Emeritus Faculty - University Medical Line, Pediatrics
Neonatal infection: Primarily the evaluation of diagnostic tests and how they may be incorporated into decisions concerning duration of antibiotic therapy. Also interested in the epidemiology and management of sepsis and meningitis.
Intraventricular hemorrhage: Involved in a multicenter randomized controlled trial of prophylactic indomethacin administration. Also involved with studies relating to the etiology of this disorder in newborn infants.
When bronchopulmonary dysplasia (BPD) was first described in 1967, the use of assisted ventilation in neonates was in its infancy. High concentrations of oxygen were implicated, and BPD was equated with 'pulmonary oxygen toxicity'. The etiologic role of not only oxygen but also peak inspiratory pressures and the duration of exposure to both was emphasized in the 1970s, but BPD remained a dreaded complication of managing respiratory distress syndrome in the 1980s. It was only after exogenous surfactant became commercially available for endotracheal administration that 'classical' BPD began to disappear and was replaced by the 'new' BPD. 'Classical' BPD was seen in more mature preterm infants (>28 weeks' gestational age) and in its severe form was characterized radiographically by micro- and macrocysts of the lung, lung hyperinflation and flattening of the diaphragms. In contrast, 'new' BPD is seen in less mature infants (<28 weeks' gestational age), has comparatively mild radiographic abnormalities and has been defined as continued oxygen requirement at 36 weeks' postmenstrual age. Pathologically, 'classical' BPD frequently revealed obstructive bronchiolitis and fibrosis of lung parenchyma, whereas 'new' BPD demonstrates minimal fibrosis but uniform arrest of development. Herein, factors which may contribute to the etiology of BPD are described, as well as possible preventative and therapeutic strategies.
View details for DOI 10.1159/000336030
View details for Web of Science ID 000304485800001
View details for PubMedID 22354063
Chronic lung disease of prematurity (CLD) is commonly considered to be a consequence of assisted ventilation. However, prior to the description in 1967 of bronchopulmonary dysplasia (BPD), following ventilator therapy for respiratory distress syndrome, Wilson-Mikity syndrome (WMS) had been described in very preterm infants on minimal oxygen supplementation. In the 1970s and 1980s, many infants treated with assisted ventilation required prolonged mechanical ventilation after developing radiographic features of coarse infiltrates, severe hyperinflation, and microcystic changes, associated with hypercarbemia and the need for increased inspired oxygen concentrations. Some infants died and showed evidence of pulmonary fibrosis, obstructive bronchiolitis, and dysplastic change. The role of supplemental oxygen, positive pressure ventilation, and the immaturity of the lung have long been considered important in the etiology of CLD/BPD. More recently, the role of inflammation (particularly antenatal exposure to cytokines) and individual susceptibility (genetic predisposition) have assumed greater etiologic importance. The historical setting into which corticosteroid treatment for BPD was introduced is also discussed. After the licensing of exogenous surfactant to treat RDS in the early 1990s and more widespread use of prenatal corticosteroids in the mid-1990s, severe BPD became an unusual event. Gradually, the diagnosis of CLD, still often referred to as BPD, was based on an oxygen requirement at 36 weeks postmenstrual age. However, it is not clear that this 'new BPD' is substantially different from WMS. It is difficult to make prognostications about long-term lung function of these infants based on oxygen 'requirement' at 36 weeks, since supplemental oxygen is frequently used unnecessarily.
View details for DOI 10.1016/j.siny.2009.07.013
View details for Web of Science ID 000271793200003
View details for PubMedID 19699162
In 1960, the terms "neonatology" and "neonatologist" were introduced. Thereafter, an increasing number of pediatricians devoted themselves to full-time neonatology. In 1975, the first examination of the Sub-Board of Neonatal-Perinatal Medicine of the American Board of Pediatrics and the first meeting of the Perinatal Section of the American Academy of Pediatrics were held. One of the most important factors that improved the care of the neonate was the miniaturization of blood samples needed to determine blood gases, serum electrolytes, glucose, calcium, bilirubin, and other biochemical measurements. Another factor was the ability to provide nutrition intravenously, and the third was the maintenance of normal body temperature. The management of respiratory distress syndrome improved with i.v. glucose and correction of metabolic acidosis, followed by assisted ventilation, continuous positive airway pressure, antenatal corticosteroid administration, and the introduction of exogenous surfactant. Pharmacologic manipulation of the ductus arteriosus, support of blood pressure, echocardiography, and changes in the management of persistent pulmonary hypertension, including the use of nitric oxide and extracorporeal membrane oxygenation, all have influenced the cardiopulmonary management of the neonate. Regionalization of neonatal care; changes in parent-infant interaction; and technological changes such as phototherapy, oxygen saturation monitors, and brain imaging techniques are among the important advances reviewed in this report. Most remarkable, a 1-kg infant who was born in 1960 had a mortality risk of 95% but had a 95% probability of survival by 2000. However, errors in neonatology are acknowledged, and potential directions for the future are explored.
View details for DOI 10.1203/01.PDR.0000151693.46655.66
View details for Web of Science ID 000232172600030
View details for PubMedID 15718376
Our multicenter Indomethacin Intraventricular Hemorrhage (IVH) Prevention Trial demonstrated a reduction of IVH in preterm infants. Analysis of our cohort by sex showed indomethacin halved the incidence of IVH, eliminated parenchymal hemorrhage, and was associated with higher verbal scores at 3 to 8 years in boys.
View details for DOI 10.1016/j.jpeds.2004.07.035
View details for Web of Science ID 000225702300025
View details for PubMedID 15580211
To determine the frequency and timing of symptoms and to evaluate the effectiveness of a sepsis-screening pathway in term and near-term infants, data were collected prospectively for a period of 1 year from December 1, 2000, to November 30, 2001. Results confirmed that a sepsis-screening pathway using a combination of at least 2 serial complete blood cell count and C-reactive protein measurements in both symptomatic and asymptomatic infants is a safe, simple strategy that prevents unnecessary treatment of infants with risk factors with antibiotics. However, most infants with presumed or suspected early-onset sepsis are symptomatic. Routine treatment of asymptomatic infants with risk factors or prior treatment with intrapartum antibiotics is unnecessary. A combined approach of screening in the presence of risk factors and /or symptoms of sepsis and adequate follow-up for infants discharged at less than 72 hours of age may help reduce unnecessary treatment of infants with antibiotics.
View details for Web of Science ID 000180798700002
View details for PubMedID 12635976
The relationship between antenatal steroids, delivery mode, and early-onset intraventricular hemorrhage was examined in very-low-birth-weight infants.A total of 505 preterm infants (birth weight 600 to 1250 gm) were enrolled in a multicenter, prospectively randomized, controlled trial evaluating the efficacy of postnatal indomethacin to prevent intraventricular hemorrhage. All infants had echoencephalography between 5 and 11 hours of life.Seventy-three infants had intraventricular hemorrhage within the first 5 to 11 hours (mean age at echoencephalography 7.5 hours). Four hundred thirty-two infants did not have early intraventricular hemorrhage. There was less antenatal steroid treatment (19% vs 32%, p = 0.03) and more vaginal deliveries (71% vs 45%, p < 0.0001) in the group with early intraventricular hemorrhage. Of 152 infants who received antenatal steroids, those delivered by cesarean section had significantly less early-onset intraventricular hemorrhage than did those delivered vaginally (4% vs 17%, p = 0.02). Of the 353 not exposed to antenatal steroids, 10% of infants delivered by cesarean section and 22% delivered vaginally had early intraventricular hemorrhage (p = 0.003).These data are the first to suggest that both antenatal steroids and cesarean section delivery have an important and independent role in lowering the risk of early-onset intraventricular hemorrhage.
View details for Web of Science ID A1995QM79500001
View details for PubMedID 7892866
To determine whether improvement in neonatal and infant mortality rates is possible or likely.Regional neonatal intensive care unit.Experience during a decade (1982-1991) was evaluated. We determined postnatal age at death and birth weight-specific and gestational age-specific mortality rates. Neonatal deaths (deaths before discharge) were categorized as "possibly preventable" or "probably unpreventable."Deaths occurring after 28 days ("postponed" deaths) contributed 9% of the total for the decade, and 5% for those with extremely low birth weight (ELBW; < 1000 gm) during the last 6 years; 47% of all deaths and 65% of deaths of ELBW infants occurred within 24 hours of birth. Congenital malformations accounted for 7%, 54%, and 66% of deaths when birth weight was 500 to 1499 gm, 1500 to 2499 gm, and > or = 2500 gm, respectively. In infants with birth weight > or = 1000 gm, probably unpreventable deaths (predominantly from congenital malformations, but also including hydrops and inborn errors of metabolism) accounted for 61% of deaths. Of deaths of ELBW infants, extreme prematurity (500 to 750 gm) accounted for 58%; major malformations and pulmonary hypoplasia contributed an additional 9%.During the decade, the gestational age at which there was a 50% survival rate fell from 26 weeks to 24 weeks and a marked increase in the survival rate occurred at birth weights < 1500 gm (VLBW) after the introduction of exogenous surfactant therapy. The number of possibly preventable deaths is now very small. For any substantial impact on mortality rates, it will be necessary to lower VLBW and ELBW rates.
View details for DOI 10.1016/S0022-3476(95)70463-9
View details for Web of Science ID A1995QL57900018
View details for PubMedID 7869206
The incidence, etiology and timing of neonatal infection were assessed in a regional neonatal intensive care unit from 1983 through 1992. Infection onset was considered as very early (< 24 hours), early (1 to 7 days) or late (8 to 60 days). Case-fatality rates were determined for different weight groups and time periods (1983 to 1987 vs. 1988 to 1992). Overall neonatal sepsis incidence changed very little, but there was a marked decrease in very early onset sepsis in 1988 to 1992 especially in very low birth weight (< 1500 g) infants, possibly attributable to increased use of prenatal antibiotics. There was an accompanying increase in late onset sepsis, primarily nosocomial infection associated with improved survival of tiny infants, most striking after exogenous surfactant became readily available. During 1988 to 1992, because of very few very early-onset cases, very low birth weight infants had overall case fatality rates of about 10%, which were the same as for larger infants. The predominant organism in very early onset infection was Group B Streptococcus (GBS) (27 of 58) and in late onset infection was coagulase-negative staphylococcus (57 of 103). More cases of early onset GBS pneumonia were seen in the last 5 years. Neonatal meningitis was seen rarely during this decade, with only one case documented in the first 24 hours of life.
View details for Web of Science ID A1994PW48600005
View details for PubMedID 7892077
We enrolled 61 neonates of 600 to 1250 gm birth weight with evidence of low-grade intraventricular hemorrhage at 6 to 11 hours of age in a prospective, randomized, placebo-controlled trial to test the hypothesis that indomethacin (0.1 mg/kg given intravenously at 6 to 12 postnatal hours and every 24 hours for two more doses) would prevent extension of intraventricular hemorrhage. Twenty-seven infants were assigned to receive indomethacin; 34 infants received saline placebo. There were no significant differences between the two groups in birth weight, gestational age, sex, Apgar scores, percentage of infants treated with surfactant, or distribution of hemorrhages at the time of the first cranial sonogram (echo-encephalogram). Within the first 5 days, 9 of 27 indomethacin-treated and 12 of 34 saline solution-treated infants had extension of their initial intraventricular hemorrhage (p = 1.00). Four indomethacin-treated and three saline solution-treated infants had parenchymal extension of the hemorrhage. Indomethacin was associated with closure of a patent ductus arteriosus by the fifth day of life (p = 0.003). There were no differences in adverse events attributed to indomethacin. We conclude that in very low birth weight infants with low grade intraventricular hemorrhage within the first 6 postnatal hours, prophylactic indomethacin therapy promotes closure of the patent ductus arteriosus and is not associated with adverse events, but does not affect the cascade of events leading to parenchymal involvement of intracranial hemorrhage.
View details for Web of Science ID A1994NQ52100023
View details for PubMedID 8201485
Parenchymal involvement of intraventricular hemorrhage (IVH) is a major risk factor for neurodevelopmental handicap in very low birth weight neonates. Previous trials have suggested that indomethacin would lower the incidence and severity of IVH in very low birth weight neonates.We enrolled 431 neonates of 600- to 1250-g birth weight with no evidence for IVH at 6 to 11 hours of age in a prospective, randomized, placebo-controlled trial to test the hypothesis that low-dose indomethacin (0.1 mg/kg intravenously at 6 to 12 postnatal hours and every 24 hours for two more doses) would lower the incidence and severity of IVH. Serial cranial ultrasound examinations and echocardiographs were performed.There were no differences in the birth weight, gestational age, sex, Apgar scores, and percent of neonates treated with surfactant between the indomethacin and placebo groups. Within the first 5 days, 25 (12%) indomethacin-treated and 40 (18%) placebo-treated neonates developed IVH (P = .03, trend test). Only one indomethacin-treated patient experienced grade 4 IVH compared with 10 placebo-treated neonates (P = .01). Sixteen indomethacin-treated neonates and 29 control neonates died (P = .08); there was a difference favoring indomethacin with respect to survival time (P = .06). Eighty-six percent of all neonates had a patent ductus arteriosus on the first postnatal day; indomethacin was associated with significant ductal closure by the fifth day of life (P < .001). There were no differences in adverse events attributed to indomethacin between the two treatment groups.Low-dose prophylactic indomethacin significantly lowers the incidence and severity of IVH, particularly the severe form (grade 4 IVH). In addition, indomethacin closes the patent ductus arteriosus and is not associated with significant adverse drug events in very low birth weight neonates.
View details for Web of Science ID A1994ND36300001
View details for PubMedID 8134206
Because earlier studies suggested that preterm infants with germinal matrix hemorrhage or intraventricular hemorrhage or both (GMH/IVH) present within the first 12 postnatal hours are at greatest risk for the development of high-grade hemorrhage and neurodevelopmental disability, we examined the risk factors for this insult among 229 neonates of 600 to 1250 gm birth weight in a multicenter study. All had echoencephalography (ECHO) within the first 11 hours and serially for the next 20 days; risk factor data were collected prospectively. Forty-three infants had GMH/IVH within the first 5 to 11 hours (mean age at ECHO 7.7 hours): 18 GMH and 21 grade II, 1 grade III, and 3 grade IV IVH. One hundred eighty-six infants did not have GMH/IVH at a mean age of 7.9 hours. Both groups of infants were similar in birth weight, gestational age, maternal risk factors, cord pH values, and surfactant therapy before ECHO. The group with early IVH had more vertex presentations than the group without early IVH (79% vs 55%, p = 0.043), less maternal tocolytic use (42% vs 60%, p = 0.029), and more vaginal deliveries (67% vs 44%, p = 0.005). In the first 21 days, severe IVH developed in 12 infants with early IVH and in 6 infants without early IVH (p < 0.001). There were more neonatal deaths (16% vs 6%, p = 0.035) and more deaths at any time during the primary hospitalization (23% vs 9%, p = 0.010) among the early IVH group than among the group without early IVH. Multivariate analysis indicated that the mode of delivery, fetal presentation, and birth weight were important and independent prognostic indicators of IVH.
View details for Web of Science ID A1992JY69500024
View details for PubMedID 1432433
We evaluated the nucleated red blood cell (NRBC) counts in all infants with very low birth weight admitted to our neonatal intensive care unit from 1983 to 1986. There were 374 infants with birth weights of 500 g to 1500 g admitted in the first 24 hours after birth, but 31 died before studies were obtained. Of the remainder, 282 were appropriate for gestational age (AGA) and 61 were small for gestational age (SGA). Over 80% of both AGA and SGA infants were inborn and were evaluated within three hours of delivery. Nucleated red blood cell counts were significantly increased in SGA infants compared with AGA infants. The percent of infants with NRBC counts higher than 4.0 and 10.0 x 10(9)/L were 48% and 26%, respectively, in SGA infants compared with 19% and 6%, respectively, in AGA infants. Similarly, the percent of SGA infants with more than 40 or 100 NRBCs per 100 white blood cells were 62% and 36%, respectively, compared with 25% and 6%, respectively, in AGA infants. Data for specific weeks of gestation are provided and the differences were present at each gestational age. Recent data in fetuses with growth retardation, when blood was obtained directly from the fetal umbilical vein, showed an association between elevated NRBC counts and chronic hypoxemia. When increased NRBC counts are seen soon after birth, the possibility of a chronic intrauterine insult should be considered.
View details for Web of Science ID A1989T107000017
View details for PubMedID 2916486
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