Auditory toxicity in late preterm and term neonates with severe jaundice.

AIM: Jaundice may cause auditory toxicity (auditory neuropathy and hearing loss). However, total serum bilirubin (TSB) does not discriminate neonates at risk for auditory toxicity. We compared TSB, bilirubin:albumin molar ratio (BAMR), and unbound bilirubin for their association with auditory toxicity in neonates with severe jaundice (TSB ≥342µmol/L, or that met exchange transfusion). METHOD: Neonates greater or equal to 34 weeks gestational age with severe jaundice during the first 2 postnatal weeks were eligible for prospective cohort study, unless they had craniofacial malformations, chromosomal disorders, toxoplasmosis, other infections, rubella, cytomegalovirus, herpes simplex infections, surgery, or family history of congenital deafness. RESULTS: Twenty-eight out of 100 neonates (mean gestational age 37.4wks; 59 males, 41 females) had auditory toxicity. Peak unbound bilirubin, but not peak TSB and BAMR, was associated with auditory toxicity (p<0.05) in neonates with severe (TSB <427.5µmol/L) and extreme hyperbilirubinemia (TSB ≥427.5µmol/L). Area under the receiver operating characteristic curve for unbound bilirubin (0.78) was significantly greater (p=0.03) than TSB (0.54) among neonates with severe but not extreme hyperbilirubinemia. INTERPRETATION: Unbound bilirubin is more strongly associated with auditory toxicity than TSB and/or BAMR in greater or equal to 34 weeks gestational age neonates with severe jaundice. Unbound bilirubin is a better predictor than TSB in neonates with severe hyperbilirubinemia.

Unbound Bilirubin and Auditory Neuropathy Spectrum Disorder in Late Preterm and Term Infants with Severe Jaundice.

OBJECTIVE: This study evaluates whether unbound bilirubin is a better predictor of auditory neuropathy spectrum disorder (ANSD) than total serum bilirubin (TSB) or the bilirubin:albumin molar ratio (BAMR) in late preterm and term neonates with severe jaundice (TSB ≥20 mg/dL or TSB that met exchange transfusion criteria). STUDY DESIGN: Infants ≥34 weeks' gestation with severe jaundice during the first 2 weeks of life were eligible for the prospective observational study. A comprehensive auditory evaluation was performed within 72 hours of peak TSB. ANSD was defined as absent or abnormal auditory brainstem evoked response waveform morphology at 80-decibel click intensity in the presence of normal outer hair cell function. TSB, serum albumin, and unbound bilirubin were measured using the colorimetric, bromocresol green, and modified peroxidase method, respectively. RESULTS: Five of 44 infants developed ANSD. By logistic regression, peak unbound bilirubin but not peak TSB or peak BAMR was associated with ANSD (OR, 4.6; 95% CI, 1.6-13.5; P = .002). On comparing receiver operating characteristic curves, the area under the curve for unbound bilirubin (0.92) was significantly greater (P = .04) compared with the area under the curve for TSB (0.50) or BAMR (0.62). CONCLUSIONS: Unbound bilirubin is a more sensitive and specific predictor of ANSD than TSB or BAMR in late preterm and term infants with severe jaundice.

Target ranges of oxygen saturation in extremely preterm infants.

BACKGROUND: Previous studies have suggested that the incidence of retinopathy is lower in preterm infants with exposure to reduced levels of oxygenation than in those exposed to higher levels of oxygenation. However, it is unclear what range of oxygen saturation is appropriate to minimize retinopathy without increasing adverse outcomes. METHODS: We performed a randomized trial with a 2-by-2 factorial design to compare target ranges of oxygen saturation of 85 to 89% or 91 to 95% among 1316 infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. The primary outcome was a composite of severe retinopathy of prematurity (defined as the presence of threshold retinopathy, the need for surgical ophthalmologic intervention, or the use of bevacizumab), death before discharge from the hospital, or both. All infants were also randomly assigned to continuous positive airway pressure or intubation and surfactant. RESULTS: The rates of severe retinopathy or death did not differ significantly between the lower-oxygen-saturation group and the higher-oxygen-saturation group (28.3% and 32.1%, respectively; relative risk with lower oxygen saturation, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P=0.21). Death before discharge occurred more frequently in the lower-oxygen-saturation group (in 19.9% of infants vs. 16.2%; relative risk, 1.27; 95% CI, 1.01 to 1.60; P=0.04), whereas severe retinopathy among survivors occurred less often in this group (8.6% vs. 17.9%; relative risk, 0.52; 95% CI, 0.37 to 0.73; P<0.001). There were no significant differences in the rates of other adverse events. CONCLUSIONS: A lower target range of oxygenation (85 to 89%), as compared with a higher range (91 to 95%), did not significantly decrease the composite outcome of severe retinopathy or death, but it resulted in an increase in mortality and a substantial decrease in severe retinopathy among survivors. The increase in mortality is a major concern, since a lower target range of oxygen saturation is increasingly being advocated to prevent retinopathy of prematurity. (ClinicalTrials.gov number, NCT00233324.)

Early CPAP versus surfactant in extremely preterm infants.

BACKGROUND: There are limited data to inform the choice between early treatment with continuous positive airway pressure (CPAP) and early surfactant treatment as the initial support for extremely-low-birth-weight infants. METHODS: We performed a randomized, multicenter trial, with a 2-by-2 factorial design, involving infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. Infants were randomly assigned to intubation and surfactant treatment (within 1 hour after birth) or to CPAP treatment initiated in the delivery room, with subsequent use of a protocol-driven limited ventilation strategy. Infants were also randomly assigned to one of two target ranges of oxygen saturation. The primary outcome was death or bronchopulmonary dysplasia as defined by the requirement for supplemental oxygen at 36 weeks (with an attempt at withdrawal of supplemental oxygen in neonates who were receiving less than 30% oxygen). RESULTS: A total of 1316 infants were enrolled in the study. The rates of the primary outcome did not differ significantly between the CPAP group and the surfactant group (47.8% and 51.0%, respectively; relative risk with CPAP, 0.95; 95% confidence interval [CI], 0.85 to 1.05) after adjustment for gestational age, center, and familial clustering. The results were similar when bronchopulmonary dysplasia was defined according to the need for any supplemental oxygen at 36 weeks (rates of primary outcome, 48.7% and 54.1%, respectively; relative risk with CPAP, 0.91; 95% CI, 0.83 to 1.01). Infants who received CPAP treatment, as compared with infants who received surfactant treatment, less frequently required intubation or postnatal corticosteroids for bronchopulmonary dysplasia (P<0.001), required fewer days of mechanical ventilation (P=0.03), and were more likely to be alive and free from the need for mechanical ventilation by day 7 (P=0.01). The rates of other adverse neonatal outcomes did not differ significantly between the two groups. CONCLUSIONS: The results of this study support consideration of CPAP as an alternative to intubation and surfactant in preterm infants. (ClinicalTrials.gov number, NCT00233324.)

An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products.

OBJECTIVE: To evaluate the health benefits of an exclusively human milk-based diet compared with a diet of both human milk and bovine milk-based products in extremely premature infants. STUDY DESIGN: Infants fed their own mothers' milk were randomized to 1 of 3 study groups. Groups HM100 and HM40 received pasteurized donor human milk-based human milk fortifier when the enteral intake was 100 and 40 mL/kg/d, respectively, and both groups received pasteurized donor human milk if no mother's milk was available. Group BOV received bovine milk-based human milk fortifier when the enteral intake was 100 mL/kg/d and preterm formula if no mother's milk was available. Outcomes included duration of parenteral nutrition, morbidity, and growth. RESULTS: The 3 groups (total n = 207 infants) had similar baseline demographic variables, duration of parenteral nutrition, rates of late-onset sepsis, and growth. The groups receiving an exclusively human milk diet had significantly lower rates of necrotizing enterocolitis (NEC; P = .02) and NEC requiring surgical intervention (P = .007). CONCLUSIONS: For extremely premature infants, an exclusively human milk-based diet is associated with significantly lower rates of NEC and surgical NEC when compared with a mother's milk-based diet that also includes bovine milk-based products.

Prenatal diagnosis of total arhinia associated with normal chromosomal analysis: a case report.

BACKGROUND: Complete, congenital arhinia is a rare condition characterized by total absence of the nose and generally associated with other facial anomalies, including absence of the underlying nasal structures and frontal sinuses. There have been 2 case reports of prenatal diagnosis of arhinia in the second and early third trimesters. To our knowledge, however, this is the first case of total arhinia suspected prenatally with an associated normal chromosomal microarray. CASE: A 20-year-old primigravida presented for her first obstetric ultrasound evaluation at 27 weeks' gestation. Ultrasound was limited by maternal habitus but revealed a flattened midface with an abnormal profile. Repeat ultrasound at 38 weeks showed a flattened midface without a distinguishable fetal nose. The diagnosis of complete arhinia was confirmed at delivery. Chromosomal analysis revealed a 46,XX karyotype, with normal 500K SNP microarray. CONCLUSION: This report reviews both the diagnosis of arhinia and the associated neonatal care and outcome. Arhinia should be considered when the fetal profile appears to have a flattened midface and a prominent upper lip. Diagnosis may be aided by third or fourth ultrasound imaging. Due to neonatal airway issues, delivery with pediatric support available is recommended if the condition is suspected prenatally.

Chronic Auditory Toxicity in Late Preterm and Term Infants With Significant Hyperbilirubinemia.

BACKGROUND AND OBJECTIVES: Significant hyperbilirubinemia (SHB) may cause chronic auditory toxicity (auditory neuropathy spectrum disorder and/or sensorineural hearing loss); however, total serum bilirubin (TSB) does not discriminate neonates at risk for auditory toxicity. Our objective was to compare TSB, bilirubin albumin molar ratio (BAMR), and unbound bilirubin (UB) for their association with chronic auditory toxicity in neonates with SHB (TSB ≥20 mg/dL or TSB that met criteria for exchange transfusion). METHODS: Infants ≥34 weeks' gestational age (GA) with SHB during the first 2 postnatal weeks were eligible for a prospective longitudinal study in India. Comprehensive auditory evaluations were performed at 2 to 3 months of age by using auditory brainstem response, tympanometry, and an otoacoustic emission test and at 9 to 12 months of age by using audiometry. The evaluations were performed by an audiologist unaware of the degree of jaundice. RESULTS: A total of 93 out of 100 infants (mean GA of 37.4 weeks; 55 boys, 38 girls) who were enrolled with SHB were evaluated for auditory toxicity. Of those, 12 infants (13%) had auditory toxicity. On regression analysis controlling for covariates, peak UB (but not peak TSB or peak BAMR), was associated with auditory toxicity (odds ratio 2.41; 95% confidence interval: 1.43-4.07; P = .001). There was significant difference in the area under the receiver operating characteristic curves between UB (0.866), TSB (0.775), and BAMR (0.724) for auditory toxicity (P = .03) after controlling for covariates. CONCLUSIONS: Unconjugated hyperbilirubinemia indexed by UB (but not TSB or BAMR) is associated with chronic auditory toxicity in infants ≥34 weeks' GA with SHB.

Effect of dexamethasone therapy on serum vitamin E concentrations in premature infants with bronchopulmonary dysplasia.

OBJECTIVE: To investigate the effect of dexamethasone therapy on serum vitamin E concentrations in premature infants with bronchopulmonary dysplasia. STUDY DESIGN: A total of 10, 24 to 29 weeks' gestational age, infants enrolled in a prospective study designed to evaluate the effect of dexamethasone on lipid intolerance were eligible for the study. Eight of these 10 infants had serum vitamin E concentrations measured simultaneously with serum triglyceride concentrations before the start of dexamethasone therapy (baseline) and within 5 days of the initiation of dexamethasone therapy. Charts were reviewed for vitamin E intake at baseline and on dexamethasone therapy for each of these eight infants. RESULTS: All eight infants had physiological serum vitamin E concentrations (1 to 3 mg/dl) at baseline, while six of eight infants had pharmacological serum vitamin E concentrations (> or =3 mg/dl) on dexamethasone therapy. All infants with an increase in serum vitamin E concentration also had a simultaneous increase in serum triglyceride concentrations with a significant correlation between vitamin E and triglyceride concentrations (Spearman's rho=0.92). There was a significant difference in mean serum vitamin E concentration between baseline and post-dexamethasone therapy (P=0.01, Wilcoxon's signed-rank test). There was no significant difference in vitamin E intake between baseline and post-dexamethasone therapy. CONCLUSION: Dexamethasone therapy in premature infants induces significant increase in serum vitamin E concentrations to pharmacological levels independent of vitamin E intake.

Comparison of breast- and formula-fed normal newborns in time to first stool and urine.

BACKGROUND: Although the time to an infant's first stool is used as a marker for a normal GI tract, there have been no studies to date which have evaluated the contribution of the first 24 hours' feeding type to time to first meconium stool, directly comparing breast feeding vs formula feeding. OBJECTIVE: To compare breast- and formula-fed healthy infants > or =34 weeks gestation in time to first stool and urine. STUDY DESIGN: A chart review of 1000 consecutive infants > or =34 weeks of gestational age admitted to the normal newborn nursery of Children's Hospital of Buffalo from June to October 2000. Infants (n=979) were grouped based on feeding type in the first 24 hours: breast-fed (n=211), formula-fed (n=540), and mixed feeding (n=228); n=21 excluded for Neonatal Intensive Care Unit admission. We initially compared the time to first stool and urine between the breast- and formula-fed groups and then examined multiple maternal and infant demographic and clinical factors for their effect on time to first stool using univariate and multivariate analyses. RESULTS: Breast-fed infants were fed earlier and more frequently than formula-fed but there was no significant difference in time to first stool (7.6 vs 7.9 hours). Breast-fed infants were earlier in time to first urine (p=0.03) (7.3 vs 8.5 hours). In multiple regression analysis, gestational age was the only significant (p=0.000) factor in predicting time to first stool. CONCLUSION: Type of feeding did not predict time to first stool but gestational age was important even in this near-term and term population of infants > or =34 weeks gestation.

The religious and cultural bases for breastfeeding practices among the Hindus.

In Hindu communities, breastfeeding is nearly universal and continues for most children beyond infancy. This review examines the religious and cultural basis for the contemporary breastfeeding practices amongst the Hindu. Practices at the time of birth and feeding rituals like prelacteal feeds, importance and timing of complementary feeds, and protections for the breastfeeding mother are examined from the published medical literature and available religious texts. Hindu Vedic literature and ancient ayurvedic texts underscore the importance of breastfeeding in the Hindu society. Although almost every Hindu child gets some breastfeeding, exclusive breastfeeding for the recommended duration and early initiation of breastfeeding are not that common. As birth of a baby is a celebration for family and society, breastfeeding is strongly influenced by cultural and religious ceremonies. In today's context, although women may receive guidance from health care professionals, relatives--especially grandmothers--have an important influence on breastfeeding practices.