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BackgroundInitial trials of lung-targeted budesonide (0.25 mg/kg) in surfactant to prevent bronchopulmonary dysplasia (BPD) in premature infants have shown benefit; however, the optimal safe dose is unknown.MethodsDose-escalation study of budesonide (0.025, 0.05, 0.10 mg/kg) in calfactatant in extremely low gestational age neonates (ELGANs) requiring intubation at 3-14 days. Tracheal aspirate (TA) cytokines, blood budesonide concentrations, and untargeted blood metabolomics were measured. Outcomes were compared with matched infants receiving surfactant in the Trial Of Late SURFactant (TOLSURF).ResultsTwenty-four infants with mean gestational age 25.0 weeks and 743 g birth weight requiring mechanical ventilation were enrolled at mean age 6 days. Budesonide was detected in the blood of all infants with a half-life of 3.4 h. Of 11 infants with elevated TA cytokine levels at baseline, treatment was associated with sustained decrease (mean 65%) at all three dosing levels. There were time- and dose-dependent decreases in blood cortisol concentrations and changes in total blood metabolites. Respiratory outcomes did not differ from the historic controls.ConclusionsBudesonide/surfactant had no clinical respiratory benefit at any dosing levels for intubated ELGANs. One-tenth the dose used in previous trials had minimal systemic metabolic effects and appeared effective for lung-targeted anti-inflammatory action.

ObjectiveTo evaluate the relationship between maternal self-reported race/ethnicity and persistent wheezing illness in former high-risk, extremely low gestational age newborns, and to quantify the contribution of socioeconomic, environmental, and biological factors on this relationship.Study designWe assessed persistent wheezing illness determined at 18-24 months corrected (for prematurity) age in survivors of a randomized trial. Parents/caregivers were surveyed for wheeze and inhaled asthma medication use quarterly to 12 months, and at 18 and 24 months. We used multivariable analysis to evaluate the relationship of maternal race to persistent wheezing illness, and identified mediators for this relationship via formal mediation analysis.ResultsOf 420 infants (25.2 ± 1.2 weeks of gestation and 714 ± 166 g at birth, 57% male, 34% maternal black race), 189 (45%) had persistent wheezing illness. After adjustment for gestational age, birth weight, and sex, infants of black mothers had increased odds of persistent wheeze compared with infants of nonblack mothers (OR = 2.9, 95% CI 1.9, 4.5). Only bronchopulmonary dysplasia, breast milk diet, and public insurance status were identified as mediators. In this model, the direct effect of race accounted for 69% of the relationship between maternal race and persistent wheeze, whereas breast milk diet, public insurance status, and bronchopulmonary dysplasia accounted for 8%, 12%, and 10%, respectively.ConclusionsAmong former high-risk extremely low gestational age newborns, infants of black mothers have increased odds of developing persistent wheeze. A substantial proportion of this effect is directly accounted for by race, which may reflect unmeasured environmental influences, and acquired and innate biological differences.Trial registrationClinicalTrials.gov: NCT01022580.

ObjectiveTo determine the effects of late surfactant on respiratory outcomes determined at 1-year corrected age in the Trial of Late Surfactant (TOLSURF), which randomized newborns of extremely low gestational age (≤28 weeks' gestational age) ventilated at 7-14 days to late surfactant and inhaled nitric oxide vs inhaled nitric oxide-alone (control).Study designCaregivers were surveyed in a double-blinded manner at 3, 6, 9, and 12 months' corrected age to collect information on respiratory resource use (infant medication use, home support, and hospitalization). Infants were classified for composite outcomes of pulmonary morbidity (no PM, determined in infants with no reported respiratory resource use) and persistent PM (determined in infants with any resource use in ≥3 surveys).ResultsInfants (n = 450, late surfactant n = 217, control n = 233) were 25.3 ± 1.2 weeks' gestation and 713 ± 164 g at birth. In the late surfactant group, fewer infants received home respiratory support than in the control group (35.8% vs 52.9%, relative benefit [RB] 1.28 [95% CI 1.07-1.55]). There was no benefit of late surfactant for No PM vs PM (RB 1.27; 95% CI 0.89-1.81) or no persistent PM vs persistent PM (RB 1.01; 95% CI 0.87-1.17). After adjustment for imbalances in baseline characteristics, relative benefit of late surfactant treatment increased: RB 1.40 (95% CI 0.89-1.80) for no PM and RB 1.24 (95% CI 1.08-1.42) for no persistent PM.ConclusionTreatment of newborns of extremely low gestational age with late surfactant in combination with inhaled nitric oxide decreased use of home respiratory support and may decrease persistent pulmonary morbidity.Trial registrationClinicalTrials.gov: NCT01022580.

Fluconazole is an effective agent for prophylaxis of invasive candidiasis in premature infants. The objective of this study was to characterize the population pharmacokinetics (PK) and dosing requirements of fluconazole in infants with birth weights of 2,000 ng/ml in 80% of simulated infants at week 1 and 59% at week 4 of treatment. Developmental changes in fluconazole clearance are best predicted by serum creatinine in this population. A twice-weekly dose of 6 mg/kg achieves appropriate levels for prevention of invasive candidiasis in extremely premature infants.

Patent ductus arteriosus (PDA) is a blood vessel that critically supports fetal circulation. The ductus naturally closes within a few days after birth. However, it can stay open in premature neonates for an extended period of time, which is associated with increased mortality and various co‐morbidities. Ibuprofen and indomethacin are currently the only 2 drugs approved for inducing PDA closure, but both have been associated with adverse renal and bleeding events. Clinical evidence suggests that combining acetaminophen (APAP) and ibuprofen treatments can decrease the need for surgical ligation. The objective of this study was to establish a disease–drug–trial model to characterize and predict PDA closure following single and combination drug therapy with ibuprofen and/or APAP in children at less than 29 weeks of gestation. The model was informed by a comprehensive literature review. The results of our analysis suggest that ibuprofen and APAP achieve therapeutic synergy. They further suggest that the younger the preterm neonates, the higher the treatment benefit. A 5‐day oral dosing regimen consisting of ibuprofen (20 mg/kg Q24h on day 1, followed by 10 mg/kg Q24h on days 2‐5) plus APAP (15 mg/kg Q6h) was deemed appropriate to achieve at least 90% PDA in all preterm neonates evaluated within 1 month of life. The model can now be used to design prospective pediatric trials to evaluate optimal drug combinations for PDA closure in preterm neonates and to refine optimal dosing regimens in cohorts of differing gestational age. [ABSTRACT FROM AUTHOR]

ObjectiveTo assess whether late surfactant treatment in extremely low gestational age (GA) newborn infants requiring ventilation at 7-14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD).Study designExtremely low GA newborn infants (GA ≤28 0/7 weeks) who required mechanical ventilation at 7-14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide and either surfactant (calfactant/Infasurf) or sham instillation every 1-3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, as evaluated by physiological oxygen/flow reduction.ResultsA total of 511 infants were enrolled between January 2010 and September 2013. There were no differences between the treated and control groups in mean birth weight (701 ± 164 g), GA (25.2 ± 1.2 weeks), percentage born at GA

OBJECTIVES: The American Academy of Pediatrics National Registry for the Surveillance and Epidemiology Of Perinatal coronavirus disease 2019(COVID-19) (NPC-19) was developed to provide information on the Effects of perinatal severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) infection. METHODS: National Registry for the Surveillance and Epidemiology of Perinatal COVID-19 participating centers entered maternal and newborn data for pregnant persons who tested positive for SARS-CoV-2 infection between 14 days before and 10 days after delivery. Incidence of and morbidities associated with maternal and newborn SARS-CoV-2 infection were assessed. RESULTS: From April 6, 2020 to March 19, 2021, 242 centers in the United States centers reported data for 7524 pregnant persons; at the time of delivery, 78.1%of these persons were asymptomatic, 18.2% were symptomatic but not hospitalized specifically for COVID-19, 3.4%were hospitalized for COVID-19 treatment, and 18 (0.2%) died in the hospital of COVID-related complications. Among 7648 newborns, 6486 (84.8%) were tested for SARS-CoV-2, and 144 (2.2%) were positive; the highest rate of newborn infection was observed when mothers first tested positive in the immediate postpartum period (17 of 125, 13.6%). No newborn deaths were attributable to SARS-CoV-2 infection. Overall, 15.6% of newborns were preterm: among tested newborns, 30.1%of polymerase chain reaction positive and 16.2%of polymerase chain reaction-negative were born preterm (P< .001). Need for mechanical ventilation did not differ by newborn SARS-CoV-2 test result, but those with positive tests were more likely to be admitted to a NICU. CONCLUSIONS: Early in the pandemic, SARS-CoV-2 infection was acquired by newborns at variable rates And without apparent short-term effects. During a period that preceded widespread availability of vaccines, we observed higher than expected numbers of preterm births and maternal in-hospital deaths. [ABSTRACT FROM AUTHOR]

Timely access to appropriate health care from the prenatal period onward is one of several pillars essential to optimize the health of a child preparing to become an adult. In 1967, Congress passed legislation that specified an Early and Periodic Screening, Diagnostic and Treatment standard as the mandatory child health component of Medicaid. Subsequent legislative amendments have generally strengthened this standard. In particular, state Medicaid programs must provide any health care service for children that is covered by the federal Medicaid program even if the state does not cover that service for adults. An initial set of detailed recommendations concerning the best preventive care services for children, adolescents, and young adults was published in 1994 based on deliberations of a large group of expert pediatric health care providers and family representatives. The most recent updated recommendations are available in the 2017 fourth edition of Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents. The Patient Protection and Affordable Care Act of 2010 (Pub L No. 114-148) referenced Bright Futures recommendations as a standard for access to and design of age-appropriate health insurance benefits for neonates, infants, children, adolescents, and young adults. This policy statement summarizes recent developments pertaining to the scope of health care benefits offered for children by public and private payers. The statement identifies barriers that impede achievement of a uniform standard that all payers can adopt. Finally, the statement refreshes a recommended set of health insurance benefits for neonates, infants, children, adolescents, and young adults through age 26. [ABSTRACT FROM AUTHOR]

Through this policy statement, the American Academy of Pediatrics advocates that all health care insurers adopt consistent medical necessity definitions that reflect the needs of infants, children, adolescents, and young adults (hereafter noted as "children") as a function of developmental, epidemiologic, dependency, demographic, and cost-related factors that change over the pediatric continuum and that differ from adults. Optimally, the scope of benefits defined in health care contracts should address the complete spectrum of health care needs of children and families, but in reality, many plans offer a limited scope of benefits for children. Even if a proposed intervention falls within the scope of benefits or is not specifically excluded from coverage, the health plan may still deny the intervention. In such cases, contractual language may allow an appeal to succeed if the provider demonstrates medical necessity. With the assistance of experienced pediatric physicians and other providers with pediatric expertise, health care payers and agencies should clearly detail the processes that define, evaluate, and determine medical necessity and through which providers may appeal decisions. A basic requirement for any medical necessity process is the consideration of input from the physician(s) caring for a pediatric patient for whom a medical necessity determination is necessary. [ABSTRACT FROM AUTHOR]

Objective  The study aimed to evaluate the efficacy of dual medication therapy (DMT) with oral acetaminophen and oral ibuprofen for the closure of a hemodynamically significant patent ductus arteriosus (hsPDA). Study Design  In a prospective case–control cohort study (July 2017–May 2019), infants <29 weeks' gestational age and birth weight <1,000 g at ≤14 postnatal days with hsPDA and ratio of the smallest ductal diameter to the ostium of the left pulmonary artery diameter >0.5 were eligible. Infants received 10 mg/kg oral ibuprofen followed by two additional doses of 5 mg/kg at 24 and 48 hours after the initial ibuprofen dose and concomitant treatment with 15 mg/kg oral acetaminophen every 6 hours for 3 days (12 doses). Success of PDA treatment was defined as a small or absent PDA as ascertained by echocardiographic measurements. The p -values of comparisons were adjusted for multiple comparisons to preserve an error rate of 5%. Results  Overall, 20 infants received oral DMT and 11 infants received intravenous single medication therapy (SMT) with ibuprofen. The rates of successful PDA treatment following the first treatment in DMT and SMT groups were not statistically different (11/20 [55%] vs. 4/11 [36%], p  = 0.46). However, DMT significantly decreased PDA size (mean difference = 0.54 mm, 95% confidence interval [CI]: 0.21–0.96, adjusted p -value = 0.0002) and PDA/LPA ratio (mean difference = 0.27, 95% CI: 0.10–0.47, adjusted p -value = 0.0004). We observed no evidence of hematologic, hepatic, or renal impairment. Conclusion  DMT achieved a greater degree of PDA closure than SMT and did not result in abnormalities in hepatic and renal profile. Key Points No consensus on optimal medication for PDA treatment is available. Dual oral medication therapy (ibuprofen and acetaminophen) could be an effective alternative treatment for PDA. Dual oral medication therapy (ibuprofen and acetaminophen) may have a better safety profile than currently approved medications such as intravenous indomethacin and intravenous ibuprofen. [ABSTRACT FROM AUTHOR]

An editorial is presented on the preterm infant born to a mother with an acute severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2) infection presenting with features similar to multisystem inflammatory syndrome in children. It expresses various case reports on neonatal COVID-19 focusing on controversies in the diagnosis of MIS-C in the neonatal period. An overview of the Infection with SARS-CoV-2 initiates a cell-mediated and humoral immune response is presented.