Trends in severe bronchopulmonary dysplasia rates between 1994 and 2002

OBJECTIVE: To examine temporal trends in the rates of severe bronchopulmonary dysplasia (BPD) between 1994 and 2002. STUDY DESIGN: In a retrospective cohort study, all infants with a gestational age (GA) <33 weeks in a large managed care organization were identified. Annual rates of BPD (defined as an oxygen requirement at 36 weeks corrected GA), severe BPD (defined as respiratory support at 36 weeks corrected GA), and death before 36 weeks corrected GA were examined. RESULTS: Of the 5115 infants in the study cohort, 603 (12%) had BPD, including 246 (4.9%) who had severe BPD. There were 481 (9.5%) deaths before 36 weeks corrected GA. Although the decline in BPD in this period was not significant, the rates of severe BPD declined from 9.7% in 1994 to 3.7% in 2002. Controlling for gestational age, the odds ratio (95% CI) for annual rate of decline in severe BPD was 0.890 (0.841-0.941). Controlling for gestational age, deaths before 36 weeks corrected GA also declined, with the odds ratio (CI) for the annual decline being 0.944 (0.896-0.996). CONCLUSIONS: In this study population, the odds of having of BPD remained constant after controlling for GA. However, the odds of having severe BPD declined on average 11% per year between 1994 and 2002.     

Outcomes of extremely low birth weight infants with bronchopulmonary dysplasia: impact of the physiologic definition

Aims

We compared neurodevelopmental outcomes of extremely low birth weight (ELBW) infants with and without bronchopulmonary dysplasia (BPD), using the physiologic definition.

Study design

ELBW (birth weights < 1000 g) infants admitted to the Neonatal Research Network centers and hospitalized at 36 weeks postmenstrual age (n = 1189) were classified using the physiologic definition of BPD. Infants underwent Bayley III assessment at 18–22 months corrected age. Multivariable logistic regression was used to determine the association between physiologic BPD and cognitive impairment (score < 70).

Results

BPD by the physiologic definition was diagnosed in 603 (52%) infants, 537 of whom were mechanically ventilated or on FiO₂ > 30% and 66 who failed the room air challenge. Infants on room air (n = 505) and those who passed the room air challenge (n = 51) were classified as “no BPD” (n = 556). At follow up, infants with BPD had significantly lower mean weight and head circumference. Moderate to severe cerebral palsy (7 vs. 2.1%) and spastic diplegia (7.8 vs. 4.1%) and quadriplegia (3.9 vs. 0.9%) phenotypes as well as cognitive (12.8 vs. 4.6%) and language scores < 70 (24.2 vs. 12.3%) were significantly more frequent in those with BPD compared to those without BPD. BPD was independently associated (adjusted OR 2.4; 95% CI 1.40–4.13) with cognitive impairment.

Conclusions

Rates of adverse neurodevelopmental outcomes in early childhood were significantly higher in those with BPD. BPD by the physiologic definition was independently associated with cognitive impairment using Bayley Scales III. These findings have implications for targeted post-discharge surveillance and early intervention.     

Excess mortality and morbidity among small-for-gestational-age premature infants: a population-based study

OBJECTIVE: We examined the effect of intrauterine growth restriction on mortality and morbidity in the Israel cohort of very low birth weight premature infants. METHODS: The study population included 2764 singleton very low birth weight infants without congenital malformations born from 24 to 31 weeks of gestation during 1995 to 1999. Four hundred six (15%) were born small for gestational age (SGA). The effect of SGA on death, bronchopulmonary dysplasia, and retinopathy of prematurity was assessed using multiple logistic regression analysis. RESULTS: After adjustment for perinatal risk factors, SGA infants had a 4.52-fold risk for death (95% CI, 3.24-6.33), a 3.42-fold risk for bronchopulmonary dysplasia (95% CI, 2.29-5.13), and a 2.06-fold risk for grade 3 to 4 retinopathy of prematurity (95% CI, 1.15-3.66). CONCLUSIONS: SGA premature infants had an increased risk for death, and major morbidity among survivors was increased.     

Association between fluid intake and weight loss during the first ten days of life and risk of bronchopulmonary dysplasia in extremely low birth weight infants

OBJECTIVE: To demonstrate the association between fluid intake and weight loss during the first 10 days of life and the risk of bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants. STUDY DESIGN: A retrospective analysis of data from a cohort of ELBW infants enrolled in the Neonatal Research; 1,382 infants with birth weight between 401 and 1,000 g were randomized. The daily fluid intake and weight loss during the first 10 days of life were compared between the infants who survived without BPD and those who either died or developed BPD. Demographic and clinical neonatal variables were also compared. Multivariate logistic regression was used to analyze the effect of fluid intake and weight loss on death or BPD, controlling for demographic and clinical factors that are significantly associated with BPD by univariate analysis. RESULTS: 585 infants survived without BPD and 797 infants either died or developed BPD. Univariate analysis showed that the daily fluid intakes were higher (day 2-10) and weight loss less (day 6-9) in the group of infants who either died or developed BPD. In addition, lower birth weight, lower gestational age, male gender, lower 1 and 5-minute Apgar Scores, higher oxygen requirement at 24 hours of age, longer duration of assisted ventilation, use of postnatal steroids for BPD and presence of severe intraventricular hemorrhage, proven necrotizing enterocolitis, patent ductus arteriosus, and late onset sepsis, were associated with higher incidence of death or BPD. The adjusted risk of higher fluid intake and less weight loss during the first 10 days of life remained significantly related to death or BPD. CONCLUSION: In this cohort of ELBW infants treated during the post surfactant era, higher fluid intake and less weight loss during the first 10 days of life were associated with an increased risk of BPD. The finding suggests that careful attention to fluid balance might be an important means to reduce the incidence of BPD.     

Trends in severe brain injury and neurodevelopmental outcome in premature newborn infants: the role of cystic periventricular leukomalacia

OBJECTIVES: To determine if the incidence of sonographically detected cystic periventricular leukomalacia (PVL) and periventricular hemorrhagic infarction (PVHI) have changed over the past decade and to determine if a decline in cystic PVL was associated with a change in neurodevelopmental outcome. STUDY DESIGN: Premature newborn infants admitted to our intensive care nursery from 1992 to 2002 were identified in a comprehensive nursery database. Premature newborn infants had routine neurosonography by means of a standardized protocol. Infants weighing < or =1500 g at birth surviving to nursery discharge were enrolled in a nursery follow-up clinic. RESULTS: Adjusting for gestational age, there was a significant decrease in cystic PVL from 1992 to 2002 (P=.003) without a concurrent decrease in PVHI (P=0.5). Cystic PVL and PVHI accounted for only 9 of the 28 cases of cerebral palsy and 12 of 90 cases of abnormal Developmental Scores in infants weighing <1500 g at birth. The decline in cystic PVL was not associated with improved developmental outcome from 1992 to 2002. CONCLUSIONS: The incidence of cystic PVL declined significantly from 1992 to 2002 at our center. Cystic PVL was detected by ultrasound in a minority of infants with abnormal neurodevelopmental outcome, indicating that other forms of cerebral injury account for the majority of abnormal neurodevelopmental outcomes in premature newborn infants.     

Case-control study of symptoms and neonatal outcome of human milk-transmitted cytomegalovirus infection in premature infants

OBJECTIVE: Preterm infants are at risk of acquiring human cytomegalovirus (CMV) infection through breast milk transmission, possibly leading to serious symptoms, as suggested by previous studies. Over a period of 8.5 years, we compared infants infected postnatally with CMV with noninfected controls to determine whether CMV infection transmitted through breast milk poses serious acute risks. STUDY DESIGN: CMV monitoring included maternal serologic testing and biweekly viral culture and polymerase chain reaction in breast milk and infant urine. Clinical and laboratory test findings were assessed retrospectively in infected infants and controls matched for gestational age during the initial hospital stay. RESULTS: Forty CMV-infected infants met the study criteria. They had lower minimal platelet and neutrophil counts and a higher frequency of C-reactive protein (CRP) elevations to 10 to 20 mg/L than their matched controls (P < or = .001). But no association of CMV infection with bronchopulmonary dysplasia, necrotizing enterocolitis, growth, or CRP elevations to > 20 mg/L was found. Cholestasis appeared in 3 infants in the CMV-infected group, but disappeared within 10 weeks. CONCLUSIONS: Neonatal symptoms related to postnatal CMV infection were transient and had no affect on neonatal outcome in these infants, in contrast with uncontrolled reports. Whether withholding or pasteurizing breast milk is warranted, however, depends on long-term outcome.     

Wheezing illness and re-hospitalization in the first two years of life after neonatal respiratory distress syndrome

OBJECTIVES: To determine the impact of respiratory distress syndrome (RDS) on wheezing illnesses and re-hospitalizations in children as old as 2 years of age. STUDY DESIGN: We observed 2 geographically defined cohorts of children with RDS born after 26 weeks of gestation during 1990 to 1995 and 1996 to 1999 and gestationally paired control subjects. Recurrent wheezing illness and the re-hospitalizations caused by a respiratory condition were recorded. RESULTS: In the first year of life, 47 of 224 infants with RDS and 18 of 224 control subjects born in 1990 to 1995 had recurrent wheezing illness (P <.005) compared with 21 of 109 infants with RDS and 14 of 109 control subjects in the latter cohort (P=.27). A higher number of infants with RDS were readmitted to the hospital (25% versus 13%, P=.002) in the former period, and they spent more days in hospital during both periods. The frequencies of wheezing remained constant in the second year of life, but hospital admissions decreased. Siblings at home, male sex, and bronchopulmonary dysplasia were additional risk factors of wheezing illnesses. CONCLUSION: RDS increases the incidence of wheezing illnesses during the first 2 years of life. Changes in the management of RDS during the 1990s was associated with a decreased incidence of subsequent RDS-associated respiratory morbidity.     

Predicting neurosensory disabilities at two years of age in a national cohort of extremely premature infants

Background

Extreme prematurity carries a high risk of neurosensory disability.

Aims

Examine which information obtained pre-, peri- and postnatally may be predictive of neurosensory disabilities at 2 years of age.

Study design

Prospective observational study of all infants born in Norway in 1999 and 2000 with gestational age (GA) 22-27 completed weeks or birth weight (BW) of 500-999 g.

Outcome measures

Incidence of neurosensory disabilities.

Results

Of 373 surviving children, 30 (8%) had major neurosensory disabilities (26 CP, 6 blind, 3 deaf), and a further 46 (12%) had minor visual or hearing disabilities. The rate of major neurosensory disabilities was 19 of 99 (19%) for children with GA 23-25 vs. 8 of 189 (4%) for GA 26-27 weeks (p < 0.001). In a multivariable model, only morbidities detected in the neonatal intensive care unit (NICU) were associated with major neurosensory disabilities; adjusted odds ratios (95% confidence intervals) were 68.6 (18.7, 252.2) for major abnormalities on cerebral ultrasound, 6.8 (1.7, 27.4) for retinopathy of prematurity (ROP) grade > 2, 3.2 (1.0, 9.7) for ROP grade 1-2, 6.5 (1.9, 22.3) for prolonged use (≥ 21 days) of steroid treatment for lung disease and 3.1 (1.0, 9.4) for clinical chorioamnionitis. The visual outcome was strongly related to the degree of ROP (p < 0.001), and all who had a normal hearing screen in the NICU had normal hearing at 2 years.

Conclusion

NICU morbidities, rather than GA or intrauterine growth are the significant predictors of major neurosensory disabilities among extreme prematurity surviving to discharge from the NICU.     

Factors associated with rehospitalizations of very low birthweight infants: impact of a transition home support and education program

Objective

To determine the effects of a transition-home education and support program, BPD, and health insurance type on VLBW infant rehospitalizations at 3 and 7 months corrected age. It was hypothesized that the transition-home program would be associated with decreased rehospitalizations between Phase 1 and 2, and public health insurance and BPD would be associated with increased rehospitalizations.

Methods

274 infants with birth weight < 1500 g were enrolled in two successive years of a transition-home program (Phase 1—start-up) and (Phase 2—full implementation) and followed to 7 months CA.

Results

The Phase 2 rehospitalization rates were lower but not statistically significant at both 3 months (20% and 15%; p = 0.246), and 7 months (24% and 17%; p = 0.171). Infants with public insurance had twice as many rehospitalizations by 3 months (28% versus 11%; p = 0.018) in Phase 1. In regression analyses the intervention effects did not achieve significance for the cohort at 3 months (OR = 0.63; CI = 0.33 to 1.20) or 7 months (OR = 0.61; CI = 0.33 to 1.13). BPD and public insurance did not reach significance in the models whereas siblings were significantly associated with increased odds of rehospitalization. In subgroup analyses for infants on pubic health insurance the intervention significantly decreased the odds of rehospitalization between Phase 1 and 2(OR = 0.43; CI = 0.19 to 0.96) at 3 months.

Conclusions

Our findings suggest that a transition-home program may be beneficial to reduce the rehospitalization rate for VLBW infants, and infants on public insurance may derive greater benefit.     

Eosinophil cationic protein in tracheal aspirates of preterm infants with bronchopulmonary dysplasia

Eosinophil cationic protein was elevated during the first week of life in tracheal aspirates from 11 preterm infants in whom bronchopulmonary dysplasia subsequently developed compared with 8 preterm and 8 term infants without bronchopulmonary dysplasia. Eosinophil cationic protein levels increased progressively with continued intubation in the infants with bronchopulmonary dysplasia but remained low in a comparison group of term infants. We suggest that eosinophils participate in the inflammatory process in bronchopulmonary dysplasia and may contribute to lung injury. (J Pediatr 1997;130:944-7)     

Pretreatment cortisol values may predict responses to hydrocortisone administration for the prevention of bronchopulmonary dysplasia in high-risk infants

OBJECTIVES: To investigate the effect of hydrocortisone treatment on survival without bronchopulmonary dysplasia (BPD) and to study whether serum cortisol concentrations predict the response. STUDY DESIGN: We performed a randomized, placebo-controlled trial on infants with gestation < or =30 weeks, body weight of 501 to 1250 g, and respiratory failure. Hydrocortisone was started before 36 hours of age and given for 10 days at doses from 2.0 to 0.75 mg/kg per day. Shortly before hydrocortisone treatment, basal and stimulated (ACTH, 0.1 microg/kg) serum cortisols were measured. RESULTS: The study was discontinued early, because of gastrointestinal perforations in the hydrocortisone group (4/25 vs 0/26, P = .05); 3 of the 4 had received indomethacin/ibuprofen. The incidence of BPD (28% vs placebo 42%, P = 0.28) tended to be lower, and patent ductus arteriosus (36% vs 73%, P = .01) was lower in the hydrocortisone group. The hydrocortisone-treated infants with serum cortisol concentrations above the median had a high risk of gastrointestinal perforation. In infants with cortisol values below the median, hydrocortisone treatment increased survival without BPD. CONCLUSIONS: Serum cortisol concentrations measured shortly after birth may identify those very high-risk infants who may benefit from hydrocortisone supplementation.