Inhaled nitric oxide therapy for preterm infants after 7 days of age: a scoping review protocol.

INTRODUCTION: Inhaled nitric oxide (iNO) use is recommended for persistent pulmonary hypertension of the newborn in term and late preterm infants. Recently, iNO therapy to prevent bronchopulmonary dysplasia (BPD) or rescue for hypoxic respiratory failure and pulmonary hypertension secondary to BPD has increasingly been used in preterm infants after 7 days of postnatal age (in the postacute phase), despite its off-label use. However, the initiation criteria of iNO therapy for preterm infants in the postacute phase are varied. The aim of this scoping review is to identify the clinical and/or echo findings at the initiation of iNO therapy in preterm infants in the postacute phase. METHODS AND ANALYSIS: We will search PubMed, Embase and the Japanese database 'Ichushi.' The following studies will be included in the review: randomised controlled trials, prospective/retrospective cohort studies, case-control studies and case series on iNO therapy for preterm infants in the postacute phase; studies published between January 2003 and August 2023; studies conducted in developed countries and studies written in English or Japanese. We will independently screen, extract and chart data using the population-concept-context framework following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. We will summarise the characteristics and findings of the included studies. ETHICS AND DISSEMINATION: Obtaining an institutional review board approval is not required because of the nature of this review. A final report of review findings will be published and disseminated through a peer-reviewed journal and presentation at relevant conferences. TRIAL REGISTRATION NUMBER: UMIN000051498.

Trends in Bronchopulmonary Dysplasia Among Extremely Preterm Infants in Japan, 2003-2016.

OBJECTIVE: To investigate recent trends in bronchopulmonary dysplasia (BPD) and its risk factors among extremely preterm infants. STUDY DESIGN: Demographic and clinical data were reviewed for 19 370 infants born at 22-27 weeks of gestation registered in the affiliated hospitals of the Neonatal Research Network of Japan between 2003 and 2016. We investigated the overall survival and prevalence of bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age and risk factors for developing BPD among the survivors. RESULTS: Among 19 370 infants, 2244 (11.6%) died by 36 weeks' postmenstrual age. The mortality rate decreased from 19.0% (99% CI, 15.7%-22.8%) in 2003 to 8.0% (99% CI, 6.2%-10.3%) in 2016. Among 17 126 survivors, BPD developed in 7792 (45.5%) infants, and its proportion significantly increased from 41.4% (99% CI, 36.5%-46.4%) in 2003 to 52.0% (99% CI, 48.2%-55.9%) in 2016. A multivariable analysis of the survivors showed a positive association of BPD with ≥4 weeks' supplemental oxygen or invasive ventilation, birth weight <750 g, small for gestational age, ≥4 weeks' noninvasive positive pressure ventilation, chorioamnionitis, <26 weeks' gestational age, <20 cases per year of center patient volume, or treated patent ductus arteriosus. Although the median duration of invasive ventilation was shortened, the proportions of factors associated adversely with BPD generally showed increasing trends over time. CONCLUSIONS: The mortality rate of extremely preterm infants has decreased, but the rate of BPD has increased in survivors between 2003 and 2016. Despite the decreasing duration of invasive ventilation over time, increasing rates of BPD suggest that differences in the patient population or other management strategies influence the development of BPD.

Longitudinal analysis of serum cystatin C for estimating the glomerular filtration rate in preterm infants.

BACKGROUND: Cystatin C (Cys-C) is a more sensitive marker of renal function than creatinine (Cre) in pediatric and adult populations. However, the reference values of serum Cys-C for estimating glomerular filtration rates (eGFRs) in premature infants during the first year of life have not been sufficiently studied. METHODS: In this prospective study, 481 blood samples were collected from 261 preterm infants with uncomplicated clinical courses during their first year of life. Infants were divided into three groups according to gestational age at birth: 27-30 weeks, 31-33 weeks, and 34-36 weeks. Serum Cys-C and Cre levels were measured at 6-30 days, 3-5 months, 7-9 months, and 12-14 months after birth and the eGFR was calculated using two previously published equations. RESULTS: The median serum Cys-C levels were 1.776, 1.248, 1.037, and 0.960 mg/L at the first, second, third, and fourth measurement time-point, respectively, with the value significantly decreasing with age up to 12-14 months. Cys-C levels were independent of gestational age and gender. In contrast to Cys-C, serum Cre values declined rapidly up to 3-5 months, then remained constant up to 12-14 months. Using the Cys-C-based equation, the eGFR significantly increased with increasing age until approximately 1 year after birth; however, no such trend was noted using the equation based on Cys-C + Cre. CONCLUSIONS: Reference ranges for Cys-C in premature infants decline gradually over the first year after birth. Cys-C appears to be a more reliable marker than Cre for estimating GFR in preterm infants.