Mujahid Anwar

The Apgar Score and Its Components in the Preterm Infant

Objective. The Apgar score is well-characterized in full-term infants but not in premature infants. The objective of this study was to assess the Apgar score in preterm infants with respect to the relationships between the 1- and 5-minute scores, the correlation of the Apgar score with pH and with other variables, and the relationship among the individual Apgar components. Methodology. We recorded Apgar scores at 1 and 5 minutes in a population-based cohort of preterm infants (n = 1105) with birth weight <2000 g, from three intensive care nurseries in central New Jersey. Linear correlation analysis was used to examine the relationship between 1- and 5-minute Apgar scores and between the individual components of the Apgar score. Multiple regression analysis was used to explore the relationship between various perinatal characteristics and the Apgar score, and between pH and Apgar score. Stepwise logistic regression analysis was used to assess the determinants of mortality. Results. The 1-minute Apgar score median (25%, 75%) was 6(4,8) and correlated with the 5-minute score of 8(7,9) atr = .78. Slight but significant differences were seen between male (n = 557) and female (n = 508) infants in the 1-minute (6[4,8] and 7[4,8]) Apgar scores. One- and 5-minute scores of white infants (7[4,8] and 8[7,9]; n = 713) were significantly higher than those of black infants (5[3,7] and 8[6,9]; n = 280). Birth weight and gestational age were both linearly related to both Apgar scores. Low Apgar score (<3 at 1 minute and <6 at 5 minutes) was significantly associated with birth weight, gestational age and mode of delivery. Low arterial blood pH (<7.01) at birth was significantly related to low Apgar score. One hundred fifty-nine infants died; these infants were significantly smaller (983 ± 382 vs 1462 ± 369 g), less mature (27 vs 31 weeks), had lower arterial blood pH (7.20 ± 0.18 vs 7.31 ± 0.11), had lower 1- (3[2,6] vs 7[4,8]) and 5-minute Apgar scores (6[4,8] vs 8[7,9]), and a greater incidence of low Apgar score (32% vs 6%) than did survivors. Conclusions. Among the components of the Apgar score, respiratory effort, muscle tone, and reflex activity correlated well with one another; heart rate correlated less well; and color the least. Our data confirms the limited use of the Apgar score in preterm infants and demonstrates the different responses of the Apgar scores components.

Umbilical vein interleukin 6 and tumor necrosis factor alpha plasma concentrations in the very preterm infant

Objective. To examine the relationship between umbilical vein plasma concentrations of interleukin 6 (IL‐6) and tumor necrosis factor (TNF)‐alpha and early neonatal sepsis in the very preterm infant, and the histopathologic findings of chorioamnionitis in the placentas from these pregnancies. Methods. A prospective study was conducted in 43 very preterm, singleton infants delivered at or before 32 weeks of gestation. IL‐6 and TNF‐alpha were measured by enzyme‐linked immunoassay. Placentas from these pregnancies were histologically examined for the presence of chorioamnionitis. Infants were prospectively classified as confirmed sepsis group, clinical sepsis group or control group. IL‐6 and TNF‐alpha plasma concentrations were not normally distributed, so they were transformed to their natural log values for statistical analysis. Results. The enrolled infants had a mean gestational age of 27.2 ± 2.7 weeks and a mean birth weight of 956 ± 325 g. Three (7%) infants had confirmed sepsis, 18 (42%) were in the clinical sepsis group and 22 (51%) were in the control group. IL‐6 concentrations but not TNF‐alpha were significantly higher (P < 0.05) in the confirmed (8.9 ± 1.7) and clinical sepsis (5.5 ± 2.4) groups in comparison with the control group (2.1 ± 1.6). We examined 42 placentas. Twenty‐three (55%) had no evidence of chorioamnionitis, 1 (2%) had mild grade, 8 (19%) had a moderate grade and 10 (24%) had a severe grade of chorioamnionitis. IL‐6 was significantly elevated in the moderate (5.9 ± 1.6 vs. 1.9 ± 1.6) and severe grade (7.2 ± 2.3 vs. 1.9 ± 1.6) of chorioamnionitis, in the presence of acute deciduitis (6.0 ± 2.7 vs. 2.1 ± 1.8), chorionic vasculitis (6.8 ± 2.1 vs. 2.2 ± 1.9) and funisitis (7.3 ± 1.9 vs. 2.7 ± 2.3) (P < 0.05) TNF‐alpha plasma concentrations were not significantly different. Conclusion. An elevated umbilical vein IL‐6 concentration is a good indicator of sepsis syndrome in the very preterm infant and also correlates with histologic chorioamnionitis in these pregnancies.

Blood pressure ranges in premature infants. I. The first hours of life

We studied blood pressure in the first hours of life in a cohort of 1105 preterm infants weighing 501 to 2000 gm; these infants represented 83% of all births at these weights that resulted in admission to three intensive care nurseries during a 34-month period between 1984 and 1987. To assess the effects of specific risk factors, we identified 244 healthy infants, 164 infants who received mechanical ventilation but had no other conditions, 47 infants whose only risk factor was the presence of hypertension or preeclampsia in the mother, and 86 infants with depressed Apgar scores regardless of the presence of the other conditions. We documented each infants minimum and maximum systolic (Smin, Smax) and diastolic (Dmin, Dmax) pressures during the first 3 to 6 hours of life. In the healthy group, Smin was 47 mmHg; Smax, 59 mmHg; Dmin, 24 mmHg; and Dmax, 35 mmHg. In the ventilation group, Smin was 41 mmHg; Smax, 57 mmHg; Dmin, 22 mmHg; and Dmax, 35 mmHg. The Smin and Dmin values were both significantly lower in infants who received mechanical ventilation than in healthy infants (p < 0.01). In the maternal hypertension group, Smin was 49 mmHg; Smax, 59 mmHg; Dmin, 25 mmHg; and Dmax, 34 mmHg. Only the Smin value was significantly higher than in healthy infants. In the group with low Apgar scores, Smin was 33 mmHg; Smax, 51 mmHg; Dmin, 19 Hg; and Dmax, 34 mmHg. Thus all these values were significantly lower than in all the other groups (p < 0.05). Of infants with low Apgar scores, 20% to 50% had values below the 5th percentile for healthy infants. Birth weight and gestational age correlated with blood pressure limits only in the infants with low Apgar scores. We conclude that in healthy premature infants the limits of systolic and diastolic blood pressure are independent of birth weight and gestational age. Infants with low Apgar scores tend to have lower pressures, and infants whose mothers have hypertension have higher pressures than infants in the healthy cohort.

Autoradiographic determination of regional cerebral blood flow during hypoglycemia in newborn dogs.

ABSTRACT: To ascertain the regional cerebral blood flow (CBF) responses to hypoglycemia, nine newborn dogs were treated with insulin to blood glucose concentrations ranging from 1 to 35 mg/dl (mean 22 mg/dl). Systemic physiologic monitoring revealed no differences in mean arterial blood pressure, heart rate, paO2, paCO2, pHa, or blood lactate in the hypoglycemis animals and five normoglycemic controls. Significant increases in CBF occurred in 17 of 20 analyzed structures of brain in the hypoglycemic puppies, ranging from 158 to 446% of the normoglycemic values. The percent increases in CBF were greatest in brainstem structures compared to other major regions of brain. A positive correlation existed between mean arterial blood pressure and cerebral cortical blood flow, suggesting a loss of CBF autoregulation during hypoglycemia. The patho-physiologic mechanism for the elevations in regional CBF might relate to stimulation of β-adrenergic receptors in brain, as has been shown in adults.

Effects of isoflurane on transport across the blood-brain barrier

The blood-brain barrier (BBB) plays an important role in regulating and restricting transfer of molecules into the interstitial space of the brain. Anesthetic agents may affect the permeability of the BBB. In this investigation, the effect of isoflurane on the transport of small hydrophilic molecules across the BBB was studied in rats by measuring the blood-brain transfer coefficient (Ki) and the regional cerebral blood flow (rCBF) and by calculating the capillary permeability-surface area (PS) product. In the control group, after a femoral artery and vein were catheterized under isoflurane anesthesia, rats were allowed to remain awake for 2 h before measuring Ki (n = 6) or rCBF (n = 11). In the two experimental groups, rats were anesthetized with 1% and 2% isoflurane respectively, and their lungs were mechanically ventilated through a tracheal tube. Ki was measured (1% n = 6, 2% n = 7) using 14C-alpha-aminoisobutyric acid, and rCBF was measured (2% n = 7) using 14C-iodoantipyrine. Two percent isoflurane did not affect rCBF in 9 of 13 brain regions. Blood flow was less in the lateral and posterior cortex and greater in the medulla and pons when compared with the control group. Ki was less in 11 of 13 brain regions in both the 1% and 2% isoflurane groups than in the control group. There was no significant difference between 1 and 2% isoflurane in any brain region.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid peroxidation in cord blood and neonatal outcome

Background: Periventricular–intraventricular hemorrhage, necrotizing enterocolitis, chronic lung disease and retinopathy of prematurity have been referred to as oxygen radical diseases (ORD) because they are thought to be related to excess oxidant stress relative to anti‐oxidant defenses in premature infants. 8‐Isoprostane is a product of lipid peroxidation that can be used as a measure of free radical exposure or injury. The aim of the present study was to determine whether fetal oxidant stress is associated with adverse effects in preterm infants.

Serial lumbar punctures in prevention of post-hemorrhagic hydrocephalus in preterm infants

We studied 47 infants with either grade 3 or grade 4 intraventricular hemorrhage, to assess the efficacy of intermittent lumbar punctures in the prevention of post-hemorrhagic hydrocephalus in a prospective controlled trial. The control group received supportive care only, whereas the treatment group additionally underwent intermittent spinal taps. The spinal taps were started at postnatal age 11 +/- 5 days and continued for 20 +/- 16 days, with the removal of 67 +/- 101 ml cerebrospinal fluid using 16 +/- 12 taps. The two groups were comparable with regard to birth weight, gestational age, race, sex, Apgar score, and severity of hemorrhage. Three infants in the control group died, compared with two infants in the study group. Nine infants in the control group and 10 infants in the study group developed hydrocephalus requiring a ventriculoperitoneal shunt or a ventricular catheter reservoir. These differences in the outcome in the two groups are not statistically significant. We conclude that serial lumbar punctures were unsuccessful in prevention of hydrocephalus in this group of preterm infants with intraventricular hemorrhage.

Impact of Race and Ethnicity on the Outcome of Preterm Infants Below 32 Weeks Gestation

OBJECTIVES: To determine the impact of race/ethnicity on mortality and morbidity such as intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD) and bacteriologically confirmed sepsis, assisted ventilation, surfactant administration, intrauterine growth retardation (IUGR), and patent ductus arteriosus (PDA) among very prematurely delivered infants.STUDY DESIGN: Retrospective study of a cohort of 1006 preterm neonates with gestational age ranging from 22 to 32 weeks discharged from the Neonatal Intensive Care Unit (NICU) between 1998 and 2001. Subgroup analysis according to gestational age (GA) (22 to 24, 25 to 28, and 29 to 32 weeks) and plurality (singleton and multiple) was performed using the χ 2 test and an analysis of variance.RESULTS: Of the 1006 infants, 54.3% were white, 21.7% black, 13.7% Hispanic, and 10.3% were classified as Other. Multiple births among white infants were approximately twice that in (42.4%) black infants (22.1%), and was also significantly higher than in the Hispanic (28.3%) and other race/ethnic groups (25.2%). Overall, a higher proportion of black infants were born with a GA ≤28 weeks (n=115, 55.3%) than white (n=201, 37.1%) and Hispanic (n=53, 38.4%), p<0.05. Therefore, black neonates had a lower GA (27.9±2.9 weeks) and birth weight (1170±463 g) as compared to white (p<0.0002) and Hispanic infants (p<0.0001). There was no significant impact of race/ethnicity on the mean gestational age in any of the gestational age categories. Infant mortality and morbidity in each gestational age category by race/ethnicity were comparable. The multiple birth black infants were seen to have a lower gestational age and birth weight as compared to singleton black as well as to white, Hispanic and other race/ethnic groups. However, this did not influence morbidity and mortality in multiple birth black neonates. The result of this study showed that the level of prematurity and not plurality predominantly influences the rate of infant mortality and morbidity in each race/ethnic category.CONCLUSIONS:The reduction in gestational age and birth weight in black neonates is not associated with an increased risk of infant mortality and morbidity. In general, the outcomes of black singleton and multiple pregnancies were comparable with those of white, Hispanic and other race/ethnic groups.

Effects of MK-801 on cerebral regional oxygen consumption in focal cerebral ischemia in rats.

This investigation tested in rats whether MK-801, an N-methyl-D-aspartate receptor antagonist, would improve the balance of oxygen supply and consumption in the focal ischemic area of the brain induced by occlusion of the middle cerebral artery. Fifteen minutes after middle cerebral artery occlusion, 5 mg/kg MK-801 was administered intravenously to the MK-801 group (n = 12), and normal saline was given to the control group (n = 12). One hour after the occlusion in each group, regional cerebral blood flow was determined in six rats using [14C]iodoantipyrine, and regional arterial and venous oxygen saturations were determined using a microspectrophotometric technique in the other six rats. In both groups of animals, the cerebral blood flow of the ischemic cortex was significantly lower than that of the contralateral cortex (36 +/- 16 [SD] and 67 +/- 14 ml/min/100 g for the control group; 33 +/- 10 and 58 +/- 11 ml/min/100 g for the MK-801 group, respectively). Oxygen extraction was significantly higher in the ischemic cortex (8.8 +/- 2.1 ml O2/100 ml blood) than in the contralateral cortex (5.6 +/- 0.3) for the control group. However, for the MK-801 group, there was no significant difference between the ischemic cortex (6.1 +/- 1.0) and the contralateral cortex (5.7 +/- 1.1). Oxygen extraction in the ischemic cortex of the MK-801 group was significantly lower than that of the control group. Calculated ischemic regional oxygen consumption was similar to the nonischemic values in the control group, whereas the ischemic value was reduced to 61% of the value of the contralateral cortex in the MK-801 group.(ABSTRACT TRUNCATED AT 250 WORDS)

Association of Lipid Peroxidation with Antenatal Betamethasone and Oxygen Radical Disorders in Preterm Infants

Introduction: Premature infants are highly susceptible to ‘oxygen radical diseases’ (ORD), including bronchopulmonary dysplasia, intraventricular hemorrhage/white matter injury, retinopathy of prematurity, and necrotizing enterocolitis. The incidence of ORD is reduced following antenatal treatment with betamethasone. Oxidant-mediated injury is characterized at the cellular level by peroxidation of lipid membranes. This results in the generation of malondialdehyde (MDA), which can be quantified indirectly by measurement of thiobarbituric acid-reacting substances (TBARS). There is currently no effective way to quantify the risk for ORD. In this study, we analyzed the correlation of early urinary MDA and TBARS with prenatal betamethasone administration and with the development of ORD. Methods: Preterm infants (<30 weeks gestation, n = 25) born at St. Peter’s University Hospital were enrolled. Urine samples were collected during the first 10 days of life and stored at –70°C for 0–21 days. TBARS were quantified by spectrophotometric assay, and malondialdehyde levels measured by HPLC. Subjects were screened for the subsequent development of ORD. Betamethasone administration was defined as one or more doses ≧24 h prior to delivery. Results: Urinary MDA levels increased on days 2–3 and 5–10 relative to day 1 from birth. Maximal urinary MDA concentrations were significantly higher in the ORD group compared to controls, and there was a trend toward increased urinary TBARS in the presence of ORD. Infants receiving prenatal betamethasone demonstrated higher maximal urinary TBARS values during the first 10 days of life than control infants. The length of sample storage from 0 to 3 weeks at –70°C did not significantly affect TBARS measurements. Conclusions: Elevated urinary MDA measurements in the first 10 days are correlated with the risk for ORD. Urinary TBARS concentrations, which are correlated with MDA measurements, can be quantified rapidly and are stable for short-term storage. Our findings suggest that urinary TBARS may be adaptable as a practical tool for assessing the risk for ORD in neonatal intensive care unit patients, allowing clinicians to optimize the use of preventive strategies. Antenatal betamethasone is associated with increased urinary TBARS in the first 10 days of life, indicating that the protective effects of corticosteroids are not mediated through reductions in oxidant-mediated lipid peroxidation.