M. Jeffrey Maisels

Phototherapy for Neonatal Jaundice

n engl j med 358;9 www.nejm.org february 28, 2008 920 A male infant weighing 3400 g was born at 37 weeks’ gestation after an uncomplicated pregnancy. The mother is a 24-year-old primipara who has type A Rh-positive blood. The infant’s course in the hospital nursery was uncomplicated. Although his mother needed considerable help in establishing effective breast-feeding, he was exclusively breast-fed. Jaundice was noted at the age of 34 hours. The total serum bilirubin level was 7.5 mg per deciliter (128 μmol per liter). The infant was discharged at the age of 40 hours and is seen in the pediatrician’s office 2 days later, now with marked jaundice. The results of his physical examination are otherwise normal, but his weight, at 3020 g, is 11% below his birth weight. His total serum bilirubin level is 19.5 mg per deciliter (333 μmol per liter), and his conjugated (direct) bilirubin level 0.6 mg per deciliter (10 μmol per liter). The complete blood count and peripheral-blood smear are normal. The infant has type A Rh-positive blood. The pediatrician consults a neonatologist regarding the need for phototherapy.

Kernicterus: Epidemiological Strategies for Its Prevention through Systems-Based Approaches

Kernicterus, thought to be due to severe hyperbilirubinemia, is an uncommon disorder with tragic consequences, especially when it affects healthy term and near-term infants. Early identification, prevention and treatment of severe hyperbilirubinemia should make kernicterus a preventable disease. However, national epidemiologic data are needed to monitor any preventive strategies. Recommendations are provided to obtain prospective data on the prevalence and incidence of severe hyperbilirubinemia and associate mortality and neurologic injury using standardized definitions, explore the clinical characteristics and root causes of kernicterus in children identified in the Kernicterus Pilot Registry, identify and test an indicator for population surveillance, validating systems-based approaches to the management of newborn jaundice, and explore the feasibility of using biologic or genetic markers to identify infants at risk for hyperbilirubinemia. Increased knowledge about the incidence and consequences of severe hyperbilirubinemia is essential to the planning, implementation and assessment of interventions to ensure that infants discharged as healthy from their birth hospitals have a safer transition to home, avoiding morbidity due to hyperbilirubinemia and other disorders.At a recent NIHCD-sponsored conference, key questions were raised about kernicterus and the need for additional strategies for its prevention. These questions and an approach to their answers form the basis of this report.

Preventable Newborn Readmissions Since Passage of the Newborns’ and Mothers’ Health Protection Act

BACKGROUND. Congress passed the Newborns’ and Mothers’ Health Protection Act in 1996, reversing the trend of shorter newborn nursery lengths of stay. Hope existed that morbidities would lessen for this vulnerable population, but some reports indicate that the timeliness and quality of postdischarge care may have worsened in recent years. OBJECTIVE. Our goal was to determine risk factors for the potentially preventable readmissions because of jaundice, dehydration, or feeding difficulties in the first 10 days of life in Pennsylvania since passage of the Newborns’ and Mothers’ Health Protection Act. PATIENTS AND METHODS. Birth records from 407826 newborns ≥35 weeks’ gestation from 1998 to 2002 were merged with clinical discharge records. A total of 2540 newborns rehospitalized for jaundice, dehydration, or feeding difficulties in the first 10 days of life were then compared with 5080 control infants. Predictors of readmission were identified by using multiple logistic regression analysis. RESULTS. An unadjusted comparison of baseline characteristics revealed numerous predictors of readmission. Subsequent adjusted analysis revealed that Asian mothers, those 30 years of age or older, nonsmokers, and first-time mothers were more likely to have a readmitted newborn, as were those with diabetes and pregnancy-induced hypertension. For neonates, female gender and delivery via cesarean section were protective for readmission, whereas vacuum-assisted delivery, gestational age <37 weeks, and nursery length of stay <72 hours were predictors of readmission in the first 10 days of life. CONCLUSIONS. Although readmissions for jaundice, dehydration, and feeding difficulties may be less common for some minority groups and Medicaid recipients in the era of the Newborns’ and Mothers’ Health Protection Act compared with nonminorities or privately insured patients, several predictors of newborn readmission have established associations with inexperienced parenting and/or breastfeeding difficulty. This is one indication that this well-intentioned legislation and current practice may not be sufficiently protecting the health of newborns and suggests that additional support for mothers and newborns during the vulnerable postdelivery period may be indicated.

Transcutaneous Bilirubin Levels in the First 96 Hours in a Normal Newborn Population of ≥35 Weeks' Gestation

OBJECTIVE. To obtain transcutaneous bilirubin (TcB) measurements, at 6-hour intervals, in the first 96 hours after birth in a normal newborn population (gestational age: ≥35 weeks). METHODS. We performed 9397 TcB measurements on 3984 healthy newborn infants (gestational age: ≥35 weeks) from 6 to 96 hours of age. All measurements were performed in the well-infant nursery with a Draeger Air-Shields transcutaneous jaundice meter (model JM-103), within 2 hours of the designated time. RESULTS. There was a distinct pattern to the velocity of the increase in TcB levels over different time periods. TcB levels increased in a linear manner most rapidly in the first 6 to 18 hours and then less rapidly from 18 to 42 hours, followed by a much slower increase until peak levels occurred. Decreasing gestational age was associated significantly with higher TcB levels. CONCLUSIONS. We provide data on neonatal bilirubinemia, based on TcB levels determined in a large, predominately white and breastfed, North American population. Infants who require closer evaluation and observation initially are those whose bilirubin levels are ≥95th percentile, ie, increasing more rapidly than 0.22 mg/dL per hour in the first 24 hours, 0.15 mg/dL per hour between 24 and 48 hours, and 0.06 mg/dL per hour after 48 hours. These data should be useful for detecting aberrant trends, identifying infants who need additional evaluation, and planning appropriate follow-up for jaundiced newborns.

Neonatal pancytopenia and severe combined immunodeficiency associated with antenatal administration of azathioprine and prednisone

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Bilirubin: On Understanding and Influencing its Metabolism in the Newborn Infant

An elevated serum bilirubin concentration in the newborn presents as much of a therapeutic as a diagnostic problem to the physician. In the first part of this paper both the older and more recent work on the metabolism of bile pigment in the fetus and newborn are reviewed; the second part deals with the prevention of kernicterus.

Endogenous production of carbon monoxide in normal and erythroblastotic newborn infants

The endogenous production of carbon monoxide ( V(CO)) in newborn infants was measured by serial determinations of blood carboxyhemoglobin during rebreathing in a closed system. Mean V(CO) in nine full-term infants was 13.7 +/-3.6 mul CO/kg per hr (SD), and in four erythroblastotic infants V(CO) ranged from 37 to 154 mul CO/kg per hr preceding exchange transfusion. Mean red cell life-span (MLS) and total bilirubin production were calculated from V(CO). MLS in normal newborns was 88 +/-15 days (SD), and bilirubin production was 8.5 +/-2.3 mg/kg per 24 hr. This is more than twice the amount of bilirubin normally produced in the adult per kilogram of body weight. Normal infants achieved a net excretion of bilirubin of at least 5.6 +/-2.3 mg/kg per 24 hr (SD) as calculated from the bilirubin production and the measured rise in serum bilirubin concentration.The measurement of V(CO) should prove valuable in the study of red blood cell survival and bilirubin metabolism in the newborn infant.

Indomethacin Disposition and Indomethacin-Induced Platelet Dysfunction in Premature Infants

Indomethacin failed to produce permanent ductal closure in any of four premature infants with patent ductus arteriosus to whom the drug was given. Indomethacin half-lives measured in two premature infants were 21 and 24 hours, respectively, much longer than in full-term newborns or adults. Platelet function, as measured by platelet aggregation, was grossly abnormal for two to four days after indomethacin administration, normal values returning only by the ninth and tenth days. Gastrointestinal bleeding and transient renal dysfunction occurred in one infant. Measurement of plasma indomethacin concentrations in sick, low-birthweight infants could help guide indomethacin dose and dosage interval, prevent drug accumulation, and reduce toxicity. Further studies of potential toxicity seem to be indicated before instituting widespread indomethacin administration for ductal closure in premature infants.

Phototherapy--traditional and nontraditional.

An observation by an English nurse in 1956 led to the discovery that visible light could lower serum bilirubin levels in newborn infants, and subsequent research showed how photons of light energy are absorbed by the bilirubin molecule converting it into isomers that are readily excreted by the liver and the kidney. Understanding the dose–response effect and other factors that influence the way light works to lower bilirubin levels has led to the effective use of phototherapy and has eliminated the need for exchange transfusion in almost all jaundiced infants.

The contribution of hemolysis to early jaundice in normal newborns.

OBJECTIVE. Neonatal jaundice is the result of an imbalance between bilirubin production and elimination, and our objective was to clarify the contribution of an increase in bilirubin production to hyperbilirubinemia in newborns. METHODS. We measured the end-tidal carbon monoxide concentration corrected for ambient carbon monoxide concentration in 108 jaundiced newborns (total serum bilirubin level >75th percentile) and 164 control newborns in our well-infant nursery, for the first 4 days after birth. RESULTS. Mean end-tidal carbon monoxide levels decreased in the control infants in the first 4 days but increased in the hyperbilirubinemic group. The differences between the jaundiced and nonjaundiced infants were statistically significant on all days. CONCLUSIONS. Before hospital discharge, most infants with bilirubin levels >75th percentile are producing significantly more bilirubin than those with lower bilirubin levels. Because the ability of newborns to conjugate bilirubin is significantly impaired in the first few days, even a small increase in the rate of production can contribute to the development of hyperbilirubinemia. These data suggest that increased heme catabolism is an important mechanism responsible for hyperbilirubinemia in the first 4 days after birth.