OBJECTIVES. The objectives of this study were to assess whether (1) in-hospital growth velocity is predictive of neurodevelopmental and growth outcomes at 18 to 22 months’ corrected age among extremely low birth weight (ELBW) infants and (2) in-hospital growth velocity contributes to these outcomes after controlling for confounding demographic and clinical variables. METHODS. Infants 501 to 1000 g birth weight from a multicenter cohort study were divided into quartiles of in-hospital growth velocity rates. Variables considered for the logistic-regression models included gender, race, gestational age, small for gestational age, mother’s education, severe intraventricular hemorrhage, periventricular leukomalacia, age at regaining birth weight, necrotizing enterocolitis, late-onset infection, bronchopulmonary dysplasia, postnatal steroid therapy for pulmonary disease, and center. RESULTS. Of the 600 discharged infants, 495 (83%) were evaluated at 18 to 22 months’ corrected age. As the rate of weight gain increased between quartile 1 and quartile 4, from 12.0 to 21.2 g/kg per day, the incidence of cerebral palsy, Bayley II Mental Developmental Index (MDI) CONCLUSIONS. These analyses suggest that growth velocity during an ELBW infant’s NICU hospitalization exerts a significant, and possibly independent, effect on neurodevelopmental and growth outcomes at 18 to 22 months’ corrected age.

Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants.

Objectives. The purposes of this study were to report the neurodevelopmental, neurosensory, and functional outcomes of 1151 extremely low birth weight (401–1000 g) survivors cared for in the 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network, and to identify medical, social, and environmental factors associated with these outcomes. Study Design. A multicenter cohort study in which surviving extremely low birth weight infants born in 1993 and 1994 underwent neurodevelopmental, neurosensory, and functional assessment at 18 to 22 months9 corrected age. Data regarding pregnancy and neonatal outcome were collected prospectively. Socioeconomic status and a detailed interim medical history were obtained at the time of the assessment. Logistic regression models were used to identify maternal and neonatal risk factors for poor neurodevelopmental outcome. Results. Of the 1480 infants alive at 18 months of age, 1151 (78%) were evaluated. Study characteristics included a mean birth weight of 796 ± 135 g, mean gestation (best obstetric dates) 26 ± 2 weeks, and 47% male. Birth weight distributions of infants included 15 infants at 401 to 500 g; 94 at 501 to 600 g; 208 at 601 to 700 g; 237 at 701 to 800 g; 290 at 801 to 900 g; and 307 at 901 to 1000 g. Twenty-five percent of the children had an abnormal neurologic examination, 37% had a Bayley II Mental Developmental Index Conclusion. ELBW infants are at significant risk of neurologic abnormalities, developmental delays, and functional delays at 18 to 22 months9 corrected age.

/pdf/neurodevelopmental-and-functional-outcomes-of-extremely-low-2yo5nlj1yc.pdf

Neurodevelopmental and Functional Outcomes of Extremely Low Birth Weight Infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993–1994

Objective. A number of definitions of bronchopulmonary dysplasia (BPD), or chronic lung dis- ease, have been used. A June 2000 National Institute of Child Health and Human Development/National Heart, Lung, and Blood Institute Workshop proposed a severity- based definition of BPD for infants 28 days but not at 36 weeks' postmenstrual age (PMA) or discharge, moderate BPD as O2 for >28 days plus treatment with 28 days plus >30% O2 and/or positive pressure at 36 weeks' PMA. The objective of this study was to determine the predictive validity of the severity-based, consensus definition of BPD. Methods. Data from 4866 infants (birth weight <1000 g, GA <32 weeks, alive at 36 weeks' PMA) who were entered into the National Institute of Child Health and Human Development Neonatal Research Network Very Low Birth weight (VLBW) Infant Registry between Jan- uary 1, 1995 and December 31, 1999, were linked to data from the Network Extremely Low Birth Weight (ELBW) Follow-up Program, in which surviving ELBW infants have a neurodevelopmental and health assessment at 18 to 22 months' corrected age. Linked VLBW Registry and Follow-up data were available for 3848 (79%) infants. Selected follow-up outcomes (use of pulmonary medica- tions, rehospitalization for pulmonary causes, receipt of respiratory syncytial virus prophylaxis, and neurodevel- opmental abnormalities) were compared among infants who were identified with BPD defined as O2 for 28 days (28 days definition), as O2 at 36 weeks' PMA (36 weeks' definition), and with the consensus definition of BPD. Results. A total of 77% of the neonates met the 28- days definition, and 44% met the 36-weeks definition. Using the consensus BPD definition, 77% of the infants had BPD, similar to the cohort identified by the 28-days definition. A total of 46% of the infants met the moderate (30%) or severe (16%) consensus definition criteria, iden- tifying a similar cohort of infants as the 36-weeks defi- nition. Of infants who met the 28-days definition and 36-weeks definition and were seen at follow-up at 18 to 22 months' corrected age, 40% had been treated with pulmonary medications and 35% had been rehospital- ized for pulmonary causes. In contrast, as the severity of BPD identified by the consensus definition worsened, the incidence of those outcomes and of selected adverse neurodevelopmental outcomes increased in the infants who were seen at follow-up. Conclusion. The consensus BPD definition identifies a spectrum of risk for adverse pulmonary and neurode- velopmental outcomes in early infancy more accurately than other definitions. Pediatrics 2005;116:1353-1360; bronchopulmonary dysplasia, chronic lung disease, ex- tremely preterm infants, neurodevelopmental.

https://umanitoba.ca/faculties/health_sciences/medicine/units/pediatrics/sections/neonatology/media/BPD1.pdf

Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia.

Outcomes of children of extremely low birthweight and gestational age in the 1990's.

background We studied the outcomes at school age in children who had participated in a doubleblind, placebo-controlled trial of early postnatal dexamethasone therapy (initiated within 12 hours after birth) for the prevention of chronic lung disease of prematurity. methods Of the 262 children included in the initial study, 159 lived to school age. Of these children, 146 (72 in the dexamethasone group and 74 in the control group) were included in our study. All the infants had had severe respiratory distress syndrome requiring mechanical ventilation shortly after birth. In the dexamethasone group, 0.25 mg of dexamethasone per kilogram of body weight was given intravenously every 12 hours for one week, and then the dose was tapered. We evaluated the children’s growth, neurologic and motor function, cognition, and school performance. results Children in the dexamethasone group were significantly shorter than the controls (P=0.03 for boys, P=0.01 for girls, and P=0.03 for all children) and had a significantly smaller head circumference (P=0.04). Children in the dexamethasone group had significantly poorer motor skills (P<0.001), motor coordination (P<0.001), and visual– motor integration (P=0.02). As compared with the controls, children in the dexamethasone group also had significantly lower full IQ scores (mean [±SD], 78.2±15.0 vs. 84.4±12.6; P=0.008), verbal IQ scores (84.1±13.2 vs. 88.4±11.8, P=0.04), and performance IQ scores (76.5±14.6 vs. 84.5±12.7, P=0.001). The frequency of clinically significant disabilities was higher among children in the dexamethasone group than among controls (28 of 72 [39 percent] vs. 16 of 74 [22 percent], P=0.04). conclusions Early postnatal dexamethasone therapy should not be recommended for the routine prevention or treatment of chronic lung disease, because it leads to substantial adverse effects on neuromotor and cognitive function at school age.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa032089

Outcomes at School Age after Postnatal Dexamethasone Therapy for Lung Disease of Prematurity

Objectives.  To study the outcome at 2-year corrected age of infants who participated in a double-blind controlled trial of early ( Methods and Materials.  A total of 133 children (70 in the control group, 63 in the dexamethasone-treated group) who survived the initial study period and lived to 2 years of age were studied. All infants had birth weights of 500 to 1999 g and had severe respiratory distress syndrome requiring mechanical ventilation within 6 hours after birth. For infants in the treatment group, dexamethasone was started at a mean age of 8.1 hours and given 0.25 mg/kg every 12 hours for 1 week and then tapered off gradually over a 3-week period. The following variables were evaluated: interim medical history, socioeconomic background, physical growth, neurologic examinations, mental and psychomotor development index score (MDI and PDI), pulmonary function, electroencephalogram, and auditory and visual evoked potential. Results.  Infants in the control group tended to have a higher incidence of upper respiratory infection and rehospitalization than did the dexamethasone-treated group because of respiratory problems. Although there was no difference between the groups in somatic growth in girls, the dexamethasone-treated boys had significantly lower body weight and shorter height than the control boys (10.7 ± 3.0 vs 11.9 ± 2.0 kg; 84.9 ± 5.7 vs 87.5 ± 4.8 cm). The dexamethasone-treated group had a significantly higher incidence of neuromotor dysfunction (25/63 vs 12/70) than did the control group. The dexa-methasone-treated infants also had a lower PDI score (79 ± 26) than did the control group (87 ± 23), but the difference was not statistically significant. Both groups were comparable in MDI, incidence of vision impairment, and auditory and visual evoked potential. Significant handicap, defined as severe neurologic defect and/or intellectual defect (MDI and/or PDI ≤ 69), was seen in 22 children (31.4%) in the control group and 26 (41.2%) in the dexamethasone-treated group. Conclusions.  Although early postnatal dexamethasone therapy for 4 weeks significantly reduces the incidence of CLD, this therapeutic regimen cannot be recommended at present because of its adverse effects on neuromotor function and somatic growth in male infants, detected at 2 years of age. A longer follow-up is needed. If early dexamethasone therapy is to be used for the prevention of CLD, the therapeutic regimen should be modified. The proper route of administration, the critical time to initiate the therapy, and the dosage and duration of therapy remain to be defined further.

https://pediatrics.aappublications.org/content/pediatrics/101/5/e7.full.pdf

Early dexamethasone therapy in preterm infants: a follow-up study.

Objectives  To study whether early postnatal ( Materials and Methods  A multicenter randomized, double-blind clinical trial was undertaken on 262 (saline placebo, 130; dexamethasone, 132) preterm infants ( 4 , and 6-keto prostaglandin F 1α  All infants were observed for possible side effects, including hypertension, hyperglycemia, sepsis, intraventricular hemorrhage, retinopathy of prematurity, cardiomyopathy, and alterations in calcium homeostasis, protein metabolism, and somatic growth Results  Infants in the dexamethasone group had a significantly lower incidence of chronic lung disease than infants in the placebo group either judged at 28 postnatal days (21/132 vs 40/130) or at 36 postconceptional weeks (20/132 vs 37/130) More infants in the dexamethasone group than in the placebo group were extubated during the study There was no difference between the groups in mortality (39/130 vs 44/132); however, a higher proportion of infants in the dexamethasone group died in the late study period, probably attributable to infection or sepsis There was no difference between the groups in duration of oxygen therapy and hospitalization Early postnatal use of dexamethasone was associated with a significant decrease in tracheal aspirate cell counts, protein, leukotriene B 4 , and 6-keto prostaglandin F 1α , suggesting a suppression of pulmonary inflammatory response Significantly more infants in the dexamethasone group than in the placebo group had either bacteremia or clinical sepsis (43/132 vs 27/130) Other immediate, but transient, side effects observed in the dexamethasone group are: an increase in blood glucose and blood pressure, cardiac hypertrophy, hyperparathyroidism, and a transient delay in the rate of growth Conclusions  In preterm infants with severe respiratory distress syndrome requiring assisted ventilation shortly after birth, early postnatal dexamethasone therapy reduces the incidence of chronic lung disease, probably on the basis of decreasing the pulmonary inflammatory process during the early neonatal period Infection or sepsis is the major side effect that may affect the immediate outcome Other observable side effects are transient In view of the significant side effects and the lack of overall improvement in outcome and mortality, and the lack of long term follow-up data, the routine use of early dexamethasone therapy is not yet recommended

https://pediatrics.aappublications.org/content/pediatrics/100/4/e3.full.pdf

Early postnatal dexamethasone therapy for the prevention of chronic lung disease in preterm infants with respiratory distress syndrome: a multicenter clinical trial.

Recent studies suggest that early dexamethasone therapy may lessen the pulmonary inflammation in preterm infants with respiratory distress syndrome (RDS). To investigate whether early (<12 hr) postnatal dexamethasone therapy would reduce the incidence of chronic lung disease (CLD), a randomized, double-blind, controlled trial was conducted in 40 infants (birth weights from 500 to 1,999 gm) who had severe RDS and required mechanical ventilation within 6 hr of birth. All infants received one dose of Survanta® before they were randomly assigned to control (saline placebo) or dexamethasone-treated groups (0.5 mg/kg/d for 1 week, then tapered over 3 weeks). Sequential analysis was performed with the end point of assessment being the presence or absence of CLD on postnatal Day 28.



Statistical significance favoring dexamethasone was reached when 12 consecutive pairs in which one infant had CLD and the other did not have CLD showed that ten pairs favored dexamethasone and two pairs favored control treatment. Among the survivors, 12/15 were extubated in the dexamethasone group and 9/16 in the control group at the end of study. Infants in the treated group had transient hyperglycemia and hypertension. There was no difference between the groups in mortality and in incidence of sepsis or intraventricular hemorrhage. We conclude that early postnatal dexamethasone therapy is potentially effective in the lessening of CLD in preterm infants. To substantiate our result, large randomized controlled trials are needed and warranted. Pediatr Pulmonol. 1999; 27:21–26. © 1999 Wiley-Liss, Inc.

Prevention of chronic lung disease in preterm infants by early postnatal dexamethasone therapy

Clinical Trial Disease in Preterm Infants With Respiratory Distress Syndrome: A Multicenter Early Postnatal Dexamethasone Therapy for the Prevention of Chronic Lung

Wu S. Hsieh

Papers

Early dexamethasone therapy in preterm infants: a follow-up study.

Early postnatal dexamethasone therapy for the prevention of chronic lung disease in preterm infants with respiratory distress syndrome: a multicenter clinical trial.

Prevention of chronic lung disease in preterm infants by early postnatal dexamethasone therapy

Clinical Trial Disease in Preterm Infants With Respiratory Distress Syndrome: A Multicenter Early Postnatal Dexamethasone Therapy for the Prevention of Chronic Lung