Alistair G. S. Philip

Antenatal steroids, delivery mode, and intraventricular hemorrhage in preterm infants

OBJECTIVE The relationship between antenatal steroids, delivery mode, and early-onset intraventricular hemorrhage was examined in very-low-birth-weight infants. STUDY DESIGN 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. RESULTS 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). CONCLUSION 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.

The Evolution of Neonatology

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.

Use of C-Reactive Protein in Minimizing Antibiotic Exposure: Experience With Infants Initially Admitted to a Well-Baby Nursery

Objective. To evaluate the use of a clinical pathway for neonatal sepsis in decisions about initiating and continuing antibiotic treatment. Setting. A district hospital primarily served by private pediatricians practicing in a managed care environment. Patients and Laboratory Tests. All infants admitted to the well-baby nursery in 1997–1998 were eligible for this study. Infants born with a variety of risk factors (eg, borderline prematurity, membranes ruptured for over 18 hours, mother positive for group B streptococcus [GBS], and maternal fever) or clinical manifestations suggesting possible infection (either clinical signs or persistent hypoglycemia) were evaluated with white blood cell count, differential, and C-reactive protein (CRP) soon after birth and 12 hours later. Decisions to transfer to the neonatal intensive care unit and to treat with antibiotics were based on abnormal laboratory test results, particularly an increased level of CRP (>1 mg/dL), persistent hypoglycemia, or clinical signs. Discontinuation of antibiotic treatment was primarily based on return to normal of the CRP. Results. Of 8299 live births, 7562 initially went to the well-baby nursery. Evaluation occurred in 1894 (25%) and 425 were transferred to the neonatal intensive care unit. In 162, antibiotics were discontinued within 48 hours. The majority were treated for 3 to 5 days, with only 19 (3 with GBS sepsis) treated for 6 days or more. There were 216 infants transferred because of risk factors and 209 because of clinical findings. Peak CRP primarily determined the duration of antibiotic treatment, with the mean peak CRP rising from 2.8 mg/dL in those treated for 3 days, to 3.8, 4.3, 8.4, 8.9, and 13.7 mg/dL in those treated for 4, 5, 6, 7, or >7 days, respectively. The mean duration of treatment was 3.1 days. No infant initially treated with antibiotics and discharged when the CRP returned to normal was readmitted within the next month. No infant with normal values on the sepsis screen was readmitted within 1 month with evidence of bacterial infection, but 1 infant with no risk factors was readmitted at 22 days of age with GBS sepsis and meningitis. Conclusions. Using a clinical pathway for neonatal sepsis, which is based primarily on CRP determinations, can minimize antibiotic exposure and shorten hospital stays.

The changing face of neonatal infection: experience at a regional medical center

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.

Risk factors for early intraventricular hemorrhage in low birth weight infants

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.

Coagulase-negative staphylococci as true pathogens in newborn infants: a cohort study

We examined the pathogenicity of coagulase-negative staphylococci (CONS) in newborn infants by comparing presenting nonspecific signs of infection in infants with and without CONS bacteremia. During a 6-month period 799 blood cultures were obtained in a tertiary care nursery; 81 (10.1%) grew CONS and 25 (3.0%) grew other bacteria. A comparison group of 121 infants was selected randomly from ill patients whose blood cultures were negative. In addition 70 well infants were matched to CONS-positive cases. Abnormal clinical signs, complete blood cell counts, C-reactive protein, alpha-1-acid glycoprotein and prealbumin were determined at the time of culture. Signs that discriminated best between infants with and without CONS bacteremia were identified by logistic regression analysis. Infants with CONS bacteremia did not differ from infants with sepsis caused by recognized pathogens, except for lethargy, which was significantly more common in unequivocal infection. Infants with presumed infection but negative blood cultures, and noninfected control patients had abnormal signs significantly less often than CONS-positive infants. C-reactive protein, hyperthermia, increased oxygen requirements and lethargy were the most useful signs in identifying neonatal bloodstream infection. This cohort study provides objective evidence for the pathogenicity of CONS in newborn infants.

Bronchopulmonary Dysplasia: Then and Now

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.

Placental transfusion as an intrauterine phenomenon in deliveries complicated by foetal distress.

The details of the deliveries of 10 infants whose cords were clamped before the onset of respiration and within one minute of delivery of the chin but whose residual placental volumes were unexpectedly low are compared with 20 control infants whose cords were clamped under similar conditions but who had the expected residual placental volumes. The only statistically significant difference between these groups was in the high number of patients with foetal distress and low Apgar scores in the former group. It is concluded that placental transfusion occurred before delivery in these patients and that foetal asphyxia facilitated this transfusion, which may be the underlying mechanism of neonatal erythrocythaemia or transient tachypnoea of the newborn.

Cerebrospinal fluid C-reactive protein in neonatal meningitis.

determination of C-reactive protein using lasernephelometer. Scand J Clin Lab invest 40:293, 1980. 6. Peltola H, Rfis/inen JA: Quantitative C-reactive protein in relation to erythrocyte sedimentation rate, fever, and duration of antimicrobial therapy in bacteraemic diseases of childhood. J Infect 5:257, 1982. 7. Peltola H, Laipio M-L, Slimes MA: Quantitative C-reactive protein (CRP) determined by an immunoturbidimetric method in rapid differential diagnosis of acute bacterial and viral diseases of children. Acta Paediatr Scand. (In press.) 8. Squire EN Jr, Reich HM, Merenstein GB, Favara BE, Todd JK: Criteria for the discontinuation of antibiotic therapy during presumptive treatment of suspected neonatal infection. Pediatr Infect Dis 1:85, 1982. 9. Cherry JD: Croup. In Feigin RD, Cherry JD, editors: Textbook of pediatric infectious diseases. Philadelphia, 1981, WB Saunders, pp 146-155. 10. Howard .IB, McCracken GH Jr, Luby JP: Influenza A2 virus as a cause of croup requiring tracheotomy. J PED1ATR 81:1148, 1972.

Delayed cord clamping in preterm infants.

During the 1960s and 1970s, there were multiple studies of the effects on the neonate of varying the time of umbilical cord clamping. Interest in this area of investigation lay dormant for ∼15 years, but in the past decade there has been renewed investigation of this topic, particularly in the preterm infant. In a recent article, Dr Saroj Saigal and I reviewed the history and implications of early and late umbilical cord clamping in both term and preterm infants,1 noting that definitions have varied widely over the years. More than a century ago, “early” was sometimes considered to be within 1 minute, whereas “late” may have been after 5 minutes. Currently, “early” is generally defined as “immediate,” which may take up to 15 seconds, and “late” as 45 to 60 seconds after delivery of the body, by which time the majority of available blood in the placenta will have been transferred to the infant in the form of a “placental transfusion.” In our article we suggested that lack of interest in the timing of umbilical cord clamping in preterm infants might have been a result of the introduction of surfactant as therapy for respiratory distress syndrome (RDS).1 A recent Cochrane review also evaluated the effects of different times of umbilical cord clamping in preterm infants.2 In an earlier era, the possibility that RDS (also … Address correspondence to Alistair G.S. Philip, MD, FRCPE, Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, 750 Welch Rd, Palo Alto, CA 94304. E-mail: aphilip{at}stanford.edu