythematosus (OR 1.21, CI 0.48-3.02), Crohn's disease (OR 1.19, CI 0.75-1.9), and Sjogren's syndrome (OR 1.18, CI 0.65-2.15), but no significance was reached in these analyses. Multivariable analysis of risk factors associated with haematological malignancy subtypes was done. It showed no associations between maternal autoimmune disease and childhood haematological malignancies. We found no significant relationship between maternal autoimmune disease and childhood haematological malignancies. The influence of maternal immune dysregulation on the next generation with respect to haematological malignancies development may be limited. There was no funding source for this study.

Activity restriction and risk of adverse pregnancy outcomes

BackgroundActivity restriction is a common recommendation given to patients during pregnancy for various indications, despite lack of definitive data showing improvements in pregnancy outcomes. ObjectiveTo determine if activity restriction (AR) in pregnancy is associated with decreased odds of adverse pregnancy outcomes (APOs). Study designSecondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) prospective cohort. Nulliparous singletons were followed at 8 sites from October 2010–September 2013. Demographic and clinical data were collected at 4 timepoints, and participants were surveyed about AR recommendations at 22w0d-29w6d and delivery. We excluded participants missing data on AR and age. Participants were grouped according to history of AR, and APOs included: gestational hypertension (gHTN), preeclampsia/eclampsia, preterm birth (PTB), and small for gestational age (SGA) neonate. Associations between AR and APOs were examined using uni- and multivariable logistic regression models adjusting for a priori identified APO risk factors. ResultsOf 10,038 nuMoM2b participants, 9,312 met inclusion criteria and 1,386 (14.9%) were recommended AR; participants identifying as Black (aOR 0.81 [95% CI 0.68–0.98]) or Hispanic (aOR 0.73 [95% CI 0.61–0.87]) were less likely to be placed on AR when compared to those identifying as White. Overall, 3,197 (34.3%) experienced at least one APO (717 [51.7%] of participants with AR compared to 2,480 [31.3%] participants without AR). After adjustment for baseline differences, the AR group had increased odds of gHTN (aOR 1.61 [95% CI 1.35–1.92]), preeclampsia/eclampsia (aOR 2.52 [95% CI 2.06–3.09]) and iatrogenic and spontaneous PTB (aOR 2.98 [95% CI 2.41–3.69]), but not delivery of an SGA neonate. ConclusionAR in pregnancy was independently associated with increased odds of hypertensive disorders of pregnancy and PTB, but future prospective work is needed to determine potential causality. Further, participants identifying as Black or Hispanic were significantly less likely to be recommended AR compared to those identifying as White. While AR is not an evidence-based practice, these findings suggest bias may impact which patients receive advice to limit activity in pregnancy.El resumen está disponible en Español al final del artículo.

Effect of gestational age on cerebral lesions in neonatal encephalopathy

ObjectiveTo determine the risk on brain lesions according to gestational age (GA) in neonates with neonatal encephalopathy.DesignSecondary analysis of the prospective national French population-based cohort, Long-Term Outcome of NeonataL EncePhALopathy.SettingFrench...

Effect of combined exposure to phthalates and polycyclic aromatic hydrocarbons during early pregnancy on gestational age and neonatal size: A prospective cohort study

Many studies have indicated that individual exposure to phthalates (PAEs) or polycyclic aromatic hydrocarbons (PAHs) affects pregnancy outcomes. However, combined exposure to PAEs and PAHs presents a more realistic situation, and research on the combined effects of PAEs and PAHs on gestational age and newborn size is still limited. This study aimed to assess the effects of combined exposure to PAEs and PAHs on neonatal gestational age and birth size. Levels of 9 PAE and 10 PAH metabolites were measured from the urine samples of 1030 women during early pregnancy from the Zunyi Birth Cohort in China. Various statistical models, including linear regression, restricted cubic spline, Bayesian kernel machine regression, and quantile g-computation, were used to study the individual effects, dose–response relationships, and combined effects, respectively. The results of this prospective study revealed that each ten-fold increase in the concentration of monoethyl phthalate (MEP), 2-hydroxynaphthalene (2-OHNap), 2-hydroxyphenanthrene (2-OHPhe), and 1-hydroxypyrene (1-OHPyr) decreased gestational age by 1.033 days (95 % CI: −1.748, −0.319), 0.647 days (95 % CI: −1.076, −0.219), 0.845 days (95 % CI: −1.430, −0.260), and 0.888 days (95 % CI: −1.398, −0.378), respectively. Moreover, when the concentrations of MEP, 2-OHNap, 2-OHPhe, and 1-OHPyr exceeded 0.528, 0.039, 0.012, and 0.002 µg/g Cr, respectively, gestational age decreased in a dose–response manner. Upon analyzing the selected PAE and PAH metabolites as a mixture, we found that they were significantly negatively associated with gestational age, birth weight, and the ponderal index, with 1-OHPyr being the most important contributor. These findings highlight the adverse effects of single and combined exposure to PAEs and PAHs on gestational age. Therefore, future longitudinal cohort studies with larger sample sizes should be conducted across different geographic regions and ethnic groups to confirm the impact of combined exposure to PAEs and PAHs on birth outcomes.

Comparison of SGA and Severe SGA rates using six size standards – Is there a difference?

BackgroundSmall for gestational age (SGA) neonates are known to be at an elevated risk for neonatal morbidity. Despite this, there is a growing array of proposed size standards for identifying SGA fetuses. Given the inherent differences in design, acquisition methods, and the characteristics of the populations they represent, the generalizability of these standards to diverse populations remains uncertain. IntroductionThis study aimed to assess variations in rates of SGA and severe SGA using six distinct size standards: Hadlock, Fetal Medicine Foundation (FMF), World Health Organization (WHO), Intergrowth-21 (IG-21), and two locally derived population-based size standards. The objective was to examine the differences in SGA and severe SGA rates among these size standards. MethodsA retrospective cohort study was conducted, encompassing all singleton deliveries in two tertiary referral hospital campuses with an annual birth count exceeding 10,000, from January 2019 to July 2022. SGA and severe SGA were defined as birthweights below the 10th or 3rd percentile, respectively, based on each growth standard. The study design included details on the setting, subjects (singleton deliveries), and the chosen size standards. Comparative analyses were performed to assess variations in SGA and severe SGA rates among these size standards. ResultsOur study analyzed 32,912 singleton deliveries. We found that the choice of growth standard significantly impacted the rates of both SGA and severe SGA infants. Notably, the WHO criteria identified 5,548 (16.9 %) fetuses as SGA, compared to only 1,716 (5.2 %) using the INTERGROWTH-21 standard (p < 0.001). Similarly, for severe SGA, the FMF charts classified 2098 (6.37 %) infants, significantly higher than the 320 (1 %) identified by Dolberg’s local population-based charts (p < 0.001). ConclusionOur study demonstrates a significant variety of SGA and severe SGA rates using different size standards. Therefore, the decision on the size standards in use is critical given the significant influence on clinical management. SynopsisThere are significant variations in SGA and Severe SGA rates depending on the chosen size standard.

Genetic and Clinical Factors Influencing Congenital Anomalies of the Kidney and Urinary Tract in Children: Insights from Prenatal and Postnatal Assessments.

Congenital anomalies of the kidney and urinary tract (CAKUT) significantly contribute to pediatric morbidity, often necessitating ureterorenal surgery. This study explored the relationship between genetic mutations, renal surgery requirements, and prenatal, postnatal, and parental risk factors in children with CAKUT. A retrospective analysis of 651 children diagnosed with CAKUT included patient demographics, parental risk factors, ultrasound findings, genetic mutations, and surgical incidence. Antenatal ultrasounds showed normal findings in 32.1%, hydronephrosis in 46.9%, and other abnormalities in 21% of cases. Surgical intervention correlated with higher hydronephrosis reduction than non-intervention. Genetic mutations were identified in 5.4% of cases, with 24.6% requiring surgery. Low neonatal birth weight (odds ratio [OR] = 0.98, p < 0.001), advanced maternal age (OR = 1.06, p < 0.001), and postnatal abnormal ultrasound findings (OR = 2.62, p < 0.001) were associated with increased genetic mutation risks. Antenatal hydronephrosis (OR = 3.85, p < 0.001) and postnatal urinary tract infections (OR = 4.85, p < 0.001) increased the likelihood of surgical intervention. Neonatal birth weight, maternal age, and postnatal ultrasound findings were identified as independent risk factors for genetic mutations, while no significant link was found between these genetic factors and the need for surgery. Surgical needs were associated with urinary tract infections and antenatal hydronephrosis, indicating that timely surgical intervention may benefit these patients.

Sex differences in pediatric sepsis—a systematic review protocol

BackgroundPediatric sepsis remains a leading cause of childhood morbidity and mortality worldwide. Despite advancements in modern medicine, it accounts for more than 3 million childhood deaths per year. Multiple studies have emphasized that sex and gender have an impact on the treatment and outcome of various diseases. Adult studies have revealed sex differences in pathophysiological responses to septic shock, as well as a possible protective effect of estrogens on critical illness. Sex-specific maturational and developmental differences in host immunology have been previously demonstrated for neonatal and pediatric age groups. At present, there are no studies assessing the impact of sex on outcomes of children with sepsis.MethodsThe goal of this study is to assess sex-specific differences in childhood sepsis survival outcomes. We will systematically assess associations of sex and gender with outcomes in pediatric sepsis in the literature by performing a systematic search of MEDLINE and Embase databases. We will include all English language randomized trials and cohort studies. The study population will include children > 37 weeks gestational age and < 18 years of age. Exposure will be sepsis, severe sepsis, and septic shock and the main comparison will be between male and female sex. The primary outcome will be hospital mortality. Secondary outcomes will be the pediatric intensive care unit and hospital length of stay.DiscussionResults from this review are expected to provide important information on the association of sex with the outcomes of pediatric sepsis. If an association is noted, this study may serve as a foundation for further research evaluating the pathophysiological aspects as well as potential socioeconomic factors responsible for the clinically detected sex differences.Systematic review registrationPROSPERO CRD42022315753.

Does atenolol use during pregnancy cause small for gestational age neonates? A meta-analysis.

Atenolol is a commonly used beta bloscker in non-pregnant women. Many providers are hesitant in prescribing atenolol in pregnancy because of a possible association with poor fetal growth. We aimed to assess the association between atenolol and the occurrence of small for gestational age neonates compared to other beta blockers, as described in the existing literature. We used the meta-analytic method to generate a forest plot for risk ratios (RR) of small for gestational age in patients who used atenolol vs. other beta blockers. Statistical heterogeneity was assessed with the I2 statistic. Two studies were included, with a resultant RR of 1.94 [95 % confidence interval (CI) 1.60; 2.35]. A study by Duan etal. in 2018 noted the following rate of small for gestational age for each beta blocker use: 112/638 atenolol, 590/3,357 labetalol, 35/324 metoprolol, and 50/489 propranolol. A study by Tanaka etal. in 2016 noted the following rate of small for gestational age: 8/22 for propranolol, 2/12 for metoprolol, 2/6 for atenolol, 0/5 for bisoprolol. Heterogeneity (I2) was 0 %. Our results suggested an elevated risk of small for gestational age associated with atenolol use in comparison to other beta blockers, specifically labetalol, propranolol, bisoprolol, and metoprolol.

Effect of β-lactam antibiotics on the gut microbiota of term neonates

β-Lactam antibiotics are a class of antibiotics commonly used to treat bacterial infections. However, the effects of β-lactam antibiotics on term neonatal intestinal flora have not been fully elucidated. Hospitalized full-term newborns receiving β-lactam antibiotics formed the antibiotic group (n = 67), while those without antibiotic treatment comprised the non-antibiotic group (n = 47). A healthy group included healthy full-term newborns (n = 16). Stool samples were collected for 16 S rDNA sequencing to analyze gut microbiota variations. Further investigation was carried out within the β-lactam antibiotic group, exploring the effects of antibiotic use on the newborns’ gut microbiota in relation to the duration and type of antibiotic administration, delivery method, and feeding practices. The antibiotic group exhibited significant difference of microbial community composition compared to the other groups. Genera like Klebsiella, Enterococcus, Streptococcus, Alistipes, and Aeromonas were enriched, while Escherichia-Shigella, Clostridium sensu stricto 1, Bifidobacterium, and Parabacteroides were reduced. Klebsiella negatively correlated with Escherichia-Shigella, positively with Enterobacter, while Escherichia-Shigella negatively correlated with Enterococcus and Streptococcus. Regardless of neonatal age, β-lactam antibiotics induced an elevated abundance of Klebsiella and Enterococcus. The impact on gut microbiota varied with the duration and type of antibiotic (cefotaxime or ampicillin/sulbactam). Compared to vaginal delivery, cesarean delivery after β-lactam treatment heightened the abundance of Klebsiella, Enterobacteriaceae_Unclassified, Lactobacillales_Unclassified, and Pectobacterium. Feeding patterns minimally influenced β-lactam-induced alterations. In conclusion, β-lactam antibiotic treatment for neonatal pneumonia and sepsis markedly disrupted intestinal microbiota, favoring Klebsiella, Enterococcus, Streptococcus, Alistipes, and Aeromonas. The impact of β-lactam varied by duration, type, and delivery method, emphasizing heightened disruptions post-cesarean delivery.

Cord blood transfusions in extremely low gestational age neonates to reduce severe retinopathy of prematurity: results of a prespecified interim analysis of the randomized BORN trial

BackgroundPreterm infants are at high risk for retinopathy of prematurity (ROP), with potential life-long visual impairment. Low fetal hemoglobin (HbF) levels predict ROP. It is unknown if preventing the HbF decrease also reduces ROP.MethodsBORN is an ongoing multicenter double-blinded randomized controlled trial investigating whether transfusing HbF-enriched cord blood-red blood cells (CB-RBCs) instead of adult donor-RBC units (A-RBCs) reduces the incidence of severe ROP (NCT05100212). Neonates born between 24 and 27 + 6 weeks of gestation are enrolled and randomized 1:1 to receive adult donor-RBCs (A-RBCs, arm A) or allogeneic CB-RBCs (arm B) from birth to the postmenstrual age (PMA) of 31 + 6 weeks. Primary outcome is the rate of severe ROP at 40 weeks of PMA or discharge, with a sample size of 146 patients. A prespecified interim analysis was scheduled after the first 58 patients were enrolled, with the main purpose to evaluate the safety of CB-RBC transfusions.ResultsResults in the intention-to-treat and per-protocol analysis are reported. Twenty-eight patients were in arm A and 30 in arm B. Overall, 104 A-RBC units and 49 CB-RBC units were transfused, with a high rate of protocol deviations. A total of 336 adverse events were recorded, with similar incidence and severity in the two arms. By per-protocol analysis, patients receiving A-RBCs or both RBC types experienced more adverse events than non-transfused patients or those transfused exclusively with CB-RBCs, and suffered from more severe forms of bradycardia, pulmonary hypertension, and hemodynamically significant patent ductus arteriosus. Serum potassium, lactate, and pH were similar after CB-RBCs or A-RBCs. Fourteen patients died and 44 were evaluated for ROP. Ten of them developed severe ROP, with no differences between arms. At per-protocol analysis each A-RBC transfusion carried a relative risk for severe ROP of 1.66 (95% CI 1.06–2.20) in comparison with CB-RBCs. The area under the curve of HbF suggested that HbF decrement before 30 weeks PMA is critical for severe ROP development. Subsequent CB-RBC transfusions do not lessen the ROP risk.ConclusionsThe interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP.Trial registrationProspectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212.

Impact of postoperative necrotizing enterocolitis after neonatal cardiac surgery on neurodevelopmental outcome at 1 year of age.

We analyzed the impact of postoperative necrotizing enterocolitis (NEC) after cardiac surgery in neonatal age on neurodevelopmental (ND) outcome at 1 year of age. Using data from the Swiss Neurodevelopmental Outcome Registry for Children with Congenital Heart Disease (ORCHID), we analyzed perioperative variables including postoperative NEC (Bell's stage ≥2) and 1-year ND outcome (Bayley III). The included patients (n = 101) had congenital heart disease (CHD), categorized as follows: 77 underwent biventricular repair for CHD with two functional chambers, 22 underwent staged palliation until the Fontan procedure for CHD with single ventricle physiology (n = 22), or 4 underwent single ventricle palliation or biventricular repair for borderline CHD (n = 4). Neonatal cardiopulmonary bypass (CBP) surgery was performed at a median age (IQR) of 8 (6) days. NEC occurred in 16 patients. Intensive care unit (ICU) length of stay (LOS) and the total duration of the hospitalization were longer in children with NEC than those in others (14 with vs. 8 days without NEC, p < 0.05; 49 with vs. 32 days without NEC, p < 0.05). The Bayley III scores of the analyzed patients determined at an age of 11.5 ± 1.5 months showed cognitive (CCS) (102.2 ± 15.0) and language scores (LCS) (93.8 ± 13.1) in the normal range and motor composite scores (MCS) (88.7 ± 15.9) in the low-normal range. After adjusting for socioeconomic status and CHD type, patients with NEC had lower CCS scores [β = -11.2 (SE 5.6), p = 0.049]. Using a cumulative risk score including NEC, we found a higher risk score to be associated with both lower CCS [β = -2.8 (SE 1.3), p = 0.030] and lower MCS [β = -3.20 (SE 1.3), p = 0.016]. Postoperative NEC is associated with longer ICU and hospital LOS and contributes together with other complications to impaired ND outcome at 1 year of age. In the future, national and international patient registries may provide the opportunity to analyze large cohorts and better identify the impact of modifiable perioperative risk factors on ND outcome. ClinicalTrials.gov identifier: NCT05996211.

Epigenetic associations with neonatal age in infants born very preterm, particularly among genes involved in neurodevelopment

The time from conception through the first year of life is the most dynamic period in human development. This time period is particularly important for infants born very preterm (< 30 weeks gestation; VPT), as they experience a significant disruption in the normal developmental trajectories and are at heightened risk of experiencing developmental impairments and delays. Variations in the epigenetic landscape during this period may reflect this disruption and shed light on the interrelationships between aging, maturation, and the epigenome. We evaluated how gestational age (GA) and age since conception in neonates [post-menstrual age (PMA)], were related to DNA methylation in buccal cells collected at NICU discharge from VPT infants (n = 538). After adjusting for confounders and applying Bonferroni correction, we identified 2,366 individual CpGs associated with GA and 14,979 individual CpGs associated with PMA, as well as multiple differentially methylated regions. Pathway enrichment analysis identified pathways involved in axonogenesis and regulation of neuron projection development, among many other growth and developmental pathways (FDR q < 0.001). Our findings align with prior work, and also identify numerous novel associations, suggesting that genes important in growth and development, particularly neurodevelopment, are subject to substantial epigenetic changes during early development among children born VPT.

Preventing Hypothermia in Newborns With Congenital Anomalies in the Delivery Room.

Thermoregulation interventions in the delivery room have historically focused on preterm infants and studies often exclude term infants or those infants with known congenital anomalies. The purpose of this quality improvement project was to reduce the rate of admission hypothermia in neonates of all gestational ages born with congenital anomalies and admitted to the intensive care unit (ICU). Utilizing the Institute for Healthcare Improvement model for improvement, implementation of plan, do study, act cycles focused on standardizing temperatures of the delivery room and resuscitation bed, recommendations for temperature monitoring, trialing polyethylene lined hats, and implementing a delivery room thermoregulation checklist. Overall, the mean rate of neonates admitted to the ICU hypothermic (<36.5°C) decreased from 27% to 9% over an 8-month period. The interventions significantly reduced the number of neonates admitted to the ICU with hypothermia. Implementation of thermoregulation bundles should apply to all neonates with congenital anomalies to decrease risks associated with hypothermia.