Clinical trial of tin mesoporphyrin to prevent neonatal hyperbilirubinemia.

OBJECTIVE: To assess the efficacy of the heme oxygenase inhibitor, tin mesoporphyrin (SnMP), to reduce total bilirubin (TB) levels. STUDY DESIGN: Masked, SnMP (4.5 mg kg(-1)), placebo-controlled, multicenter trial of single intramuscular injection to newborns ⩾35 weeks gestational age whose predischarge screening transcutaneous bilirubin (TcB) was >75th percentile. RESULTS: Two hundred and thirteen newborns (median age 30 h) were randomized to treatment with SnMP (n=87) or 'sham' (n=89). We found that the duration of phototherapy was halved. Within 12 h of SnMP administration, the natural TB trajectory was reversed. At age 3 to 5 days, TB in the SnMP-treated group was +8% but sixfold lower than the 47% increase in the sham-treated group (P<0.001). At age 7 to 10 days, mean TB declined 18% (P<0.001) compared with a 7.1% increase among controls. No short-term adverse events from SnMP treatment were noted other than photoreactivity due to inadvertent exposure to white light phototherapy. CONCLUSION: Early, predischarge SnMP administration decreased the duration of phototherapy, reversed TB trajectory and reduced the severity of subsequent hyperbilirubinemia.

Effect of storage on breast milk antioxidant activity.

BACKGROUND: Human milk, which contains compounds beneficial to infants, is often expressed and stored before use. Changes in its antioxidant activity with storage have not been studied. OBJECTIVES: To measure antioxidant activity of fresh, refrigerated (4 degrees C), and frozen human milk (-20 degrees C), stored for two to seven days; to compare the antioxidant activity of milk from mothers delivering prematurely and at term; to compare the antioxidant activity of infant formulas and human milk. METHODS: Sixteen breast milk samples (term and preterm) were collected from mothers within 24 hours of delivery and divided into aliquots. Fresh samples were immediately tested for antioxidant activity, and the rest of the aliquots were stored at -20 degrees C or 4 degrees C to be analysed at 48 hours and seven days respectively. The assay used measures the ability of milk samples to inhibit the oxidation of 2,2'-azino-di-3-(ethylbenzthiazolinesulphonate) to its radical cation compared with Trolox. RESULTS: Antioxidant activity at both refrigeration and freezing temperatures was significantly decreased. Freezing resulted in a greater decrease than refrigeration, and storage for seven days resulted in lower antioxidant activity than storage for 48 hours. There was no difference in milk from mothers who delivered prematurely or at term. Significantly lower antioxidant activity was noted in formula milk than in fresh human milk. CONCLUSIONS: To preserve the antioxidant activity of human milk, storage time should be limited to 48 hours. Refrigeration is better than freezing and thawing.

Urinary thiobarbituric acid-reacting substances as potential biomarkers of intrauterine hypoxia.

BACKGROUND: Currently available clinical tools cannot accurately identify the extent of perinatal hypoxic injuries. During hypoxia, reactive oxygen species cause lipid peroxidation of cell membranes, yielding oxidation products that constitute thiobarbituric acid-reacting substances (TBARS). OBJECTIVE: To see if the concentrations of TBARS excreted in urine would be elevated during the first day of life in term and preterm infants following chronic hypoxia or acute asphyxia. DESIGN: Thiobarbituric acid-reacting substances levels were measured by a spectrophotometric assay in urine samples collected from term and near-term (>/= 34 weeks gestation, n = 22), and preterm (<34 weeks gestation, n = 52) infants on the first day of life. PATIENTS: Infants were admitted to the St Peter's University Hospital (New Brunswick, NJ) neonatal intensive care unit from July 1997 to January 1999. Acute asphyxia was defined as umbilical cord blood pH values less than 7.05, or Apgar scores of less than 5 at 5 minutes. Chronic hypoxia was defined as intrauterine growth retardation or low birth weight (small for gestational age) associated with pregnancy-induced hypertension or reversal of umbilical arterial blood flow. RESULTS: Among term infants, urinary TBARS levels were significantly increased following acute asphyxia (P =.02). Levels of TBARS also tended to be elevated following chronic hypoxia. Urinary TBARS levels in term infants tended to be increased in those requiring mechanical ventilation (P =.05) or delivery room resuscitation (P =.15), as well as in those passing intrauterine meconium (P =.13) or having clinical evidence of hypoxic-ischemic encephalopathy (P =.24). CONCLUSIONS: The results show a correlation between elevated urinary TBARS levels in term and near-term infants, and perinatal hypoxia (as determined by low Apgar scores or umbilical cord blood acidosis). We speculate that TBARS concentrations may be useful as a biomarker for perinatal hypoxic injury in newborns. Further studies are needed to determine whether elevations in TBARS levels are better predictors of the extent of hypoxic injury than existing markers.

Parental compliance with home cardiorespiratory monitoring.

AIMS: To evaluate parental compliance with home cardiorespiratory monitoring of premature infants with apnoea, siblings of infants who died of sudden infant death syndrome (SIDS), and infants with an apparent life threatening event (ALTE), during the first month of use. METHODS: A retrospective review of the first month's recordings was conducted on 39 premature infants with apnoea, 13 siblings of SIDS, and 16 infants with ALTE. All infants were singletons. Recommendations during the study period (1992-1994) were for daily use for 23 hours per day. Measurements were average daily hours of use and consistency of use (daily or variable). Gestational age, maternal age, and socioeconomic status as measured by receipt of public assistance were also recorded. RESULTS: Siblings of SIDS were monitored for fewer hours than were premature or ALTE infants. Only 54% of sibings of SIDS were monitored daily, compared to 87% of premature infants and 93% of ALTEs. Within each diagnostic category socioeconomic status did not affect average hours of monitoring. Consistency of use was more evident in those with private insurance, although the trend did not reach significance. CONCLUSIONS: Parents of infants with apnoea of prematurity or ALTE are highly compliant with cardiorespiratory monitoring recommendations in the first month of monitor usage. Siblings of SIDS are monitored for fewer hours and are less likely to be monitored on a daily basis.

Effects of perinatal hypoxia on serum unbound free fatty acids and lung inflammatory mediators.

Cellular injury during tissue hypoxia is due, in part, to reactive intermediates released by activated leukocytes. We found that the inflammatory mediators tumor necrosis factor (TNF)-alpha, IL-6, and IL-1beta are elevated in situ in lung macrophages on day 14 following exposure of rats to intermittent or chronic hypoxia from birth. Because inflammatory mediators can increase lipolysis in adipocytes, we also measured serum unbound free fatty acids (FFAu)--the biologically active compartment of FFA--in rat pups exposed to intermittent or chronic hypoxia. FFAu values were markedly elevated during the first 2 days of life in all rats, displaying an approximately 3-fold decrease from day 2 to day 3. Exposure to chronic hypoxia significantly increased FFAu levels measured on day 13. Since elevated serum FFAu are known to suppress leukocyte activation, we speculate that increased FFAu levels represent a mechanism for attenuating inflammation and tissue injury following sublethal hypoxia in the perinatal period, either physiologically in the immediate newborn period, or as a late response to ongoing hypoxic insult.

Topographic mapping of brain potentials in the newborn infant: the establishment of normal values and utility in assessing infants with neurological injury.

AIM: To demonstrate that quantitative EEG (qEEG) can be used as a non-invasive measure of brain injury by establishing normative data in term infants and contrasting it with other modalities of brain imaging. DESIGN: qEEG during quiet sleep was performed on 13 healthy full-term infants comprising a normal group and on 10 infants with neurological abnormalities identified on brain imaging studies (abnormal group) at 36-47 wk postconceptional age. Quantitative analysis was performed and topographic maps were produced for each patient. The EEG data from the normal group, after spectral analysis, yielded power data in the delta, theta, alpha, and beta frequency bands and coherence information, which then formed the normative database. qEEG from the infants in the abnormal group was then compared to this normative data. RESULTS: The normal group's mean absolute power in the delta, theta, alpha, and beta bands for all EEG leads combined were 278.48+/-83.83, 31.71+/-10.12, 29.20+/-2.04, and 35.76+/-11.35 uv2, respectively. The median frequency was 1.49+/-0.07, 5.45+/-3.46, 9.74+/-5.11, and 18.01+/-3.38 Hz, respectively. The qEEG was abnormal in all 10 study infants, while abnormalities were noted in the clinical EEG in 4 of 10, in the neuroultrasound in 5 of 10, in the CT in one of 6, and in the MRI in 2 of 2 tested. CONCLUSIONS: qEEG appears to be a useful non-invasive method for measuring brain injury as it correlates well with other modalities of brain imaging and, if corroborated by further study, may, in fact, be more sensitive in determining abnormalities in brain function.

A multicenter long-term safety and efficacy trial of preterm formula supplemented with long-chain polyunsaturated fatty acids.

BACKGROUND: The tissue accretion of long-chain polyunsaturated fatty acids is compromised in infants born prematurely. Human milk contains long-chain polyunsaturated fatty acids, but most preterm infant formulas do not. The long-term effects of preterm formula supplemented with arachidonic acid and docosahexaenoic acid, in proportions typical of those in human milk, were therefore investigated. METHODS: In this double-blind, randomized study, 288 preterm infants received experimental formula (n = 77), unsupplemented (control) formula (n = 78), or human milk (n = 133) until 48 weeks postconceptional age (PCA). Term formula, without supplemental long-chain polyunsaturated fatty acids, was administered from 48 to 92 weeks PCA to formula-fed infants and to infants weaned from human milk. Anthropometric and fatty acid data were assessed by using analysis of variance. RESULTS: At 92 weeks PCA, no statistically significant anthropometric measurement differences were found except for midarm circumference, which was smaller in human milk-fed infants than in those fed formula. Phospholipid concentrations were similar in the experimental and human milk-fed groups, and docosahexaenoic acid levels were significantly greater than in the control group. The types and incidences of adverse events were similar among the feeding groups. CONCLUSIONS: The results of this study demonstrate the efficacy and long-term safety of preterm formula supplemented with long-chain polyunsaturated fatty acids.

Antioxidant capacity and oxygen radical diseases in the preterm newborn.

BACKGROUND: Bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity may be different manifestations of oxygen radical diseases of prematurity (ORDP). OBJECTIVE: To test the hypothesis that the antioxidant capacity of cord blood serum will predict risk of ORDP. DESIGN: An inception cohort of premature neonates was followed up from birth until discharge or death to determine if outcome was related to cord blood serum antioxidant capacity, as determined by a manual assay measuring the relative inhibition of oxidation of 2,2'-azino-di-(3-ethylbenzthiazoline)-6 sulfonic acid (ABTS). Possible correlations between antioxidant capacity and various perinatal factors were also tested. SETTING: Level 3 newborn intensive care unit. PATIENTS: All inborn very low-birth-weight neonates from whom cord blood was available and for whom maternal consent was obtained were included. Newborns who died in the first week of life or who had major congenital malformations were excluded. A convenience sample of newborns weighing more than 1500 g was used to perfect assay and explore confounders. MAIN OUTCOME MEASURES: Significant ORDP was defined as the presence of intraventricular hemorrhage greater than grade 2, retinopathy of prematurity greater than stage 1, bronchopulmonary dysplasia at the postconceptional age of 36 weeks, or necrotizing enterocolitis with the hypothesis that neonates with ORDP will have lower antioxidant capacity in cord blood serum. RESULTS: Serum antioxidant capacity at birth correlated with gestational age for the entire sample of 41 neonates and for the 26 neonates born before 32 weeks' gestation. After correction for gestational age, cord serum antioxidant capacity did not correlate with maternal smoking, preeclampsia, chorioamnionitis, cord pH Apgar scores, or any of the ORDP studied. CONCLUSION: Cord serum antioxidant capacity correlates with gestational age but does not predict ORDP risk.

Spectral analysis of heart variability in the newborn infant.

We investigated the relationship between spectral power and both mean heart rate (HR) and heart rate variability (HRV). Spectral power was calculated using digital heart rate recordings from term infants. Regression analysis revealed a positive correlation between low-frequency (LF) sympathetic power and HR, and a negative correlation between high-frequency (HF) parasympathetic power and HR. HRV correlated positively in all regions of the power spectrum. In awake infants, the contribution of HF power to total power (HF/TP) was significantly decreased. LF power tended to be greater, however, this trend was not statistically significant. By following expected autonomic patterns, the findings of this study confirm that spectral analysis provides a noninvasive method for the assessment of autonomic activity influencing the newborn heart. The correlation between spectral power and HRV can serve as an additional tool in the study of autonomic dysfunction.

Spectral analysis of heart rate variability in premature infants with feeding bradycardia.

An elevated level of baseline parasympathetic activity was noted in a group of premature infants suffering from bradycardia during feeding. At approximately 34 wk post-conceptional age, the heart rates of 12 infants with feeding bradycardia (birth weight = 1539 +/- 279 g; gestational age = 31.0 +/- 1.6 wk) and 10 controls (birth weight = 1710 +/- 304 g; gestational age = 32.0 +/- 1.4 wk) were recorded 1 h before and 1 h after feeding. EKG data were digitized and 3.2-min segments of data were analyzed to determine the spectral power at very low (VLF = 0.003-0.03 Hz), low (LF = 0.03-0.39 Hz), and high (HF = 0.40-1.00 Hz) frequencies. In preterm infants with feeding bradycardia, an elevation in baseline parasympathetic activity was evident before feeding, as indicated by significantly higher HF power and a lower LF/HF ratio. This elevation in baseline parasympathetic activity may contribute to the observed bradycardia during feeding.

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.

Antecedents and neonatal consequences of low Apgar scores in preterm newborns: a population study.

BACKGROUND: To examine the antenatal and early neonatal correlates of low Apgar scores (<3 and <6 at 1 and 5 minutes) in preterm newborns (23-34 weeks' gestation). OBJECTIVE: The use of Apgar scoring for premature newborns remains widespread, despite controversy regarding its reliability as a measure of morbidity and mortality in the neonatal period. DESIGN: A cohort of 852 preterm newborns born during a 34-month period between 1984 and 1987 was studied. Newborns were stratified into 2 groups by gestational age (23-28 weeks and 29-34 weeks), and data were analyzed, controlling for gestational age in single weeks. SETTING: Two academic and 1 community hospital, which together accounted for 83% of all preterm births in a tri-county area of central New Jersey during the study period. PATIENTS: All premature newborns (birth weight <2000 g and gestational age <35 weeks) born in the participating hospitals during the study period were evaluated. MAIN OUTCOME MEASURES: Antecedents included maternal illness during pregnancy, maternal complications of labor and delivery, and fetal heart rate abnormalities during labor and delivery. Consequences included delivery room resuscitation, abnormal physical findings, diagnoses, and therapeutic interventions in the first 6 to 8 hours of life. RESULTS: Premature newborns with low Apgar scores received more cardiopulmonary resuscitation in the delivery room and in the first 6 to 8 hours of neonatal intensive care. Mortality was significantly increased among newborns with low Apgar scores (54% vs. 26% in the 23- to 28-week stratum, 30% vs 6% in the 29- to 34-week stratum). Newborns with low Apgar scores in the 29- to 34-week stratum more often required intubation, positive pressure ventilation, and umbilical vessel catheterization. Newborns with low Apgar scores had higher rates of bradycardia, pneumothoraces, acidosis, and increased oxygen requirement during the first 6 to 8 hours of life. Maternal illness, complications of labor and delivery;, and fetal heart rate decelerations did not correlate with subsequent Apgar scores of newborns. The presence of severe bradycardia (<90/min) and fetal heart rate accelerations correlated with low Apgar scores in the 29- to 34-week group. CONCLUSION: Low Apgar scores are associated with increased neonatal morbidity and mortality in preterm newborns. Antenatal maternal history, and pregnancy complications are not clearly associated with low Apgar scores. Therefore, the Apgar score is a useful tool in assessing neonatal short-term prognosis and the need for intensive care among preterm newborns.

Maternal behavior toward premature twins: implications for development.

Assisted reproductive techniques and fertility enhancing therapies have increased multiple births and, therefore, the risk of prematurity and its developmental consequences. Parent intervention is an effective source of compensation for the cognitive effects of prematurity. We hypothesized that relative to parents of preterm singletons, parents of preterm twins are less able to provide such enhancing care, resulting in a developmental disadvantage for preterm twins. Maternal-infant interactions of premature singletons (n = 22; birth weight = 1668 +/- 350 g, gestational age = 32.3 +/- 2.1 weeks) and premature twins (n = 8; birth weight = 1618 +/- 249 g; gestational age = 32.0 +/- 2.6 weeks) with comparable demographic and medical status were observed at home at 1 and 8 months corrected age using a 30 min checklist of developmentally facilitative behavior. Mental (MDI) and psychomotor (PDI) indices of the Bayley Scales of Infant Development and Caldwell Home Observations for Measurement of the Environment (HOME) inventories were administered (18 months corrected age). Compared with mothers of premature singletons, mothers of premature twins exhibited fewer initiatives (P < 0.001) and responses (P < 0.01) and were less responsive to positive signals (P < 0.01) and crying (P < 0.01). Unprompted by the infant, twin mothers lifted or held (P < 0.05), touched (P < 0.01), patted (P < 0.05) or talked (P < 0.01) less. Singleton MDIs surpassed twins (119.4 +/- 7.7 vs 103.6 +/- 7.7; P < 0.01). Maternal verbal behavior and the acceptance of child factor (HOME), both favoring singletons, correlated with MDI (R-square = 0.46, P < 0.0002). Mothers of premature twins exhibited fewer initiatives and responses toward offspring than did mothers of premature singletons. Maternal behavior was predictive of cognitive development.

Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants. Developmental Epidemiology Network Investigators.

Echolucent images (EL) of cerebral white matter, seen on cranial ultrasonographic scans of very low birth weight newborns, predict motor and cognitive limitations. We tested the hypothesis that markers of maternal and feto-placental infection were associated with risks of both early (diagnosed at a median age of 7 d) and late (median age = 21 d) EL in a multi-center cohort of 1078 infants <1500 x g. Maternal infection was indicated by fever, leukocytosis, and receipt of antibiotic; fetoplacental inflammation was indicated by the presence of fetal vasculitis (i.e. of the placental chorionic plate or the umbilical cord). The effect of membrane inflammation was also assessed. All analyses were performed separately in infants born within 1 h of membrane rupture (n = 537), or after a longer interval (n = 541), to determine whether infection markers have different effects in infants who are unlikely to have experienced ascending amniotic sac infection as a consequence of membrane rupture. Placental membrane inflammation by itself was not associated with risk of EL at any time. The risks of both early and late EL were substantially increased in infants with fetal vasculitis, but the association with early EL was found only in infants born > or =1 after membrane rupture and who had membrane inflammation (adjusted OR not calculable), whereas the association of fetal vasculitis with late EL was seen only in infants born <1 h after membrane rupture (OR = 10.8; p = 0.05). Maternal receipt of antibiotic in the 24 h just before delivery was associated with late EL only if delivery occurred <1 h after membrane rupture (OR = 6.9; p = 0.01). Indicators of maternal infection and of a fetal inflammatory response are strongly and independently associated with EL, particularly late EL.

Evaluation of a long-chain polyunsaturated fatty acid supplemented formula on growth, tolerance, and plasma lipids in preterm infants up to 48 weeks postconceptional age.

BACKGROUND: The last trimester of pregnancy is a period of rapid accretion of long-chain polyunsaturated fatty acids, both in the central nervous system and the body as a whole. Human milk contains these fatty acids, whereas some preterm infant formulas do not. Infants fed formulas without these fatty acids have lower plasma and erythrocyte concentrations than infants fed human milk. Preclinical and clinical studies have demonstrated that single-cell sources (algal and fungal) of long-chain polyunsaturated fatty acids are bioavailable. A balanced addition of fatty acids from these oils to preterm formula results in blood fatty acid concentrations in low birth weight infants comparable to those of infants fed human milk. METHODS: In the present study the growth, acceptance (overall incidence of discontinuation, reasons for discontinuation, overall incidence and type of individual adverse events), and plasma fatty acid concentrations were compared in three groups of infants fed a long-chain polyunsaturated fatty acid-supplemented preterm infant formula, an unsupplemented control formula, or human milk. The study was prospective, double-blind (formula groups only), and randomized (formula groups only). Two hundred eighty-eight infants were enrolled (supplemented formula group, n = 77; control formula group, n = 78; human milk group, n = 133). RESULTS: Anthropometric measurements at enrollment, at first day of full oral feeding, and at both 40 and 48 weeks postconceptional age did not differ between the formula groups, whereas the human milk-fed group initially grew at a lower rate. The incidence of severe adverse events was rare and not significantly different between formula groups. The groups fed either human milk or supplemented formula had long-chain polyunsaturated fatty acid concentrations higher than those in the control formula group. CONCLUSIONS: The results of this study demonstrate the safety and efficacy of a preterm formula supplemented with long-chain polyunsaturated fatty acids from single-cell oils.

Heart rate and oxygen saturation correlates of infant apnea.

OBJECTIVE: To analyze the effects of apnea duration on changes in heart rate and oxygen saturation and to examine the temporal relationships among these variables. STUDY DESIGN: An event analysis sheet was designed to analyze numerous variables reflecting changes in heart rate and oxygen saturation associated with infant apnea. From July 1, 1991 through June 30, 1992 we identified 32 infants enrolled in The Infant Apnea Program at St. Peter's Medical Center, New Brunswick, NJ who had apnea > or = 15 seconds in duration on consecutive 12-hour multichannel recordings of heart rate, thoracic impedance, nasal thermistry, and oxygen saturation. The apnea epochs of these patients were subdivided into apnea of short (10 to 14 seconds), medium (15 to 19 seconds), and long (> or = 20 seconds) duration, and a total of 236 apnea epochs were analyzed. The significance of differences was assessed by analysis of variance and Newman-Keuls multiple comparisons. RESULTS: We found that the duration of apnea has significant effects on perturbations in both heart rate and oxygen saturation, however, the degree of oxygen desaturation can not be predicted by the perturbation in heart rate. Analysis of the temporal relationship of apnea, bradycardia, and oxygen desaturation reveals that, although apnea precedes both heart rate and oxygen saturation drops in most infants as the length of apneic interval increases, the interval between apnea onset and associated drops in heart rate and/or oxygen saturation also increases. CONCLUSION: Oxygen saturation monitoring may provide important physiologic data that can not be assessed by cardiorespiratory monitoring alone.

Developmental implications of head growth following intracranial hemorrhage.

This study examined the association between head size at birth, discharge, and 1 year and developmental outcome at 1 year in preterm infants, with and without intracranial hemorrhages (ICH) or associated periventricular echodensities (PVE). The data indicated that most sick preterm infants with small heads at discharge achieved appropriate head sizes at 1 year. Analyses of the 1-year mental and motor performances of 125 subjects revealed that for subjects who did not develop ICH, appropriate head sizes at birth and discharge were associated with good developmental outcome, whereas infants with small heads (< two standard deviations below the mean for age) before hospital discharge were more likely to show poorer developmental outcome at 1 year. For subjects with ICH, birth and discharge head circumference were not predictive of 1-year developmental status; however, normal head size at 1 year was associated with better outcome. This was true for children with transient PVE as well. However, persistent periventricular echodensities were associated with both mental and motor deficits at 1 year, regardless of head growth.

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) at r = .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 score's components.

Prolonged rupture of membranes in the term newborn.

Of 8791 consecutive newborns, we studied 205 (2.3%) women with a history of prolonged rupture of membranes (PROM) greater than 24 hr to assess the incidence of infection, to identify the rate of clinical symptoms, and to examine the use of the white blood count (WBC) and neutrophil values as screening tools to predict infection. Blood culture and complete blood counts (CBC) were obtained in 175 (85%). Fifteen (8.2%) had positive blood cultures including group B streptococcus, streptococcus viridans, streptococcus pneumoniae, staphlococcus epidermidis, and staphlococcus aureus. In the remaining 8586 infants born to mothers without PROM, 10 had positive blood cultures for an incidence of 0.1%. In the PROM group, the six who manifested clinical symptoms had abnormal CBCs; abnormal white blood count (2), abnormal neutrophil count (5), high band/metatamyelocyte count (4), and increased immature to total neutrophil ratio (4). Of the nine asymptomatic infants, seven (78%) had abnormal CBCs, five (56%) with a high WBC, five (56%) had a high neutrophil count, two (22%) had a high band/metatamyelocyte count, and one a high immature to total neutrophil ratio. CBC values were obtained from infants with PROM and negative blood cultures. Five of these 15 controls had an abnormal CBC. In the term newborn, PROM is associated with significantly increased incidence of positive blood cultures. The sensitivity of the CBC was 86% and specificity 66%. In view of this data a conservative clinical approach utilizing blood cultures and CBC evaluations in the management of PROM is warranted.

Maternal receipt of magnesium sulfate does not seem to reduce the risk of neonatal white matter damage.

OBJECTIVE: To investigate whether in utero exposure to magnesium sulfate is associated with a lower incidence of cranial ultrasonographic abnormalities that predict cerebral palsy in infants who weigh less than 1501 g at birth. DESIGN: For a prospective study of the antecedents of cranial ultrasonographic abnormalities, we enrolled infants who weighed 500 to 1500 g when born at five institutions. Data were collected by interview of the mothers and review of medical records. Protocol cranial ultrasonograms were obtained as close as possible to postnatal days 1, 7, and 21. Abnormality on cranial ultrasound scans was determined by a consensus committee of three sonologists. RESULTS: Of the 1518 infants for whom we knew whether the mothers received magnesium sulfate, the first protocol cranial ultrasound scan was available for 1409 infants, the second for 1274 infants, and the third for 1050 infants. Forty-five percent of infants were exposed to magnesium sulfate before delivery. The major correlates of magnesium sulfate exposure were receipt of antenatal corticosteroids and a diagnosis of preeclampsia and/or pregnancy-induced hypertension. Maternal magnesium receipt was not associated with a reduced incidence of hypoechoic or hyperechoic images of white matter parenchyma, intraventricular hemorrhage, or ventriculomegaly, even when the sample was stratified by each of six potential confounders. When adjustment was made for gestational age, a measure of birth weight for gestational age, antenatal corticosteroid exposure, preeclampsia and pregnancy-induced hypertension, route of delivery, and the occurrence of any labor, the risk ratios for each cranial ultrasonographic abnormality associated with magnesium sulfate exposure hovered close to 1. CONCLUSION: Maternal receipt of magnesium sulfate does not seem to be associated with an appreciably reduced risk of cranial ultrasonographically defined neonatal white matter damage, intraventricular hemorrhage, or ventriculomegaly.