Surfactant replacement therapy: A new risk factor in developing retinopathy of prematurity?

We documented the prevalence of retinopathy of prematurity (ROP) in a group of 46 infants suffering from a moderate or severe respiratory distress syndrome and treated with surfactant replacement therapy (SRT) and 61 controls admitted in the year prior to the institution of SRT. Mortality in the treatment group was lower than in the control group (15.5% versus 23.8;P=0.29). The ROP prevalence in the treatment group was 47.8% and in the control group was 47.8% and in the control group 27.9%. To analyse the contribution of SRT alone to the prevalence of ROP, multivariate analysis using logistic regression technique was used. The odds ratio for SRT was 5.2 with a 95% confidence interval of 1.3–20.7,P=0.02. The prevalence of severe ROP in the surfactant treated group was not increased compared to the control group. From our data we conclude that SRT increases the risk of developing ROP but is not associated with more severe forms of ROP.     

New developments in neonatology: less severe retinopathy of prematurity?

PURPOSE: To determine the effects of surfactant replacement therapy (SRT), high-frequency oscillatory ventilation (HFOV), and general improvements in quality of care on the incidence of severe retinopathy of prematurity (ROP). METHODS: Retrospective comparison of the incidence and severity of ROP in two groups of preterm infants admitted to our neonatal intensive care unit (NICU) in two consecutive 5-year periods (1986-1995) and screened for ROP. During the second study period, natural surfactant was introduced in the treatment of respiratory distress syndrome (RDS) and HFOV was used for treatment of respiratory insufficiency of any origin. The effects of these developments and general improvements on the incidence of severe ROP were analyzed with stepwise logistic regression. RESULTS: The overall incidence of ROP from 1986-1990 was not significantly different from the incidence of ROP from 1991-1995. The incidence of severe ROP (ROP stage 3 or greater) was significantly lower in the second period (15.7% versus 6.4%, P=.015). For infants <1000 g, the incidence of overall ROP was increased significantly during the second study period (47.6% versus 60.1 %, P=.045), although the incidence of severe ROP remained unchanged. Only SRT was associated with a decreased risk for severe ROP; HFOV and general improvements in quality of care had no influence on the outcome. In patients with RDS, the incidence of severe ROP decreased significantly during the second period. CONCLUSION: Of the recent new developments in neonatology, only SRT was associated with a decreased risk for severe ROP.     

Race, Candida sepsis, and retinopathy of prematurity

The objective of this observational cohort study at Georgetown University Hospital from January 1, 1994 through December 31, 1997 was to investigate race, Candida sepsis, and duration of oxygen exposure in infants with retinopathy of prematurity (ROP) with birth weight < or = 1,000 g. The incidence of ROP was 70.8% (114/161). The incidence of stage III or greater ROP in the Caucasian infants was significantly higher at 46.7% (14/30) than in the African-American infants at 23.8% (20/84) with p < 0.02. In addition, the incidence of threshold disease was higher in Caucasian infants 33.3% (10/30) when compared to African-American infants 9.5% (8/84) with p < 0.002. Using multiple logistic regression, African-American race was found to be an independent protective factor against developing severe ROP [adjusted odds ratio 0.39; 95% confidence interval (UCI) 0.16-0.97]. Extremely-low-birth-weight African-American infants with comparable severity of illness (including birth weight, gestational age, duration of supplemental oxygen exposure, and Candida sepsis) are less likely to develop severe ROP than Caucasian infants.     

Association of genetic polymorphisms of vascular endothelial growth factor and risk for proliferative retinopathy of prematurity

The intention of our retrospective study was to determine whether vascular endothelial growth factor (VEGF) genetic polymorphisms are associated with risk for proliferative retinopathy of prematurity (ROP), a condition that is characterized by abnormal retinal neovascularization and can lead to retinal detachment and result in blindness. We enrolled 86 very low birth weight infants (birth weight < or =1500 g) who had been treated with cryo/laser therapy because of the risk for proliferative ROP (treated group). Their VEGF T-460C and G+405C genotypes were determined from dried blood samples and were compared with VEGF genotypes of 115 VLBW infants who were not treated with cryo/laser therapy (untreated group). We found that the allele frequency of VEGF +405C was higher in the treated group than in the untreated group (0.30 versus 0.41; p <0.05). The likelihood of being treated for ROP was higher in heterozygous and homozygous carriers of VEGF +405C alleles [odds ratios adjusted for risk factors of ROP (95% CI): 2.00 (1.02-3.92; p=0.04) and 3.37 (1.17-9.65; p=0.007), respectively]. VEGF -460TT/+405CC haplotype was more prevalent in the treated patients than in the untreated patients (13 of 86 versus 1 of 115; p <0.001), and the association remained significant (p <0.01) even after the adjustment for risk factors of ROP (gestational age, supplemental oxygen therapy, and gender). These findings suggest that the VEGF genotype may be associated with risk for proliferative ROP in VLBW infants.     

Relationship between serum inositol concentration and development of retinopathy of prematurity: a prospective study

PURPOSE: To examine the relationship between the intake of sugar inositol, serum inositol levels, and ROP in three groups of low birthweight infants receiving feedings containing various concentrations of inositol. METHODS: Infants with a birthweight <1500 g, with severe lung disease, were eligible for the study when they began enteral feedings. Infant formulas contained three different inositol concentrations: 2500, 710, and 242 micromol/L. Serum inositol concentrations were averaged over specific time intervals. A logistic regression model was used to investigate the confounding effect of duration of mechanical ventilation and oxygen therapy, birthweight, Apgar score, and serum inositol concentration on development of ROP. RESULTS: Infants receiving high inositol formula and with higher serum inositol concentrations at birth and after 30 days had a statistically significant lower incidence of severe ROP than those receiving the lower inositol formula and with lower serum concentrations (P<.05). The effective serum inositol concentration (EC90) associated with lesser disease was >215 micromol/L. By logistic regression, the odds of developing severe ROP were greater among infants with low serum inositol concentration (odds ratio=4.7, 95% confidence interval 0.90-24.8, P=.017). CONCLUSION: Inositol supplementation may help prevent the most severe form of ROP.     

Carbamoyl phosphate synthetase polymorphisms as a risk factor for necrotizing enterocolitis

A C-to-A nucleotide transversion (T1405N) in the gene that encodes carbamoyl-phosphate synthetase 1 (CPS1) has been correlated with low plasma concentrations of L-arginine in neonates. As plasma L-arginine concentrations are decreased in premature infants with necrotizing enterocolitis (NEC), we hypothesized that the CPS1 T1405N polymorphism would correlate with the presence of NEC. We analyzed the CPS1 genotypes for the T1405N polymorphism in 17 preterm infants (相似文献   

Late postnatal systemic steroids predispose to retinopathy of prematurity in very-low-birth-weight infants: a comparative study

BACKGROUND AND OBJECTIVE: Retinopathy of prematurity (ROP) develops mostly in very-low-birth-weight (VLBW) premature infants. Besides prematurity and hyperoxia, other variables have been brought up as risk factors for ROP. We aimed to search risk factors for ROP by comparing two groups of preemies, one with and the other without ROP. PATIENTS AND METHODS: During 2004-2006, 27 VLBW premature infants developed ROP (ROP group). For each neonate in the ROP group, we chose a neonate born at similar gestational age (GA) (+/-1 week) but without ROP (control group). For each neonate of both groups, we recorded demographic, maternal, gestational, intrapartum, neonatal, interventional, growth and ophthalmologic data from patients' medical records. RESULTS: Eleven of the tested variables were significantly different between the ROP and control groups in univariate analysis. However, only seven of these variables remained significantly different between groups when controlling each variable for GA: bronchopulmonary dysplasia (BPD, p=0.04), duration of hospitalization (p=0.017), high-frequency oscillatory ventilation (HFOV, p=0.033), duration of oxygen therapy (p=0.023), surfactant therapy (p=0.045), inhaled steroids (p=0.015) and systemic steroids for BPD (p=0.007). These seven significant variables were related to respiratory morbidity and interventions. Multiple stepwise logistic regression including all significant variables in the univariate analysis showed that only systemic steroids remained significantly different between groups (p=0.007, OR 5.42, 95% CI 1.60-18.34). CONCLUSION: Significantly more neonates in the ROP group received late postnatal systemic steroids as compared to controls. We speculate that steroids, by altering insulin growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) expression, might contribute to the pathogenesis of ROP.     

Incidence of hyponatraemia and hyponatraemic seizures in severe respiratory syncytial virus bronchiolitis

AIM: To document the incidence and early evolution of hyponatraemia (serum sodium < 136 mmol l(-1)) associated with respiratory syncytial virus (RSV) bronchiolitis in infants requiring intensive care. METHODS: In a retrospective review over two winter seasons, 130 infants were admitted with confirmed RSV infection, of whom 39 were excluded because of either pre-existing risk factors for hyponatraemia: diuretic therapy (n = 14), cardiac disease (n = 10), renal disease (n = 2) or lack of admission sodium data (n = 13). RESULTS: The incidence of admission hyponatraemia in the remaining infants (median age 6 wk) was 33% (30/91), with 11% (10/91) exhibiting a serum sodium less than 130 mmol l(-1) . Hyponatraemic and normonatraemic infants were of a similar age (median 6 vs 7 wk, p = 0.82). With fluid restriction and diuretic therapy, the incidence of hyponatraemia at 48 h had decreased to 3.3%, odds ratio 0.07 (95% confidence interval 0.02-0.24, p < 0.001). Four infants (4%) suffered hyponatraemic seizures at admission (sodium 114-123 mmol l(-1)); three had received hypotonic intravenous fluids at 100-150 ml kg(-1) d(-1) before referral to intensive care. All four were managed successfully with hypertonic (3%) saline, followed by fluid restriction, resulting in immediate termination of seizure activity and normalization of serum sodium values over 48 h. CONCLUSION: Hyponatraemia is common among infants with RSV bronchiolitis presenting to intensive care. Neurological complications may occur and fluid therapy in vulnerable infants should be tailored to reduce this risk.     

Increased calcium supplementation is associated with morbidity and mortality in the infant postoperative cardiac patient.

OBJECTIVE: The purpose of this study was to assess the association of calcium replacement therapy with morbidity and mortality in infants after cardiac surgery involving cardiopulmonary bypass. DESIGN: Retrospective chart review. SETTING: The cardiac intensive care unit at a tertiary care children's hospital. PATIENTS: Infants undergoing cardiac surgery involving cardiopulmonary bypass between October 2002 and August 2004. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total calcium replacement (mg/kg calcium chloride given) for the first 72 postoperative hours was measured. Morbidity and mortality data were collected. The total volume of blood products given during the first 72 hrs was recorded. Infants with confirmed chromosomal deletions at the 22q11 locus were noted. Correlation and logistic regression analyses were used to generate odds ratios and 95% confidence intervals, with p < .05 being significant. One hundred seventy-one infants met inclusion criteria. Age was 4 +/- 3 months and weight was 4.9 +/- 1.7 kg at surgery. Six infants had deletions of chromosome 22q11. Infants who weighed less required more calcium replacement (r = -.28, p < .001). Greater calcium replacement correlated with a longer intensive care unit length of stay (r = .27, p < .001) and a longer total hospital length of stay (r = .23, p = .002). Greater calcium replacement was significantly associated with morbidity (liver dysfunction [odds ratio, 3.9; confidence interval, 2.1-7.3; p < .001], central nervous system complication [odds ratio, 1.8; confidence interval, 1.1-3.0; p = .02], infection [odds ratio, 1.5; confidence interval, 1.0-2.2; p < .04], extracorporeal membrane oxygenation [odds ratio, 5.0; confidence interval, 2.3-10.6; p < .001]) and mortality (odds ratio, 5.8; confidence interval, 5.8-5.9; p < .001). Greater calcium replacement was not associated with renal insufficiency (odds ratio, 1.5; confidence interval, 0.9-2.3; p = .07). Infants with >1 sd above the mean of total calcium replacement received on average fewer blood products than the total study population. CONCLUSIONS: Greater calcium replacement is associated with increasing morbidity and mortality. Further investigation of the etiology and therapy of hypocalcemia in this population is warranted.     

Chorioamnionitis, mechanical ventilation, and postnatal sepsis as modulators of chronic lung disease in preterm infants

OBJECTIVE: This case-control study of chronic lung disease (CLD) evaluated the hypothesis that chorioamnionitis promotes CLD and interacts with other risk factors for CLD, including mechanical ventilation and postnatal infection. STUDY DESIGN: We identified a population of 193 infants who met our case criteria for CLD whose birth weights were 7 days and culture-documented sepsis. In multivariable analyses, infants were at greatest risk for CLD when they had exposure to both chorioamnionitis and either mechanical ventilation >7 days (odds ratio, 3.2; 95% confidence interval, 0.9-11) or postnatal infection (odds ratio, 2.9; 95% confidence interval, 1.1-7.4). CONCLUSIONS: We conclude that prolonged mechanical ventilation or postnatal infection increases the risk of CLD among surviving preterm infants and that these 2 factors interact with antenatal infection to further increase the risk of CLD.     

Population based study on the outcome of small for gestational age newborns

OBJECTIVE: To explore whether and how population based data from a regional quality control programme can be used to investigate the hypothesis that small for gestational age (SGA) very low birthweight infants (VLBW, <1500 g) are at increased risk of death, severe intraventricular haemorrhage (IVH), and periventricular leucomalacia (PVL), but at decreased risk of respiratory distress syndrome (RDS). METHODS: Analyses of population based perinatal/neonatal data (1991-96) from a quality control programme in Lower Saxony, Germany. After assessment of data validity and representativeness, exclusion criteria were defined: birth weight >90th centile, severe malformations, siblings of multiple births, and gestational age (GA) <25 or >29 weeks. Outcomes of interest were death, severe IVH, PVL, and RDS. Multivariable analyses were performed by Cox proportional hazard and logistic regression models. RESULTS: Within the data validation procedure, an increase in proportions of both VLBW (from 0.95% in 1991 to 1.11% in 1996; +17%) and SGA (from 22.7% to 27.4%; +21%) infants became apparent (p<0.05). The study population consisted of 1623 infants (173 SGA). Mortality was 12.1% (n = 196), with an adjusted hazard ratio for SGA infants of 2.54, 95% confidence interval (CI) 1.70 to 3.79. Both groups were at similar risk of severe IVH (adjusted odds ratio 0.93, 95% CI 0.5 to 1.65) and PVL (1.54, 95% CI 0.78 to 2.87), but SGA infants had less RDS (0.57, 95% CI 0.35 to 0.93). Male sex, multiple birth, hypothermia (<35.5 degrees C), and sepsis were associated with IVH and RDS. Infants admitted to hospitals with <36 VLBW admissions/year had increased mortality (adjusted hazard ratio 1.56, 95% CI 1.12 to 2.18). CONCLUSIONS: SGA VLBW infants are at increased risk of death, but not of IVH and PVL, and at decreased risk of RDS. That mortality is higher in smaller hospitals needs further investigation.     

Short-term outcome after active perinatal management at 23-25 weeks of gestation. A study from two Swedish perinatal centres. Part 3: neonatal morbidity

Aim: To determine major neonatal morbidity in surviving infants born at 23-25 weeks, and to identify maternal and infant factors associated with major morbidity. Methods: The medical records of 224 infants who were delivered at two tertiary care centres in 1992-1998 were reviewed retrospectively. At these centres, policies of active perinatal and neonatal management were universally applied. Of the 213 liveborn infants, 140 (66%) survived to discharge. Data were analysed by gestational age and considered in three time periods. Logistic regression models were used to identify factors associated with morbidity. Results: Of the survivors, 6% had intraventricular haemorrhage grade ≥3 (severe IVH) or periventricular leukomalacia (PVL), 15% retinopathy of prematurity ≥stage 3 (severe ROP) and 36% bronchopulmonary dysplasia (BPD). On logistic regression analysis, severe IVH or PVL was associated with duration of mechanical ventilation (odds ratio, OR: 1.53 per 1-wk increment in duration; 95% confidence interval, CI: 1.01-2.33). Severe ROP was associated with the presence of a patent ductus arteriosus (PDA) (OR: 3.31; 95% CI: 1.11-9.90) and birth in time period 3 versus time periods 1 and 2 combined (OR: 6.28; 95% CI: 2.10-18.74). BPD was associated with duration of mechanical ventilation (OR: 2.71 per 1-wk increment in duration; 95% CI: 1.76-4.18) and with the presence of any obstetric complication (OR: 2.67; 95% CI: 1.07-6.65). Gestational age and birthweight were not associated with major morbidity. Of all survivors, 81% were discharged home without severe IVH, PVL or severe ROP.

Conclusions: Increased survival as a result of active perinatal and neonatal management was associated with favourable morbidity rates compared with those in recent studies. Among survivors born at 23-25 weeks, neither gestational age nor birthweight was a significant determinant of major morbidity.     

Effect of sustained pharmacologic vitamin E levels on incidence and severity of retinopathy of prematurity: a controlled clinical trial

The incidence and severity of retinopathy of prematurity (ROP) as affected by vitamin E prophylaxis at pharmacologic serum levels (5 mg/dl) were evaluated in a double-masked clinical trial of infants with a birth weight less than or equal to 2000 gm or a gestational age less than or equal to 36 weeks. The infants were enrolled by age 5 days and randomly assigned to receive parenterally administered, and later orally administered, free alpha-tocopherol (vitamin E) or its placebo. Study medication was continued until retinal vascularization was complete or active ROP had subsided, except in infants with a diagnosis of severe disease, in whom vitamin E was substituted for study medication. Acute ROP data were collected on 755 infants. Logistic regression analysis, with control for immaturity, oxygen exposure, and other illness risk factors, showed a decrease in incidence of ROP in vitamin E-treated infants (p = 0.003, all infants; p = 0.035, infants weighing less than or equal to 1500 gm at birth). Among the 424 infants weighing less than or equal to 1500 gm at birth, the age at enrollment influenced treatment effect (age day 0 to 1, p = 0.006 (n = 288) vs age day 2 to 5, p greater than 0.1 (n = 136]. Overall, 77.6% of infants with ROP had mild disease. Moderate to severe ROP was confined to infants weighing greater than or equal to 1500 gm at birth (25 given placebo, 25 given vitamin E), with progression to severe disease in nine placebo-treated versus three vitamin E-treated infants (p = 0.048). The incidence of severe ROP per se was not significantly decreased (all birth weights, p = 0.086; less than or equal to 1500 gm birth weight, p = 0.080); the sample size was too small, however, to assess this end point adequately. An increased incidence of sepsis and late-onset necrotizing enterocolitis was found among vitamin E-treated infants weighing less than or equal to 1500 gm at birth who received study medication for greater than or equal to 8 days (p = 0.006). Because most ROP is mild in degree and regresses completely, the risk/benefit ratio of pharmacologic prophylaxis for ROP is unfavorable. Treatment of moderate and severe ROP with vitamin E above physiologic serum levels (greater than 3 mg/dl) appears promising and should be further investigated. The interpretation of cicatricial outcome was confounded by the small number of patients involved and by subsequent treatment of severe ROP in placebo-treated infants with vitamin E.     

The Pediatric Investigators Collaborative Network on Infections in Canada study of predictors of hospitalization for respiratory syncytial virus infection for infants born at 33 through 35 completed weeks of gestation

BACKGROUND: Infants born at 33 through 35 completed weeks of gestation (33-35GA) are at risk for severe respiratory syncytial virus (RSV) infection, and palivizumab prophylaxis lowers hospitalizations for RSV infection by as much as 80%. The 33-35GA cohort comprises 3-5% of annual births; thus expert panels recommend limiting prophylaxis to situations in which frequency or health care impact of RSV infection is high. This study sought to identify independent risk factors for hospitalization for RSV infection. METHODS: This was a multicenter, prospective, observational cohort study of 33-35GA infants followed through their first RSV season (2001/2002 or 2002/2003). Baseline data were collected by interview with parents and review of medical records. Respiratory tract illnesses were identified by monthly phone calls, and medical records were reviewed for emergency room visits or hospitalizations. Risk factors were determined by stepwise logistic regression. RESULTS: Of 1,860 enrolled subjects, 1,832 (98.5%) were followed for at least 1 month, and 1,760 (94.6%) completed all follow-ups. Of 140 (7.6%) subjects hospitalized for respiratory tract illnesses, 66 infants had proven RSV infection. Independent predictors for hospitalization for RSV infection were: day-care attendance (odds ratio, 12.32; 95% confidence interval, 2.56, 59.34); November through January birth (odds ratio, 4.89; 95% confidence interval, 2.57, 9.29); preschool age sibling(s) (odds ratio, 2.76; 95% confidence interval, 1.51, 5.03); birth weight <10th percentile (odds ratio, 2.19; 95% confidence interval, 1.14, 4.22); male gender (odds ratio, 1.91; 95% confidence interval, 1.10, 3.31); > or = 2 smokers in the home (odds ratio, 1.87; 95% confidence interval, 1.07, 3.26); and households with >5 people, counting the subject (odds ratio, 1.79; 95% confidence interval, 1.02, 3.16). Family history of eczema (odds ratio, 0.42; 95% confidence interval, 0.18, 0.996) was protective. CONCLUSIONS: Specific host/environmental factors can be used to identify which 33-35GA infants are at greatest risk of hospitalization for RSV infection and likely to benefit from palivizumab prophylaxis.     

Targeted fluconazole prophylaxis for high-risk very low birth weight infants

Antifungal prophylaxis is increasingly used in very low birth weight (VLBW) infants who are at risk for severe fungal infections. Our objective was to assess the effectiveness of targeted fluconazole prophylaxis for high-risk VLBW infants. A retrospective cohort study with historical controls was performed. During the period 2007-2008, all high-risk VLBW infants (birth weight, ≤1,000?g; gestational age, ≤28?weeks; seven antimicrobial therapy or additional risk factors present) received fluconazole prophylaxis until risk factors were not present. Treated infants were compared to a gestational age- and birth weight-matched untreated cohort. Statistical analyses used univariate and multivariate analyses. The main outcome variable was a breakthrough fungal bloodstream infection (BSI). The prophylaxis cohort of 130 VLBW infants was compared to 319 control infants. The rate of fungal infections was significantly lower in the fluconazole prophylaxis group (1 of 130 vs. 19 of 319, p?=?0.016); however, they did not differ in mortality (16.2 vs. 15?%, p?=?0.77) or complications of prematurity. Fluconazole prophylaxis was associated with a significant decrease in candidal BSI (odds ratio, 0.05; 95?% confidence interval, 0.005-0.523). Selective vs. nonselective prophylaxis reduced the number of infants treated from 247 to 130. Conclusion Targeted fluconazole prophylaxis in VLBW infants is effective in preventing fungal infections without increasing the risk of BSI among low-risk infants.     

Predictors of failure of nasal continuous positive airway pressure in treatment of preterm infants with respiratory distress syndrome

A case-control study was carried out on 97 consecutive preterm (< 37 weeks) infants to determine predictors associated with failure of nasal continuous positive airway pressure (CPAP) in the treatment of respiratory distress syndrome (RDS). Logistic regression analysis showed that only three risk factors were significantly associated with failed CPAP. These were: moderate or severe RDS (odds ratio: 5.9; 95 per cent confidence interval (CI): 2.2-16.0); septicemia during CPAP therapy (OR: 8.8; 95 per cent: CI 1.5-50.7); and pneumothorax during CPAP therapy (odds ratio: 6.9; 95 per cent: CI 1.1-41.7).     

Outcome and prognostic factors in neonates with septic shock.

OBJECTIVE: Few accurate data are available on the outcome of septic shock in the neonatal period. The objective was to describe outcome and to determine variables associated with death or adverse outcome in neonates with septic shock. DESIGN: Retrospective cohort study. SETTING: A tertiary neonatal intensive care unit in a university hospital. PATIENTS: All patients admitted to the neonatal intensive care unit over a 6-yr period meeting the following criteria: hypotension and/or need for intravenous fluid administration or vasoactive drugs, in the presence of proven or highly probable infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Main outcomes were 28-day mortality and adverse outcome at 18 months of corrected age, defined as death or severe sequelae (cerebral palsy, severe developmental delay, hearing impairment, blindness, or short bowel syndrome). Forty-eight infants were included. Follow-up data at 18 months were obtained for 46 of 48 infants. The 28-day mortality was 40% (19 deaths). Adverse outcome at 18 months of corrected age was observed in 24 of 46 infants (52%; death = 19, severe sequelae = 5). Twenty-eight percent of the infants were alive and had a normal examination at 18 months. Infants with adverse outcome had significantly lower gestational age, birth weight, Apgar score, weight at onset of sepsis, and pH and more often had gram-negative infection, fetal growth restriction, hypoglycemia, and thrombocytopenia. Significant predictors (multivariate analysis) of 28-day mortality and of adverse outcome at 18 months of corrected age were weight (kg) at the onset of sepsis (odds ratio 0.14, 95% confidence interval 0.03-0.55; odds ratio 0.21, 95% confidence interval 0.06-0.74, respectively) and gram-negative infection (odds ratio 10.1, 95% confidence interval 1.5-65.7; odds ratio 45.5, 95% confidence interval 3-637, respectively). CONCLUSIONS: Septic shock in the neonatal period has a very poor outcome. Data underscore the extreme vulnerability of very low birth weight infants to septic shock, particularly to gram-negative species.     

"Benign" extra-axial fluid in survivors of neonatal intensive care

OBJECTIVES: To identify the prevalence of "benign" extra-axial fluid (BEAF), the risk factors associated with this condition, and the natural history in "graduates" of neonatal intensive care. DESIGN: Cross-sectional study. SETTING: Neonatal follow-up clinic at a tertiary care center. PATIENTS: Seventy-seven infants with a head circumference greater than the 95th percentile by growth percentiles from either the National Center for Health Statistics or the Infant Health and Development Program growth percentile graphs who attended the Neonatal Follow-up Program at The Children's Hospital of Philadelphia between January 1, 1998, and December 31, 2001. MAIN OUTCOME MEASURES: Bronchopulmonary dysplasia, extracorporeal membrane oxygenation; development at 18 to 24 months. RESULTS: There were 26 infants (34%) in the BEAF group, 43 (56%) in the control group without extra-axial fluid, and 8 (10%) in the hydrocephalus group. Compared with the control group, infants with BEAF were more likely to have bronchopulmonary dysplasia or to require use of extracorporeal membrane oxygenation in the immediate neonatal period (risk ratio, 6.1; 95% confidence interval, 1.5-29.8). Measurements of head circumference in the BEAF group showed rapid growth between 3 and 12 months, followed by growth greater than and parallel to the 95th percentile. Head circumference measurements in the control group showed continued growth along the 95th percentile for age. Infants with BEAF were more likely than controls to develop cerebral palsy (risk ratio, 9.9; 95% confidence interval, 1.3-77.9) and to have evidence of developmental delay at adjusted ages 12 and 18 to 24 months. CONCLUSION: The presence of extra-axial fluid in macrocephalic survivors of neonatal intensive care is associated with an increased risk of developmental delay and cerebral palsy compared with control macrocephalic survivors.     

Second-generation consequences of small-for-dates birth

This is the first reported study of birth outcomes of a group of women whose own birth weights and gestational ages had been previously recorded. Births occurring from 1972 to 1983 among 1154 Swedish women, born from 1955 to 1965, were studied. Women who were themselves small for gestational age (SGA) at birth were at increased risk of giving birth to a SGA infant (odds ratio = 2.21, 95% confidence interval = 1.41, 3.48). Women who had been SGA had an even greater increase in risk of giving birth to a preterm infant (odds ratio = 2.96, 95% confidence interval = 1.47, 5.94). Women who were preterm at birth were not at increased risk of giving birth to either preterm (odds ratio = 0.65, 95% confidence interval = 0.15, 2.74) or SGA (odds ratio 1.21, 95% confidence interval = 0.62, 2.38) infants. It is concluded that the long-term effects of intrauterine growth retardation may extend to the next generation; women who had been SGA should be considered at increased risk to give birth to both growth-retarded and preterm infants.     

Maternal glucocorticoid therapy and reduced risk of bronchopulmonary dysplasia

Because of substantial clinical and laboratory evidence of the efficacy of glucocorticoids in the treatment of acute pulmonary surfactant deficiency in preterm newborns, we explored the hypothesis that maternal antenatal glucocorticoid receipt is followed by reduced risk of bronchopulmonary dysplasia (BPD). A sample of 223 intubated infants weighing less than 1751 g birth weight provided 76 infants with BPD (defined by both oxygen requirement and compatible chest radiograph) and 147 who had neither BPD characteristic by day 28 of life. When compared to babies who received a complete and timely course of antenatal glucocorticoids, those whose mothers received no glucocorticoids were at prominently increased risk of BPD (odds ratio = 3.0; 95% confidence interval = 1.1, 8.2). Babies whose mothers received a partial course of glucocorticoids were not at increased risk of BPD (odds ratio = 1.3; 95% confidence interval = 0.4, 4.3). Stratification by gender and birth weight at 1 kg showed a benefit of therapy in all strata except that of extremely low birth weight male infants. These data support the hypothesis that maternal antenatal glucocorticoid therapy offers very low birth weight infants protection against BPD.