Effect of chest shielding during phototherapy for hyperbilirubinemia on symptomatic patent ductus arteriosus - a double-blind randomized placebo-controlled trial.

BACKGROUND: Meta-analysis of randomized trials suggests that phototherapy is associated with patent ductus arteriosus (PDA). We hypothesized that chest shielding during phototherapy would decrease the incidence of symptomatic PDA (sPDA) compared to sham shielding. METHODS: A single center, double-blind, randomized, placebo-controlled trial was performed to evaluate the effect of chest shielding during phototherapy on sPDA in infants ≤ 29 weeks gestational age (GA) or with birth weight (BW) ≤ 1000 g. Infants were randomized to either chest shield (with aluminum foil, intervention group) or sham shield (without aluminum foil, control group) during phototherapy. The primary outcome was sPDA during the period 24 h after phototherapy initiation until 3 days after phototherapy cessation. RESULTS: 160 infants were randomized with 10 infants withdrawn from each group due to shield placement after phototherapy initiation. Of 140 infants analyzed, the mean GA and BW was 26.6 weeks and 872 g, respectively. There was no difference in the incidence of sPDA between the intervention (n = 70) and control group (n = 70) (10% vs 11%, respectively, adjusted odds ratio 0.78, 95% CI:0.33-1.82; p = 0.57). CONCLUSIONS: Chest shielding during phototherapy had no effect on sPDA in infants ≤ 29 weeks GA or with BW ≤ 1000 g. TRIAL REGISTRATION: http://clinicaltrials.gov , Identifier: NCT02552927. IMPACT: Meta-analysis of randomized clinical trials suggests that chest shielding during phototherapy used for hyperbilirubinemia may decrease the incidence of patent ductus arteriosus. The effect of chest shielding during phototherapy on symptomatic patent ductus arteriosus has not been evaluated in a double-blind randomized trial. In this double-blind, randomized, placebo-controlled trial, chest shielding during phototherapy was not associated with a decreased incidence of symptomatic patent ductus arteriosus in premature infants.

Unbound Bilirubin and Acute Bilirubin Encephalopathy in Infants Born Late Preterm and Term with Significant Hyperbilirubinemia.

OBJECTIVE: To compare the association of unbound bilirubin (UB), total serum bilirubin (TSB), and bilirubin:albumin molar ratio (BAMR) with acute bilirubin encephalopathy (ABE), as assessed by bilirubin-induced neurologic dysfunction (BIND) score, in infants with significant hyperbilirubinemia (TSB ≥20 mg/dL or underwent exchange transfusion). STUDY DESIGN: In this prospective cohort study, infants ≥34 weeks of gestational age with significant hyperbilirubinemia during the first 2 postnatal weeks were eligible, unless they had craniofacial malformations, chromosomal disorders, TORCH (toxoplasmosis, other infections, rubella, cytomegalovirus and herpes simplex) infections, surgery, or a family history of congenital deafness. TSB, serum albumin, and UB were measured at hospital admission using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Infants were evaluated on admission for ABE using a standardized neurologic examination and assigned a BIND score by trained physicians. Infants with a total BIND score of 0 were deemed to not have ABE, whereas those with a score ≥1 were deemed to have ABE. RESULTS: A total of 151 infants were studied, among whom 37 (24.5%) had ABE. Of these, 19 had mild ABE (BIND score 1-3) and 18 had moderate-to-severe ABE (BIND score 4-9). On logistic regression, UB, but not TSB or BAMR, was associated with ABE (aOR 1.64; 95% CI 1.17-2.3). On ordered logistic regression, UB, but not TSB or BAMR, was associated with severity of ABE (aOR 1.76; 95% CI 1.28-2.4). CONCLUSIONS: Our findings of the association between UB and ABE indicate that BIND scoring may be useful for evaluation of ABE in infants ≥34 weeks of gestational age.

Bilirubin-Displacing Effect of Ceftriaxone in Infants With Unconjugated Hyperbilirubinemia Born at Term.

OBJECTIVE: To evaluate the effect of intravenous (IV) ceftriaxone on free bilirubin concentrations in infants with unconjugated hyperbilirubinemia born at term. STUDY DESIGN: A prospective study was performed with subjects serving as their own controls. Our inclusion criteria were infants born at term <7 days old with sepsis and receiving IV antibiotics for >3 days and resolving hyperbilirubinemia with total serum bilirubin levels between 6 and12 mg/dL by day 4 of life. Free bilirubin concentrations were measured by the peroxidase method using a UB analyzer and a Zone Fluidics device before (baseline) and 15 minutes after (follow-up) IV ceftriaxone administration on postnatal days 4 to 6. Paired measurements of free bilirubin were analyzed using a Student paired t-test or Wilcoxon signed-rank test. RESULTS: In total, 27 infants were studied. The mean free bilirubin (µg/dL) at follow-up was not different from that at baseline when measured by the UB analyzer (P = .78). The mean free bilirubin was significantly lower at follow-up compared with baseline when measured by the Zone Fluidics device (P = .02). The ratio of a free bilirubin with and without ceftriaxone, an index of displacing effect, was 1.02 (95% CI 0.89-1.14) using the UB analyzer and 0.58 (95% CI 0.30-0.86) using the Zone Fluidics device. CONCLUSIONS: Ceftriaxone is not associated with a bilirubin-displacing effect in infants with a mild unconjugated hyperbilirubinemia. Home therapy with once-daily intramuscular ceftriaxone may be an alternative option for management of sepsis in asymptomatic infants with a mild unconjugated hyperbilirubinemia born at term.

Soybean-Oil Lipid Minimization for Prevention of Intestinal Failure-Associated Liver Disease in Late-Preterm and Term Infants With Gastrointestinal Surgical Disorders.

BACKGROUND: Intestinal failure-associated liver disease (IFALD), a multifactorial disease, is common among infants with gastrointestinal surgical disorders (GISDs). Prolonged soy-based intravenous lipid emulsion (S-ILE) intake is associated with IFALD, but preventive studies of limiting S-ILE have been inconclusive. Furthermore, a double-blind, randomized preventive trial (DBRPT) of S-ILE intake has not been performed in infants with GISDs. Our objective was to compare the effect of 1 g/kg/d vs 2 g/kg/d S-ILE intake for 6 weeks on the incidence of IFALD and the rate of rise of direct bilirubin (DB) in infants with GISDs. METHODS: A DBRPT was conducted in infants with GISDs at ≥34 weeks' gestational age (GA) admitted to the NICU within 72 hours after birth. Infants were randomized in a 1:1 ratio to receive either 1 or 2 g/kg/d S-ILE for 6 weeks. IFALD was defined as DB ≥2 mg/dL. RESULTS: Forty infants were studied. The 2 groups had similar clinical characteristics except for GA and blood group incompatibility. Thirty percent of infants in each group developed IFALD (P = .94). However, infants in the group receiving 1 g/kg/d S-ILE (n = 20) had a lower rate of rise of DB compared with infants in the group receiving 2 g/kg/d S-ILE (n = 20). CONCLUSIONS: Reducing S-ILE intake for 6 weeks in infants with GISD at ≥34 weeks' GA may not prevent IFALD. The extrapolated data on the rate of rise of DB suggest a possible risk of earlier development of IFALD with S-ILE intake of 2 g/kg/d, as compared with 1 g/kg/d, beyond the 6-week study period.

Developmental influence of unconjugated hyperbilirubinemia and neurobehavioral disorders.

Bilirubin-induced brain injury in the neonatal period has detrimental effects on neurodevelopment that persist into childhood and adulthood, contributing to childhood developmental disorders. Unconjugated bilirubin is a potent antioxidant that may be useful for protecting against oxidative injuries, but it becomes a potent neurotoxin once it crosses the blood brain barrier. Because bilirubin toxicity involves a myriad of pathological mechanisms, can damage most types of brain cells, and affects brain circuits or loops that influence cognition, learning, behavior, sensory, and language, the clinical effects of bilirubin-induced neurotoxicity are likely to be manifold. One possible effect that several experts have identified is bilirubin-induced neurological dysfunction (subtle kernicterus). However, the underlying biological mechanisms or pathways by which subtle kernicterus could lead to developmental disorders has not been elucidated previously. Our aim in this review is to describe a spectrum of developmental disorders that may reflect subtle kernicterus and outline plausible biological mechanisms for this possible association. We review existing evidence that support or refute the association between unconjugated hyperbilirubinemia and developmental disorders, and limitations associated with these studies.

Copper Supplementation in Premature Infants With Parenteral Nutrition-Associated Cholestasis.

The aim of this study was to evaluate the effect of intermittent parenteral copper supplementation (IPC) on serum copper status and biochemical and hematological measures of copper toxicity and deficiency in premature infants with parenteral nutrition (PN)-associated cholestasis (PNAC). We performed a prospective nested observational study in premature infants with PNAC who received IPC after the development of PNAC. Infants with chromosomal disorders, TORCH (toxoplasmosis, parvovirus, syphilis, rubella, cytomegalovirus, herpes, human immunodeficiency virus) infection, metabolic disorder, and/or surgical abnormality of the hepatobiliary system were excluded. Serum copper concentrations were measured once every 2-4 weeks while receiving PN; 24 premature infants were studied. The mean gestational age (GA) of infants was 28.6 ± 4.7 weeks. On regression analysis, there was no significant association between IPC and serum copper concentration (coefficient 2.72, 95% CI: -27 to 32; P = .84) after controlling for GA, gender, and baseline copper intake before PNAC. There was no significant association of IPC with alanine and aspartate transaminases levels (hepatotoxicity) and platelet count, hematocrit, white blood cell count, and neutrophil count (measures of copper deficiency) after controlling for confounders. GA and postmenstrual age were independently and positively associated with serum copper concentration after controlling for confounders on regression analyses. Thus, IPC in premature infants with PNAC does not influence copper status and is not associated with biochemical and hematological measures of copper deficiency and/or toxicity. Serum copper concentration in premature infants with PNAC receiving IPC is determined by the degree of prematurity and postmenstrual age.

Bilirubin Albumin Binding and Unbound Unconjugated Hyperbilirubinemia in Premature Infants.

OBJECTIVE: To evaluate the associations between unbound bilirubin (UB) and total serum bilirubin (TSB), bilirubin:albumin molar ratio (BAMR), and bilirubin albumin binding affinity (Ka) as a function of gestational age (GA) in infants born at 24-33 weeks GA. STUDY DESIGN: In a prospective observational study, TSB and UB were measured twice daily at least 8 hours apart during the first postnatal week. Serum albumin was measured to calculate BAMR on each day. The highest UB on each day, corresponding TSB, and serum albumin were used to calculate the Ka on each day. RESULTS: For the 166 infants studied, peak UB significantly correlated with concomitant Ka (r = -0.44, P = .001) but not with concomitant TSB or BAMR after adjusting for GA. On multiple regression analyses, there was a significant association of concomitant Ka (-0.06, 95% CI -0.08 to -0.04, P = .0001), but not concomitant TSB or BAMR with peak UB after controlling for GA, birth weight, race, and sex. GA group was a significant effect modifier for the association between Ka and peak UB (0.03, 95% CI 0.02-0.04, P < .001). Interaction analyses showed the association between concomitant Ka and peak UB was significant for the 24-30 weeks GA group infants, but not for the 301/7-33 weeks GA group infants. CONCLUSIONS: Peak UB was primarily associated with a decrease in binding affinity in infants ≤30 weeks GA. Interventions aimed at improving binding affinity may be important in decreasing the risk of bilirubin-induced neurotoxicity.

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.

A Randomized Controlled Trial of Glycerin Suppositories During Phototherapy in Premature Neonates.

OBJECTIVE: To determine if glycerin suppositories were effective in reducing total duration of phototherapy in premature neonates. We hypothesized that glycerin suppositories would have no effect on phototherapy duration or total serum bilirubin levels. DESIGN: Prospective randomized controlled double-blinded trial. SETTING: Level IV NICU. PARTICIPANTS: Neonates born between 30 weeks, 0 days and 34 weeks, 6 days gestational age who developed physiologic hyperbilirubinemia needing phototherapy. METHODS: Neonates were randomized to the no-suppository group or to the suppository group. Neonates were randomized to receive glycerin suppositories every 8 hours while under phototherapy or to a sham group. The primary outcome was total hours of phototherapy. Secondary outcomes included peak total serum bilirubin levels, time from start to discontinuation of phototherapy, rate of decline in bilirubin levels, repeat episodes of phototherapy, and number of stools while the neonates received phototherapy. RESULTS: A total of 39 neonates were assigned to the no-suppository group and 40 to the suppository group. Withholding suppositories was not inferior to providing suppositories. The total hours of phototherapy were not longer (i.e., noninferior) among neonates not provided suppositories (61 ± 53 hours) than among those given suppositories (72 ± 49 hours). There were no differences in peak bilirubin levels, rate of bilirubin decline, or repeat episodes of phototherapy. CONCLUSION: Routine use of glycerin suppositories among preterm neonates who receive phototherapy does not affect bilirubin levels or phototherapy duration.

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.

Meta-Analysis of the Effect of Chest Shielding on Preventing Patent Ductus Arteriosus in Premature Infants.

Objective This study aims to perform a meta-analysis of randomized studies to evaluate if chest shielding during phototherapy is associated with decreased incidence of patent ductus arteriosus (PDA) in premature infants. Design/Methods We used published guidelines for the meta-analysis of clinical trials. The search strategy included electronic searches of CINAHL, CENTRAL Cochrane Library, MEDLINE, PubMed, and abstracts presented at the Pediatric Academic Societies. Inclusion criteria were randomized controlled trials (RCTs), quasi-RCTs or cluster RCTs published in English and involving chest shielding during phototherapy in premature infants with PDA as an outcome. Exclusion criteria involved case reports, case series, and multiple publications from the same author. Heterogeneity testing using Q statistics was performed to evaluate the variance between studies. Results Two RCTs met study criteria. There was heterogeneity (I2: 55.4%) between the two trials. Meta-analysis of RCTs using the random effect model demonstrated that chest shielding during phototherapy was associated with decreased incidence of PDA (odds ratio: 0.47, 95% confidence interval: 0.23-0.96). There was no publication bias on Eggers test. Heterogeneity was seen in gestational age, gender, prophylactic use of postnatal indomethacin, duration of phototherapy, and assessment of PDA. Conclusion Chest shielding during phototherapy may be associated with decreased incidence of PDA among premature infants.

Bilirubin Binding Capacity in the Preterm Neonate.

Total serum/plasma bilirubin (TB), the biochemical measure currently used to evaluate and manage hyperbilirubinemia, is not a useful predictor of bilirubin-induced neurotoxicity in premature infants. Altered bilirubin-albumin binding in premature infants limits the usefulness of TB in premature infants. In this article, bilirubin-albumin binding, a modifying factor for bilirubin-induced neurotoxicity, in premature infants is reviewed.

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.

Parenteral Nutrition-Associated Cholestasis in Premature Infants: Role of Macronutrients.

PURPOSE: To evaluate whether intravenous lipid (IL) intake is associated with the development of parenteral nutrition-associated cholestasis (PNAC) in infants younger than 32 weeks gestational age (GA). METHODS: A retrospective matched case-control study (1:1) was performed including infants younger than 32 weeks GA admitted to the neonatal intensive care unit within 48 hours after birth. Infants with a chromosomal disorder, TORCH infection (toxoplasmosis, syphilis, rubella, cytomegalovirus, herpes, human immunodeficiency virus, and parvovirus), metabolic disorder, and/or surgical abnormality of the hepatobiliary system were excluded. Infants with PNAC (direct bilirubin 2 mg/dL or higher) comprised the case group, while infants without PNAC comprised the control group. Duration of parenteral nutrition, intravenous fluid intake on the day of development of PNAC, and GA were used as matching criteria. RESULTS: A total of 46 subjects were studied. Daily average intravenous dextrose (ID) intake was significantly higher in infants with PNAC compared with infants without PNAC (12.72 ± 2.5 g/kg/d and 10.64 ± 2.1 g/kg/d, respectively, P = .004). On comparison of receiver operating characteristic curves, the area under the curve for ID intake (0.74) was significantly higher (P = .01) compared with the area under the curve for IL intake (0.59) and intravenous protein (IP) intake (0.52). On logistic regression, daily ID intake was associated with PNAC (odds ratio 1.7; 95% CI, 1.04-2.9, P = .03) after controlling for daily IP and IL intake. CONCLUSIONS: ID intake may be associated with the development of PNAC in premature infants. Our findings suggest that limiting ID intake may be more useful than limiting IL intake in reducing the incidence of PNAC in premature infants.

Latent iron deficiency at birth influences auditory neural maturation in late preterm and term infants.

BACKGROUND: In utero latent iron deficiency has been associated with abnormal neurodevelopmental outcomes during childhood. Its concomitant effect on auditory neural maturation has not been well studied in late preterm and term infants. OBJECTIVE: The objective was to determine whether in utero iron status is associated with auditory neural maturation in late preterm and term infants. DESIGN: This prospective cohort study was performed at Sir Ganga Ram Hospital, New Delhi, India. Infants with a gestational age ≥34 wk were eligible unless they met the exclusion criteria: craniofacial anomalies, chromosomal disorders, hemolytic disease, multiple gestation, third-trimester maternal infection, chorioamnionitis, toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex virus infections (TORCH), Apgar score <5 at 5 min, sepsis, cord blood not collected, or auditory evaluation unable to be performed. Sixty consecutive infants with risk factors for iron deficiency, such as small for gestational age and maternal diabetes, and 30 without risk factors for iron deficiency were enrolled. Absolute wave latencies and interpeak latencies, evaluated by auditory brainstem response within 48 h after birth, were measured and compared between infants with latent iron deficiency (serum ferritin ≤75 ng/mL) and infants with normal iron status (serum ferritin >75 ng/mL) at birth. RESULTS: Twenty-three infants had latent iron deficiency. Infants with latent iron deficiency had significantly prolonged wave V latencies (7.10 ± 0.68 compared with 6.60 ± 0.66), III-V interpeak latencies (2.37 ± 0.64 compared with 2.07 ± 0.33), and I-V interpeak latencies (5.10 ± 0.57 compared with 4.72 ± 0.56) compared with infants with normal iron status (P < 0.05). This difference remained significant on regression analyses after control for confounders. No difference was noted between latencies I and III and interpeak latencies I-III. CONCLUSION: Latent iron deficiency is associated with abnormal auditory neural maturation in infants at ≥34 wk gestational age. This trial was registered at clinicaltrials.gov as NCT02503397.

Unbound unconjugated hyperbilirubinemia is associated with central apnea in premature infants.

OBJECTIVE: To evaluate whether jaundice, indexed by unbound bilirubin (UB), is associated with central apnea in premature infants. STUDY DESIGN: A prospective observational study was performed with 27-33 weeks' gestational age infants who were not requiring either mechanical ventilation or noninvasive ventilation with continuous positive airway pressure beyond 24 hours after birth. Infants with congenital infections, chromosomal disorders, craniofacial anomalies, and/or family history of hearing loss were excluded. Total serum bilirubin and UB were measured twice daily during the first postnatal week and then when clinically indicated. Central apnea was evaluated by visual inspection of continuous, electronic cardiorespiratory recordings until 2 weeks of age. RESULTS: One hundred infants were subdivided into 2 groups via median peak UB level: the high UB group (greater than median) and low UB group (less than median). The high UB group had an increased frequency of apnea events during the first 2 weeks compared with infants in the low UB group. After we controlled for confounders, the high UB group had more events of apnea during the first 2 postnatal weeks compared with the low UB group (incidence rate ratio: 1.9, 95% CI 1.2-3.2). CONCLUSIONS: Our findings suggest that jaundice, as indexed by UB, is associated with central apnea in premature infants.

Central auditory processing disorder profile in premature and term infants.

OBJECTIVE: The aim of this study is to compare central auditory processing disorder (CAPD) profile between children born prematurely and at term. METHODS: A retrospective study involving children 7 to 13 years of age who were referred for CAPD evaluation over the past 3 years. Parental reports and medical records were used to collect information. Children with a score ≥ two standard deviations below the mean for at least one ear on at least two different CAPD tests were considered to have CAPD. RESULTS: A total of 82 children were evaluated for CAPD of which 22 met exclusion criteria, resulting in 60 children with CAPD (15 premature and 45 term). Premature children had higher prevalence of cesarean section delivery and neonatal jaundice compared with term children. Premature children had a higher total number of failed CAPD tests compared with the term children. Among CAPD tests, there was an increased frequency of abnormal Phonemic Synthesis test (PST) and decreased frequency of abnormal Staggered Spondaic Word test (SSW) among premature children compared with term children. CONCLUSION: Premature children differ in CAPD profile compared with term children. Findings suggest possible etiological differences for CAPD such as jaundice or differential susceptibility of premature children for altered PST and SSW performance when compared with the term children.

Apnea in acute bilirubin encephalopathy.

Central apnea, defined as cessation of breathing for ≥20s, is frequent in premature infants born at <34 weeks׳ gestation but uncommon among healthy late preterm (34(0/7)-36(6/7) weeks׳ gestation) and term (≥37 weeks׳ gestation) infants, where it is usually a clinical manifestation of a neurological or metabolic problem. There is growing evidence that marked unconjugated hyperbilirubinemia is associated with central apnea in neonates. This article explores the reported association between acute bilirubin encephalopathy and symptomatic apneic events in newborns and the possible mechanisms involved in the pathogenesis of this phenomenon. The prevalence of symptomatic apneic events in reports of acute bilirubin encephalopathy suggests this clinical finding should be considered a sign of bilirubin neurotoxicity.