Long QT and Hearing Loss in High-Risk Infants Prospective Study Registry.

The objective of this study is to determine the prevalence of an abnormal electrocardiogram showing a prolonged QTc greater than 450 ms in infants with unilateral or bilateral sensorineural hearing loss. We conducted a prospective study of healthy term infants (≥37 weeks gestational age) who failed their newborn auditory brainstem response hearing screen, were seen by an audiologist and diagnosed as having sensorineural hearing loss during follow-up to 1 year of age. In infants with a diagnosis of hearing loss, we collected a detailed family history and performed an ECG between 2 and 6 months of age. We obtained follow-up for 1 year by calling the parent requesting the hearing and cardiac status of their child. Two of the 40 infants with sensorineural hearing loss (5%) had a QTc greater than 450 ms. Both had mild bilateral hearing loss and genetic testing did not identify a known mutation for long QT syndrome. The remaining 38 infants had QTc intervals of ≤ 450 ms. One patient diagnosed with bilateral severe sensorineural hearing loss had a normal ECG (QTc = 417 ms). Several months after the ECG was performed, the infant's mother contacted the study cardiologist after she learned that the infant's maternal grandmother was diagnosed with a cardiomyopathy and arrhythmias. Genetic testing was recommended even though the child was asymptomatic and was positive for a pathogenic mutation in the KCNQ1 gene. We speculate that molecular genetic testing in infants with hearing loss may become the standard of care rather than targeted electrocardiograms.Clinical Trial Registration NCT02082431 https://www.clinicaltrials.gov/ct2/show/NCT02692521?cond=NCT02692521&rank=1 .

Low Rate of Spontaneous Closure in Premature Infants Discharged with a Patent Ductus Arteriosus: A Multicenter Prospective Study.

OBJECTIVES: To assess the rate of spontaneous closure and the incidence of adverse events in infants discharged home with a patent ductus arteriosus. STUDY DESIGN: In a prospective multicenter study, we enrolled 201 premature infants (gestational age of 23-32 weeks at birth) discharged home with a persistently patent ductus arteriosus (PDA) and followed their PDA status at 6-month intervals through 18 months of age. The primary study outcome was the rate and timing of spontaneous ductal closure. Secondary outcomes included rate of assisted closure and the incidence of serious adverse events. RESULTS: Spontaneous ductal closure occurred in 95 infants (47%) at 12 months and 117 infants (58%) by 18 months. Seventeen infants (8.4%) received assisted closure with surgical ligation or device assisted occlusion. Three infants died (1.5%). Although infants with spontaneous closure had a higher mean birth weight and gestational age compared with infants with a persistent PDA or assisted closure, we did not identify other factors predictive of spontaneous closure. CONCLUSIONS: Spontaneous closure of the PDA occurred in slightly less than one-half of premature infants discharged with a patent ductus by 1 year, lower than prior published reports. The high rate of assisted closure and/or adverse events in this population warrants close surveillance following discharge. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02750228.

Longitudinal Survey of COVID-19 Burden and Related Policies in U.S. Neonatal Intensive Care Units.

OBJECTIVE: This study aimed to determine the prevalence of confirmed novel coronavirus disease 2019 (COVID-19) disease or infants under investigation among a cohort of U.S. neonatal intensive care units (NICUs). Secondarily, to evaluate hospital policies regarding maternal COVID-19 screening and related to those infants born to mothers under investigation or confirmed to have COVID-19. STUDY DESIGN: Serial cross-sectional surveys of MEDNAX-affiliated NICUs from March 26 to April 3, April 8 to April 19, May 4 to May 22, and July 13 to August 2, 2020. The surveys included questions regarding COVID-19 patient burden and policies regarding infant separation, feeding practices, and universal maternal screening. RESULTS: Among 386 MEDNAX-affiliated NICUs, responses were received from 153 (42%), 160 (44%), 165 (45%), 148 (38%) across four rounds representing an active patient census of 3,465, 3,486, 3,452, and 3,442 NICU admitted patients on the day of survey completion. Confirmed COVID-19 disease in NICU admitted infants was rare, with the prevalence rising from 0.03 (1 patient) to 0.44% (15 patients) across the four survey rounds, while the prevalence of patients under investigation increased from 0.8 to 2.6%. Hospitals isolating infants from COVID-19-positive mothers fell from 46 to 20% between the second and fourth surveys, while centers permitting direct maternal breastfeeding increased 17 to 47% over the same period. Centers reporting universal severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) screening for all expectant mothers increased from 52 to 69%. CONCLUSION: Among a large cohort of NICU infants, the prevalence of infants under investigation or with confirmed neonatal COVID-19 disease was low. Policies regarding universal maternal screening for SARS-CoV-2, infant isolation from positive mothers, and direct maternal breastfeeding for infants born to positive mothers are rapidly evolving. As universal maternal screening for SARS-CoV-2 becomes more common, the impact of these policies requires further investigation. KEY POINTS: · In this cohort, neonatal COVID-19 is rare.. · Policies regarding isolation and breastfeeding for infants are rapidly evolving.. · Most hospitals are now providing universal screening for expectant mothers for SARS-CoV-2..

Two-Year Outcomes of Infants with Stage 2 or Higher Retinopathy of Prematurity: Results from a Large Multicenter Registry.

OBJECTIVE: To define the incidence of ophthalmologic morbidities in the first 2 years of life among infants diagnosed with stage 2 or higher retinopathy of prematurity (ROP). STUDY DESIGN: We prospectively enrolled premature infants with stage 2 or higher ROP. The infants were followed up for 2 years, and we report on data collected from outpatient ophthalmology and primary care visits. RESULTS: We enrolled 323 infants who met inclusion criteria, of which 112 (35%) received treatment with laser surgery (90) or bevacizumab (22). Two-year follow-up was available for 292 (90%) of the cohort. The most common ophthalmologic conditions at follow-up were hyperopia (35%), astigmatism (30%), strabismus (21.9%), myopia (19.2%), anisometropia (12%), and amblyopia (12%). Severe ophthalmologic morbidities such as retinal detachment and cataracts were rare, but occurred in both treated and untreated infants. Overall, 22.6% of the infants were wearing glasses at 2 years, including 8.5% of the untreated infants. CONCLUSION: Patients with stage 2 or higher ROP remain at significant risk for ophthalmological morbidity through 2 years of age. Infants with regression of subthreshold ROP who do not require treatment represent an underrecognized population at long-term ophthalmological risk. CLINICALTRIALS. GOV IDENTIFIER: NCT01559571.

The impact of altitude on screening for critical congenital heart disease.

OBJECTIVES: The objectives were to determine the frequency with which pulse oximetry identifies critical congenital heart defects in asymptomatic full-term and late preterm newborns using the AAP expert panel algorithm in a variety of different hospital settings and to evaluate the impact of altitude on the rate of positive screens. METHODS: We conducted a prospective clinical study of implementation of a newborn pulse oximetry screening for congenital heart disease in 34 independent hospitals. Infants were eligible for enrollment if their gestational age was 35-44 weeks. RESULTS: Of the 34 sites which enrolled infants into our study, 24 were located at or below 2000 feet; 5 were located between 4700 and 6000 feet and 5 were located above 6000 feet in altitude. We screened 6109 infants; 65 (1.1%) had a positive screen. There were no differences in median gestational age, birth weight, mode of delivery or race/ethnicity for infants with a positive screen compared to infants with a negative screen. Infants with positive screens were more often male and more often born at sites located at high altitudes. The frequency of a positive screen increased from 0.2% for infants born at sites at or less than 2000 feet to 6% for sites located above 6000 feet. We stopped enrollment at the site located at 8163 feet after enrolling 65 infants because 23 (35%) were positive. CONCLUSIONS: Screening infants for critical cardiac defects at altitude is complicated by the increased false positive screens.

Etiologies of NICU deaths.

BACKGROUND AND OBJECTIVES: Infant mortality is an indicator of overall societal health, and a significant proportion of infant deaths occur in NICUs. The objectives were to identify causes of death and to define potentially preventable factors associated with death as areas for quality improvement efforts in the NICU. METHODS: In a prospectively defined study, the principal investigator in 46 level III NICUs agreed to review health care records of infants who died. For each infant, the principal investigator reviewed the medical record to identify the primary cause of death and to look for preventable factors associated with the infant's death. Infants born at ≥22 weeks estimated gestational age who were born alive were included. Stillborn infants were excluded. RESULTS: Data were collected on 641 infants who died. At lower gestational ages, mortality was most commonly due to extreme prematurity and the complications of premature birth (respiratory distress progressing to respiratory failure, intraventricular hemorrhage, necrotizing enterocolitis, and sepsis). With increasing gestational age, the etiology of mortality shifted to hypoxic-ischemic encephalopathy and genetic or structural anomalies. Reviewers of clinical care identified 197 (31%) infants with potentially modifiable factors that may have contributed to their deaths. CONCLUSIONS: The factors associated with death in infants admitted for intensive care are multifactorial and diverse, and they change with gestational age. In 31% of the deaths, potentially modifiable factors were identified, and these factors suggest important targets for reducing infant mortality.

Gestational age and age at sampling influence metabolic profiles in premature infants.

OBJECTIVE: To describe the influence that gestational age and chronological age have on amino acid and acylcarnitine profiles in an at-risk population of premature infants. METHODS: Metabolic profiles (15 amino acids and 35 acylcarnitines) were obtained by using standard newborn techniques on infants born between 23 and 31 completed weeks of gestation. The profiles were drawn within the first 24 hours after birth and on approximately days 7, 28, and 42 of life or at discharge. A single, central, contract laboratory analyzed and managed the samples. RESULTS: We studied 995 patients; none was subsequently diagnosed with an inborn error of metabolism. Of the 3579 samples, there were 257 (7.2%) amino acid or acylcarnitine alerts reported in 214 infants (21.5% of infants studied). Both gestational age and postbirth chronological age significantly influenced the metabolic profile. Twenty-nine percent of infants at 23 to 26 weeks' gestational age had an abnormal metabolic profile compared with 17% of infants at 29 to 31 weeks' gestational age (P < .01). On the day of birth, 12% of the profiles were abnormal compared with 2% on day 28 (P < .01). The highest rate of abnormal values occurred on day 7 in the infants 23 to 26 weeks' gestational age (21%). CONCLUSIONS: These results demonstrate the complexity of understanding the impact of immaturity and disease on metabolic profiles used to screen for inborn errors of metabolism. Our data provide reference values for studies aimed at better understanding metabolism in preterm infants.

Utility of genetic testing for the detection of late-onset hearing loss in neonates.

PURPOSE: The purpose of this study was to demonstrate the utility of molecular testing in the detection of potentially important causes of delayed hearing loss missed by current audiometric screening at birth. METHOD: We enrolled infants who had received a newborn audiometric hearing screen and a filter paper blood collection for state newborn screening. A central laboratory ran the SoundGene® panel. RESULTS: Of 3,681 infants studied, 35 (0.95%) had a positive SoundGene panel, 16 had mitochondrial mutations, 9 had Pendred mutations, 5 were cytomegalovirus (CMV) DNA positive, 2 had connexin mutations, and 3 had a combination of different mutations. Infants with an abnormal SoundGene panel were at increased risk for hearing loss compared to neonates without mutations. Three (8.6%) of the 35 subjects had persistent hearing loss compared to 5 (0.21%) of 2,398 subjects with no report of mutation (p < .01). Of 3,681 infants studied, 8 (0.22%) had persistent hearing loss: 5 (62.5%) had abnormal newborn audiometric screens, 2 (25%) had an abnormal SoundGene panel (1 was CMV positive, 1 had a mitochondrial mutation), and 1 (12.5%) had no identifiable risk factors. CONCLUSION: A positive SoundGene panel identifies infants who are not identified by audiometric testing and may be at risk for hearing loss.

Complex multifactorial nature of significant hyperbilirubinemia in neonates.

OBJECTIVE: To determine whether glucose-6-phosphate dehydrogenase (G6PD), uridine-diphosphoglucuronosyltransferase 1A1 (UGT1A1), and hepatic solute carrier organic anion transporter 1B1 (SLCO1B1) gene variants occur at greater frequency in neonates with significant hyperbilirubinemia. METHODS: Infants with gestational ages of >or=37 weeks and ages of <7 days were studied. Case subjects had >or=1 bilirubin level above the 95th percentile (high-risk zone), whereas control subjects had bilirubin levels of <40th percentile (low-risk zone) at study entry. RESULTS: A total of 153 case subjects (median bilirubin level: 15.7 mg/dL) and 299 control subjects (median bilirubin level: 4.6 mg/dL) were evaluated. There were no statistical differences in the frequencies of G6PD, UGT1A1, and SCLO1B1 gene variants between case and control subjects (G6PD: 5.2% vs 3.3%; UGT1A1: 14.4% vs 9.4%; SLCO1B1: 73.2% vs 73.6%). However, coexpression of the G6PD African A- mutation with UGT1A1 and/or SLCO1B1 variants was seen more frequently for case subjects. Case subjects more often demonstrated >or=2 factors contributing to hyperbilirubinemia, including ABO blood group heterospecificity in which the mother had blood group O (47.7% vs 11.4%), positive direct Coombs test results (33.3% vs 4%), sibling treated with phototherapy (16.3% vs 5.4%), maternal circulating blood group antibodies (10.5 vs 0.7%), maternal diabetes mellitus (13.1% vs 6.4%), and maternal East Asian ethnicity (6.5% vs 1.3%). CONCLUSIONS: Clinical contributors to hyperbilirubinemia were identified more frequently for case subjects but individually G6PD, UGT1A1, and SLCO1B1 variants were not. Coexpression of the G6PD African A- mutation with UGT1A1 and SLCO1B1 variants was seen more often for case subjects.