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Biomedical subjects

A G Philip

Publications and source records attributed to A G Philip.

At least 19 recordsLinked to original sources

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.

Anti-Bacterial Agents↗

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.

Cerebral Hemorrhage↗

Neonatal mortality rate: is further improvement possible?

OBJECTIVE: To determine whether improvement in neonatal and infant mortality rates is possible or likely. SETTING: Regional neonatal intensive care unit. METHODS: 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." RESULTS: 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%. CONCLUSION: 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.

Birth Weight↗

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.

Anti-Bacterial Agents↗

Low-dose indomethacin and prevention of intraventricular hemorrhage: a multicenter randomized trial.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cerebral Hemorrhage↗

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.

Birth Weight↗

Prolonged dexamethasone therapy reduces the incidence of cryotherapy for retinopathy of prematurity in infants of less than 1 kilogram birth weight with bronchopulmonary dysplasia.

To determine whether prolonged dexamethasone therapy, used in the treatment of bronchopulmonary dysplasia (BPD), affects the incidence of cryotherapy for retinopathy of prematurity, the authors conducted a retrospective review of all infants admitted to a neonatal intensive care unit between October 1988 and October 1990 (n = 957) whose birth weights were less than 1 kg (n = 90). All admissions were reviewed to determine birth weight, gestational age, survival, incidence of BPD and cryotherapy, use and duration of dexamethasone therapy, length of mechanical ventilation, continuous positive airway pressure, and additional supplemental oxygen. Of all neonatal intensive care unit admissions, 9.4% weighed less than 1 kg, and 64% survived for greater than 28 days (n = 58). Of the survivors, 82% had BPD. Cryotherapy for retinopathy of prematurity was used only in those with birth weights of less than 1 kg and with BPD. All those treated with dexamethasone (n = 23) had BPD and significantly lower gestational ages (25.6 vs 26.4 weeks) (P = .05) and birth weights (759 vs 824 g) (P < .05) than those not treated (n = 25). Dexamethasone was used in 23 of 48 infants (9 for < or = 24 days, 14 for > 24 days). Eleven required cryotherapy: 5 of 25 with no dexamethasone, 5 of 9 treated for 24 days or less, and 1 of 14 treated for longer than 24 days (P < .04). In those treated with prolonged (> 24 days) dexamethasone, cryotherapy was significantly reduced compared with those treated for shorter periods. Although the probability was significant, the 95% confidence intervals were wide.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchopulmonary Dysplasia↗

Does cesarean section protect against intraventricular hemorrhage in preterm infants?

A declining incidence of periventricular-intraventricular hemorrhage (PV-IVH) in preterm infants less than 35 weeks' gestational age during the years 1980 through 1987 led us to investigate the role of the route of delivery. Routine cephalic ultrasound was used to detect PV-IVH in 490 vaginal and 411 cesarean section deliveries. A lower incidence of all PV-IVH and severe PV-IVH was noted in cesarean section deliveries for each 2-year period, with a decline in all PV-IVH in vaginal and cesarean section deliveries from 39% and 31%, respectively, in 1980-1981 to 23% and 11% in 1986-1987. Striking differences were noted for infants less than 1500 g, less than 1000 g, or less than 27 weeks' gestation. For example, in infants less than 1000 g, the incidence of all PV-IVH was 52% in vaginal (n = 101) and 25% in cesarean section deliveries (n = 88), and of severe PV-IVH was 26% and 11%, respectively. These differences did not seem to be influenced by presence or absence of labor, breech presentation, or low Apgar scores. Route of delivery should be considered as an important variable in pharmacologic intervention studies.

Cerebral Hemorrhage↗

A multicenter randomized, placebo-controlled trial of surfactant therapy for respiratory distress syndrome.

We carried out a multicenter randomized, placebo-controlled trial to evaluate the efficacy and safety of surfactant in the treatment of respiratory distress syndrome. The study population was made up of newborn infants weighing 750 to 1750 g who were receiving assisted ventilation with 40 percent or more oxygen. The eligible infants received a single dose of either surfactant (100 mg of phospholipid per kilogram of body weight [4 ml per kilogram]) or an air placebo (4 ml per kilogram), administered into the trachea within eight hours of birth by an investigator not involved in the clinical care of the infant. When compared with the infants who received the placebo (n = 81), the infants who were treated with surfactant (n = 78) had a 0.12 greater average increase in the ratio of arterial to alveolar oxygen tension (P less than 0.0001), a 0.20 greater average decrease in the fractional inspiratory oxygen concentration (P less than 0.0001), and a 0.26-kPa greater average decrease in the mean airway pressure (P less than 0.0001) during the 72 hours after treatment. Pneumothorax was less frequent among the infants treated with surfactant than in the control group (13 percent vs. 37 percent; P = 0.0005). There were no statistically significant differences between the groups in the proportion of infants in each of five ordered clinical-status categories on day 7 (P = 0.08) or day 28 (P = 0.75) after treatment. There were also no significant differences between the groups in the frequency of bronchopulmonary dysplasia, patent ductus arteriosus, necrotizing enterocolitis, or periventricular-intraventricular hemorrhage. In each group, 17 percent of the infants died by day 28. We conclude that treatment with the single-dose surfactant regimen used in this study reduces the severity of respiratory distress during the 72 hours after treatment and decreases the frequency of pneumothorax, but that it does not significantly improve clinical status later in the neonatal period and does not reduce neonatal mortality. Further study of different surfactant regimens and patient-selection criteria will be required to determine whether this initial improvement can be translated into reductions in mortality or serious morbidity.

Bronchopulmonary Dysplasia↗

Increased nucleated red blood cell counts in small for gestational age infants with very low birth weight.

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.

Erythrocyte Count↗

Intraventricular hemorrhage in preterm infants: declining incidence in the 1980s.

Ultrasound has been routinely used since late 1979 to diagnose periventricular-intraventricular hemorrhage in infants whose gestational age was 34 weeks or less. During the years 1980 to 1987 the ultrasound scans were interpreted by one person, and a steady decline in incidence of periventricular-intraventricular hemorrhage was observed. Both for infants of 34 weeks or less and for very low birth weight (less than 1500 g) infants, periventricular-intraventricular hemorrhage incidence decreased, respectively, from 34% and 39% in 1980 to 1981 to 19% and 25% in 1986 to 1987. This decrease was confined to true intraventricular hemorrhages, which decreased from 22% in 1980 to 1981 to 7% in 1986 to 1987 for infants of less than or equal to 34 weeks' gestation. These results were not influenced by a change in the distribution of birth weights or gestational ages of the infants evaluated nor by a change in the inborn to outborn ratio. The incidence of periventricular-intraventricular hemorrhage was lower in infants born by cesarean section than those delivered vaginally, but the decrease could not be attributed to an increased number of deliveries by cesarean section. Although there were undoubtedly changes in neonatal care during this time period, no planned intervention occurred. It was concluded that pharmacologic intervention studies must be interpreted with caution.

Cerebral Hemorrhage↗

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.

Acute-Phase Proteins↗