Respiratory Severity Score and Neurodevelopmental Outcomes at Age 3 Years in Extremely Preterm Infants.

OBJECTIVE: We aimed to examine the association between respiratory severity score (RSS; mean airway pressure × fraction of inspired oxygen) and neurodevelopmental outcomes in extremely preterm infants. STUDY DESIGN: This was a single-center, retrospective cohort study. We analyzed data from extremely preterm infants who were admitted to the neonatal intensive care unit at Okayama Medical Center between 2010 and 2019. Infants without invasive respiratory management during the first day of life were excluded. The exposure variable was the highest RSS during the first day of life. RSS was categorized into two groups: low (<3.5) and high (≥3.5) RSS. The primary outcome was death or neurodevelopmental impairment at age 3 years, defined as cognitive impairment (developmental quotient <70) or the presence of cerebral palsy. Secondary outcomes were the components of the primary outcome. We conducted robust Poisson regression analyses to investigate the association between RSS category and primary and secondary outcomes, adjusting for perinatal confounders. RESULTS: The cohort included 97 infants with neurodevelopmental data, of whom 34 and 63 infants were in the low- and high-RSS categories, respectively. The median (interquartile range) gestational age and birth weight were 26.0 (24.7-26.9) and 25.7 (24.6-26.7) weeks and 761 (584-866) and 806 (618-898) g for infants in the low- and high-RSS categories, respectively. Compared with infants in the low-RSS category, those in the high-RSS category had a greater risk of death or neurodevelopmental impairment at age 3 years (26.3 vs. 42.3%; adjusted risk ratio [RR], 2.0; 95% confidence interval [CI], 1.1-3.5) and neurodevelopmental impairment at age 3 years (17.6 vs. 28.6%; adjusted RR, 2.7; 95% CI, 1.3-5.9). CONCLUSION: High RSS (≥3.5) during the first day of life was associated with an increased risk of neurodevelopmental impairment at age 3 years in extremely preterm infants. KEY POINTS: · RSS is a valuable tool for assessing respiratory failure.. · RSS = Mean airway pressure × fraction of inspired oxygen.. · RSS at age 1 day was associated with neurodevelopment..

Delivery room intubation and neurodevelopment among extremely preterm infants.

BACKGROUND: The impact of delivery room intubation (DRI) on neurodevelopment in extremely preterm infants remains unclear. METHODS: We retrospectively analyzed data for infants born at 24-27 gestational weeks between 2003 and 2018. The primary outcome was neurodevelopmental impairment (NDI), defined as cerebral palsy or hearing, visual, or cognitive impairment at age 3 years. Secondary outcomes were NDI components and death before and after discharge from the neonatal intensive care unit. We conducted robust Poisson regression analyses, adjusting for perinatal confounders. RESULTS: The full cohort included 4397 infants with NDI data, of whom 3703 were intubated in the delivery room and 694 were not intubated in the delivery room. The mean gestational age and birth weight were 26.0 ± 1.1 weeks and 778 ± 184 g for infants with DRI and 26.6 ± 1.0 weeks and 873 ± 184 g for infants without DRI. Compared with infants without DRI, those with DRI had a higher risk for NDI (32.4% vs. 23.3%; adjusted risk ratio 1.18, 95% confidence interval: 1.01-1.37). There were no differences in secondary outcomes between infants with and without DRI. CONCLUSIONS: DRI was associated with an increased risk for NDI at age 3 years among extremely preterm infants. IMPACT: Few studies have examined the impact of delivery room intubation on neurodevelopment in infants born extremely preterm, and the results have been inconsistent. A total of 4397 infants born at 24-27 gestational weeks who had neurodevelopmental data at age 3 years were included in the present study. The present study found that delivery room intubation was associated with an increased risk for neurodevelopmental impairment at age 3 years among extremely preterm infants.

A nationwide birth cohort in Japan showed increased risk of early childhood hospitalisation in infants born small for gestational age.

AIM: To examine associations between children being born small for gestational age and childhood hospitalisation following term and preterm births. METHODS: This study included 34 564 children from a nationwide population-based longitudinal survey starting in 2010, comprising 32 603 term births and 1961 preterm births. Children's hospitalisation history was examined during two observational periods, 6-18 and 6-66 months of age. Logistic regression analysis was conducted, adjusting for child and parental confounders, with children born appropriate for gestational age as reference. RESULTS: Children born small for gestational age were more likely to be hospitalised during early childhood than those born appropriate for gestational age. The odds ratio (95% confidence interval) for hospitalisation from 6 to 66 months of age was 1.19 (1.05-1.34) in term children born small for gestational age and 1.47 (1.05-2.06) for preterm children born small for gestational age, compared with those born appropriate for gestational age. The risk of hospitalisation from 6 to 66 months of age in children born small for gestational age was observed for bronchitis/pneumonia. CONCLUSION: We observed the adverse effects of small for gestational age on hospitalisation during early childhood in both term and preterm births, particularly for bronchitis and pneumonia.

Postnatal longitudinal analysis of serum Nitric oxide and eosinophil counts in extremely preterm infants.

BACKGROUND: Nitric oxide (NO) may be related to the pathogenesis of several morbidities in extremely preterm infants, including late-onset adrenal insufficiency. However, eosinophilia is observed under pathological conditions with adrenal insufficiency. Therefore, this study explored postnatal changes in NO levels and eosinophil counts in extremely preterm infants with and without morbidities. METHODS: Nineteen extremely preterm infants with a median gestational age of 27.0 weeks and median birth weight of 888 g were enrolled in this study. Serum levels of nitrogen oxides (NOx) and peripheral blood eosinophil counts were measured at birth and every 2 weeks thereafter. Morbidities of the study group were diagnosed using a single criterion. RESULTS: Serum NOx levels (mean ± standard deviation) were 22.5 ± 14.9 µmol/L, 51.2 ± 23.7 µmol/L, 42.4 ± 15.2 µmol/L, and 33.8 ± 9.4 µmol/L at birth and 2, 4, and 6 weeks of age, respectively. The serum NOx level at 2 weeks of age was significantly higher than that at birth and 6 weeks of age. Eosinophil counts, which increase with adrenal insufficiency, were measured simultaneously and were 145 ± 199/µL, 613 ± 625/µL, 466 ± 375/µL, and 292 ± 228/µL at birth and 2, 4, and 6 weeks of age, respectively. These values showed that the eosinophil count was significantly higher at 2 weeks of age than at birth and 6 weeks of age. The serum NOx level of infants without chorioamnionitis was significantly increased at 4 weeks of age, and the eosinophil count of infants with necrotizing enterocolitis was significantly increased at 2 weeks of age. No correlation with the NOx level or eosinophil count was observed in infants with late-onset circulatory collapse. CONCLUSION: The postnatal serum NOx level and eosinophil count were significantly correlated with each other and peaked at 2 weeks of age.

Delivery room intubation and severe intraventricular hemorrhage in extremely preterm infants without low Apgar scores: A Japanese retrospective cohort study.

The purpose of this study was to assess the associations between delivery room intubation (DRI) and severe intraventricular hemorrhage (IVH), as well as other neonatal outcomes, among extremely preterm infants without low Apgar scores using data from a large-scale neonatal registry data in Japan. We analyzed data for infants born at 24-27 gestational weeks between 2003 and 2019 in Japan using robust Poisson regression. Infants with low Apgar scores (≤ 1 at 1 min or ≤ 3 at 5 min) were excluded. The primary outcome was severe IVH. Secondary outcomes were other neonatal morbidities and mortality. The full cohort included 16,081 infants (intubation cohort, 13,367; no intubation cohort, 2714). The rate of DRI increased over time (78.6%, 2003-2008; 83.4%, 2009-2014; 87.8%, 2015-2019), while the rate of severe IVH decreased (7.1%, 2003-2008; 5.7%, 2009-2014; 5.3%, 2015-2019). Infants with DRI had a higher risk of severe IVH than those without DRI (6.8% vs. 2.3%; adjusted risk ratio, 1.86; 95% confidence interval, 1.33-2.58). The results did not change substantially when stratified by gestational age. Despite conflicting changes over time in DRI and severe IVH, DRI was associated with an increased risk of severe IVH among extremely preterm infants in Japan.

Three Cases of Down Syndrome with Transient Abnormal Myelopoiesis who Underwent Liver Biopsy before Induction of Low-Dose Cytarabine.

Among patients with transient abnormal myelopoiesis (TAM) associated with Down syndrome, approximately 20% die within 6 months from multiorgan failure, especially liver fibrosis. We experienced three children with TAM who had low white blood cell counts but increased bilirubin levels. Here, we discuss the detailed clinical courses of these patients, including the pathological findings of liver biopsies. Our cases, together with previous literature, suggest that liver biopsy can be performed safely and provides useful information, especially regarding disease activities, and that low-dose cytarabine is a reasonable option to prevent early death in TAM patients with liver dysfunction.

Congenital intrahepatic portosystemic shunt with spontaneous resolution in a newborn with severe fetal growth restriction.

Owing to the advances in ultrasound, there are increasing reports of intrahepatic portosystemic shunt (IPSS) diagnosis in utero. However, few neonatal cases of IPSS diagnosed by abdominal ultrasonography screening at birth have been reported. This case demonstrated abdominal ultrasonography at birth was useful for the early detection of congenital IPSS.

Longitudinal Measurement of Histidine-Rich Glycoprotein Levels in Bronchopulmonary Dysplasia: A Pilot Study.

Histidine-rich glycoprotein (HRG) has been reported to inhibit signaling leading to the release of high mobility group box 1 protein, a damage-associated molecular pattern. The present study aimed to determine the longitudinal change in HRG levels in extremely preterm infants and assess whether complications such as bronchopulmonary dysplasia (BPD) were associated with differences in HRG levels. In this multicenter, prospective, observational study, we measured serum HRG levels every 2 weeks from birth to 8 weeks of age. Serum HRG was measured using an enzyme-linked immunosorbent assay. We included 19 extremely preterm infants in the study and 74 samples were analyzed. The median gestational age was 26.0 weeks, and the median birth weight was 858 g. Serum HRG levels showed a significant upward trend after birth (p < 0.001); median HRG concentrations at birth and at 2, 4, 6, and 8 weeks of age were 1.07, 1.11, 2.86, 6.05, and 7.49 µg/mL, respectively. Onset of BPD was not associated with differences in serum HRG levels. Further, the serum HRG levels increased significantly after birth in extremely preterm infants.

Neonatal sepsis and Kawasaki disease.

The purpose of this study is to clarify the relationship between neonatal sepsis and future development of Kawasaki disease (KD). We analyzed data from the National Hospital Organization Neonatal Intensive Care Unit (NHO-NICU) registry study in Japan. Participants in this study were children with a history of hospitalization in the NICU at the participating institutions from 2010 to 2014. A questionnaire was administered at age 3 years to obtain information about the patient's history of KD. There were 8275 infants who were eligible for this study. At 3 years of age, parents of 2161 children responded to the follow-up survey (follow-up rate, 26.1%). Multivariate logistic regression analysis adjusted for preterm birth, sex, use of antibiotics in the NICU, parity, and maternal smoking showed that children with neonatal sepsis were more likely to have a history of KD at 3 years of age (adjusted odds ratio [aOR]: 11.67, 95% confidence interval [CI]: 2.84-47.96). CONCLUSIONS: Among infants admitted to the NICU, neonatal sepsis might be associated with development of KD later in life. Further large studies are needed to elucidate the relationship between neonatal infections and KD development. WHAT IS KNOWN: • Preterm birth is known to be a risk factor for Kawasaki disease. •It is not yet known which factors related to preterm birth increase the risk of developing Kawasaki disease. WHAT IS NEW: •Neonatal sepsis is associated with an increased risk of subsequent development of Kawasaki disease. •Antibiotic use in the neonatal intensive care unit may also be an independent risk factor for subsequent development of Kawasaki disease.

Preterm birth and Kawasaki disease: a nationwide Japanese population-based study.

BACKGROUND: Previous studies showed that preterm birth increased the risk for hospital admissions in infancy and childhood due to some acute diseases. However, the risk of preterm children developing Kawasaki disease remains unknown. In the present study, we investigate whether preterm birth increased the morbidity of Kawasaki disease. METHODS: We included 36,885 (34,880 term and 2005 preterm) children born in 2010 in Japan. We examined the association between preterm birth and hospitalization due to Kawasaki disease using a large nationwide survey in Japan. RESULTS: In log-linear regression models that were adjusted for children's characteristics (sex, singleton birth, and parity), parental characteristics (maternal age, maternal smoking, paternal smoking, maternal education, and paternal income), and residential area, preterm infants were more likely to be hospitalized due to Kawasaki disease (adjusted risk ratio: 1·55, 95% confidence interval: 1.01-2.39). We then examined whether breastfeeding status modified the potential adverse effects of preterm birth on health outcome. Preterm infants with partial breastfeeding or formula feeding had a significantly higher risk of hospitalization due to Kawasaki disease compared with term infants with exclusive breastfeeding. CONCLUSIONS: Preterm infants were at a high risk for Kawasaki disease, and exclusive breastfeeding might prevent this disease among preterm infants. IMPACT: Previous studies showed that preterm birth increased the risk for hospital admissions in infancy and childhood due to some acute diseases, however, the risk of preterm children developing Kawasaki disease remains unknown. This Japanese large population-based study showed that preterm infants were at a high risk for Kawasaki disease for the first time. Furthermore, this study suggested that exclusively breastfeeding might prevent Kawasaki disease among preterm infants.

Cytomegalovirus-related sepsis-like syndrome in very premature infants in Japan.

BACKGROUND: Very premature infants are at high risk of developing a symptomatic postnatal cytomegalovirus (CMV) disease, such as CMV-related sepsis-like syndrome (CMV-SLS). To address the limited data regarding its clinical features, a nationwide survey of CMV-SLS was conducted. METHODS: A questionnaire regarding CMV status and the clinical outcomes of CMV-SLS was sent to centers with reported cases of CMV-SLS. RESULTS: Twelve CMV-SLS cases, nine confirmed and three probable cases, were reported during the 3-year survey period. The median gestational age and birthweight were 25 weeks and 547 g, respectively. At disease onset, the median age was 49 days, and the corrected age was 31 weeks. Untreated breast milk was given in four cases (33%), whereas frozen breast milk was given in nine (75%). No specific symptoms and laboratory data regarding CMV-SLS were found. CONCLUSIONS: Very premature infants developed CMV-SLS after 1 month of age. There are no symptoms and signs specific for the diagnosis of CMV-SLS, so CMV-SLS should be considered as a differential diagnosis for premature infants who have unexplained sepsis-like symptoms during the convalescent phase.

Sports participation and preterm birth: a nationwide birth cohort in Japan.

BACKGROUND: Children born preterm may be less physically active than children born term because of neurocognitive problems, reduced lung function, and poor physical fitness. We evaluated sports participation of children and adolescents who had been born preterm (<37 weeks) and early term (37-38 weeks) in 2001. METHODS: Data from a nationwide longitudinal survey (n = 47,015, including 2375 children born preterm) were analyzed. As indicators of sports participation, we used responses to questions about participation in sports clubs at 7 and 10 years old and in extracurricular school sports at 15 years old. RESULTS: Children born very preterm (25-31 weeks) and moderately to late preterm (32-36 weeks) were less likely to participate in sports clubs at 7, 10, and 15 years old than children born full term (39-41 weeks). Compared with children born full term, the adjusted risk ratios for participation in extracurricular school sports at 15 years old were 0.86 (95% confidence interval: 0.75-0.98) for children born very preterm, 0.92 (0.88-0.97) for children born moderately to late preterm, and 1.00 (0.98-1.02) for children born early term. CONCLUSIONS: Our findings suggest that preterm birth is associated with less participation in organized sports during childhood and adolescence than full-term birth. IMPACT: Research investigating associations between preterm birth and physical activity among children born in the 2000s is limited. This study shows that preterm birth was associated with less participation in organized sports during childhood and adolescence than full-term birth, especially in boys, and the participation in organized sports of children born preterm decreased as gestation shortened. During childhood, boys born early term were also less likely to participate in organized sports than boys born full term, suggesting a continuum with preterm births. These findings offer important additional insights into the limited evidence available for predicting future health outcomes for preterm infants.

Associations of Birth Weight for Gestational Age with Child Health and Neurodevelopment among Term Infants: A Nationwide Japanese Population-Based Study.

OBJECTIVE: To examine the association of specific Z-score categories of birth weight for gestational age with child health and neurodevelopment using a large nationwide survey in Japan, focusing on term infants. STUDY DESIGN: We included 36 321 children born in 2010. Hospitalization up to 66 months of age was used as an indicator of health status, and responses to questions about age-appropriate behaviors at 30 and 66 months of age were used to indicate neurobehavioral development. We conducted binomial log-linear regression analyses, controlling for child and parental variables. A restricted cubic spline function was used to model the relationship. RESULTS: Compared with children with birth weight appropriate for gestational age (-1.28 to 1.28 SDs of expected birthweight for gestational age), children who were small for gestational age (SGA) (<-1.28 SD) had higher risks of hospitalization and unfavorable neurobehavioral development, and the risks increased as SGA status became more severe. Compared with the appropriate for gestational age group, the adjusted risk ratios for hospitalization for all causes were 2.5 (95% CI, 1.7-3.6), 1.3 (95% CI, 1.1-1.6), and 1.1 (95% CI, 1.0-1.2) for children who were severely, moderately, and mildly SGA and 1.0 (95% CI, 0.9-1.1), 1.1 (95% CI, 0.9-1.2), and 1.4 (95% CI, 0.9-2.1) for children who were mildly, moderately, and severely large for gestational age, respectively. Severely large for gestational age children also had higher risks of unfavorable neurobehavioral development. These results were supported by spline analyses. CONCLUSIONS: Among term infants, the risks of unfavorable child health and neurodevelopment increased with the severity of SGA.

Catch-up growth and behavioral development among preterm, small-for-gestational-age children: A nationwide Japanese population-based study.

OBJECTIVE: To examine the relationship between the catch-up growth of preterm, SGA children and their behavioral development. METHODS: We analyzed data from a large Japanese, nationwide, population-based, longitudinal survey that started in 2001. We restricted the study participants to preterm children with information on height at 2 years of age (n = 1667). Catch-up growth for SGA infants was defined as achieving a height at 2 years of age above -2.0 standard deviations for chronological age. We then used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations of SGA/catch-up status with neurobehavioral development both at 5.5 and 8 years of age, adjusting for potential infant- and parent-related confounding factors. RESULTS: Twenty-six percent of preterm SGA infants failed to catch up. SGA children without catch-up growth were more likely to be unable to listen without fidgeting (OR 2.51, 95% CI: 1.06-5.93) and unable to focus on one task (OR 2.66, 95% CI: 1.09-6.48) compared with non-SGA children at 5.5 years of age. Furthermore, SGA children without catch-up growth were at significant risk for inattention at 8 years of age. CONCLUSIONS: SGA infants with poor postnatal growth were at risk for attention problems throughout preschool-age to school-age among preterm infants. Early detection and intervention for attention problems among these infants is warranted.

Associations of gestational age with child health and neurodevelopment among twins: A nationwide Japanese population-based study.

BACKGROUND: The prevalence of multiple births has recently increased. However, the association between gestational age and long-term morbidity among twins remains unclear. AIMS: To examine the association of gestational age with child health and neurological development in early childhood among twins. STUDY DESIGN: Population-based longitudinal study. SUBJECTS: We included 947 children from 479 pairs of twins with information on gestational age. OUTCOME MEASURES: Hospitalization was used as an indicator of physical health, and responses to questions about age-appropriate behaviors were used as an indicator of neurobehavioral development. We conducted binomial log-linear regression analyses, controlling for both child and maternal variables in the model. We accounted for correlations within the pairs with generalized estimating equations. RESULTS: The early term group (i.e., 37 to 38 weeks of gestation) had a lower risk of poor child health and unfavorable neurodevelopment compared with the full term group (≥39 weeks of gestation) and preterm group (<37 weeks of gestation). Compared with the early term group, the adjusted risk ratios for hospitalization for all causes during the period from 7 to 18 months of age was 2.2 (95% confidence interval: 1.3-3.8) for very preterm children (<32 weeks of gestation), 1.1 (0.8-1.6) for moderately and late preterm children (32 to 36 weeks of gestation), and 1.8 (1.0-3.2) for full term children. CONCLUSION: We observed a U-shaped association of gestational age with child health and neurodevelopment. The early term group had the lowest risk of poor outcomes among twins.

Physical fitness of non-disabled school-aged children born with extremely low birth weights.

BACKGROUND: The assessment of long-term outcomes in survivors born with extremely low birth weights (ELBWs) has become increasingly important. However, little has been reported on the physical fitness of non-disabled school-aged children born with ELBWs. AIMS: To assess the physical fitness of non-disabled school-aged children born with ELBWs. STUDY DESIGN: Retrospective cohort study. SUBJECTS: We analyzed 169 ELBW infants without cerebral palsy or intellectual disability (based on the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) Full Scale intelligence quotient (IQ) test < 70). OUTCOME MEASURES: Physical fitness was assessed using the grip strength, sit-up repetitions, sit & reach, side steps, standing long jump, and softball throw tests. T-scores were calculated using national survey data. RESULTS: The T-scores for the grip strength, sit-up repetitions, sit & reach, side steps, standing long jump, softball throw tests, and the overall T-score were 43.7 ±â€¯7.5, 44.2 ±â€¯10.5, 46.0 ±â€¯9.7, 40.9 ±â€¯8.0, 40.0 ±â€¯9.8, 42.4 ±â€¯8.1, and 42.9 ±â€¯5.5, respectively. After adjusting for other age-related factors, the height (SD score), WISC-III Performance IQ score, and percent predicted forced vital capacity (FVC) independently predicted the overall T-scores. Their standardized partial regression coefficients (ß) were 0.334 (p = 0.009), 0.190 (p = 0.022), and 0.187 (p = 0.032), respectively. CONCLUSIONS: Our cohort's physical fitness at approximately 8 years of age was significantly impaired compared to average Japanese children of the same age. Height, FVC, and Performance IQ independently predicted physical fitness, with height being the strongest predictor.