Neonatology[JOURNAL]
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200 papers
Maternal and Neonatal Factors Associated with Delayed Closure of Ductus Arteriosus in Term-Born Neonates: Insights from the Copenhagen Baby Heart Cohort Study.
Mariager AF, Hammeken A, Malham M … +6 more , Raja RA, Sellmer A, Navne J, Bundgaard H, Iversen KK, Jeppesen DL
Neonatology · 2025 · PMID 39938495 · Full text
INTRODUCTION: The prenatal shunt, ductus arteriosus (DA), typically closes during the cardio-pulmonary transition at birth. We evaluated maternal and neonatal factors associated with delayed closure of DA in term-born ne...
INTRODUCTION: The prenatal shunt, ductus arteriosus (DA), typically closes during the cardio-pulmonary transition at birth. We evaluated maternal and neonatal factors associated with delayed closure of DA in term-born neonates. METHODS: We conducted a retrospective cohort study that included full-term neonates from the prospective observational Copenhagen Baby Heart cohort study. We assessed the association between maternal and neonatal factors and delayed ductal closure. RESULTS: We included 19,566 neonates, of whom 48% were female. Echocardiography was performed at a median age of 12 (IQR: 9-15) and 8 (IQR: 2-13) days for neonates with no DA and an open DA, respectively. Associations with delayed ductal closure included maternal obesity adjusted risk ratio = 2 (95% CI: 1-3.8), maternal hypothyroidism during pregnancy aRR = 2.02 (95% CI: 1.2-3.4), low Apgar 2.6 (95% CI: 1.2-6), high weight aRR = 1.81 (95% CI: 1.2-2.6), and length at birth aRR = 1.7 (95% CI: 1.1-2.6). CONCLUSION: The identified risk factors for delayed ductal closure in term-born neonates may help increase clinical attention and improve neonatal care.
European Reference Network for Inherited and Congenital Anomalies Evidence-Based Guideline on Surgical Aspects of Necrotizing Enterocolitis in Premature Neonates.
Hulscher J, Irvine W, Conforti A … +23 more , Di Cesare A, Ichino M, Sfeir R, Madadi Sanjani O, Strohm J, Hukkinen M, Moschino L, Norsa L, Kokešová A, Bakx R, Kooi E, Obermann-Borst S, Palleri E, Vermeulen M, Spruce M, Rolle U, Miserez M, de Haro Jorge I, Keyzer-Dekker C, Fascetti Leon F, den Uijl I, Eaton S, Burgos CM
Neonatology · 2025 · PMID 39925108 · Full text
Necrotizing enterocolitis (NEC) is a severe intestinal condition primarily affecting preterm neonates. It has a high mortality rate, particularly in infants with a birthweight of below 1,500 g or for those requiring surg...
Necrotizing enterocolitis (NEC) is a severe intestinal condition primarily affecting preterm neonates. It has a high mortality rate, particularly in infants with a birthweight of below 1,500 g or for those requiring surgical intervention. The European Reference Network for Inherited and Congenital Anomalies (ERNICA) has developed a clinical practice guideline to aid clinical decision-making pertaining to the surgical treatment and management of NEC in preterm neonates. This guideline was developed in accordance with the Guidelines 2.0 checklist and GRADE methodology. A multidisciplinary group of Europe's top experts collaborated with patient representatives to develop this guideline. After selecting critical points in care for which recommendations are required, a systematic review of the literature and critical appraisal of the evidence was performed. The Evidence to Decision framework was used as a guide to structure the consensus meetings and draft the recommendations. The panel developed seven recommendations and three good practice statements on the following topics: indications for surgery, peritoneal drainage, surgical technique, management of extensive NEC, enteral feeding, and neurodevelopmental outcomes in premature neonates with NEC. The certainty of evidence was graded as (very) low for most recommendations. However, the panel weighed up the benefits and harms in light of all relevant arguments and expert opinion. This guideline provides recommendations on caring for premature neonates with NEC. These recommendations can assist clinicians in their care decisions and can inform families on treatment options and relevant considerations. This guideline will be revised every 5 years to ensure it remains up to date.
Neonatal Care in Low- and Middle-Income Countries: A Fresh Look.
Saugstad OD, Lawn JE, Waiswa P … +1 more , Bhutta ZA
Neonatology · 2025 · PMID 39904328 · Full text
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Use of Macrogol to Accelerate Feeding Advancement in Extremely Preterm Infants.
Faust KB, Lupatsii M, Römer F … +13 more , Graspeuntner S, Waschina S, Zimmermann S, Humberg A, Fortmann MI, Hanke K, Böckenholt K, Dirks J, Silwedel C, Rupp J, Herting E, Göpel W, Härtel C
Neonatology · 2025 · PMID 39900010 · Publisher ↗
INTRODUCTION: Delayed enteral nutrition is associated with a higher risk for adverse outcomes in extremely preterm infants. Limited evidence exists on therapeutic options to support meconium evacuation and increase gastr...
INTRODUCTION: Delayed enteral nutrition is associated with a higher risk for adverse outcomes in extremely preterm infants. Limited evidence exists on therapeutic options to support meconium evacuation and increase gastrointestinal motility. The aim of this study was to determine the effect of macrogol on feeding tolerance and microbiome establishment in preterm infants <27 weeks of gestation. METHODS: We investigated the impact of early macrogol administration in two observational cohort studies: the multi-center German-Neonatal-Network (GNN) study comparing extremely preterm infants born in neonatal intensive care units (NICUs) using macrogol in the first week of life in >30% of their infants as compared to the remaining units, and the single-center Immunoregulation-of-the-Newborn (IRoN) study including gut microbiome assessment of infants born before and after implementation of macrogol use in this NICU. RESULTS: In the GNN study cohort including 4,290 infants, advancement to full enteral feedings was significantly faster in macrogol-using NICUs compared to the remaining NICUs (median/IQR: 14/12 vs. 16/14 days, p = 0.001). Risk for short-term outcomes such as sepsis or abdominal complications was not elevated in units with regular use of macrogol. In the IRoN cohort (n = 68), macrogol treated infants had a shorter time to reach full enteral feeding (median/IQR: macrogol 12/6, control 16/6 days, p = 0.004). Higher Bifidobacterium longum abundance in the gut microbiome correlated with acceleration to full enteral nutrition. CONCLUSION: Our observational data suggests that early off-label use of macrogol may support feeding advancement in highly vulnerable babies. These data provide a basis for a randomized controlled trial.
Microstructural Maturation of the Splenium of Corpus Callosum and Cognitive and Motor Outcome in Very Preterm Infants.
Winkler I, Posod A, Gizewski ER … +5 more , Mangesius S, Neubauer V, Pupp Peglow U, Kiechl-Kohlendorfer U, Griesmaier E
Neonatology · 2025 · PMID 39899995 · Publisher ↗
INTRODUCTION: Common brain injuries of preterm infants do not entirely explain the incidence of neurodevelopmental impairment observed in this population. Evidence suggests an association with microstructural maturation...
INTRODUCTION: Common brain injuries of preterm infants do not entirely explain the incidence of neurodevelopmental impairment observed in this population. Evidence suggests an association with microstructural maturation of the splenium of corpus callosum. This study aimed to investigate a correlation between microstructural maturation of the splenium of corpus callosum and neurodevelopmental outcome in very preterm infants. METHOD: In a cohort study of 373 very preterm infants, we used fractional anisotropy (FA) and apparent diffusion coefficient (ADC) derived from diffusion tensor imaging at term equivalent age (TEA) to quantitatively reflect microstructural maturation of the splenium of corpus callosum, and standardized follow-up assessments of cognitive and motor function at 24 months corrected age and 5 years chronological age. Correlation was tested by Spearman's rank correlation coefficients and multivariate regression analysis. RESULTS: At 24 months, we found significantly lower FA and higher ADC values in infants with abnormal mental indices, psychomotor developmental indices, and fine motor function. Scores of all three correlated positively with FA and negatively with ADC. Aged 5 years, lower FA values correlated significantly with abnormal overall motor function, and higher ADC values correlated significantly with abnormal full-scale intelligence quotient (FSIQ) and overall motor function. Scores of FSIQ, overall, and fine motor function correlated negatively with ADC. CONCLUSION: The results emphasize an association between microstructural maturation of the splenium of corpus callosum at TEA and neurodevelopmental outcome, and suggest that ADC may be more strongly linked to these outcomes than FA, especially in the long-term.
Interventions to Prevent and Manage Infections in Pregnancy.
Yasin R, Jiang L, Das JK … +1 more , Bhutta ZA
Neonatology · 2025 · PMID 39874953 · Full text
BACKGROUND: Care interventions aimed at preventing and treating maternal infections during the gestational period are of paramount importance. Timely immunizations, screening strategies, and management of maternal infect...
BACKGROUND: Care interventions aimed at preventing and treating maternal infections during the gestational period are of paramount importance. Timely immunizations, screening strategies, and management of maternal infections reduce the risk of complications for the developing fetus and play a pivotal role in improving neonatal outcomes. SUMMARY: We aim to summarize evidence for a total of thirteen interventions, pertaining to the prevention and treatment of maternal infections during the antenatal period, from Every Newborn Series published in The Lancet 2014. We identified the most recent systematic reviews, extracted data from each review, and conducted a sub-group meta-analysis for low-income countries and lower-middle-income countries (LMICs) for outcomes relevant to neonatal health. Findings from our papers indicate limited evidence from LMICs, highlighting the pressing need for coordinated efforts to close this gap and strengthen the body of inclusive evidence on prevention and treatment of maternal infections during pregnancy. KEY MESSAGES: Evidence from LMICs suggests that influenza virus vaccination had no effect on stillbirth, preterm birth, small for gestational age, or low birthweight (LBW). Insecticide-treated bed nets in pregnancy reduced the risk of fetal loss and improved the babies' birthweight. Changing a two-dose intermittent preventive treatment (IPTp) regimen to more frequent IPTp dosing decreased the risk of LBW and significantly improved babies' birthweight. Addition of antibacterial antibiotic to the IPTp regimen significantly reduced the risk of LBW. Antibiotic treatments for syphilis and chlamydia had a significant effect on LBW. Treatment of documented periodontal disease during pregnancy reduced the risk of LBW. BACKGROUND: Care interventions aimed at preventing and treating maternal infections during the gestational period are of paramount importance. Timely immunizations, screening strategies, and management of maternal infections reduce the risk of complications for the developing fetus and play a pivotal role in improving neonatal outcomes. SUMMARY: We aim to summarize evidence for a total of thirteen interventions, pertaining to the prevention and treatment of maternal infections during the antenatal period, from Every Newborn Series published in The Lancet 2014. We identified the most recent systematic reviews, extracted data from each review, and conducted a sub-group meta-analysis for low-income countries and lower-middle-income countries (LMICs) for outcomes relevant to neonatal health. Findings from our papers indicate limited evidence from LMICs, highlighting the pressing need for coordinated efforts to close this gap and strengthen the body of inclusive evidence on prevention and treatment of maternal infections during pregnancy. KEY MESSAGES: Evidence from LMICs suggests that influenza virus vaccination had no effect on stillbirth, preterm birth, small for gestational age, or low birthweight (LBW). Insecticide-treated bed nets in pregnancy reduced the risk of fetal loss and improved the babies' birthweight. Changing a two-dose intermittent preventive treatment (IPTp) regimen to more frequent IPTp dosing decreased the risk of LBW and significantly improved babies' birthweight. Addition of antibacterial antibiotic to the IPTp regimen significantly reduced the risk of LBW. Antibiotic treatments for syphilis and chlamydia had a significant effect on LBW. Treatment of documented periodontal disease during pregnancy reduced the risk of LBW.
Validation of a New Classification for Severe Bronchopulmonary Dysplasia in Extremely Preterm Infants: Insights from a Large Japanese Cohort.
Nakanishi H, Ito M, Kato S … +6 more , Saito M, Miyahara N, Arai H, Ota E, Namba F, Neonatal Research Network, Japan
Neonatology · 2025 · PMID 39870062 · Full text
INTRODUCTION: A recent scoping review identified histological chorioamnionitis (HCA), small for gestational age (SGA), and bubbly/cystic appearance on chest X-ray (bubbly/cystic CXR) as risk factors for severe bronchopul...
INTRODUCTION: A recent scoping review identified histological chorioamnionitis (HCA), small for gestational age (SGA), and bubbly/cystic appearance on chest X-ray (bubbly/cystic CXR) as risk factors for severe bronchopulmonary dysplasia (BPD). To further validate these results, a large-scale database was analyzed. METHODS: This retrospective multicenter cohort study included infants born at <28 weeks' gestational age between 2003 and 2016. The validated risk factors identified from the scoping review were analyzed for independent associations with severe BPD using multivariable logistic regression. Additionally, the association of these factors with long-term outcomes at 3 years, including home oxygen therapy (HOT) and neurodevelopmental impairments (NDIs), was analyzed. RESULTS: Among 15,834 extremely preterm infants, HCA, SGA, and bubbly/cystic CXR on postnatal day 28 were significantly and independently associated with severe BPD (adjusted odds ratio, 1.20; 95% confidence interval, 1.06-1.36) (1.73; 1.51-1.98) (1.79; 1.60-2.01), respectively. These three factors were also linked to HOT at 3 years (1.54; 1.14-2.08) (1.70; 1.21-2.39) (2.63; 1.94-3.56), respectively. Their combination significantly increased the prevalence of severe BPD and HOT at 3 years, particularly with bubbly/cystic CXR. Only SGA was independently associated with NDIs in BPD infants (1.55; 1.32-1.83). CONCLUSIONS: HCA, SGA, and bubbly/cystic CXR on postnatal day 28 were identified as important risk factors for severe BPD and long-term respiratory outcomes. While further research is needed to validate their role in endotype-specific classification of BPD, these findings may contribute to early prognostic strategies and targeted interventions before 36 weeks' postmenstrual age.
Association of Early Nutrition with Bronchopulmonary Dysplasia Severity and Magnetic Resonance Imaging Lung Characteristics in Preterm Infants.
Dianova E, Higano NS, McNelis KM … +4 more , Ehrlich SR, Liu C, Woods JC, Kingma PS
Neonatology · 2025 · PMID 39842412 · Full text
INTRODUCTION: Restricted fetal and neonatal growth is a known risk factor for bronchopulmonary dysplasia (BPD) in premature infants. However, the impact of nutrition and infant growth specifically on lung growth in BPD i...
INTRODUCTION: Restricted fetal and neonatal growth is a known risk factor for bronchopulmonary dysplasia (BPD) in premature infants. However, the impact of nutrition and infant growth specifically on lung growth in BPD is unknown. Moreover, whether all lung growth in BPD is beneficial is unclear. We hypothesized that lung growth and development and severity of BPD directly relate to caloric and protein intake, weight gain, and linear growth of premature neonates. METHODS: In this retrospective study, caloric and protein intake for the first 4 weeks of life, growth parameters along with lung volume, mass, density, and BPD severity obtained by ultrashort echo time (UTE) MRI, were analyzed. RESULTS: The cohort included 95 neonates with mean GA 26.1 weeks and BW 790 g. Infants with grade 2 and 3 BPD had less caloric and protein intake during first 4 weeks of life vs. grade 1 BPD (96/98 vs. 106 kcal/kg/day; 3.79/3.75 vs. 3.99 g protein/kg/day; p < 0.05). UTE MRI showed that lung mass per body surface area increased with increasing BPD severity (237, 311, 384 g/m2 for grade 1, 2, and 3, respectively, p < 0.05). Increased caloric intake was associated with decreased lung mass (p = 0.02) and improved BPD score on MRI (p = 0.04). CONCLUSION: Decreased nutritional intake during the first 4 weeks of life appears to be associated with more severe BPD, increased lung mass and more severe lung disease on MRI.
Near-Term and Intrapartum Care of Mothers for Perinatal and Newborn Outcomes.
Yasin R, Azhar M, Naseem HA … +3 more , Ali AA, Das JK, Bhutta ZA
Neonatology · 2025 · PMID 39837301 · Full text
INTRODUCTION: Near-term and intrapartum care play pivotal roles in ensuring a safe childbirth experience and are essential components of a comprehensive approach to maternal and neonatal health. METHODS: The following in...
INTRODUCTION: Near-term and intrapartum care play pivotal roles in ensuring a safe childbirth experience and are essential components of a comprehensive approach to maternal and neonatal health. METHODS: The following interventions were identified: antibiotics for preterm premature rupture of membrane, antenatal corticosteroids for fetal lung maturation, partograph use during labor and delivery, induction of labor at or post-term, skilled birth care and safe childbirth checklist during labor and delivery. A scoping exercise was conducted to ascertain the most up-to-date evidence, and reviews of topics of interest were updated in case the evidence was not recent, with a focus on low- and middle-income countries (LMICs). RESULTS: Antibiotics reduced the overall risk of neonatal infection including pneumonia (RR 0.67 [0.52 to 0.85]). LMIC evidence showed a significant effect of antenatal steroids on the risk of neonatal mortality (RR 0.64 [0.43 to 0.97]) and respiratory distress syndrome (RR 0.65 [0.44 to 0.96]). Induction of labor practices at term or post-term reduced the risk of meconium aspiration syndrome (RR 0.51 [0.34 to 0.76]). The use of the WHO childbirth checklist significantly raised the standard of preeclampsia care (OR 8.09 [2.55 to 25.63]) as well as of maternal infection management (OR 25.44 [4.09 to 158.08]). LMIC-specific evidence also demonstrated a significant reduction in the risk of stillbirth (OR 0.92 [0.87 to 0.96]). CONCLUSION: Further research initiatives pertaining to health interventions delivered to expectant mothers near-term or during the intrapartum period can contribute to a more inclusive understanding of health challenges in LMICs. INTRODUCTION: Near-term and intrapartum care play pivotal roles in ensuring a safe childbirth experience and are essential components of a comprehensive approach to maternal and neonatal health. METHODS: The following interventions were identified: antibiotics for preterm premature rupture of membrane, antenatal corticosteroids for fetal lung maturation, partograph use during labor and delivery, induction of labor at or post-term, skilled birth care and safe childbirth checklist during labor and delivery. A scoping exercise was conducted to ascertain the most up-to-date evidence, and reviews of topics of interest were updated in case the evidence was not recent, with a focus on low- and middle-income countries (LMICs). RESULTS: Antibiotics reduced the overall risk of neonatal infection including pneumonia (RR 0.67 [0.52 to 0.85]). LMIC evidence showed a significant effect of antenatal steroids on the risk of neonatal mortality (RR 0.64 [0.43 to 0.97]) and respiratory distress syndrome (RR 0.65 [0.44 to 0.96]). Induction of labor practices at term or post-term reduced the risk of meconium aspiration syndrome (RR 0.51 [0.34 to 0.76]). The use of the WHO childbirth checklist significantly raised the standard of preeclampsia care (OR 8.09 [2.55 to 25.63]) as well as of maternal infection management (OR 25.44 [4.09 to 158.08]). LMIC-specific evidence also demonstrated a significant reduction in the risk of stillbirth (OR 0.92 [0.87 to 0.96]). CONCLUSION: Further research initiatives pertaining to health interventions delivered to expectant mothers near-term or during the intrapartum period can contribute to a more inclusive understanding of health challenges in LMICs.
A New Tool to Assess Patient-Ventilator Synchrony in Preterm Infants Receiving Non-Invasive Ventilation: A Randomized Crossover Pilot Study.
Cresi F, Maggiora E, Rubino C … +7 more , Ferroglio M, Ruzzante E, Piga E, Giraudo I, Limone M, Terrin G, Coscia A
Neonatology · 2025 · PMID 39837293 · Publisher ↗
INTRODUCTION: Nasal synchronized intermittent positive pressure ventilation (nSIPPV) is an effective non-invasive ventilation technique, especially for preterm infants. Patient-ventilator synchrony is essential for provi...
INTRODUCTION: Nasal synchronized intermittent positive pressure ventilation (nSIPPV) is an effective non-invasive ventilation technique, especially for preterm infants. Patient-ventilator synchrony is essential for providing effective respiratory support; however, no automated system is currently available for monitoring this parameter. A new tool for automatic assessment of patient-ventilator synchrony, the SyncNIV system, was developed and applied in this pilot study to evaluate differences between nSIPPV and non-synchronized nasal intermittent positive pressure ventilation (nIPPV) in preterm infants with respiratory distress. METHODS: This study involved designing a custom algorithm for signal analysis. Data were collected through a polygraph that could simultaneously gather respiratory data from the patients and the ventilator. Patient-ventilator synchrony was evaluated by applying the SyncNIV system in a randomized crossover study designed to compare nSIPPV and nIPPV. The primary outcome was the mean instant Synchrony Index (i-SI), defined as the portion of the inspiration effort sustained by ventilator inflation, expressed as a percentage. RESULTS: Fourteen infants with a median (IQR) gestational age of 28.6 (25.6-30.3) were enrolled. We analyzed 43,304 ventilator inflations and 50,221 patient breaths. The i-SI was 54.69% (44.49-60.09) in nSIPPV and 39.54% (33.40-48.75) in nIPPV, p < 0.05. CONCLUSION: The SyncNIV system confirmed better i-SI during nSIPPV than during nIPPV, demonstrating its effectiveness in assessing the differences between these two modes of non-invasive ventilation in preterm infants. The SyncNIV system could be a useful tool for optimizing the ventilation parameters and improving the effectiveness and comfort of respiratory support systems.
Association between Early Postnatal Hydrocortisone and Retinopathy of Prematurity in Extremely Preterm Infants.
Petrishka-Lozenska M, Pivodic A, Flisberg A … +4 more , Hansen-Pupp I, Smith LEH, Lundgren P, Hellström A
Neonatology · 2025 · PMID 39837291 · Full text
INTRODUCTION: Retinopathy of prematurity (ROP) is a leading cause of preventable childhood blindness. We investigated the association of early postnatal low-dose intravenous hydrocortisone used for the prevention of bron...
INTRODUCTION: Retinopathy of prematurity (ROP) is a leading cause of preventable childhood blindness. We investigated the association of early postnatal low-dose intravenous hydrocortisone used for the prevention of bronchopulmonary dysplasia (BPD) with ROP outcome among extremely preterm infants in a Swedish cohort. METHODS: This retrospective cohort study included extremely preterm infants born before 28 weeks of gestational age (GA). Infants born September 2020-August 2022, treated with low-dose intravenous hydrocortisone for prevention of BPD, were compared to untreated controls born September 2016-August 2020. Hydrocortisone was administered postnatally with a dose of 0.5 mg/kg twice daily for 7 days, followed by 0.5 mg/kg per day for 3 days. Logistic regression, adjusted for GA, birth weight (BW), sex, and parenteral nutrition, was used in the primary analysis. For robustness, we performed 1:1 propensity score (PS) matching followed by logistic regression. RESULTS: Of 245 preterm infants included, 65 were treated with low-dose hydrocortisone and 180 were untreated controls. Incidence of ROP treatment was reduced in the hydrocortisone group 18.5% (12/65) versus controls 32.2% (58/180), p = 0.038. One-to-one PS matching (n = 62 + 62) confirmed the reduced incidence of ROP treatment in the hydrocortisone-treated infants (odds ratio [OR]: 0.38, 95% confidence interval [95% CI]: 0.16-0.88, p = 0.025). After adjusting for GA, BW, sex, and parenteral nutrition ≥14 days, the reduced risk of ROP treatment after early hydrocortisone treatment persisted (OR: 0.31, 95% CI: 0.16-0.60, p = 0.0005). CONCLUSION: Early postnatal low-dose intravenous hydrocortisone used to prevent BPD may reduce the risk of ROP treatment among extremely preterm infants.
Erratum.
Neonatology · 2025 · PMID 39832487 · Full text
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The Prevalence of Neonatal Hypoglycemia in Twins versus Singletons following Exposure to Antenatal Steroid Therapy Is Comparable: A Retrospective Study in a Single Center.
Yoeli-Ullman R, Zemet R, Zloto K … +4 more , Toren A, Alexandroni H, Schushan Eisen I, Mazaki-Tovi S
Neonatology · 2025 · PMID 39761659 · Publisher ↗
INTRODUCTION: Antenatal corticosteroids (ACS) administration before anticipated preterm birth is one of the most important interventions available to improve neonatal outcomes. Nevertheless, this treatment is associated...
INTRODUCTION: Antenatal corticosteroids (ACS) administration before anticipated preterm birth is one of the most important interventions available to improve neonatal outcomes. Nevertheless, this treatment is associated with an increased risk of neonatal hypoglycemia. The aim of this study was to determine whether preterm twins who receive ACS are at increased risk for developing neonatal hypoglycemia. METHODS: This was a retrospective cohort study of indicated and spontaneous preterm births of twins at a single center between 2011 and 2018. The study population included 3 groups matched for gestational age at delivery and birth weight: (1) Twin neonates who received a course of ACS 1-7 days before birth (n = 532); (2) twins who did not receive ACS at that time interval (n = 532); and (3) singletons receiving ACS 1-7 days before birth (n = 266). The primary outcome was neonatal hypoglycemia (<40 mg/dL/2.2 mmol/L) within the first 24 h and 48 h of life. RESULTS: The rate of neonatal hypoglycemia during the first 24 h of life was significantly higher in singletons exposed to ACS compared to twins not exposed to ACS (p = 0.019) and in twins exposed to ACS compared to twins not exposed to ACS (p = 0.047). The rate of neonatal hypoglycemia was almost identical between twins and singletons exposed to ACS (p = 0.72). Regression analysis revealed that exposure to ACS and birth weight were independently associated with neonatal hypoglycemia after adjustment for maternal age, body mass index, gravidity, gestational diabetes mellitus, and gestational age at delivery. CONCLUSION: Exposure to ACS, rather than plurality, is associated with short-lived neonatal hypoglycemia.
Association between Enteral Protein Intake and Fat-Free Mass Accretion in Very Preterm Infants.
Jerome M, Gunawan E, Aristizabal N … +2 more , Chandler-Laney P, Salas AA
Neonatology · 2025 · PMID 39746346 · Full text
INTRODUCTION: For preterm infants, the first 2 weeks after birth are a time when nutrition and protein intake is variable and often falls below recommended intakes. Our objective was to investigate the relationship betwe...
INTRODUCTION: For preterm infants, the first 2 weeks after birth are a time when nutrition and protein intake is variable and often falls below recommended intakes. Our objective was to investigate the relationship between protein intake, including source of protein, during the first 2 weeks after birth and fat-free mass (FFM) accretion in a group of very preterm infants. METHODS: In this observational cohort study, body composition was assessed using air displacement plethysmography in eligible infants <32 weeks gestational age at 2 weeks after birth and prior to discharge. FFM accretion was calculated as difference between the two measurements. We collected daily nutrition data for the first 2 weeks. Multivariable linear regression was used to assess the relationship between protein intake and body composition and weight gain. RESULTS: Seventy-eight infants were included (mean birthweight: 1,408±278 g). Mean cumulative protein intake of this cohort in the first 2 weeks was 2.4±0.8 g/kg/day of which 74±19% was enteral (1.7±0.6 g/kg/day). Enteral protein intake was associated with higher FFM while parenteral protein was associated with lower FFM. Total protein intake from both sources during the first 2 weeks after birth was positively associated with greater weight gain. CONCLUSION: Enteral protein intake during the first 2 weeks after birth is associated with higher FFM and weight in preterm infants. Future interventional studies should investigate the effects of higher enteral protein intake during the first 2 weeks after birth on growth and body composition.
Third-Trimester Development of Central Autonomic Network Connectivity Is Altered in an Extrauterine Environment.
Christoffel K, De Asis Cruz J, Cook KM … +5 more , Kapse K, Andescavage N, Basu S, Limperopoulos C, du Plessis A
Neonatology · 2025 · PMID 39746339 · Full text
INTRODUCTION: The central autonomic network (CAN), which involves complex interconnected brain regions that modulate the autonomic nervous system, may be key to understanding higher risk for psychosocial and behavioral c...
INTRODUCTION: The central autonomic network (CAN), which involves complex interconnected brain regions that modulate the autonomic nervous system, may be key to understanding higher risk for psychosocial and behavioral challenges in preterm neonates. METHODS: We compared resting-state functional connectivity of the CAN in 94 healthy term-born controls and 94 preterm infants at term-equivalent age. In preterm infants, we correlated CAN connectivity with postmenstrual age (PMA). The preterm cohort underwent the Infant-Toddler Social and Emotional Assessment at 18-month follow-up, and these scores were correlated with CAN connectivity. RESULTS: CAN connectivity at the amygdala (p < 0.001), hippocampus (p < 0.001), insula (p < 0.001), brainstem (p = 0.003), and thalamus (p = 0.032) was significantly higher in term (n = 94) than preterm (n = 94) neonates. In preterm neonates, CAN connectivity positively correlated with PMA at the thalamus (r = 0.438, p < 0.001), insula (r = 0.304, p < 0.001), precuneus (r = 0.288, p < 0.001), hippocampus (r = 0.283, p < 0.001), and amygdala (r = 0.142, p = 0.034). At 18-month follow-up (n = 30, mean age 19.8 ± 3.4 months), CAN connectivity at the insula was negatively correlated with externalizing behaviors (r = -0.529, p = 0.003). CONCLUSION: In preterm neonates, the CAN evolves dynamically over the extrauterine third trimester and is measurably different compared to term-born neonates in ways that impact developmental outcomes. This is the first study to describe CAN connectivity using resting-state functional MRI in large cohort of term and preterm neonates and to report an association of CAN connectivity and behavioral outcomes.
"Enriching the Hospital's Scientific Fame": Research at the Vienna Foundling Hospital.
Obladen M
Neonatology · 2025 · PMID 39709959 · Publisher ↗
BACKGROUND: Little is known about medical research at the Vienna Foundling Hospital during the 18th and 19th centuries. SUMMARY: The present article focuses on nutrition, medical care, and research concerning newborn inf...
BACKGROUND: Little is known about medical research at the Vienna Foundling Hospital during the 18th and 19th centuries. SUMMARY: The present article focuses on nutrition, medical care, and research concerning newborn infants. In 1784, Emperor Joseph II merged obstetric and foundling hospitals under common leadership with specific statutes. Admissions rose from 1,704 in 1785 to 9,797 in 1859. A third of all infants born in Vienna in the 1890s were "foundlings" - correctly: abandoned infants, illegitimate birth was a prerequisite for admission. Differing from other foundling hospitals, the statutes obliged physicians to research, which focused on the great baby killers of the 18th century: smallpox, puerperal sepsis, connatal syphilis, tuberculosis, and malformations. Researchers included Anton Rechberger, Lucas Boër, Ignaz Semmelweis, Carl Rokitansky, Alois Bednar, and Carl Friedinger. Major scientific achievements were Rechberger's introduction of smallpox inoculation in Austria in 1768; Semmelweis' prevention of puerperal sepsis in 1847, and Bednar's classification of congenital heart malformations in 1852. Mortality statistics were doctored: deaths within 1 year were related to admissions from several years, which yielded maximum "mortality rates" of 76% in 1811, and a minimum rate of 13% in 1829. Actual mortality, however, per number of admissions, was over 90% in the first year of life. The institution persisted for 126 years because of the strict anonymity of extramarital birth, faked statistics deceiving supervisors, and esteem for the imperial inaugurator even beyond the end of the Austrian Empire. KEY MESSAGE: Despite appalling mortality, successful research was conducted at the Vienna Foundling Hospital.
Oxygenation of Immature Infants in the Delivery Room and Beyond: A Quest for Future Research.
Saugstad OD, Speer CP, Vento M
Neonatology · 2025 · PMID 39701051 · Full text
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Caffeine Therapy for Apnea of Prematurity: Single-Center Study on Dosing Practices and Perceived Effectiveness.
Storm KK, Flint RB, Onland W … +4 more , van Kaam AH, Reiss IKM, Hutten GJ, Simons SHP
Neonatology · 2025 · PMID 39681093 · Full text
INTRODUCTION: Caffeine is the registered pharmacologic treatment for apnea of prematurity and is extensively used in the neonatal intensive care units (NICUs) based on evidence from randomized controlled trials. This stu...
INTRODUCTION: Caffeine is the registered pharmacologic treatment for apnea of prematurity and is extensively used in the neonatal intensive care units (NICUs) based on evidence from randomized controlled trials. This study aimed to describe the clinical use of caffeine based on real-world data, hypothesizing a divergence from the registered dosing regimen. METHODS: A retrospective analysis included infants born before 30 weeks of gestation, admitted to the NICU of the Erasmus MC Rotterdam from 2018 to 2021. Exclusion criteria comprised infants admitted after postnatal day 2, those not receiving caffeine during admission, patients admitted for less than 24 h, those who spent less than 24 h on non-invasive support, and cases lacking medication data. The primary outcome was the proportion of patients receiving an average caffeine dose higher than registered on the label. RESULTS: A total of 451 patients with a median gestational age of 28+0 weeks (IQR 26+2-29+0) and birthweight of 1,015 g (IQR 800-1,218) were included. Of these, 402 infants (89%) received an average daily caffeine dosage exceeding the registered dose range. The median caffeine maintenance dose per patient was 5.3 mg/kg/day (IQR 5.0-5.8), with additional therapy (mini-load, doxapram, or intubation) needed in 318 patients (71%). CONCLUSION: This study highlights the frequent use of higher caffeine dosages in clinical practice than registered and recommended based on long-term safety data. Despite these high dosages and frequent mini-loads, 28% of patients still required additional treatment with doxapram and/or invasive mechanical ventilation, indicating the need for individualized dosing strategies or alternative therapies.
Gut Pathogen Colonization: A Risk Factor to Bloodstream Infections in Preterm Neonates Admitted in the Neonatal Intensive Care Unit - A Prospective Cohort Study.
Iqbal F, Siva N, Shenoy PA … +3 more , Lewis LES, Purkayastha J, Eshwara VK
Neonatology · 2025 · PMID 39675351 · Full text
INTRODUCTION: Gut pathogen colonization, where pathogens disrupt the normal gut microbiota, has been implicated in the development of bloodstream infections (BSIs). This study investigates the association between gut pat...
INTRODUCTION: Gut pathogen colonization, where pathogens disrupt the normal gut microbiota, has been implicated in the development of bloodstream infections (BSIs). This study investigates the association between gut pathogen colonization and BSI, hypothesizing that species causing BSI primarily originated from gut. METHODS: A prospective cohort study was conducted in the neonatal intensive care unit (NICU) of tertiary care hospital in Karnataka, India, from January 2021 to September 2023. Inborn preterm infants were enrolled. The study population was divided into two groups: group A (neonates without sepsis) and group B (neonates with sepsis). Demographic details and blood culture results were collected. Stool samples were taken on day 4 and day 14 for group A, and on day 4 and the day of sepsis diagnosis for group B. RESULTS: Group B had a lower mean birthweight (1,649.6 ± 652.1 g) compared to group A (1,757 ± 656 g). Klebsiella pneumoniae was the most common pathogen causing BSIs (44.1%). The analysis revealed a high abundance of potential pathogens in the gut microbiome of group B neonates, with a concurrent decrease in beneficial gut flora. CONCLUSION: This study provides strong evidence for the association between gut pathogen colonization and BSI development in preterm neonates in NICUs. Gut microbiota modulation may serve as preventive strategy against BSIs, emphasizing the need for further research in this area to improve outcomes in vulnerable population. INTRODUCTION: Gut pathogen colonization, where pathogens disrupt the normal gut microbiota, has been implicated in the development of bloodstream infections (BSIs). This study investigates the association between gut pathogen colonization and BSI, hypothesizing that species causing BSI primarily originated from gut. METHODS: A prospective cohort study was conducted in the neonatal intensive care unit (NICU) of tertiary care hospital in Karnataka, India, from January 2021 to September 2023. Inborn preterm infants were enrolled. The study population was divided into two groups: group A (neonates without sepsis) and group B (neonates with sepsis). Demographic details and blood culture results were collected. Stool samples were taken on day 4 and day 14 for group A, and on day 4 and the day of sepsis diagnosis for group B. RESULTS: Group B had a lower mean birthweight (1,649.6 ± 652.1 g) compared to group A (1,757 ± 656 g). Klebsiella pneumoniae was the most common pathogen causing BSIs (44.1%). The analysis revealed a high abundance of potential pathogens in the gut microbiome of group B neonates, with a concurrent decrease in beneficial gut flora. CONCLUSION: This study provides strong evidence for the association between gut pathogen colonization and BSI development in preterm neonates in NICUs. Gut microbiota modulation may serve as preventive strategy against BSIs, emphasizing the need for further research in this area to improve outcomes in vulnerable population.
Growth and Cognitive Outcome in Very Preterm Infants with Postnatal Cytomegalovirus Infection.
Griesmaier E, Hammerl M, Sappler M … +5 more , Zimmermann M, Gande N, Winkler I, Kiechl-Kohlendorfer U, Neubauer V
Neonatology · 2025 · PMID 39662062 · Publisher ↗
INTRODUCTION: There are conflicting data on the association between postnatal cytomegalovirus (CMV) infection and growth and cognitive outcome in very preterm infants. The aim of the current study was to systematically e...
INTRODUCTION: There are conflicting data on the association between postnatal cytomegalovirus (CMV) infection and growth and cognitive outcome in very preterm infants. The aim of the current study was to systematically evaluate the effect of postnatal CMV infection on growth and cognitive outcome in an unselected, contemporary cohort of very preterm infants. METHODS: Infants <32 gestational weeks (2011-2018) were screened for postnatal CMV infection. We compared head circumference, weight and length from birth to 3 months corrected age, mental development at 12 and 24 months corrected age (Bayley Scales of Infant (Toddler) Development II/III), and intelligence quotient at 5 years (Kaufman Assessment Battery for Children-II, Wechsler Preschool and Primary Scale of Intelligence-III or Snijders-Oomen Non-verbal Intelligence Test) between infants with and without postnatal CMV infection. RESULTS: The final study cohort consisted of 431 infants with a median gestational age of 29.9 (23.7-31.9) weeks. Of these, 20 (4.6%) infants had a postnatal CMV infection. Median ∆ z scores from birth to the corrected age of 3 months for head circumference, weight, and length did not differ between infants with and without postnatal CMV infection. Continuous and categorized parameters of cognitive development did not differ between the two groups. A subgroup analysis of infants <28 gestational weeks showed similar results. CONCLUSION: We did not observe a negative effect of postnatal CMV infection on growth or cognitive development of very preterm infants. These findings should be taken into account when discussing the use of raw mother's milk in the feeding of preterm infants.
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