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Background: Numerous studies have demonstrated that hypothermia in preterm infants correlates with increased morbidity and mortality, especially among those with very low or extremely low birth weights (VLBW/ELBW). An increasing number of healthcare facilities are implementing quality improvement (QI) bundles to lower the incidence of hypothermia at birth in this vulnerable population. However, the effectiveness and safety of these interventions have yet to be fully assessed. A meta-analysis is necessary to evaluate the efficacy and safety of QI bundles in reducing hypothermia at birth among VLBW/ELBW infants., Methods: We searched PubMed, Embase, the Cochrane Library and Web of Science through April 22nd, 2024. Study selection, data extraction, quality evaluation and risk bias assessment were performed independently by two investigators. Meta-analysis was performed using Review Manager 5.4.1., Results: A total of 18 studies were included for qualitative analysis and 12 for meta-analysis. For VLBW infants, meta-analysis revealed a reduction in hypothermia and an increase in hyperthermia following the introduction of QI bundles (mild hypothermia, OR 0.22, 95% CI [0.13-0.37]; moderate hypothermia, OR 0.18, 95% CI [0.15-0.22]; hyperthermia, OR 2.79, 95% CI [1.53-5.09]). For ELBW infants, meta-analysis showed a decrease in hypothermia but no increase in hyperthermia after implementing QI bundles (mild hypothermia, OR 0.46, 95% CI [0.26-0.81]; moderate hypothermia, OR 0.21, 95% CI [0.08-0.58]; hyperthermia, OR 1.10, 95% CI [0.22-5.43])., Conclusion: QI bundles effectively reduce hypothermia in VLBW/ELBW infants, but they may also increase hyperthermia, especially in VLBW infants., Competing Interests: The authors declare that they have no competing interests., (© 2024 Zhong et al.)

Background: Preterm infants are a group cohort of transfusion recipients due to their low blood volume and underdeveloped hematopoietic system. The objective of this study was to probe the effect of days of age at first blood transfusion on intraventricular hemorrhage (IVH) in very low and extremely low birth weight VLBW and ELBW infants., Research Design and Methods: Data of 150 VLBW and ELBW infants receiving blood transfusions were reviewed. IVH and non-IVH groups were established. General data on infants and their mothers and data related to blood transfusion, IVH risk factors, and the predictive value of the relevant factors for IVH were analyzed., Results: The IVH group had lower birth weight, hemoglobin levels on admission, and days of age at first blood transfusion and higher 5-min Apgar score ≤7 points and early transfusion rate. Spontaneous delivery and 5-min Apgar score ≤7 points were risk factors for IVH. Birth weight and days of age at first blood transfusion had predictive value for IVH in VLBW and ELBW infants., Conclusions: The younger the days of age at first blood transfusion, the higher the IVH risk. It is necessary to delay the days of age at first blood transfusion and reduce early blood transfusion.

Background: There is limited evidence on benefits of SMOF lipids (mixed fatty acid emulsion of 30% soybean oil, 30% medium chain triglycerides, 25% olive oil, and 15% fish oil) in reducing parenteral nutrition-associated cholestasis in extremely low birth weight infants, compared with soybean oil-based Intralipid., Aim: To compare incidence of parenteral nutrition-associated cholestasis in preterm infants who received Intralipid vs SMOF lipid., Methods: We conducted a retrospective study on infants with birth weight <1000 g, admitted between January 2013 to December 2022, who received parenteral nutrition for >14 days and divided them into two groups based on lipid emulsion received (Intralipid, n = 187, SMOF, n = 127). Primary outcome was incidence of parenteral nutrition-associated cholestasis, defined as direct bilirubin ≥2 mg/dl., Results: Baseline characteristics did not differ between the two groups. No significant difference was noted in parenteral nutrition-associated cholestasis between the two groups on logistic regression, (adjusted odds ratio: 0.71, 95% confidence interval 0.35-1.42, P value 0.33) after adjusting for gestational age, parenteral nutrition days, lipid days, and late-onset sepsis., Conclusion: There was no difference in the rates of parenteral nutrition-associated cholestasis between preterm infants administered SMOF lipids and those given Intralipid., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Former Extremely Low Birthweight (ELBW) neonates suffer from adverse renal and cardiovascular outcomes later in life. Less is known about additional perinatal risk factors for these adverse outcomes which we have investigated in this study. We compared renal outcome between ELBW children and controls, to find perinatal risk factors for poorer renal outcome and to unveil associations between kidney function and blood pressure. This study included 93 former ELBW children and 87 healthy controls with a mean age of 11 years at assessment. We measured cystatin C-based estimated glomerular filtration rate (eGFR) and blood pressure. Blood pressure and eGFR levels were compared between cases and controls. We subsequently investigated perinatal risk factors for adverse outcome amongst ELBW children. ELBW children have significantly higher blood pressure (mean SBP percentile 75 th vs. 47 th , p <0.001) and lower mean eGFR (94 vs. 107 ml/min/1.73 m 2 , p = 0.005) compared to the control group. Elevated blood pressure did not correlate with perinatal characteristics and none of them had microalbuminuria. ELBW children with eGFR <90 ml/min/1.73 m 2 were ventilated longer (17 vs. 9 days, p = 0.006), more frequently male (OR = 3.33, p = 0.055) and tended to suffer more from intraventricular hemorrhage (40% vs. 15.8%, p = 0.056). There was no association between blood pressure and kidney dysfunction., Conclusions: Understanding risk profiles for unfavorable outcomes may help to identify children at increased risk for kidney dysfunction. Poorer eGFR was associated with longer ventilation, male sex, and intra-ventricular hemorrhage but not with blood pressure. This knowledge can lead to safer neonatal therapeutic regimens for ELBW infants, a more intensive follow-up and earlier treatment initiation for children at highest risk., What Is Known: • Extremely Low Birthweight (ELBW) neonates suffer later in life from adverse renal and cardiovascular outcomes. • Perinatal risk factors that further predict the individual risk for adverse outcomes are not well known., What Is New: • Poorer eGFR in adolescence was associated with male sex, longer ventilation and intra-ventricular hemorrhage at birth but not with blood pressure. • Former ELBW infants had higher blood pressures compared to controls, but no microalbuminuria. • This knowledge can lead to potential precision medicine, safer neonatal therapeutic regimens for ELBW infants, a more intensive follow-up and earlier treatment initiation for children at highest risk., (© 2024. Crown.)

Purpose: Spontaneous intestinal perforation (SIP) and necrotizing enterocolitis (NEC) are distinct disease processes associated with significant morbidity and mortality. Initial treatment, laparotomy (LP) versus peritoneal drainage (PD), is disease specific however it can be difficult to distinguish these diagnoses preoperatively. We investigated clinical characteristics associated with each diagnosis and constructed a scoring algorithm for accurate preoperative diagnosis., Methods: A cohort of extreme and very low birth weight (<1500 g) neonates surgically treated for SIP or NEC between 07/2004-09/2022 were reviewed. Clinical characteristics included gestational age (GA), birth weight (BW), feeding history, physical exam, and laboratory/radiological findings. Intraoperative diagnosis was used to determine SIP vs NEC. Pre-drain diagnosis was used for patients treated with PD only., Results: 338 neonates were managed for SIP (n = 269, 79.6%) vs NEC (n = 69, 20.4%). PD was definitive treatment in 146 (43.2%) patients and 75 (22.2%) patients were treated with upfront LP. Characteristics associated with SIP included younger GA, younger age at initial laparotomy or drainage (ALD), and history of trophic or no feeds. Multivariate logistic regression determined pneumatosis, abdominal wall erythema, higher ALD and history of feeds to be highly predictive of NEC. A 0-8-point scale was designed based on these characteristics with the area under the receiver operating characteristic curve of 0.819 (95% CI 0.756-0.882) for the diagnosis of NEC. A threshold score of 1.5 had a 95.2% specificity for NEC., Conclusion: Utilizing clinical characteristics associated with SIP & NEC we developed a scoring system designed to assist surgeons accurately distinguish SIP vs NEC in neonates., Type of Study: Retrospective Chart Review., Level of Evidence: Level III., Competing Interests: Conflicts of interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: In extremely low birth weight infants, fluid overload has been associated with bronchopulmonary dysplasia and death. Excessive weight loss may increase the risk of meconium obstruction and intestinal perforation. As these infants display oliguria followed by polyuria, we embarked on a diuresis-led volume replacement strategy as of January 2020., Methods: This single-centre analysis presents data of infants <1000 g birth weight surviving for more than 3 days admitted 2017-2019 (n = 217, daily volume increase) versus 2020-2022 (n = 2022, diuresis-led volume replacement)., Results: The second cohort had lower gestational age (median [interquartile range]: 25 3 / 7 [24 3 / 7 -26 4 / 7 ] vs. 26 3 / 7 [25 1 / 7 -28 2 / 7 ] weeks), less antenatal steroids (58% vs. 69%), more indomethacin (66% vs. 47%) and higher initial diuresis (5.6 [4.9-6.8] vs. 4.8 [4.2-5.5] mL/kg/h) but did not differ by relative weight loss at Day 7 of life. Employing binary logistic regression with gestational age, antenatal steroids and indomethacin as covariates, the cohorts did not differ by rates of patent ductus arteriosus, abdominal surgery or severe retinopathy of prematurity, while there were significant declines in sepsis (from 32% to 19%), bronchopulmonary dysplasia (from 26% to 23%) and mortality (from 13% to 7%)., Conclusion: Diuresis-led volume replacement appears to be safe and maybe beneficial., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Objective: To determine the accuracy of two developmental screening questionnaires to detect cognitive or language delay, defined using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III), in children born extremely preterm (EP: <28 weeks' gestation) or extremely low birth weight (ELBW: <1000 g)., Design: Prospective cohort study., Setting: State of Victoria, Australia., Patients: 211 infants born EP/ELBW assessed at 2 years' corrected age (mean 2.2, SD 0.2)., Main Outcome Measures: Cognitive and language delay (<-1 SD) on the Bayley-III. The screening questionnaires were the Parent Report of Children's Abilities-Revised (PARCA-R) and the Ages & Stages Questionnaires Third Edition (ASQ-3)., Results: The PARCA-R performed better than the ASQ-3, but neither questionnaire had substantial agreement with the Bayley-III to detect cognitive delay; kappa (95% CI): PARCA-R 0.43 (0.23, 0.63); ASQ-3 0.15 (-0.05, 0.35); sensitivity (95% CI): PARCA-R 70% (53%, 84%) ASQ-3 62% (47%, 76%); specificity (95% CI): PARCA-R 73% (60%, 84%) ASQ-3 53% (38%, 68%). When both tools were used in combination (below cut-off on at least one assessment), sensitivity increased to 78% (60%, 91%) but specificity fell to 45% (29%, 62%). Similar trends were noted for language delay on the Bayley-III, although kappa values were better than for cognitive delay., Conclusions: Neither screening questionnaire identified cognitive delay well, but both were better at identifying language delay. The PARCA-R detects delay on the Bayley-III more accurately than the ASQ-3. Sensitivity for detecting delay is greatest when the PARCA-R and ASQ-3 were used in combination, but resulted in lower specificity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We compared the application value of noninvasive positive pressure ventilation (NIPPV) and intermittent positive pressure ventilation (IPPV) in the treatment of very premature infants and extremely low birth weight infants., Methods: Multivariate logistic regression analysis was used to identify factors influencing the transition from noninvasive to invasive ventilation in this infant cohort., Results: Among extremely preterm infants, 83.3% with gestational age <25 weeks transitioned from noninvasive to invasive ventilation, as did 80.6% of those with birth weight <1000 grams. Multivariate analysis indicated that gestational age <25 weeks, birth weight <1000 grams, and Apgar score ≤7 were significant factors affecting the likelihood of transitioning to invasive ventilation. The survival rate at discharge was 94% for the NIPPV group compared with 89% for the IPPV group. The NIPPV group demonstrated significantly lower rates of complications, shorter weaning times, and reduced lengths of hospital stay compared with the IPPV group., Conclusions: Both NIPPV and IPPV effectively improved oxygenation and ventilation in extremely preterm infants. However, NIPPV showed significant advantages in reducing complications, shortening weaning time, and decreasing the hospital stay duration. Prioritizing the use of NIPPV may enhance treatment outcomes and survival quality, providing evidence-based support for clinical practice., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Background: This paper aimed to investigate the clinical phenotype of Kabuki syndrome (KS) in premature infants., Methods: This paper presents a case of an extremely low birth weight infant (gestational age 29 weeks) with KS1 caused by a variant in the KMT2D gene. The clinical, pathological, and differential diagnostic findings were comprehensively analyzed. A thorough literature review was also performed to enhance the understanding of KS, revealing its unique features and prognostic significance., Results: The infant was a male with a gestational age of 29 weeks and a birth weight of 850 g. He had intrauterine growth retardation, characterized by cleft palate, sacrococcygeal skin depressions, and recurrent metabolic acidosis. Whole-exome sequencing revealed the c.4267C > T (p.Arg1423Cys) variant in the KMT2D gene, which was absent in his parents. The patient was discharged after 67 days of treatment, and he was followed up to 19 months of corrected gestational age, with growth retardation and expression language delay. Ten previous studies on preterm infants were retrieved, with 10 preterm infants. They all had characteristic facial features, such as long blepharophimosis, sparse and lateral 1/3 eyebrows, and large and prominent/cupped ears. Other manifestations were extrauterine growth delay (7/10), abnormal development of the cardiovascular system (7/10), abnormal development of the nervous system (5/10), and cleft palate (2/10)., Conclusions: Kabuki syndrome is a rare hereditary disorder involving multiple organs and systems. Genetic assessment for preterm infants with congenital abnormalities is recommended., (© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Purpose: The purpose of this study was to analyze the incidence of retinopathy of prematurity (ROP), treatment requiring ROP (TROP), course, and systemic risk factors in extreme preterm or extreme low-birth-weight babies., Methods: A retrospective analysis of neonatal intensive care unit-based ROP screening from January to December 2021 in a tier-2 city in Kerala, India, was done. Inclusion criteria were gestational age (GA) ≤28 weeks or birth weight ≤1000 g. ROP screening and treatment were done according to the International Classification of ROP guidelines. Treatment was indicated in babies with type 1 ROP or aggressive ROP. Details of ROP screening, treatment, and neonatal risk factors were collected from the records. The results were statistically analyzed, and P < 0.05 was considered statistically significant., Results: The study included 54 babies with a mean GA of 27.47 ± 1.76 weeks and a mean BW of 847.43 ± 189.22 g. ROP was detected at an average postmenstrual age of 33.8 ± 1.7 weeks. The incidence of any ROP and TROP was 87% and 19.14%, respectively. All babies with TROP were managed with laser or intravitreal antivascular endothelial growth factor injection or both. ROP resolved spontaneously in 60%, but those with Zone 2 disease had delayed regression. Inotropic support and anemia were found to increase the risk for ROP., Conclusion: The incidence and outcome of any ROP and TROP in this study are comparable to the rates reported globally, and this reflects the improvement in neonatal care. The use of inotropes and anemia may increase the risk for ROP and needs to be managed judiciously., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Middle East African Journal of Ophthalmology.)

Background: Preterm birth significantly contributes to mortality and morbidities, with recent studies linking these issues to gut microbiota imbalances. Probiotic supplementation shows promise in mitigating adverse outcomes in preterm infants, but optimal timing and guidelines remain unclear. This study assesses the benefits of probiotic supplementation for preterm infants without consistent guidelines. Methods: This retrospective study examined extremely low-birth-weight (ELBW) infants in neonatal intensive care units from 2017 to 2021. Mortality and preterm-related outcomes were compared between infants receiving probiotics and those not. Subgroup analyses based on probiotic initiation timing were conducted: early (≤14 days), late (>14 days), and non-probiotic groups. Results: The study included 330 ELBW infants: 206 received probiotics (60 early, 146 late), while 124 did not. Probiotic supplementation was associated with lower overall mortality (adjusted OR 0.22, 95% CI 0.09-0.48) and decreased mortality from necrotizing enterocolitis (NEC) or late-onset sepsis (LOS) (adjusted OR 0.12, 95% CI 0.03-0.45). Early probiotics reduced overall mortality, NEC/LOS-related mortality, and NEC/LOS-unrelated mortality. Late probiotics decreased overall mortality and NEC/LOS-related mortality. Early probiotic use also expedited full enteral feeding achievement. Conclusions: Probiotic supplementation reduces mortality and improves feeding tolerance in preterm infants. Establishing guidelines for probiotic use in this population is crucial.

The lack of pediatrics-specific equipment for nuclear medicine imaging has resulted in insufficient diagnostic information for newborns, especially low-birth-weight infants. Although PET offers high spatial resolution and low radiation exposure, its use in newborns is limited. This study investigated the feasibility of cardiac PET imaging using the latest silicon photomultiplier (SiPM) PET technology in infants of extremely low birth weight (ELBW) using a phantom model. Methods: The study used a phantom model representing a 500-g ELBW infant with brain, cardiac, liver, and lung tissues. The cardiac tissue included a 3-mm-thick defect mimicking myocardial infarction. Organ tracer concentrations were calculated assuming 18 F-FDG myocardial viability scans and 18 F-flurpiridaz myocardial perfusion scans and were added to the phantom organs. Imaging was performed using an SiPM PET/CT scanner with a 5-min acquisition. The data acquired in list mode were reconstructed using 3-dimensional ordered-subsets expectation maximization with varying iterations. Image evaluation was based on the depiction of the myocardial defect compared with normal myocardial accumulation. Results: Increasing the number of iterations improved the contrast of the myocardial defect for both tracers, with 18 F-flurpiridaz showing higher contrast than 18 F-FDG. However, even at 50 iterations, both tracers overestimated the defect accumulation. A bull's-eye image can display the flow metabolism mismatch using images from both tracers. Conclusion: SiPM PET enabled cardiac PET imaging in a 500-g ELBW phantom with a 1-g heart. However, there were limitations in adequately depicting these defects. Considering the image quality and defect contrast, 18 F-flurpiridaz appears more desirable than 18 F-FDG if only one of the two can be used., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) affect 6-8% of extremely low birth weight (ELBW) infants. SIP has lower mortality than NEC, but with similar short-term morbidity in length of stay, growth failure, and supplemental oxygen requirements. Comparative long-term neurodevelopmental outcomes have not been clarified., Methods: Data were prospectively collected from 59 North American neonatal units, regarding ELBW infants (401-1000 g or 22-27 weeks gestational age) born between 2011 and 2018 and evaluated again at 16-26 months corrected age. Outcomes were collected from infants with laparotomy-confirmed NEC, laparotomy-confirmed SIP, and those without NEC or SIP. The primary outcome was severe neurodevelopmental disability. Secondary outcomes were weight <10th percentile, medical readmission, post-discharge surgery and medical support at home. Adjusted risk ratios (ARR) were calculated., Results: Of 13,673 ELBW infants, 6391 (47%) were followed including 93 of 232 (40%) with NEC and 100 of 235 (42%) with SIP. There were no statistically significant differences in adjusted risk of any outcomes when directly comparing NEC to SIP (ARR 2.35; 95% CI 0.89, 6.26). However, infants with NEC had greater risk of severe neurodevelopmental disability (ARR 1.43; 1.09-1.86), rehospitalization (ARR 1.46; 1.17-1.82), and post-discharge surgery (ARR 1.82; 1.48-2.23) compared to infants without NEC or SIP. Infants with SIP only had greater risk of post-discharge surgery (ARR 1.64; 1.34-2.00) compared to infants without NEC or SIP., Conclusions: ELBW infants with NEC had significantly increased risk of severe neurodevelopmental disability and post-discharge healthcare needs, consistent with prior literature. We now know infants with SIP also have increased healthcare needs., Levels of Evidence: Level II., Competing Interests: Conflicts of interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sick neonates with haemodynamic instability often require complex medication regimens, which may result in the connection of a catecholamine infusion distally. This increases the dead volume of the infusion system, extending the time to medication delivery. This study evaluated the effects of body weight, and infusion connection point on the delivery rate of two medications infused through a multi-infusion system at infusion rates suitable for extremely and very low birth weight (ELBW and VLBW) neonates., Methods: An infusion system consisting of six infusions was used to investigate time to delivery, drug concentration at time to delivery and quantity of adrenaline and dopamine administered by intravenous infusions at infusion rates suitable for premature neonates., Results: In an ELBW neonate model, the measured adrenaline and dopamine concentration at 12 T was higher than expected (66.7 (7.5)% (mean (SD)) and 68.0 (4.4)%, respectively, P < 0.001). At the calculated time to delivery, neither drug reached target concentration. In a VLBW neonate model, the measured adrenaline and dopamine concentration at 12 T was higher than expected (92.2 (7.1)% and 97.1 (3.1)%, respectively, P < 0.001). Adrenaline reached target concentration at 27 (11) min and dopamine at 56 (12) min, times significantly shorter than calculated. The measured quantity of adrenaline and dopamine delivered was lower (P < 0.001) than calculated in all tested combinations except adrenaline at proximal connection (97.2 (3.4)%, P = 0.097) in the VLBW neonate model., Conclusions: Using the most proximal available infusion connection considerably improves drug delivery times and drug doses delivered, which is critical during the administration of short-acting cardiovascular medications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Treatment guidelines for postnatal cytomegalovirus (pCMV) infection in preterm have not been established yet. Neutropenia, thrombocytopenia, hepatitis, colitis, and sepsis-like disease are among the clinical manifestations, which range from moderate to serious. We present a case of autopsy diagnosed as pCMV infection in a premature infant delivered at gestational age of 24 weeks and 5 days. On the 7th and 14th days of birth, urinary CMV polymerase chain reaction samples were negative, ruling out congenital CMV infection. However, autopsy examination revealed that the patient had disseminated pCMV infection. CMV inclusion bodies were found in the majority of tissues, including the lung, liver, pancreas, breast, kidney, and adrenal gland, but not the placenta. The thymus exhibited significant cortical atrophy and T-cell immunodeficiency, possibly induced by dexamethasone treatment for bronchopulmonary dysplasia or by pCMV infection itself. If dexamethasone treatment is extended or high doses are considered, it may be beneficial to test the CMV infection status to prevent aggravation of infection. This case demonstrates that, despite the low prevalence, pCMV infection should be considered a differential diagnosis in preterm if other conditions or etiology cannot justify clinical deterioration.

Purpose Bronchopulmonary dysplasia (BPD) is one of the most fatal respiratory morbidities in preterm infants, causing adverse respiratory and neurodevelopmental outcomes. Despite advances in neonatal ventilator care, the incidence of BPD has been static or even increased. The purpose of this study was to evaluate the incidence of BPD in a single center over 10 years. Methods Preterm infants with gestational age (GA)

Background: Extremely low birth weight (ELBW) neonates (birth weight ≤ 1000 g) are at high risk to develop drug-induced acute kidney injury (AKI). However, we lack a pragmatic detection tool to capture their time-dependent (patho)physiologic serum creatinine (Scr) patterns. Pottel et al. suggested rescaling Scr by dividing Scr with the mean Scr value of the age- and sex-specific reference population. We explored if this Pottel method can detect drug-related nephrotoxicity in ELBW neonates., Methods: A previously reported dataset on Scr changes in ELBW neonates exposed to ibuprofen, amikacin, or vancomycin was updated to calculate Pottel scores for every available Scr value in the first 28 postnatal days. We hereby used previously published postnatal age-specific 50 th centile values in an ELBW population. Linear mixed models were applied, analyzing Pottel scores as response variable and continuous time (day), drug exposure, and interaction thereof in the explanatory model., Results: Serum creatinine (n = 3231) observations in 201 ELBW neonates were collected. A statistically significant rise of Pottel scores was observed with ibuprofen starting from postnatal day 4. In addition, a cumulative effect of treatment with mean Pottel scores on day 0 of 1.020 and on day 3 during treatment of 1.106 (95% CI 1.068-1.145, p < 0.001) was observed, corrected for effect of antibiotics. Antibiotic administrations showed a small but statistically significant difference up to postnatal day 5., Conclusions: As rescaled Scr biomarker, the Pottel method showed a clear association with ibuprofen-exposed ELBW neonates, suggesting its applicability as a pragmatic bedside alternative tool to assess nephrotoxicity., (© 2024. The Author(s).)

Background: Hyperkalemia is one of the most serious electrolyte disturbances, and it can cause lethal cardiac arrhythmia. Although hyperkalemia associated with ileostomies has been reported in adults, to the best of our knowledge, it has not previously been reported in neonates., Case: We report ileostomy‒induced hyperkalemia that persisted during the ileostomy and resolved promptly after the closure of the ileostomy in two extremely low birth weight (ELBW) infants, with birth weights of 850 g and 840 g and gestational ages of 27 weeks and 27 weeks 6 days., Conclusions: These cases highlight that disruption of intestinal integrity in ELBW infants may cause hyperkalemia. Ensuring the integrity of the gastrointestinal tract plays an important role in the treatment of electrolyte disorders such as hyperkalemia in ELBW infants with an ileostomy., Competing Interests: The authors declare that there is no conflict of interest.

Background: Although not universal, active care is being offered to infants weighing < 500 g at birth, referred to as ultra-low birth weight (ULBW) infants appropriate for gestational age. These infants have the greatest risk of dying or developing major morbidities. ULBW infants face challenges related to fluid and heat loss as well as skin injury in the initial days of life from extreme anatomical and physiological immaturity of the skin. Although there is an emerging literature on the outcomes of ULBW infants, there is a paucity of evidence to inform practice guidelines for delivering optimal care to this cohort of infants., Data Sources: A comprehensive review of the literature was performed using the PubMed and Embase databases. Searched keywords included "thermoregulation or body temperature regulation", "incubator humidity", "skin care", "infant, extremely low birth weight" and "ultra-low birth weight infants"., Results: Evidences for thermoregulation, incubator humidity, and skincare practices are available for preterm infants weighing < 1500 g at birth but not specifically for ULBW infants. Studies on thermoregulation, incubator humidity, or skincare practices had a small sample size and did not include a sub-group analysis for ULBW infants. Current practice recommendations in ULBW infants are adopted from research in very and/or extremely low birth weight infants., Conclusions: This narrative review focuses on challenges in thermoregulation, incubator humidity, and skincare practices in ULBW infants, highlights current research gaps and suggests potential developments for informing practices for improving health outcomes in ULBW infants. Video abstract (MP4 1,49,115 kb)., (© 2024. The Author(s).)

Objective: A ventricle-to-brain index (VBI) >0.35 is associated with low scores on the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) in preterm infants with birth weight <1,250 g. However, VBI obtained at the third ventricle has only moderate interobserver reliability. The objective of this study was to test (1) reliability of VBI measured at the foramen of Monro on the latest ultrasonogram (US) before discharge using the intraclass correlation coefficient (ICC) and (2) the relationship between VBI and BSID-III scores at ≥18 months corrected age., Study Design: The present study is a single-center retrospective cohort study., Results: The study included 270 preterm infants born at 23 0/7 to 28 6/7 weeks of gestational age. The ICC of VBI between independent measurements by two study radiologists on the first 50 patients was 0.934. Factors associated with the value of VBI included severe intraventricular hemorrhage, bronchopulmonary dysplasia, and systemic steroid administration for BPD but not postmenstrual age. In multivariate analysis, VBI was negatively and independently associated with cognitive ( p  = 0.002), language ( p  = 0.004), and motor ( p  < 0.001) BSID-III scores. The association between VBI and BSID-III scores was observed even in infants in whom the latest US was obtained before term equivalent age. The association between VBI and BSID-III scores was also observed after excluding those with severe intraventricular hemorrhage., Conclusion: In this very preterm cohort the measurement of VBI had excellent reliability. Moreover, VBI measurements were negatively associated with motor, language, and cognitive BSID-III scores., Key Points: · Mean values of VBI are stable with postmenstrual age.. · Values at the foramen of Monro are reliable and reproducible.. · VBI is negatively associated with Bayley scores.. · The association is observed even before term age.., Competing Interests: None declared, (Thieme. All rights reserved.)

Objective: To examine nutritional intake profiles and growth trajectories of extremely low birth weight (ELBW) infants who develop severe bronchopulmonary dysplasia (BPD)., Study Design: Case-control study using multiple logistic regression analysis with generalized estimating equations (GEE) to adjust for matching., Results: Cumulative and mean fluid intakes were higher (p = 0.003) and caloric intakes lower (p < 0.0001) through week two in infants who developed severe BPD (n = 120) versus those without severe BPD (n = 104). Mean caloric intake through week 12 was lower in infants who developed severe BPD (102 ± 10.1 vs. 107 ± 8.5 kcal/kg/day, p < 0.0001). In the logistic regression models, lower mean caloric intake through week 12 was associated with increased risk of developing severe BPD. Linear growth reduced the odds of BPD by ~30% for each Z-score point., Conclusions: Higher fluid and lower total caloric intakes and reductions in linear growth were independently associated with an increased risk of developing severe BPD in ELBW infants., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Vitamin A plays a key role in lung development, but there is no consensus regarding the optimal vitamin A dose and administration route in extremely low birthweight (ELBW) infants. We aimed to assess whether early postnatal additional high-dose fat-soluble enteral vitamin A supplementation versus placebo would lower the rate of moderate or severe bronchopulmonary dysplasia or death in ELBW infants receiving recommended basic enteral vitamin A supplementation., Methods: This prospective, multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial conducted at 29 neonatal intensive care units in Austria and Germany assessed early high-dose enteral vitamin A supplementation (5000 international units [IU]/kg per day) or placebo (peanut oil) for 28 days in ELBW infants. Eligible infants had a birthweight of more than 400 g and less than 1000 g; gestational age at birth of 32 +0 weeks postmenstrual age or younger; and the need for mechanical ventilation, non-invasive respiratory support, or supplemental oxygen within the first 72 h of postnatal age after admission to the neonatal intensive care unit. Participants were randomly assigned by block randomisation with variable block sizes (two and four). All participants received basic vitamin A supplementation (1000 IU/kg per day). The composite primary endpoint was moderate or severe bronchopulmonary dysplasia or death at 36 weeks postmenstrual age, analysed in the intention-to-treat population. This trial was registered with EudraCT, 2013-001998-24., Findings: Between March 2, 2015, and Feb 27, 2022, 3066 infants were screened for eligibility at the participating centres. 915 infants were included and randomly assigned to the high-dose vitamin A group (n=449) or the control group (n=466). Mean gestational age was 26·5 weeks (SD 2·0) and mean birthweight was 765 g (162). Moderate or severe bronchopulmonary dysplasia or death occurred in 171 (38%) of 449 infants in the high-dose vitamin A group versus 178 (38%) of 466 infants in the control group (adjusted odds ratio 0·99, 95% CI 0·73-1·55). The number of participants with at least one adverse event was similar between groups (256 [57%] of 449 in the high-dose vitamin A group and 281 [60%] of 466 in the control group). Serum retinol concentrations at baseline, at the end of intervention, and at 36 weeks postmenstrual age were similar in the two groups., Interpretation: Early postnatal high-dose fat-soluble enteral vitamin A supplementation in ELBW infants was safe, but did not change the rate of moderate or severe bronchopulmonary dysplasia or death and did not substantially increase serum retinol concentrations., Funding: Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN)., Competing Interests: Declaration of interests We declare no competing interests. The vitamin A study medication and placebo were provided by Aristo Pharma, Berlin, Germany. Aristo Pharma had no influence on study protocol, data compilation, and data analysis., (Copyright © 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: To understand the prevalence and survival rates of preterm birth (PTB) is of utmost importance in informing healthcare planning, improving neonatal care, enhancing maternal and infant health, monitoring long-term outcomes, and guiding policy and advocacy efforts., Methods: The medical records of preterm infants admitted to the Neonatal Intensive Care Unit (NICU) with a diagnosis of prematurity at the Maternity and Children's Hospital (MCH), Al Kharj, Saudi Arabia, were reviewed between January 2018 and December 2022. Data were collected on birth weight (BW), gender, number of live births, gestational age, mortality, nationality, APGAR score, length of stay in the NICU, and maternal details., Results: A total of 9809 live births were identified between 2018 and 2022, of which 139 (3.9%) were born preterm. The overall mortality rate of the included sample was 7.19%, whereas the mortality rate according to BW was 38.4% of those born with extremely low birth weight (ELBW). The most common intrapartum complications were malpresentation (15.1%), placental complications (4.3%), and cord complications (3.6%)., Conclusion: This study provides valuable insights into the prevalence of PTB in the country, particularly focusing on the vulnerability of extremely preterm babies., (Copyright: © Saudi Medical Journal.)

Objectives: To determine the dose-dependent associations between antenatal corticosteroids (ANS) exposure and the rates of major morbidities, and the early weight loss percentage (EWLP) in hospital among extremely preterm infants (EPI) or extremely low birthweight infants (ELBWI)., Methods: A multicentre, retrospective cohort study of EPI or ELBWI born between 2017 and 2018 was conducted. Infants were classified into no ANS, partial ANS and complete ANS exposure group; three subgroups were generated by gestational age and birth weight. Multiple logistic regression and multiple linear regression were performed., Results: There were 725 infants included from 32 centres. Among no ANS, partial ANS and complete ANS exposure, there were significant differences in the proportions of bronchopulmonary dysplasia (BPD) (24.5%, 25.4% and 16.1%), necrotising enterocolitis (NEC) (6.7%, 2.0% and 2.0%) and death (29.6%, 18.5% and 13.5%), and insignificant differences in the proportions of intraventricular haemorrhage (IVH) (12.5%, 13.2% and 12.2%), and extrauterine growth restriction (EUGR) (50.0%, 56.6% and 59.5%). In the logistic regression, compared with no ANS exposure, complete ANS reduced the risk of BPD (OR 0.58, 95% CI 0.37 to 0.91), NEC (OR 0.21, 95% CI 0.08 to 0.57) and death (OR 0.36, 95% CI 0.23 to 0.56), and partial ANS reduced the risk of NEC (OR 0.23, 95% CI 0.07 to 0.72) and death (OR 0.54, 95% CI 0.34 to 0.87). Compared with partial ANS exposure, complete ANS decreased the risk of BPD (OR 0.58, 95% CI 0.37 to 0.91). There were insignificant associations between ANS exposure and IVH, EUGR. In the multiple linear regression, partial and complete ANS exposure increased EWLP only in the ≥28 weeks (w) and <1000 g subgroup (p<0.05)., Conclusions: Different doses of ANS (dexamethasone) exposure were protectively associated with BPD, NEC, death in hospital, but not EUGR at discharge among EPI or ELBWI. Beneficial dose-dependent associations between ANS (dexamethasone) exposure and BPD existed. ANS exposure increased EWLP only in the ≥28 w and<1000 g subgroup. ANS administration, especially complete ANS, is encouraged before preterm birth., Trial Registration Number: NCT06082414., Competing Interests: Competing interests: None., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Failure of the patent ductus arteriosus to close is common among extremely low birth weight neonates and has been associated with increased morbidities. The objective of this study was to compare outcomes between early and late surgical ligation in extremely low birth weight patients., Methods: This was a single-centre retrospective cohort study of infants who required surgical closure of patent ductus arteriosus between January 2017 and August 2022., Results: A total of 43 neonates were identified with birth weight less than 1 kg that underwent surgical patent ductus arteriosus ligation. Compared to the late ligation group, the early ligation group experienced fewer total days of mechanical ventilation (43.9 days vs. 97.2 days, p < 0.05) and a shorter length of hospital stay (114.2 days vs. 169.0 days, p < 0.05)., Conclusion: Early surgical ligation of haemodynamically significant patent ductus arteriosus in extremely low birth weight neonates may improve hospital morbidity, including improved ventilatory outcomes and a shorter length of stay.

Objective: We evaluated the relationship between maternal body mass index (BMI) and death or bronchopulmonary dysplasia (BPD). We hypothesized that in extremely low birth weight (ELBW; BW < 1,000 g) infants, the risk of death or BPD would be greater if the maternal BMI deviated further from the ideal BMI of 24., Study Design: ELBW infants admitted to AdventHealth Neonatal Intensive Care Unit (NICU) between calendar years 2012 and 2017 were included in this retrospective observational study. BPD was defined as continuous supplemental oxygen use at 36 weeks post-menstrual age., Result: There was no association between the deviation of maternal BMI from the ideal of 24 and the composite outcome of death or BPD (6.9 ± 6.7 vs. 7.06 ± 6.6, pp = 0.966). However, there was a lower risk of death with a higher maternal BMI ( p  = 0.024). BPD was also associated with a higher maternal BMI ( p  = 0.045)., Conclusion: Maternal BMI was not associated with the composite variable of death or BPD in ELBW infants. The lack of association was due to the contrast between high BMI and a lower risk of death and a higher risk for BPD., Key Points: · Maternal BMI was not associated with the composite outcome of death or BPD.. · Elevated BMI was associated with a higher risk of BPD.. · Elevated BMI was associated with a lower risk of death.., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose This study aimed to evaluate the clinical and radiologic findings suggestive of spontaneous intestinal perforation (SIP) in extremely-low-birth-weight infants (ELBWIs) with persistent gasless abdomen, and to investigate the usefulness of abdominal ultrasonography for the diagnosis of SIP. Methods In total, 22 infants with birth weights less than 1,000 g who showed persistent gasless abdomen on simple abdominal radiography were included. Perinatal, neonatal, and perioperative clinical findings were retrospectively reviewed, and the risk factors for intestinal perforation were evaluated. Abdominal sonographic findings suggestive of intestinal perforation were also identified, and postoperative short-term outcomes were evaluated. Results In total, eight of the 22 infants (36.4%) with gasless abdomen had SIP. The number of infants with patent ductus arteriosus who were treated with intravenous ibuprofen or indomethacin was significantly higher in the SIP group than in the non-SIP group (P

Purpose This study was aimed to investigate the effect of early phosphorus intake on respiratory distress in extremely low-birth-weight infants (ELBWIs) with a high incidence of hypophosphatemia. Methods We performed a retrospective study to target 164 ELBWIs admitted to the neonatal intensive care unit in Seoul National University Children’s Hospital. Birth characteristics, nutritional intake, and electrolyte levels during the first week were investigated as predictors that would affect the clinical outcomes. The correlations among invasive ventilation at postnatal age of 2 weeks, moderate-to-severe bronchopulmonary dysplasia (BPD), and phosphorous intake were analyzed. Results Hypophosphatemia (phosphorus level

Importance: Observational studies often report that anemia and red blood cell (RBC) transfusions are associated with a higher risk of necrotizing enterocolitis (NEC) among extremely low-birthweight (ELBW) infants., Objective: To evaluate whether there is a temporal association between 72-hour hazard periods of exposure to RBC transfusions and NEC among ELBW infants randomized to either higher or lower hemoglobin transfusion thresholds., Design, Setting, and Participants: This post hoc secondary analysis of 1690 ELBW infants who survived to postnatal day 10 enrolled in the Transfusion of Prematures (TOP) randomized multicenter trial between December 1, 2012, and April 12, 2017, was performed between June 2021 and July 2023., Exposures: First, the distribution of RBC transfusions and the occurrence of NEC up to postnatal day 60 were examined. Second, 72-hour posttransfusion periods were categorized as hazard periods and the pretransfusion periods of variable duration as control periods. Then, the risk of NEC in posttransfusion hazard periods was compared with that in pretransfusion control periods, stratifying the risk based on randomization group (higher or lower hemoglobin transfusion threshold group)., Main Outcomes and Measures: The primary outcome was incidence of NEC stage 2 or 3. Secondary outcomes included the incidence rates of NEC within five 10-day intervals, taking into account the number of days at risk., Results: Of 1824 ELBW infants randomized during the TOP trial, 1690 were included in the present analysis (mean [SD] gestational age, 26.0 [1.5] weeks; 899 infants [53.2%] were female). After categorizing 4947 hazard periods and 5813 control periods, we identified 133 NEC cases. Fifty-nine of these cases (44.4%) occurred during hazard periods. Baseline and clinical characteristics of infants with NEC during hazard periods did not differ from those of infants with NEC during control periods. The risk of NEC was 11.9 per 1000 posttransfusion hazard periods and 12.7 per 1000 control periods (adjusted risk ratio, 0.95; 95% CI, 0.68-1.32; P = .74). This risk did not differ significantly between randomization groups, but the incidence rate of NEC per 1000 days peaked between postnatal days 20 and 29 in the lower hemoglobin transfusion threshold group., Conclusions and Relevance: The findings of this post hoc analysis suggest that, among ELBW infants with the hemoglobin ranges occurring in the TOP trial, exposure to RBC transfusions was not temporally associated with a higher risk of NEC during 72-hour posttransfusion hazard periods. Given that the incidence rate of NEC peaked between postnatal days 20 and 29 among infants with lower hemoglobin values, a more in-depth examination of this at-risk period using larger data sets is warranted., Trial Registration: ClinicalTrials.gov Identifier: NCT01702805.

Objective: Investigate daily feeding volumes and their association with clinical variables in the early postnatal care of premature infants of the "Connection Trial.", Study Design: A total of 641 infants of 510 to 1,000-g birth weight (BW, mean: 847 g) and mean 27 weeks' gestational age at birth (GA) were analyzed for total daily enteral (TDE) feeding volumes of 10, 20, 40, 80, and 120 mL/kg/d and their association with 24 clinical variables. Uni- and multivariable Cox regression models were used to calculate hazard ratios (HR) with 95% confidence intervals as a measure of the chance of reaching each of the TDE volumes., Results: Daily feeding volumes were highly variable and the median advancement from 10 to 120 mL/kg/d was 11 mL/kg/d. Univariable analyses showed the lowest chance (HR, 0.22-0.81) of reaching the TDE volumes for gastrointestinal (GI) serious adverse events (SAEs), GI perforation, GI obstruction, and necrotizing enterocolitis, as well as respiratory SAEs, persistent ductus arteriosus, and hypotension. Each GA week, 100-g BW, and point in 5-minute Apgar score at birth associated with 8 to 20% increased chance of reaching the TDE volumes. Multivariable analyses showed independent effects for BW, GA, Apgar score, GI SAEs, abdominal symptoms/signs, respiratory SAEs, days on antibiotics, and hypotension., Conclusion: This observational analysis demonstrates the variable and cautious progression of enteral feedings in contemporary extremely low BW infants and the extent to which clinical variables associate with this progression., Key Points: · Total feedings of 10 and 120 mL/kg/d were reached at median 4 and 14 day of age, respectively, and at a daily increase of 11 mL/kg.. · Each incremental GA week, 100-g BW, and point in 5-minute Apgar score associated with 8 to 20% increased chance of reaching enteral feedings of 10 to 120 mL/kg/d.. · Progression of enteral feeding associated with several clinical events and was slower than advocated in common feeding protocols.., Competing Interests: J.N. is the global coordinating investigator of the Connection Trial sponsored by Infant Bacterial Therapeutics. P.A., V.C., A.L., P.P., R.R., B.S. are principal investigators of the Connection Trial sponsored by Infant Bacterial Therapeutics Inc. M.T. is a consultant statistician employed by Infant Bacterial Therapeutics Inc. A.K., S.S., and J.R. are all employees of Infant Bacterial Therapeutics Inc. sponsoring the Connection Trail., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objective: This study aimed to evaluate whether elevated urine desmosine levels at 3 weeks of age were associated with severe radiological findings, bronchopulmonary dysplasia (BPD), and post-prematurity respiratory disease (PRD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants., Study Design: This study recruited 37 EP (22-27 completed weeks) or ELBW (<1,000 g) infants. Urine was collected between 21 and 28 postnatal days, and desmosine was measured using an enzyme-linked immunosorbent assay kit; the urine creatinine level was also measured. Bubbly/cystic lungs were characterized by emphysematous chest X-rays on postnatal day 28. Furthermore, provision of supplemental oxygen or positive-pressure respiratory support at 40 weeks' postmenstrual age defined BPD, and increased medical utilization at 18 months of corrected age defined PRD. The desmosine/creatinine threshold was determined by receiver operating characteristic analysis. The adjusted risk and 95% confidence interval (CI) for elevated urine desmosine/creatinine levels were estimated by logistic regression analysis., Results: Elevated urine desmosine/creatinine levels higher than the threshold were significantly associated with bubbly/cystic lungs (8/13 [61.5%] vs. 2/24 [8.3%], p  = 0.001), BPD (10/13 [76.9%] vs. 8/24 [33.3%], p  = 0.02), and PRD (6/13 [46.2%] vs. 2/24 [8.3%], p  = 0.01). After adjusting for gestational age, birth weight, and sex, the urine desmosine/creatinine levels were significantly higher in those who were highly at risk of bubbly/cystic lungs (odds ratio [OR], 13.2; 95% CI, 1.67-105) and PRD (OR, 13.8; 95% CI, 1.31-144)., Conclusion: Elevated urine desmosine/creatinine levels on the third postnatal week were associated with bubbly/cystic lungs on day 28 and PRD at 18 months of corrected age in EP or ELBW infants., Key Points: · Urine desmosine was prospectively measured in 3-week-old EP/ELBW infants.. · Elevated urine desmosine levels were associated with emphysematous radiological findings on day 28, PRD at 18 months of corrected age.. · Urine desmosine may be a promising biomarker indicating lung damage in EP/ELBW infants.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: This study aimed to evaluate whether there are genetic variants associated with adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants., Study Design: We conducted a candidate gene association study in two well-defined cohorts of ELBW infants (<1,000 g). One cohort was for discovery and the other for replication. The discovery case-control analysis utilized anonymized DNA samples and evaluated 1,614 single-nucleotide polymorphisms (SNPs) in 145 genes concentrated in inflammation, angiogenesis, brain development, and oxidation pathways. Cases were children who died by age one or who were diagnosed with cerebral palsy (CP) or neurodevelopmental delay (Bayley II mental developmental index [MDI] or psychomotor developmental index [PDI] < 70) by 18 to 22 months. Controls were survivors with normal neurodevelopment. We assessed significant epidemiological variables and SNPs associated with the combined outcome of CP or death, CP, mental delay (MDI < 70) and motor delay (PDI < 70). Multivariable analyses adjusted for gestational age at birth, small for gestational age, sex, antenatal corticosteroids, multiple gestation, racial admixture, and multiple comparisons. SNPs associated with adverse neurodevelopmental outcomes with p  < 0.01 were selected for validation in the replication cohort. Successful replication was defined as p  < 0.05 in the replication cohort., Results: Of 1,013 infants analyzed (452 cases, 561 controls) in the discovery cohort, 917 were successfully genotyped for >90% of SNPs and passed quality metrics. After adjusting for covariates, 26 SNPs with p  < 0.01 for one or more outcomes were selected for replication cohort validation, which included 362 infants (170 cases and 192 controls). A variant in SERPINE1, which encodes plasminogen activator inhibitor (PAI1), was associated with the combined outcome of CP or death in the discovery analysis ( p  = 4.1 × 10 -4 ) and was significantly associated with CP or death in the replication cohort (adjusted odd ratio: 0.4; 95% confidence interval: 0.2-1.0; p  = 0.039)., Conclusion: A genetic variant in SERPINE1, involved in inflammation and coagulation, is associated with CP or death among ELBW infants., Key Points: · Early preterm and ELBW infants have dramatically increased risks of CP and developmental delay.. · A genetic variant in SERPINE1 is associated with CP or death among ELBW infants.. · The SERPINE1 gene encodes the serine protease inhibitor plasminogen activator inhibitor.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Preterm infants have a higher rate of hypoglycemia and hyperglycemia, both of which have been associated with increased neonatal morbidities. The aim of this study was to evaluate the incidence of abnormal glucose homeostasis during the first 72 hours of life and study its association with major morbidities in infants admitted to our neonatal intensive care unit (NICU)., Study Design: This was a retrospective single-center study. We extracted demographic, maternal, and patient information and blood glucose levels for the first 72 hours of life for all infants with birth weight ≤1,000 g admitted to the NICU from January 2017 to December 2019. Continuous data were presented as mean ± standard deviation or as median with interquartile range. Categorical data were presented as frequency and percentage. Student's t -tests and Mann-Whitney U test were used to analyze continuous data and chi-squared test or Fisher's exact test were used to analyze categorical data. Logistic regression analysis was performed to study the relation between hyperglycemia and various morbidities after controlling for gestational age (GA). Statistical significance was set at p  < 0.05., Results: Of the 235 infants included in the study, 49% were hypoglycemic at admission to the NICU. Infants that were small for GA and those with history of maternal β-blocker use had a higher incidence of hypoglycemia. Hypoglycemia at admission was not associated with increased mortality or any major morbidities. Seventy-three percent infants who were hypoglycemic or euglycemic at birth developed iatrogenic hyperglycemia during the first 72 hours of life. The incidence of retinopathy of prematurity (ROP) and severe ROP was higher in infants with hyperglycemia on univariate analysis. However, on multivariate analysis, after adjusting for GA, no difference was noted in the incidence of ROP between the two groups. Multivariate analysis could not be performed for severe ROP due to inadequate sample size., Conclusion: Hyperglycemia in the initial 3 days of life is associated with an increased incidence of severe ROP in preterm infants. Neonatologists should aim to maintain euglycemia in these infants to decrease the risk of adverse outcomes., Key Points: · Preterm infants have a high rate of both hypoglycemia and hyperglycemia.. · Majority of infants who were euglycemic or hypoglycemic at birth develop iatrogenic hyperglycemia.. · Hyperglycemia in the initial 3 days of life is associated with an increased incidence of severe ROP in preterm infants.., Competing Interests: None declared., (Thieme. All rights reserved.)

Nosocomial infections are a frequent and serious problem in extremely low birth weight (ELBW) infants. Donor human milk (DHM) is the best alternative for feeding these babies when mother's own milk (MOM) is not available. Recently, a patented prototype of a High-Temperature Short-Time (HTST) pasteurizer adapted to a human milk bank setting showed a lesser impact on immunologic components. We designed a multicentre randomized controlled trial that investigates whether, in ELBW infants with an insufficient MOM supply, the administration of HTST pasteurized DHM reduces the incidence of confirmed catheter-associated sepsis compared to DHM pasteurized with the Holder method. From birth until 34 weeks postmenstrual age, patients included in the study received DHM, as a supplement, pasteurized by the Holder or HTST method. A total of 213 patients were randomized; 79 (HTST group) and 81 (Holder group) were included in the analysis. We found no difference in the frequency of nosocomial sepsis between the patients of the two methods-41.8% (33/79) of HTST group patients versus 45.7% (37/81) of Holder group patients, relative risk 0.91 (0.64-1.3), p = 0.62. In conclusion, when MOM is not available, supplementing during admission with DHM pasteurized by the HTST versus Holder method might not have an impact on the incidence of catheter-associated sepsis., Competing Interests: The authors declare no conflicts of interest.

Importance: High-risk infants, defined as newborns with substantial neonatal-perinatal morbidities, often undergo multiple procedures and require prolonged intubation, resulting in extended opioid exposure that is associated with poor outcomes. Understanding variation in opioid prescribing can inform quality improvement and best-practice initiatives., Objective: To examine regional and institutional variation in opioid prescribing, including short- and long-acting agents, in high-risk hospitalized infants., Design, Setting, and Participants: This retrospective cohort study assessed high-risk infants younger than 1 year from January 1, 2016, to December 31, 2022, at 47 children's hospitals participating in the Pediatric Health Information System (PHIS). The cohort was stratified by US Census region (Northeast, South, Midwest, and West). Variation in cumulative days of opioid exposure and methadone treatment was examined among institutions using a hierarchical generalized linear model. High-risk infants were identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for congenital heart disease surgery, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and other abdominal surgery. Infants with neonatal opioid withdrawal syndrome, in utero substance exposure, or malignant tumors were excluded., Exposure: Any opioid exposure and methadone treatment., Main Outcomes and Measures: Regional and institutional variations in opioid exposure., Results: Overall, 132 658 high-risk infants were identified (median [IQR] gestational age, 34 [28-38] weeks; 54.5% male). Prematurity occurred in 30.3%, and 55.3% underwent surgery. During hospitalization, 76.5% of high-risk infants were exposed to opioids and 7.9% received methadone. Median (IQR) length of any opioid exposure was 5 (2-12) cumulative days, and median (IQR) length of methadone treatment was 19 (7-46) cumulative days. There was significant hospital-level variation in opioid and methadone exposure and cumulative days of exposure within each US region. The computed intraclass correlation coefficient estimated that 16% of the variability in overall opioid prescribing and 20% of the variability in methadone treatment was attributed to the individual hospital., Conclusions and Relevance: In this retrospective cohort study of high-risk hospitalized infants, institution-level variation in overall opioid exposure and methadone treatment persisted across the US. These findings highlight the need for standardization of opioid prescribing in this vulnerable population.

Background: Gastrointestinal perforation in extremely low birth weight infants, characterized by its rapid onset, multiple complications, and critical condition, poses a significant risk of infant mortality. The aim of this study was to investigate the clinical characteristics of pneumoperitoneum in extremely low birth weight infants (ELBWI) and explore the risk factors associated with gastrointestinal perforation in very low birth weight preterm infants. Additionally, we shared our surgical experiences in managing gastrointestinal perforation among extremely low birth weight infants., Methods: The Department of Neonatology at Chengdu Women and Children's Central Hospital conducted a retrospective study on gastrointestinal perforation in extremely low birth weight infants (birth weight <1000 g) who were admitted between 2014 and 2021. After baseline analysis and comparing it with the control group, we identified the risk factors associated with gastrointestinal perforation in ELBWI by multiple logistic regression analysis. The Kaplan-Meier analysis was performed to assess the adverse effect of gastrointestinal perforation for survival in ELBW infants. Cox multivariate regression analysis was used to evaluate hazard level of different variables for ELBW infants survival., Results: Hemodynamically significant patent ductus arteriosus (hsPDA)(p = 0.043, OR = 2.779) and sepsis (p = 0.014, OR = 2.265) were significant risk factors for gastrointestinal perforation in extremely low birth weight infants. The Cox proportional hazard model revealed that intraventricular hemorrhage (HR = 2.854, p＜0.001) Sepsis (HR = 1.645, p = 0.015) and gastrointestinal perforation (HR = 1.876, p = 0.008) had detrimental effects on the survival of extremely low birth weight infants; conversely, ibuprofen (HR = 0.304, p＜0.001) and blood transfusion (HR = 0.372, p＜0.001) are beneficial factors for their survival. The preoperative indicators of infection in infants with spontaneous intestinal perforation (SIP) were significantly better than those in the necrotizing enterocolitis (NEC) group (p < 0.05)., Conclusions: Gastrointestinal perforation poses a significant threat the survival of extremely low birth weight (ELBW) infants, with hsPDA and sepsis serving as predisposing factors for gastrointestinal perforation. The gastrointestinal perforation caused by various diseases exhibits distinct clinical characteristics, necessitating tailored surgical approaches based on operative conditions., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and that there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

The purpose of the present study was to evaluate the prevalence of early adiposity rebound (EAR) and factors associated with its occurrence in a cohort of extremely low birth weight infants (ELBW). We conducted a retrospective longitudinal study including ELBW infants followed-up for up to 10 years after discharge. EAR was defined as occurring before 5 years of age. A multivariate binary logistic regression analysis was performed to evaluate maternal and perinatal variables independently associated with EAR. Out of 212 ELBW infants included in the analysis, 40.6% developed EAR and 21.5% showed it before 4 years of age. Only formula milk feeding at discharge was independently associated with a higher risk of EAR. The mean BMI of children with EAR was higher than that of children without EAR. Furthermore, the prevalence of overweight and obesity was higher in the EAR group than in the timely AR group.  Conclusions: ELBW infants in our cohort developed EAR in a relatively high percentage of cases. In this already at-risk population, EAR may represent a further risk factor for an adverse metabolic outcome. Monitoring preterm infants' growth within a long-term follow-up program and promoting and supporting human milk feeding is advisable. What is Known: • Preterm-born infants are at high risk for long-term adverse health outcomes, especially cardiovascular and metabolic. • The occurrence of early adiposity rebound (EAR) is associated with the risk of later obesity and metabolic syndrome. What is New: • The occurrence of EAR in ELBW infants may represent an additional risk factor for later adverse metabolic outcomes in an already vulnerable population. • Future preventive strategies should include a long-term follow-up and the promotion of exclusive breastfeeding., (© 2023. The Author(s).)

Background: Infants born with weights below the 10th percentile of the expected birth weight for gestational age, defined as small for gestational age (SGA), have an increased risk of neonatal mortality and prematurity-related complications. However, the relationship between SGA and postneonatal (28 days to <1 year) mortality among extremely low birth weight infants (ELBWIs) remains uncertain. Hence, this study aimed to investigate the association between birth weight percentiles and postneonatal mortality in ELBWIs., Methods: A cohort of ELBWIs with a gestational age greater than 23 weeks who were admitted to Osaka Women's and Children's Hospital between 2008 and 2019 were considered eligible. Infants with major congenital anomalies, those large for their gestational age, or those who died within 28 days of birth were excluded. Baseline characteristics and outcomes of the three groups of ELBWIs-severe SGA (sSGA; birth weight, <3rd percentile), moderate SGA (mSGA; birth weight, 3rd to <10th percentile), and appropriate for gestational age (AGA; birth weight, 10th to <90th percentile)-were compared. Logistic regression analysis was used to identify perinatal factors associated with postneonatal mortality in sSGA infants., Results: sSGA ELBWIs demonstrated higher incidence of meconium obstruction (25% vs. 8.3% vs. 7.6%, P < 0.001), cholestasis (21% vs. 4.2% vs. 9.7%, P < 0.003), and postneonatal mortality (7.3% vs. 0% vs. 0.7%, P < 0.004) than mSGA and AGA ELBWIs. In the logistic regression analysis, cholestasis (odds ratio, 30.1; 95% confidence interval, 2.98-304) and sepsis (odds ratio, 13.5; 95% confidence interval, 1.06-173) were significantly related to postneonatal mortality among ELBWIs with sSGA. The leading cause of postneonatal mortality in sSGA ELBWIs was liver failure (55.5%)., Conclusion: sSGA ELBWIs exhibited a higher rate of postneonatal mortality compared to mSGA and AGA ELBWIs. Therefore, strategies aimed at preventing liver dysfunction in severely cholestatic ELBWIs with sSGA are necessary., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Purpose: To assess the association between birth weight and the development of functional gastrointestinal disorders (FGIDs) in the first year of life. Methods: This is a secondary analysis of a prospective cohort multicenter study including neonates, consecutively enrolled at birth, and followed up for one year. At birth all infants were classified by birth weight as extremely low (ELBW), very low, or low when <1,000, <1,500, and <2,500 g, respectively, and by birth weight for gestational age as appropriate (AGA, weight in the 10-90th percentile), small (SGA, weight <10th percentile), and large (LGA, weight >90th percentile) for gestational age. FGIDs were classified according to the Rome III criteria and assessed at 1, 3, 6, and 12 months of life. Results: Among 1,152 newborns enrolled, 934 (81.1%) completed the study: 302 (32.3%) were preterm, 35 (3.7%) were ELBW, 104 (11.1%) were SGA, 782 (83.7%) were AGA, and 48 (5.1%) were LGA infants. Overall, throughout the first year of life, 718 (76.9%) reported at least one FGID. The proportion of infants presenting with at least one FGID was significantly higher in ELBW (97%) compared to LBW (74%) ( p=0.01) and in LGA (85.4%) and SGA (85.6%) compared to AGA (75.2%) ( p=0.0001). On multivariate analysis, SGA was significantly associated with infantile colic. Conclusion: We observed an increased risk of FGIDs in ELBW, SGA, and LGA neonates. Our results suggest that prenatal factors determining birth weight may influence the development of FGIDs in infants. Understanding the role of all potential risk factors may provide new insights and targeted approaches for FGIDs. [ABSTRACT FROM AUTHOR]

Objective: The medication follow-up in infants with extremely low birth-weight in a neonatal intensive care unit is described, identifying drug-related problems (DRP), drug-related negative outcomes, and the relationship between the occurrence of DRP and birth-weight of newborns and their impact on pharmacotherapy and length of hospital stay. Methods: A descriptive and exploratory study was performed in which medication follow-up of a population of infants with extremely low birth-weight admitted to the neonatal intensive care unit of a government-run maternity hospital was carried out by clinical pharmacists. Monitoring comprised assessment of patients' pharmacotherapy needs through visits to the neonatal unit, evaluation of prescriptions and information on medical records, identification of issues associated with pharmacotherapy and follow-up of the newborns' clinical evolution to determine whether desired results were achieved. Results: The subjects were 33 infants characterized by extremely low weight at birth. Analysis of patients' pharmacotherapy showed that 39.4% (n=13) of the neonates presented some type of DRP, totaling 37 DRPs and a mean of 2.8 problems/patient. Fourteen drugs were identified with the occurrence of DRP. Vancomycin and cefepime were the most prevalent, with 18.9% (n=7). Occurrence of DRPs and several clinical characteristics of newborns and their pharmacotherapy were compared. The most prevalent drug-related negative outcomes identified were "untreated health problem" (40%, n=10) and "quantitative ineffectiveness" (32%, n=8). Pharmaceutical interventions were performed for all problems associated with pharmacotherapy, with a prevalence of "treatment day count correction" and "dose correction", both with 21.6% (n=8), and "correction of dosage" (16.2%, n=6). Conclusion: The research evidenced the role of the clinical pharmacist in the solution and prevention of drug-related problems, contributing with the multidisciplinary team to obtain a safe and effective pharmacotherapy. Further, current study confirmed that there is an association between the characteristics of the newborns under analysis (eg. birth-weight, pharmacotherapy) and the occurrence of drug-related problems. [ABSTRACT FROM AUTHOR]

Objective: Examine the relationship between weight trajectory and 2-year neurodevelopmental outcomes for extremely low birthweight (ELBW) infants with BPD., Study Design: Secondary analysis of infants born from 2010 to 2019. The predictor was BPD severity and the outcome was neurodevelopmental impairment, defined as any Bayley Scales of Infant Development (BSID) III score <70 at 24 months' corrected age. Repeated measures logistic regression was performed., Results: In total, 5042 infants were included. Faster weight trajectory was significantly associated with a decreased probability of having at least one BSID III score <70 for infants with grade 1-2 BPD (p < 0.0001) and an increased probability of at least one BSID III score <70 for infants with grade 3 BPD (p < 0.009). There was no significant association between weight trajectory and BSID III score <70 for infants with grade 0 BPD., Conclusion: The association between postnatal weight trajectory and neurodevelopmental outcome in this study differs by BPD severity., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: To assess the level and the determinants of compliance with outpatient retinopathy of prematurity (ROP) examination appointments at a tertiary academic center., Methods: The medical records of babies scheduled for outpatient ROP examination between January 1, 2022, and December 31, 2022, were reviewed retrospectively. Data collected included appointments scheduled and attended, birth weight, gestational age, ROP staging at discharge, maternal ethnicity (self-identified), household type, proximity to hospital and median family income (US Census based on home zip codes). Univariate and multivariable analyses were performed. A P value of <0.05 was considered significant., Results: The records of 66 babies were analyzed. Forty-nine babies (74%) attended all scheduled ROP examination appointments (fully compliant). The mean appointment compliance rate was 86%, with a 1.5% no-show rate. Seven children (11%) required the intervention of Child Protective Services. One baby was never seen in the clinic. In unadjusted analysis, maternal ethnicity (P = 0.028) and median family income lower than the national average (P = 0.049) were sociodemographic factors associated with lower compliance. Clinical factors associated with lower compliance were lower gestational ages (P = 0.005) and lower birth weight (P = 0.006). In multivariable logistic regression adjusting for all candidate predictors, only birth weight remained significantly associated with lower compliance (P = 0.036)., Conclusions: Clinical and sociodemographic factors may be associated with compliance with outpatient ROP examination recommendations. Extremely low-birth-weight babies were at the greatest risk for noncompliance., (Published by Elsevier Inc.)

Objectives: Sodium homeostasis in extremely low birth weight (ELBW) infants is critical. While a lack of sodium delays growth, excessive supplementation increases morbidity., Methods: We performed a single-center retrospective study on sodium and fluid management during the first 2 weeks of live including all ELBW infants born between June 1, 2017 and May 31, 2019., Results: Forty-seven patients (median GA 26 + 6 weeks, median BW 845 g) were included. Mean sodium intake was above the ESPGHAN recommendation, 4.58 mmol/kg/day during the first 2 days and 1.99 mmol/kg/day during the following period. Incidence of PDA, IVH, and ROP was directly associated with sodium intake (OR 1.6, 1.3, and 1.4, respectively), but not with fluid supplementation. No association to BPD was found. The most important source for inadvertent sodium intake were 0.9% saline given by arterial lines. Sodium supplementation did not correlate directly with serum sodium levels, but a linear regression model combining sodium intake and fluid supplementation was able to predict serum sodium changes 24-48 h in advance (correlation coefficient of 0.294, p  < 0.05)., Conclusions: Sodium application substantially exceeded ESPGHAN recommendations in ELBW infants. An excess in sodium was associated with an overall increased morbidity, justifying increased efforts to identify inadvertent sodium sources in these patients with the aim to decrease sodium excess., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. JPGN Reports published by Wiley Periodicals LLC on behalf of The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: To quantify the association between necrotizing enterocolitis (NEC) and neurodevelopmental disability (NDI) in extremely low birth weight (ELBW) infants with intraventricular hemorrhage (IVH)., Study Design: ELBW survivors born 2011-2017 and evaluated at 16-26 months corrected age in the Vermont Oxford Network (VON) ELBW Follow-Up Project were included. Logistic regression determined the adjusted relative risk (aRR) of severe NDI in medical or surgical NEC compared to no NEC, stratified by severity of IVH., Results: Follow-up evaluation occurred in 5870 ELBW survivors. Compared to no NEC, medical NEC had no impact on NDI, regardless of IVH status. Surgical NEC increased risk of NDI in patients with no IVH (aRR 1.69; 95% CI 1.36-2.09), mild IVH (aRR 1.36;0.97-1.92), and severe IVH (aRR 1.35;1.13-1.60)., Conclusions: ELBW infants with surgical NEC carry increased risk of neurodevelopmental disability within each IVH severity stratum. These data describe the additive insult of surgical NEC and IVH on neurodevelopment, informing prognostic discussions and highlighting the need for preventative interventions., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)