Predicting early mortality and severe intraventricular hemorrhage in very-low birth weight preterm infants: a nationwide, multicenter study using machine learning.

Our aim was to develop a machine learning-based predictor for early mortality and severe intraventricular hemorrhage (IVH) in very-low birth weight (VLBW) preterm infants in Taiwan. We collected retrospective data from VLBW infants, dividing them into two cohorts: one for model development and internal validation (Cohort 1, 2016-2021), and another for external validation (Cohort 2, 2022). Primary outcomes included early mortality, severe IVH, and early poor outcomes (a combination of both). Data preprocessing involved 23 variables, with the top four predictors identified as gestational age, birth body weight, 5-min Apgar score, and endotracheal tube ventilation. Six machine learning algorithms were employed. Among 7471 infants analyzed, the selected predictors consistently performed well across all outcomes. Logistic regression and neural network models showed the highest predictive performance (AUC 0.81-0.90 in both internal and external validation) and were well-calibrated, confirmed by calibration plots and the lowest two mean Brier scores (0.0685 and 0.0691). We developed a robust machine learning-based outcome predictor using only four accessible variables, offering valuable prognostic information for parents and aiding healthcare providers in decision-making.

Deep Learning Model for Prediction of Bronchopulmonary Dysplasia in Preterm Infants Using Chest Radiographs.

Bronchopulmonary dysplasia (BPD) is common in preterm infants and may result in pulmonary vascular disease, compromising lung function. This study aimed to employ artificial intelligence (AI) techniques to help physicians accurately diagnose BPD in preterm infants in a timely and efficient manner. This retrospective study involves two datasets: a lung region segmentation dataset comprising 1491 chest radiographs of infants, and a BPD prediction dataset comprising 1021 chest radiographs of preterm infants. Transfer learning of a pre-trained machine learning model was employed for lung region segmentation and image fusion for BPD prediction to enhance the performance of the AI model. The lung segmentation model uses transfer learning to achieve a dice score of 0.960 for preterm infants with ≤ 168 h postnatal age. The BPD prediction model exhibited superior diagnostic performance compared to that of experts and demonstrated consistent performance for chest radiographs obtained at ≤ 24 h postnatal age, and those obtained at 25 to 168 h postnatal age. This study is the first to use deep learning on preterm chest radiographs for lung segmentation to develop a BPD prediction model with an early detection time of less than 24 h. Additionally, this study compared the model's performance according to both NICHD and Jensen criteria for BPD. Results demonstrate that the AI model surpasses the diagnostic accuracy of experts in predicting lung development in preterm infants.

Association of Neonatal Antibiotic Exposure with Long-Term Growth Trajectory Faltering in Preterm-Birth Children.

INTRODUCTION: Preterm neonates often receive a variety of duration of antibiotic exposure during admission. The aim of the study was to evaluate whether neonatal antibiotic exposure is relevant with longitudinal growth problems in preterm-birth children. METHODS: This prospective study enrolled 481 infants who were born <32 weeks of gestation, discharged, and longitudinally followed from corrected age (CA) 6-60 months. After excluding 153 infants with blood culture-confirmed bacteremia, necrotizing enterocolitis, severe cerebral palsy, intestinal ostomy, and congenital anomaly, 328 infants were included for analysis. Covariates included perinatal demographics, neonatal morbidities, extrauterine growth restriction, and antibiotic exposure accumulated by term equivalent age. The primary outcome was the anthropometric trajectories in z-score of bodyweight (zBW), body height (zBH), and body mass index (zBMI) from CA 6-60 months. RESULTS: Antibiotic exposure duration was significantly negatively associated with zBW and zBH at CA 6, 12, and 60 months, and zBMI at CA 60 months. Multivariate generalized estimating equation analyses showed antibiotic exposure duration had significantly faltering z-score increment from CA 6 to 60 months in zBW and zBH (adjusted mean [95% CI]; ΔzBW: -0.021 [-0.041 to -0.001], p = 0.042; ΔzBH: -0.019 [-0.035 to -0.002], p = 0.027) after adjustment. Children with neonatal antibiotic exposure duration >15 days were significantly lower in the mean anthropometric zBW, zBH, and zBMI at CA 6, 12, 24, and 60 months compared with children with neonatal antibiotic exposure ≤15 days (all p < 0.01). CONCLUSIONS: Growth increments were negatively associated with antibiotic exposure duration in preterm neonates implicating that antibiotic stewardship and growth follow-up for preterm neonates are thus warranted.

The Quartile Levels of Thyroid-Stimulating Hormone by Newborn Screening Stratified Risks of Neurodevelopmental Impairment in Extremely Preterm Infants - A Population Cohort Study.

BACKGROUND: To evaluate whether thyroid-stimulating hormone (TSH) by newborn screening (NBS) at birth and at discharge can be surrogate markers for neurodevelopmental impairment (NDI) in extremely preterm infants. METHODS: The population cohort enrolled infants born <29 weeks' gestation in 2008 - 2020 in southern Taiwan. Infants with a maternal history of thyroid disorders and infants who required thyroxine supplementation during hospitalization were excluded. TSH levels by NBS at birth and at term-equivalent age (TEA)/discharge were respectively categorized into the lowest quartile, the interquartile range, and the highest quartile, which were correlated to NDI outcomes. RESULTS: Among 392 patients with paired TSH data, 358 (91%) were prospectively followed until corrected age 24 months. At birth, infants with lowest-quartile TSH had higher NDI risks (OR 2.3, 95% CI 1.3 - 4.1, P = 0.004) compared to infants with interquartile-range TSH. Conversely, by TEA/discharge, infants with highest-quartile TSH had increased NDI (OR 1.9, 1.0 - 3.4, P = 0.03). By paired TSH categories, infants persistently in the lowest TSH quartile (48%, aOR 4.4, 1.4 - 14.5, P = 0.01) and those with a shift from interquartile range to the highest quartile (32%, aOR 2.7, 1.0 - 7.4, P = 0.046) had increased NDI risks compared with the reference with consistent interquartile-range TSH. CONCLUSIONS: Extremely preterm infants persistently in the lowest-quartile TSH level at birth and at discharge had the highest NDI risk. TSH quartile levels by NBS may serve as a population surrogate biomarker for assessing NDI risks in infants born extremely preterm.

Determining the Optimal Treatment for Idiopathic Clubfoot: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Clubfoot, or congenital talipes equinovarus deformity, is a common anomaly affecting the foot in infants. However, clinical equipoise remains between different interventions, especially those based on the Ponseti method. The aim of this study was to examine the clinical outcomes of the various interventions for treating idiopathic clubfoot. METHODS: Searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Scopus, and CINAHL were conducted. Randomized controlled trials comparing different interventions, including the Ponseti method, accelerated Ponseti method, Ponseti method with botulinum toxin type A (Botox) injection, Ponseti method with early tibialis anterior tendon transfer (TATT), Kite method, and surgical treatment, were included. Network meta-analyses (NMAs) were conducted according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) reporting guidelines. The primary outcomes were the change in total Pirani score and maximal ankle dorsiflexion. Secondary outcomes were the number of casts, time in casts, and rates of tenotomy, total complications, relapse, adverse events, and additional required major surgery. RESULTS: Eleven randomized controlled trials involving 740 feet were included. According to the SUCRA (surface under the cumulative ranking curve)-based relative ranking, the Ponseti method was associated with the best outcomes in terms of Pirani score changes, maximal ankle dorsiflexion, number of casts, adverse events, and total complications, whereas the accelerated Ponseti method was associated with the best outcomes in terms of time in casts and tenotomy rate. Early TATT ranked best in terms of relapse rate. The Ponseti method with Botox injection was associated with the best outcomes in terms of the need for additional major surgery. CONCLUSIONS: The NMAs suggest that the Ponseti method is the optimal treatment overall, despite potential drawbacks such as longer time in casts and higher rates of tenotomy, relapse, and the need for additional surgery compared with other modified approaches. Therefore, clinicians should consider how treatments can be tailored individually. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Neurodevelopment After Neonatal Acute Kidney Injury in Very Preterm-Birth Children.

Introduction: This study aimed to assess head circumference (HC) growth and neurodevelopmental outcomes in very preterm-birth children after neonatal acute kidney injury (AKI). Methods: This longitudinal follow-up cohort included 732 very preterm neonates of gestational age <31 weeks admitted to a tertiary center between 2008 and 2020. AKI was categorized as nonoliguric and oliguric AKI based on the urine output criteria during admission. We compared the differences in death, z scores of HC (zHC) at term-equivalent age (TEA) and at corrected ages of 6, 12, and 24 months, and the neurodevelopmental outcomes at corrected age of 24 months after neonatal nonoliguric and oliguric AKI. Results: Among the 154 neonates who developed AKI, 72 had oliguric AKI and 82 had nonoliguric AKI. At TEA, oliguric AKI, but not nonoliguric AKI, was independently associated with lower zHC than non-AKI (mean differences, -0.49; 95% confidence interval [CI], -0.92 to -0.06). Although the 3 groups were comparable in zHC at corrected ages of 6, 12, and 24 months, the oliguric AKI group, but not the nonoliguric AKI group, had a higher rate of microcephaly by corrected age of 24 months. In addition, the oliguric AKI group, but not the nonoliguric AKI group, was more likely to die (61% vs. 9%) and have neurodevelopmental impairment (41% vs. 14%) compare with the non-AKI group. After adjustment, oliguric (adjusted odds ratio [aOR], 8.97; 95% CI, 2.19-36.76), but not nonoliguric, AKI was associated with neurodevelopmental impairment. Conclusion: Neonatal oliguric AKI is associated with neurodevelopmental impairment in very preterm-birth children. Long-term head-size and neurodevelopmental follow-up after neonatal AKI is warranted.

The composition of the maternal breastmilk microbiota influences the microbiota network structure during early infancy.

BACKGROUND/PURPOSE(S): Human breastmilk (BM) is important for microbiome maturation in infants across different body sites. Streptococcus and Staphylococcus are considered universally predominant genera in the BM microbiota. However, whether the differential abundance of Streptococcus and Staphylococcus in BM can differentially affect microbiome maturation in infants remains unclear. METHODS: We recruited exclusively breastfeeding mothers from among the donors of the human milk bank established at National Cheng-Kung University Hospital. The donor mothers provided 35 BM samples at three months (3 M; before introducing children to complementary feeding) and 23 BM samples at six months (6 M; after introducing children to complementary feeding) postpartum. At both time points, samples from different body sites, including nasal swabs, oral swabs and stool, were collected from the mothers and their infants. RESULTS: Maternal BMI was inversely associated with coagulase-negative Staphylococcus (CoNS) abundance in breastmilk. Staphylococcus caprae representation in BM CoNS showed a negative correlation with Streptococcus abundance. Network analysis revealed that infants fed Staphylococcus-dominated BM had better gut and nasal microbiota networks than infants fed Streptococcus-abundant BM during early infancy. CONCLUSION: Our work suggests that maternal metabolic status plays a crucial role in Staphylococcus/Streptococcus competition in BM, which in turn can impact the development of the infant microbiota. Our microbiota co-occurrence network analysis might serve as a helpful bioinformatic tool to monitor microbiota maturation during early infancy.

Investigation of New Psychoactive Substances (NPS), Other Illicit Drugs, and Drug-Related Compounds in a Taiwanese Wastewater Sample Using High-Resolution Mass-Spectrometry-Based Targeted and Suspect Screening.

The proliferation of new psychoactive substances (NPSs) in recent years has posed a significant challenge to public health. Traditional monitoring methods have proven insufficient in tracking these constantly evolving substances, leading to the development of alternative approaches such as wastewater-based epidemiology (WBE). The present study aims to utilize high-resolution mass spectrometry (HRMS)-based targeted and suspect screening to profile NPS, other illicit drugs, and drug-related compounds in a Taiwanese wastewater sample. For the targeted analysis, 8 out 18 standards of illicit drugs have been identified. The suspect screening approach based on approximately 3600 substances in the SWGDRUG library can further identify 92 compounds, including opiate analgesics, synthetic cathinones, phenylalkylamines derivatives, phenethylamine derivatives, tryptamine derivatives, steroids, and ephedrine-related compounds. Additionally, the presence of 5-methoxy-2-aminoindane (MEAI) in the wastewater indicates that drug dealers have recently sold this potential NPS to evade drug regulations. This study firstly reports the HRMS-based comprehensive profile of NPS, other illicit drugs, and drug-related compounds in Taiwan, which could be applied as biomarkers for estimating the consumption of drugs.

Trends in Gestational Age-Related Intelligence Outcomes of School-Age Children Born Very Preterm from 2001 to 2015 in Taiwan.

OBJECTIVE: To investigate whether gestational age (GA)-related intelligence outcomes of children born very preterm improved over time. STUDY DESIGN: A multicenter cohort study recruited 4717 infants born at GA <31 weeks and admitted to neonatal intensive care units between 2001 and 2015 in Taiwan. Intelligence outcomes at age 5.5 years were classified by intelligent quotient (IQ) into no cognitive impairment (IQ > -1 SD), mild cognitive impairment (IQ = -1∼-2 SD), and moderate/severe cognitive impairment (IQ < -2 SD). Trends were assessed for neonatal morbidities, mortality, and intelligence outcomes by birth epoch (2001-2003, 2004-2006, 2007-2009, 2010-2012, 2013-2015) and GA (23-24, 25-26, 27-28, 29-30 weeks). RESULTS: Maternal education levels increased and rates of brain injury and mortality decreased over time. Among the 2606 children who received IQ tests, the rates of no, mild, and moderate/severe cognitive impairment were 54.5%, 30.5%, and 15.0%, respectively. There were significant trends in the increasing rates of no cognitive impairment and declining rates of mild and moderate/severe cognitive impairment in all GA groups across the 5 birth epochs. Relative to the occurrence in 2001-2003, the odds were significantly reduced for moderate/severe cognitive impairment from 2007-2009 (aOR 0.49, 95% CI 0.30-0.81) to 2013-2015 (0.35, 0.21-0.56) and for mild cognitive impairment from 2010-2012 (0.54, 0.36-0.79) to 2013-2015 (0.36, 0.24-0.53). CONCLUSIONS: For children born very preterm between 2001 and 2015 in Taiwan, the improvement of maternal education levels and improvements in neonatal brain injury and mortality were temporally associated with trends of decreasing intellectual impairment at school age across all GA groups.

Preceding risks and mortality outcomes of different neonatal acute kidney injury in preterm infants.

BACKGROUND: The aim of the study was to examine preceding risks and mortality outcomes of oliguric and non-oliguric acute kidney injury (AKI) in very preterm infants. METHODS: Infants born ≤30 weeks' gestation were included. AKI was diagnosed based on neonatal Kidney Disease: Improving Global Outcomes criteria and was classified as oliguric and non-oliguric according to the urine-output criteria. We used modified Poisson and Cox proportional-hazards models for statistical comparisons. RESULTS: Of 865 enrolled infants (gestational age 27.2 ± 2.2 weeks and birth weight 983 ± 288 gm), 204 (23.6%) developed AKI. Before AKI, the oliguric AKI group had significantly higher prevalence of small-for-gestational age (p = 0.008), lower 5-min Apgar score (p = 0.009) and acidosis (p = 0.009) on admission, and hypotension (p = 0.008) and sepsis (p = 0.001) during admission than the non-oliguric AKI group. Oliguric (adjusted risk ratio 3.58, 95% CI 2.33-5.51; adjusted hazard ratio 4.93, 95% CI 3.14-7.72) instead of non-oliguric AKI had significantly higher mortality risks than no AKI. Oliguric AKI showed significantly higher mortality risks than non-oliguric AKI, irrespective of serum creatinine and severity of AKI. CONCLUSIONS: Categorizing AKI as oliguric and non-oliguric was crucial because of the distinct preceding risks and mortality outcomes of these two types of AKI in very preterm neonates. IMPACT: The differences of the underlying risks and prognosis between oliguric and non-oliguric AKI in very preterm infants remain unclear. We found that oliguric AKI, but not non-oliguric AKI, carries higher mortality risks than infants without AKI. Oliguric AKI possessed higher mortality risks than non-oliguric AKI, irrespective of concomitant serum creatinine elevation and severe AKI. Oliguric AKI is more associated with prenatal small-for-the-gestational age and perinatal and postnatal adverse events, while non-oliguric AKI is associated with nephrotoxins exposures. Our finding highlighted the importance of oliguric AKI and is helpful in developing future protocol in neonatal critical care.

Adverse Effects of Denosumab in Kidney Transplant Recipients: A 20-Year Retrospective Single-Center Observation Study in Central Taiwan.

BACKGROUND: Bone loss can be noted in kidney transplantation recipients (KTRs) and can be related to fracture events. Denosumab, a potent monoclonal antibody to RANK ligand, increases lumbar bone mineral density. However, safety data for denosumab remain limited regarding transplant recipients. Hypocalcemia and increased genital tract infections have been mentioned as adverse effects in KTRs after being prescribed denosumab. METHODS: We retrospectively analyzed the electronic medical records of KTRs during the recent 20 years who had been prescribed antiresorptive therapy and were >18 years old. Medical records and their clinical data were reviewed and analyzed. We compared the frequency of adverse effects between denosumab with other antiresorptive therapies. RESULTS: A total of 70 KTRs were enrolled, with 46 patients being given denosumab and the first injection being noted on October 31, 2014. No significant differences were seen in mortality rate, opportunistic infection, pneumonia, or genitourinary tract infection. One diagnosis of osteonecrosis of the jaw was noted in the denosumab group (2.2%). A higher incidence of hypocalcemia (<8.4 mg/dL) was noted in the denosumab group (34.8%), and a higher but nonsignificant difference in the incidence of severe hypocalcemia was also noted in the group. CONCLUSIONS: Denosumab may be considered as safe as other antiresorptive therapies for KTRs. However, more hypocalcemia events have been noted, so medical personnel may need to be cautious when prescribing its use.

Early-Life Slow Enteral Feeding Progression Pattern Is Associated with Longitudinal Head-Size Growth Faltering and Neurodevelopmental Impairment Outcomes in Extremely Preterm Infants.

OBJECTIVE: To determine whether feeding progression patterns in the first eight postnatal weeks, depicted by clustering analysis of daily enteral feeding volume, are associated with longitudinal head-circumference (HC) growth and neurodevelopmental outcomes in extremely preterm (EP) infants. METHODS: 200 infants who were admitted at gestational ages 23-27 weeks between 2011 and 2018; survived to discharge; and underwent longitudinal HC growth measurements at birth, term-equivalent age (TEA), corrected age (CA) 6-month, 12-month, and 24-month; and neurodevelopmental assessment using the Bayley Scales of Infant Development at CA 24 months were included for analysis. RESULTS: kmlShape analysis identified two distinct enteral feeding progression patterns: fast progression in 131 (66%) infants and slow progression in 69 (34%) infants. Compared to the fast progression group, the slow progression group showed significantly lower daily enteral volumes after day 13, was older in postnatal age reaching full feeding, had a higher rate of Delta z scores of HC (zHC) < -1 (p < 0.001) between birth and TEA, and displayed lower longitudinal zHC from TEA to CA 24 months. The slow progression group also showed higher rates of microcephaly [42% vs. 16%, p < 0.001; adjusted odd ratio (aOR): 3.269, p = 0.001] and neurodevelopmental impairment (NDI) (38% vs. 19%, p = 0.007; aOR: 2.095, p = 0.035) at CA 24 months. For NDI, the model including feeding progression patterns showed a lower Akaike information criterion score and a better goodness of fit than the model that did not include feeding patterns. CONCLUSION: Characterizing feeding progression pattern may help identify EP infants at high-risk of head-size growth faltering and NDI at early childhood.

Postnatal corticosteroid treatment as a risk factor for false positivity in severe combined immunodeficiency newborn screening.

From 2011, 37 children were referred to a hospital due to low levels of T cell receptor excision circles (TRECs) from newborn screening. Among them, three children were immunologically characterized and followed up to show that postnatal corticosteroid usage may be among the causes of false positivity in TRECs screening.

Associations between Early Thyroid-Stimulating Hormone Levels and Morbidities in Extremely Preterm Neonates.

INTRODUCTION: High-end cutoffs of thyroid-stimulating hormone (TSH) have been emphasized for hypothyroidism therapy in extremely preterm infants, but the significance of low TSH levels remains unknown. This study hypothesized that the spectrum of TSH levels by newborn screening after birth signifies specific morbidities in extremely preterm neonates. METHODS: The multicenter population cohort analyzed 434 extremely preterm neonates receiving TSH screening at 24-96 h of age in 2008-2019. Neonates were categorized by blood TSH levels into group 1: TSH <0.5 µU/mL, group 2: 0.5 ≤ TSH <2 µU/mL, group 3: 2 ≤ TSH <4 µU/mL, and group 4: TSH ≥4 µU/mL. Neonatal morbidities were categorized using the modified Neonatal Therapeutic Intervention Scoring System. RESULTS: The four groups differed in gestational age, birth weight, and the postnatal age at blood sampling so did the proportions of mechanical ventilation usage (p = 0.01), hypoxic respiratory failure (p = 0.005), high-grade intraventricular hemorrhage (p = 0.007), and periventricular leukomalacia (p = 0.048). Group 1 had higher severity scores for respiratory distress syndrome (RDS; effect size 0.39 [95% confidence interval [CI]: 0.18-0.59]) and brain injury (0.36 [0.15-0.57]) than group 2, which remained significant after adjusting for gestational age, birth weight, dopamine usage, and the postnatal age at TSH screening (RDS: mean + 0.45 points [95% CI: 0.11-0.79]; brain injury: +0.32 [0.11-0.54]). CONCLUSIONS: Low TSH levels in extremely preterm neonates are associated with severe RDS and brain injuries. Studies recruiting more neonates with complete thyroid function data are necessary to understand central-peripheral interactions of the hypothalamic-pituitary-thyroid axis.

Predictors of Remission in Severe Childhood Immune Thrombocytopenia.

Childhood immune thrombocytopenia (ITP; platelet count < 100 × 109/L) is the most common bleeding disorder in children. A total of 3-5% of children with ITP face a greater risk of bleeding, resulting in significant morbidity and mortality. Childhood ITP is often benign and self-limited; however, children with severe ITP (platelet count < 30 × 109/L) require investigation and monitoring. In addition, 20% of ITP patients may not go into remission (platelet counts < 100 × 109/L by 12 months after diagnosis) and may develop chronic ITP. The early identifying predictors associated with the resolution of severe ITP at the time of diagnosis may be helpful for family guidance. However, there is still controversy about the associations between the clinical factors at the time of initial diagnosis and the definitions of disease remission assessed at different timepoints after diagnosis. This retrospective study aimed to analyze the shared clinical factors among the disease remission definitions at three arbitrarily set timepoints-3, 6, and 12 months after diagnosis. This study retrieved records for hospitalized children aged under 18 years and diagnosed with ITP from the hospital registry in a tertiary university hospital. Clinical variables were recorded by reviewing the medical records with structured data entry for ITP admission. The serial follow-up platelet counts within 12 months after diagnosis were recorded. The times of ITP remission were identified by experienced pediatric hematologists. Patients with mild-form ITP (platelet counts ≥ 30 × 109/L) at diagnosis or who were lost to follow-up within 3 months were excluded. From 1988 to 2019, 546 children were enrolled, and a total of 497 children with severe ITP were included in the further analysis. In total, one (0.2%) died of an intracranial hemorrhage, 363 (73.2%) children went into remission at 3 months, 40 (8.1%) went into remission between 6 and 12 months, and 104 (20.9%) developed chronic ITP. The shared significant predictors for remission by the third, sixth, and twelfth months included pre-adolescent age (<10 years) at diagnosis, abrupt onset (duration of symptoms prior to admission ≤ 2 weeks), and speedy recovery (platelet count > 100 × 109/L at 1 month post diagnosis). ITP patients with positive viral serology tests or vaccination within 4 weeks had trends of delayed remission. In conclusion, diagnosis before preadolescent age, abrupt onset, and speedy recovery may share favorable factors for the remission of childhood ITP assessed at different timepoints.

Surgical ligation, not transcatheter closure, associated with a higher severity of bronchopulmonary dysplasia in extremely preterm infant intervened for patent ductus arteriosus.

OBJECTIVE: Patent ductus arteriosus (PDA) is a common complication among premature infants, which may be responsible for prematurity-related complications such as bronchopulmonary dysplasia (BPD). It is unclear whether different interventional methods contribute to the severity of BPD, given the original National Institute of Child Health and Human Development (NICHD) 2001 definition. To date, surgical ligation and the transcatheter approach have been equally successful in premature infants with hemodynamically significant PDA after medical treatment failure. Immediate improvement in the respiratory condition has been reported after transcatheter closure. However, the short-term pulmonary outcome has not been clarified yet. METHODS: This retrospective study investigated infants born with a body weight <1000 g and who underwent either surgical ligation or transcatheter closure of PDA in a single tertiary institution. The infants were divided into groups according to the type of procedure (surgical ligation or transcatheter occlusion). The primary outcome was the severity of BPD at discharge or at a postmenstrual age of 36 weeks. The outcome was analyzed with logistic regression. RESULTS: Forty-four patients met the inclusion criteria, of whom 14 underwent transcatheter occlusion and 30 underwent surgical ligation. The overall birth body weights and gestational age ranges were not different. The univariate model revealed an association between the procedure type and BPD severity. After adjusting for confounders, the multivariate model confirmed associations between BPD severity and procedure type and severe respiratory distress syndrome requiring surfactant. CONCLUSION: Compared with the transcatheter approach, surgery for PDA in extremely preterm infants is associated with severe BPD at discharge. Further large-scale studies are needed to determine the exact mechanism.

Risk patterns associated with transient hearing impairment and permanent hearing loss in infants born very preterm: A retrospective study.

AIM: To determine the risk patterns associated with transient hearing impairment (THI) and permanent hearing loss (PHL) of infants born very preterm who failed hearing screenings. METHOD: We enrolled 646 infants (347 males, 299 females) born at no more than 30 weeks' gestation between 2006 and 2020 who received auditory brainstem response screening at term-equivalent age. Audiological examinations of infants who failed the screening revealed THI, when hearing normalized, or PHL, defined as a persistent unilateral or bilateral hearing threshold above 20 dB. Principal component analysis (PCA) was used to characterize risk patterns. RESULTS: Among the 646 infants, 584 (90.4%) had normal hearing, 42 (6.5%) had THI, and 20 (3.1%) had PHL. Compared with the group with normal hearing, the THI and PHL groups had significantly higher rates of neurodevelopmental impairment at 24 months corrected age. PCA of risk patterns showed the THI group and especially the PHL group had more severe haemodynamic and respiratory instability. Moreover, severe intraventricular haemorrhage (IVH) was also a risk for PHL. Propensity score matching revealed an association of haemodynamic and respiratory instability with PHL. INTERPRETATION: In infants born preterm, the severity and duration of haemodynamic and respiratory instability are risk patterns for both THI and PHL; severe IVH is an additional risk for PHL. WHAT THIS PAPER ADDS: Neurodevelopmental delay was more common in infants born preterm who failed hearing screening. Principal component analysis revealed the risk patterns associated with hearing impairment. Haemodynamic-respiratory instability was associated with transient and permanent hearing impairment outcomes. Severe haemodynamic-respiratory instability and intraventricular haemorrhage was associated with permanent hearing loss.

The Association of Patent Ductus Arteriosus with Inflammation: A Narrative Review of the Role of Inflammatory Biomarkers and Treatment Strategy in Premature Infants.

Patent ductus arteriosus (PDA) is a common cardiovascular complication that complicates clinical care in the intensive care of premature infants. Prenatal and postnatal infections and the inflammation process can contribute to PDA, and intrauterine inflammation is a known risk factor of PDA. A variety of inflammatory biomarkers have been reported to be associated with PDA. Chorioamnionitis induces the fetal inflammatory process via several cytokines that have been reported to be associated with the presence of PDA and may have a role in the vascular remodeling process or vessel dilation of the ductus. On the other hand, anti-inflammatory agents, such as antenatal steroids, decrease PDA incidence and severity in patients born to those with chorioamnionitis. Proinflammatory cytokines, which are expressed more significantly in preterm neonates and chorioamnionitis, are associated with the presence of PDA. In this review, we focus on the pathogenesis of PDA in preterm infants and the role of biomarkers associated with the perinatal inflammatory process.

Retinopathy of Prematurity Is a Biomarker for Pathological Processes in the Immature Brain.

INTRODUCTION: Retinopathy of prematurity (ROP) is considered a neurovascular disease. We investigated whether ROP, mild or severe, is associated with neurodevelopmental impairment (NDI) in extremely preterm children. METHODS: We conducted a multicenter retrospective cohort study in southern Taiwan. A total of 394 children <28 weeks of gestation who survived to discharge from 2011 to 2018 received neurodevelopmental assessment at corrected age of 24 months. Severe ROP was defined as ROP of stages 2 plus or worse, or recipients of retinal therapy, and mild ROP as stage 1 or 2 in at least one eye. NDI was defined as cognitive or motor impairment using the Bayley Scales of Infant and Toddler Development, moderate to severe cerebral palsy, or profound hearing loss. RESULTS: Among the 374 children validated for analysis, 157 children (42%) had non-ROP, 145 (39%) mild ROP, and 72 (19%) severe ROP. As ROP severity increased progressively from non-ROP, to mild ROP, and to severe ROP, the rates of NDI increased from 25%, to 46%, and to 61%. The multivariable logistic regression showed that the model included three levels of ROP, and neonatal morbidities achieved better overall performance for NDI than the model that included neonatal morbidities alone. Compared with non-ROP, mild ROP and severe ROP had adjusted odds ratios of 1.90 (95% CI: 1.10-3.28) and 2.75 (95% CI: 1.33-5.67) for NDI, respectively. CONCLUSION: Mild ROP and severe ROP are independent neonatal morbidities associated with NDI. Neurodevelopmental follow-up of extremely preterm children with any stage of ROP is needed.

Near-infrared light scattering and water diffusion in newborn brains.

OBJECTIVE: MRI provides useful information regarding brain maturation and injury in newborn infants. However, MRI studies are generally restricted during acute phase, resulting in uncertainty around upstream clinical events responsible for subtle cerebral injuries. Time-resolved near-infrared spectroscopy non-invasively provides the reduced scattering coefficient ( µ s ' ), which theoretically reflects tissue structural complexity. This study aimed to test whether µ s ' values of the newborn head reflected MRI findings. METHODS: Between June 2009 and January 2015, 77 hospitalised newborn infants (31.7 ± 3.8 weeks gestation) were assessed at 38.8 ± 1.3 weeks post-conceptional age. Associations of µ s ' values with MRI scores, mean diffusivity and fractional anisotropy were assessed. RESULTS: Univariable analysis showed that µ s ' values were associated with gestational week (p = 0.035; regression coefficient [B], 0.065; 95% confidence interval [CI], 0.005-0.125), fractional anisotropy in the cortical grey matter (p = 0.020; B, -5.994; 95%CI, -11.032 to -0.957), average diffusivity in the cortical grey matter (p < 0.001; B, -4.728; 95%CI, -7.063 to -2.394) and subcortical white matter (p = 0.001; B, -2.071; 95%CI, -3.311 to -0.832), subarachnoid space (p < 0.001; B, -0.289; 95%CI, -0.376 to -0.201) and absence of brain abnormality (p = 0.042; B, -0.422; 95%CI, -0.829 to -0.015). The multivariable model to explain µ s ' values comprised average diffusivity in the subcortical white matter (p < 0.001; B, -2.066; 95%CI, -3.200 to -0.932), subarachnoid space (p < 0.001; B, -0.314; 95%CI, -0.412 to -0.216) and absence of brain abnormality (p = 0.021; B, -0.400; 95%CI, -0.739 to -0.061). INTERPRETATION: Light scattering was associated with brain structure indicated by MRI-assessed brain abnormality and diffusion-tensor-imaging-assessed water diffusivity. When serially assessed in a larger population, µ s ' values might help identify covert clinical events responsible for subtle cerebral injury.