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OBJECTIVE. The goals were to identify the blood pressures of extremely low gestational age newborns that prompt intervention, to identify other infant characteristics associated with receipt of therapies intended to increase blood pressure, and to assess the interinstitutional variability in the use of these therapies. METHODS. The cohort included 1507 extremely low gestational age newborns born at 23 weeks to 27 6/7 weeks of gestation, at 14 institutions, between March 2002 and August 2004; 1387 survived the first postnatal week. Blood pressures were measured as clinically indicated. Interventions were grouped as any treatment (ie, vasopressor and/or fluid boluses of >10 mL/kg) and vasopressor treatment, and logistic regression analyses were performed. RESULTS. At each gestational age, the lowest mean arterial pressures in treated and untreated infants tended to increase with advancing postnatal age. Infants who received any therapy tended to have lower mean arterial pressures than infants who did not, but uniform thresholds for treatment were not apparent. The proportion of infants receiving any treatment decreased with increasing gestational age from 93% at 23 weeks to 73% at 27 weeks. Treatment nearly always began during the first 24 hours of life. Lower gestational age, lower birth weight, male gender, and higher Score for Neonatal Acute Physiology-II values were associated with any treatment and vasopressor treatment. Institutions varied greatly in their tendency to offer any treatment and vasopressor treatment. Neither the lowest mean arterial pressure on the day of treatment nor other characteristics of the infants accounted for center differences in treatment. CONCLUSIONS. Blood pressure in extremely premature infants not treated for hypotension increased directly with both increasing gestational age and postnatal age. The decision to provide treatment was associated more strongly with the center where care was provided than with infant attributes. Key Words premature infant, blood pressure, hypotension, HYPOTENSION IS ONE of the most common diagnoses assigned to extremely low gestational age newborns (ELGANs), and treatments to increase blood pressure are often used in this population. (1) These [...]

OBJECTIVE The goals were to identify predictor variables and to develop scoring systems and classification trees to predict death/disability or death in infants with hypoxic-ischemic encephalopathy. METHODS. Secondary analysis of data from the multicenter, randomized, controlled, National Institute of Child Health and Human Development Neonatal Research Network trial of hypothermia in hypoxioischemic encephalopathy was performed. Data for 205 neonates diagnosed as having hypoxic-ischemic encephalopathy were studied. Logistic regression analysis was performed by using clinical and laboratory variables available within 6 hours of birth, with death or moderate/ severe disability at 18 to 22 months or death as the outcomes. By using the identified variables and odds ratios, scoring systems to predict death/disability or death were developed, weighting each predictor in proportion to its odds ratio. In addition, classification and regression tree analysis was performed, with recursive partitioning and automatic selection of optimal cutoff points for variables. Correct classification rates for the scoring systems, classification and regression tree models, and early neurologic examination were compared. RESULTS. Correct classification rates were 78% for death/disability and 71% for death with the scoring systems, 80% and 77%, respectively, with the classification and regression tree models, and 67% and 73% with severe encephalopathy in early neurologic examination. Correct classification rates were similar in the hypothermia and control groups. CONCLUSIONS. Among neonates diagnosed as having hypoxic-ischemic encephalopathy, the classification and regression tree model, but not the scoring system, was superior to early neurologic examination in predicting death/disability. The 3 models were comparable in predicting death. Only a few components of the early neurologic examination were associated with poor outcomes. These scoring systems and classification trees, if validated, may help in assessments of prognosis and may prove useful for risk-stratification of infants with hypoxic-ischemic encephalopathy for clinical trials. Key Words logistic models, decision trees, asphyxia neonatorum, hypoxia-ischemia, brain, predictive value of tests Abbreviations CART--classification and regression tree GMFCS gross motor function classification system HIE--hypoxic-ischemic encephalopathy ROC--receiver operating characteristic NICHD--National Institute of Child Health and Human Development CI--confidence interval, HYPOXIC-ISCHEMIC ENCEPHALOPATHY (HIE) is a major contributor to neonatal death and morbidity. An estimated 23% of the 4 million neonatal deaths (1) and 8% of all deaths at A recent [...]

OBJECTIVE The purpose of this work was to evaluate the effects of a 42-day tapering course of dexamethasone on blood pressure and anthropometric measurements in school-age children who were born with very low birth weight. METHODS. Sixty-eight children, who as neonates participated in a randomized placebo-controlled trial of a 42-day tapering course of dexamethasone (n = 38, dexamethasone; n = 30, placebo) to facilitate weaning from the ventilator, were seen at a median of 9 years of age. Participants underwent measurements of systolic blood pressure, diastolic blood pressure, mid-arm circumference, triceps skinfold thickness, height, and weight. Mann-Whitney U tests were used to compare groups, and Spearman coefficients were used to examine correlations between variables. RESULTS. Comparing dexamethasone- and placebo-treated children, we found no differences in systolic blood pressure, mid-arm circumference, triceps skinfold thickness, height, weight, or body mass index. Twenty-nine percent of all subjects had systolic blood pressure and/or diastolic blood pressure [greater than or equal to] 90th percentile for age and gender. Thirty percent of all subjects had body mass index [greater than or equal to] 85th percentile for age and gender. CONCLUSIONS. In a group of preterm very low birth-weight infants at high risk for chronic lung disease, we found no effects of dexamethasone on blood pressure or anthropometric measurements at 8 to 11 years of age. Of concern is that a high proportion in this sample had blood pressure [greater than or equal to] 90th percentile and/or body mass index [greater than or equal to] 85th percentile. Key Words prematurity, children, glucocorticoid, very low birth weight, growth Abbreviations VLBW--very low birth weight CLD--chronic lung disease GCRC--General Clinic Research Center BMI--body mass index SBP--systolic blood pressure DBP--diastolic blood pressure, IMPROVEMENTS IN NEONATAL care have resulted in an increased rate of survival of very low birth-weight (VLBW) infants; however, the frequency of neonatal chronic lung disease (CLD) also has increased. [...]

Objective. Monitoring of regulated physiologic processes using physiomarkers such as heart rate variability may be important in the early diagnosis of subacute, potentially catastrophic illness. Early in the course of neonatal sepsis, there are physiomarkers of reduced heart rate variability and transient decelerations 7similar to fetal distress. The goal of this study was to determine the degree of increased risk for sepsis, urinary tract infection (UTI), and death when these abnormal heart rate characteristics (HRC) were observed. 8 Methods. We monitored 1022 infants at 2 tertiary care NICUs, 458 of whom were very low birth weight. We calculated an HRC index from validated regression models relating mathematical features of heart rate time series and histograms to episodes of illness. We calculated the risks for adverse events of sepsis, UTI, and death for infants stratified by HRC measurements. Results. Compared with infants with low-risk HRC measurements, infants with high-risk HRC measurements had 5- to 6-fold increased risk for an adverse event in the next day and 3-fold increased risk in the next week. Laboratory tests that were relevant to infection added information to HRC measurements. Infants with both high-risk HRC and abnormal laboratory tests had 6- to 7-fold increased risk for an adverse event in the next day compared with infants who had neither. Conclusion. HRC are noninvasively monitored physiomarkers that identify infants in the NICU who are at high risk for sepsis, UTI, and death. Pediatrics 2005;116: 1070-1074; infant, mortality prediction, sepsis, urinary tract infections, physiomarker. ABBREVIATIONS. HRC, heart rate characteristics; UTI, urinary tract infection; UVA, University of Virginia; HR, heart rate; WFU, Wake Forest University; CONS, coagulase-negative Staphylococcus; NICHD, National Institute of Child Health and Human Development; VLBW, very low birth weight., The common clinical scenario of abrupt deterioration of a stable infant in the NICU usually prompts the consideration of sepsis. Establishing the diagnosis of neonatal sepsis using current clinical and [...]

Objective. Severe abnormalities of the head ultrasound (HUS) are important predictors of cerebral palsy (CP) and mental retardation, and a normal HUS usually ensures the absence of major impairments. With the increasing survival of extremely low birth weight (ELBW) infants (birth weight Methods. Study infants were ELBW infants who were cared for in Neonatal Research Network centers in the years 1995-1999, had a normal early and late HUS, survived to discharge, and returned for follow-up assessments at 18 to 22 months' corrected age. The outcomes of interest were a score Results. Of 1749 infants with a normal early and late HUS (performed at a mean age of 6 and 47 days, respectively), 1473 (84%) returned for follow-up assessment. Infants had a birth weight of 792 [+ or -] 134 g (mean [+ or -] SD) and gestational age of 26 [+ or -] 2 weeks. Rates of CP and MDI Conclusions. Nearly 30% of ELBW infants with a normal HUS had either CP or a low MDI. Risk factors that are associated with this high rate of adverse outcomes include pneumothorax, prolonged exposure to mechanical ventilation, and educational and economic disadvantage. Improvements in pulmonary care to reduce duration of ventilation and avoid air leaks might improve neurodevelopmental outcome for ELBW infants. Pediatrics 2005;115:673-680; brain imaging, extremely preterm infants, intraventricular hemorrhage, neurobehavioral development., ABBREVIATIONS. ELBW, extremely low birth weight; CP, cerebral palsy; CLD, chronic lung disease; HUS, head ultrasound; IVH, intraventricular hemorrhage; SES, socioeconomic status; PDA, patent ductus arteriosus; MDI, Mental Developmental Index; [...]

Objectives. Parents of premature infants often perceive their infants as medically vulnerable. High parental perception of child vulnerability (PPCV) is associated with disproportionately high health care utilization. The objectives of this study were to determine whether higher PPCV is correlated with worse developmental outcome in premature infants at 1-year adjusted age and to identify factors, present at neonatal discharge, that predict high PPCV. Methods. This prospective cohort study assessed mothers of 116 premature infants who were [less than or equal to] 32 weeks' gestation and required supplemental oxygen at 36 weeks postmenstrual age. At neonatal discharge, mothers completed the Spielberger State Anxiety Inventory, Beck Depression Inventory, Impact on Family Scale, Life Orientation Test, General Health Survey, and Medical Outcomes Study social support survey. At 1-year adjusted age, child development was assessed using the Bayley Scales of Infant Development and Vineland Adaptive Behavior Scales, and mothers completed the Vulnerable Child Scale, a 16-item self-report measure of PPCV. Chart review was performed to determine the presence or absence of specific indicators of medical vulnerability at 1-year adjusted age. Results. Mean infant gestational age and birth weight were 26.5 [+ or -] 2.5 weeks and 894 [+ or -] 287 g. A total of 69% of mothers were white, and 78% were high school graduates. Higher PPCV (lower Vulnerable Child Scale score) was correlated with lower scores on the Vineland Adaptive Behavior Composite and Bayley Psychomotor Developmental Index but not on the Bayley Mental Developmental Index. After controlling for the presence of 1 or more indicators of medical vulnerability, higher PPCV was still correlated with lower adaptive development. This correlation was stronger in the group of children with no indicators of medical vulnerability. In univariate analyses, higher PPCV was predicted by nonfirstborn status; longer neonatal hospitalization; higher maternal anxiety and depression; greater impact of the illness on the family; and lower maternal optimism, life satisfaction, and social support. PPCV was not associated with maternal age, education, marital status, income, or ethnicity or with child gender, gestational age, birth weight, or length of mechanical ventilation. A linear regression model containing all variables significant at the univariate level explained 29% of the variance in PPCV. Maternal anxiety was the only variable that was statistically significant in the full model. Conclusions. Higher PPCV is associated with worse developmental outcome in premature infants at 1-year adjusted age. Maternal anxiety at neonatal discharge predicts later high PPCV. Interventions to prevent or decrease PPCV in premature infants should be targeted at parents who are more anxious at hospital discharge. Pediatrics 2004;113:267-273; vulnerable child syndrome, parental perceptions, vulnerability, prematurity., Children who are perceived by their parents as vulnerable have an increased risk of behavior problems, difficult parent-child interactions, (1-3) and disproportionately high health care utilization. (4-6) In their original [...]

The increasing number of very low birth weight infants who survive does not seem to have brought a corresponding increase in the number of children with cerebral palsy. Very low birth rate children have 40 to 100 times the risk of cerebral palsy as normal weight children. Of 2,076 very low birth weight infants born between 1982 and 1994, 1,568 survived to one year, at which time they were examined. During this time, mortality decreased from 36.8% to 13.8%, and the incidence of cerebral palsy dropped from 11.3% to 5.2%., Objective. To analyze whether the increasing survival of very low birth weight infants during the 1980s and 1990s has increased the risk of cerebral palsy among survivors. Methods. The study cohort consisted of 2076 consecutively born infants, with birth weights of 500 to 1500 g and no major anomaly, born July 1, 1982, through June 30, 1994, to residents of a 17-county region in North Carolina. These infants had a mean birth weight of 1096 g (standard deviation, 251 g) and a mean gestational age of 29 weeks (standard deviation, 3 weeks). One thousand five hundred sixty-eight infants (76%) survived to 1 year adjusted age, at which point 1282 infants (82%) were examined at our medical center. The diagnosis of cerebral palsy was made only if the examining pediatrician and a pediatric physical therapist agreed on the diagnosis. To analyze trends across time, the Cochran-Armitage [Chi square] test and logistic regression were applied to data for infants categorized into six 2-year epochs according to year of birth. Results. Mortality did not change significantly through 1990, and then began to decrease in 1990 to 1994. During the study period, mortality decreased from 36.8% between 1982 and 1984, to 13.8% between 1992 and 1994. The prevalence of cerebral palsy among survivors was constant from 1982 to 1988 (11.3%), decreased slightly from 1988 to 1990 (9.2%), and was lowest in 1990 to 1994 (5.2%). These secular trends in mortality and cerebral palsy risk remained significant when adjusted for gestational age, gender, and race. When adjusted for surfactant use, the trend in mortality was no longer significant, whereas the trend in cerebral palsy risk persisted. Conclusions. The increasing survival of very low birth weight infants in the 1980s and 1990s has not resulted in an increased prevalence of cerebral palsy among survivors. Pediatrics 1998;101:642-647; prematurity, infant mortality, cerebral palsy, very low birth weight, surfactant., Very low birth weight infants have a risk of cerebral palsy that is between 40 and 100 times greater than that of normal birth weight infants.[1] Because of improving rates [...]

Although the survival rates of extremely low birth weight (ELBW) infants have dramatically increased, there does not appear to be an increase in major developmental problems detected in these surviving infants at one year of age. A total of 513 ELBW infants born over a sixteen-year period were grouped into three birth epochs. Steadily increasing survival rates of 20%, 36%, and 59% were seen over time. The 209 surviving infants who were examined at one year of age showed the relative amounts of severe developmental impairments to remain proportionately stable at 25%, 28% and 21%., Objective. Because the survival rate has increased for extremely low birth weight neonates, many have raised the concern that the rate of developmental disability among survivors will also increase. To address this concern, we analyzed changes over time in survival and major neurosensory impairment in a sample of extremely low birth weight infants born between July 1, 1979, and June 30, 1994. Methods. The study sample included 513 infants with birth weights of 501 to 800 g who were cared for in either of the two neonatal intensive care units that serve a 17-county region in northwest North Carolina and who were born to mothers residing in that region. At 1 year of age (corrected for gestation), survivors were examined by a pediatrician and were tested using the Bayley Scales of Infant Development. Major neurosensory impairment was defined as cerebral palsy, a Bayley Mental Developmental Index [is less than] 68, or blindness. A total of 209/216 (97%) of survivors were examined at 1 year of age. Epoch of birth was defined as follows: epoch 1, July 1, 1979 to June 30, 1984; epoch 2, July 1, 1984 to June 30, 1989; and epoch 3, July 1, 1989 to June 30, 1994. Results. Survival rates for epochs 1, 2, and 3 were, respectively, 24/120 (20%), 63/175 (36%), and 129/218 (59%). In contrast, the proportions with a major neurosensory impairment did not increase over time; rates for successive epochs were 6/24 (25%), 17/61 (28%), and 26/ 124 (21%). Rates of cerebral palsy were 3/24 (13%), 12/61 (20%), and 9/124 (7%); rates of delayed mental development were 4/24 (17%), 12/61 (20%), and 17/124 (14%); and rates of blindness were 2/24 (8%), 0/62, and 5/124 (4%), respectively. Conclusions. This analysis suggests that the increasing survival of extremely low birth weight neonates since the late 1970s has not resulted in an increased rate of major developmental problems identifiable at 1 year of age. Pediatrics 1997;100:982-986; extremely low birth weight, prematurity, cerebral palsy, developmental outcome., ABBREVIATIONS. ELBW, extremely low birth weight; GA, gestational age (in weeks); CP, cerebral palsy; MDI, Bayley Mental Development Index; OR, odds ratio; CI, confidence interval. Numerous studies have indicated that [...]

To the Editor.-- The conclusion reached by O'Shea and colleagues,[1] that postnatal dexamethasone is associated with an increased risk of cerebral palsy, is undermined by important differences in gestational age [...]

OBJECTIVES. Premature infants with chronic lung disease benefit from comprehensive care, which typically is based in tertiary medical centers. When such centers are not easily accessible, alternative models of care [...]

A response by T. Michael O'Shea and colleagues to a letter to the editor about their article "Human milk intake and retinopathy of prematurity in extremely low birth weight infants" is presented.

Background and Objectives: Experts hypothesized increased weight gain in children associated with the coronavirus disease 2019 (COVID-19) pandemic. Our objective was to evaluate whether the rate of change of child body mass index (BMI) increased during the COVID-19 pandemic compared with prepandemic years., Methods: The study population of 1996 children ages 2 to 19 years with at least 1 BMI measure before and during the COVID-19 pandemic was drawn from 38 pediatric cohorts across the United States participating in the Environmental Influences on Child Health Outcomes-wide cohort study. We modeled change in BMI using linear mixed models, adjusting for age, sex, race, ethnicity, maternal education, income, baseline BMI category, and type of BMI measure. Data collection and analysis were approved by the local institutional review board of each institution or by the central Environmental Influences on Child Health Outcomes institutional review board., Results: BMI increased during the COVID-19 pandemic compared with previous years (0.24 higher annual gain in BMI during the pandemic compared with previous years, 95% confidence interval 0.02 to 0.45). Children with BMI in the obese range compared with the healthy weight range were at higher risk for excess BMI gain during the pandemic, whereas children in higher-income households were at decreased risk of BMI gain., Conclusions: One effect of the COVID-19 pandemic is an increase in annual BMI gain during the COVID-19 pandemic compared with the 3 previous years among children in our national cohort. This increased risk among US children may worsen a critical threat to public health and health equity., (Copyright © 2022 by the American Academy of Pediatrics.)

Objective: Invasive candidiasis is a leading cause of infection-related morbidity and mortality in extremely low birth weight (<1000-g) infants. We quantified risk factors that predict infection in premature infants at high risk and compared clinical judgment with a prediction model of invasive candidiasis., Methods: The study involved a prospective observational cohort of infants≤1000 g birth weight at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. At each sepsis evaluation, clinical information was recorded, cultures were obtained, and clinicians prospectively recorded their estimate of the probability of invasive candidiasis. Two models were generated with invasive candidiasis as their outcome: (1) potentially modifiable risk factors; and (2) a clinical model at time of blood culture to predict candidiasis., Results: Invasive candidiasis occurred in 137 of 1515 (9.0%) infants and was documented by positive culture from ≥1 of these sources: blood (n=96); cerebrospinal fluid (n=9); urine obtained by catheterization (n=52); or other sterile body fluid (n=10). Mortality rate was not different for infants who had positive blood culture compared with those with isolated positive urine culture. Incidence of candida varied from 2% to 28% at the 13 centers that enrolled≥50 infants. Potentially modifiable risk factors included central catheter, broad-spectrum antibiotics (eg, third-generation cephalosporins), intravenous lipid emulsion, endotracheal tube, and antenatal antibiotics. The clinical prediction model had an area under the receiver operating characteristic curve of 0.79 and was superior to clinician judgment (0.70) in predicting subsequent invasive candidiasis., Conclusion: Previous antibiotics, presence of a central catheter or endotracheal tube, and center were strongly associated with invasive candidiasis. Modeling was more accurate in predicting invasive candidiasis than clinical judgment.

Background: Studies of the relationship between ultrasound images from preterm newborns and developmental delay most often are based on small samples defined by birth weight and exclude infants not testable with standardized assessments., Methods: We evaluated associations between ultrasound-defined lesions of the brain and developmental delays at 24 months' corrected age in 1017 children born before the 28th postmenstrual week. Brain ultrasound scans were read for concordance on 4 lesions: intraventricular hemorrhage, moderate/severe ventriculomegaly, white matter echodense/hyperechoic lesions, and white matter echodense/hypoechoic lesions and 2 diagnoses-periventricular leukomalacia and periventricular hemorrhagic infarction. Certified examiners, who were not aware of the infants' ultrasound findings, administered the Bayley Scales of Infant Development-Second Edition. Children with an impairment (eg., blindness) that precluded testing with the Bayley Scales and those for whom >2 test items were omitted were classified using the Vineland Adaptive Behavior Scales Motor Skills Domain instead of the Psychomotor Development Index and the Adaptive Behavior Composite instead of the Mental Development Index., Results: Fully 26% of all of the children had delayed mental development (ie, Mental Development Index < 70), and 31% had delayed psychomotor development (ie, Psychomotor Development Index < 70). Ultrasound abnormalities were more strongly associated with low Psychomotor Development Index than with low Mental Development Index. Children without cranial ultrasound abnormality had the lowest probability (23% and 26%) of delayed mental or psychomotor development. Moderate/severe ventriculomegaly was associated with a more than fourfold increase in the risk of psychomotor delay and an almost threefold increase in the risk of mental delay. Echolucency was the next best predictor of delayed mental and psychomotor development. The probability of low scores varied with the number of zones involved and with the location of echolucency. At particularly high risk were infants with bilateral cerebellar hemorrhage, co-occurring ventriculomegaly and echolucency bilateral echolucency, or echolucency located posteriorly., Conclusions: Focal white matter damage, as characterized by echolucent/hypoechoic lesion, and diffuse damage, as suggested by late ventriculomegaly, are associated with delayed mental and psychomotor development.

Objective: Establishing enteral feeding is an important goal in the care of very low birth weight infants. In such infants, receipt of >/=50 mL/kg per day human milk during hospitalization has been associated with shorter time to full enteral feeding. The objective of this study was to determine whether high proportions (>/=50%) of human milk during feeding advancement are associated with shorter time to full enteral feeding and improved feeding tolerance., Methods: This was a prospective cohort study of very low birth weight infants (n = 127) who were grouped into low (<50%; n = 34) and high (>/=50%; n = 93) human milk consumption groups according to their human milk proportion of enteral feeding during the time of feeding advancement. The primary outcomes of interest were ages at which 100 and 150 mL/kg per day enteral feedings were achieved., Results: The high human milk group reached 100 mL/kg per day enteral feeding 4.5 days faster than the low human milk group. The high human milk group reached 150 mL/kg per day enteral feeding 5 days faster than the low human milk group. After adjustment for gestational age, gender, and respiratory distress syndrome, times to reach 100 and 150 mL/kg per day were significantly shorter for those in the high human milk group. Infants in the high human milk group had a greater number of stools per day; other indicators of feeding tolerance were not statistically different., Conclusion: In infants who weighed