We compared neurodevelopmental outcomes at 18 to 22 months' corrected age of infants born with extremely low birth weight at an estimated gestational age of <25 weeks during 2 periods: 1999–2001 (epoch 1) and 2002–2004 (epoch 2).
PATIENTS AND METHODS:
We conducted a multicenter, retrospective analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Perinatal and neonatal variables and outcomes were compared between epochs. Neurodevelopmental outcomes at 18 to 22 months' corrected age were evaluated with neurologic exams and Bayley Scales of Infant Development II. Logistic regression analyses determined the independent risk of epoch for adverse outcomes.
Infant survival was similar between epochs (epoch 1, 35.4%, vs epoch 2, 32.3%; P = .09). A total of 411 of 452 surviving infants in epoch 1 and 405 of 438 surviving infants in epoch 2 were evaluated at 18 to 22 months' corrected age. Cesarean delivery (P = .03), surgery for patent ductus arteriosus (P = .004), and late sepsis (P = .01) were more common in epoch 2, but postnatal steroid use was dramatically reduced (63.5% vs 32.8%; P < .0001). Adverse outcomes at 18 to 22 months' corrected age were common in both epochs. Moderate-to-severe cerebral palsy was diagnosed in 11.1% of surviving infants in epoch 1 and 14.9% in epoch 2 (adjusted odds ratio [OR]: 1.52 [95% confidence interval (CI): 0.86–2.71]; P = .15), the Mental Developmental Index was <70 in 44.9% in epoch 1 and 51% in epoch 2 (OR: 1.30 [95% CI: 0.91–1.87]; P = .15), and neurodevelopmental impairment was diagnosed in 50.1% of surviving infants in epoch 1 and 58.7% in epoch 2 (OR: 1.4 [95% CI: 0.98–2.04]; P = .07).
Early-childhood outcomes for infants born at <25 weeks' estimated gestational age were unchanged between the 2 periods.
extremely preterm; neurodevelopmental; outcome; cerebral palsy; Bayley Scales of Infant Development II
To determine (1) the magnitude of clustering of bronchopulmonary dysplasia (36 weeks) or death (the outcome) across centers of the Eunice Kennedy Shriver National Institute of Child and Human Development National Research Network, (2) the infant-level variables associated with the outcome and estimate their clustering, and (3) the center-specific practices associated with the differences and build predictive models.
Data on neonates with a birth weight of <1250 g from the cluster-randomized benchmarking trial were used to determine the magnitude of clustering of the outcome according to alternating logistic regression by using pairwise odds ratio and predictive modeling. Clinical variables associated with the outcome were identified by using multivariate analysis. The magnitude of clustering was then evaluated after correction for infant-level variables. Predictive models were developed by using center-specific and infant-level variables for data from 2001 2004 and projected to 2006.
In 2001–2004, clustering of bronchopulmonary dysplasia/death was significant (pairwise odds ratio: 1.3; P < .001) and increased in 2006 (pairwise odds ratio: 1.6; overall incidence: 52%; range across centers: 32%–74%); center rates were relatively stable over time. Variables that varied according to center and were associated with increased risk of outcome included lower body temperature at NICU admission, use of prophylactic indomethacin, specific drug therapy on day 1, and lack of endotracheal intubation. Center differences remained significant even after correction for clustered variables.
Bronchopulmonary dysplasia/death rates demonstrated moderate clustering according to center. Clinical variables associated with the outcome were also clustered. Center differences after correction of clustered variables indicate presence of as-yet unmeasured center variables.
logistic models; infant; premature; predictive value of tests; clustering
Preterm infants with intrauterine growth restriction are at increased risk of respiratory distress syndrome and bronchopulmonary dysplasia (BPD). A randomized clinical trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network demonstrated that vitamin A supplementation in extremely low-birth-weight (ELBW) preterm infants requiring early respiratory support decreased the risk of developing BPD.
A subgroup analysis of small-for-gestational-age (SGA) infants from the original NICHD trial was performed to test the hypothesis that in infants requiring early respiratory support, vitamin A supplementation decreases the relative risk of BPD or death in premature SGA infants to a greater extent than in gestational age–equivalent vitamin A–treated appropriate-for-gestational-age (AGA) infants.
Although vitamin A supplementation significantly increased serum retinol concentrations in AGA ELBW infants (median [5th percentile, 95th percentile]: 16.3 [−7.0, 68.8] versus 2.4 [−13.9, 55.1]; p < 0.001), no increases were noted in SGA ELBW infants.
Given the limited power of this analysis due to a low number of SGA infants, these data did not provide evidence to support the hypothesis that vitamin A supplementation in preterm SGA infants requiring early respiratory support decreases the relative risk of BPD or death as compared with preterm AGA infants.
vitamin A; IUGR–intrauterine growth restriction; BPD–bronchopulmonary dysplasia; SGA–small for gestational age; AGA–appropriate for gestational age
To evaluate maternal and neonatal risk factors associated with post-neonatal intensive care unit (NICU) discharge mortality among ELBW infants.
This is a retrospective analysis of extremely low birth weight (<1,000 g) and <27 weeks' gestational age infants born in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network sites from January 2000 to June 2007. Infants were tracked until death or 18–22 months corrected age. Infants who died between NICU discharge and the 18–22 month follow-up visit were classified as post-NICU discharge mortality. Association of maternal and infant risk factors with post-NICU discharge mortality was determined using logistic regression analysis. A prediction model with six significant predictors was developed and validated.
5,364 infants survived to NICU discharge. 557 (10%) infants were lost to follow-up, and 107 infants died following NICU discharge. Post-NICU discharge mortality rate was 22.3 per 1000 ELBW infants. In the prediction model, African-American race, unknown maternal health insurance, and hospital stay ≥120 days significantly increased risk, and maternal exposure to intra-partum antibiotics was associated with decreased risk of post-NICU discharge mortality.
We identified African-American race, unknown medical insurance and prolonged NICU stay as risk factors associated with post-NICU discharge mortality among ELBW infants.
extremely preterm infants; discharge; mortality; predictive model
The protective role of breastfeeding against severe acute lung disease in infants is well established, but its mechanism is unclear. Most hypotheses assume that breastfeeding confers similar passive protection to every infant; however, a few observations have suggested that the benefits of breast milk against severe lung disease may differ according to gender. The objective of this study was to determine whether the effect of breastfeeding on susceptibility to severe acute lung disease among infants at high risk is different for girls and boys.
A cohort was analyzed prospectively by use of 2 different strategies: (1) predictors of first episode of rehospitalization by univariate and multivariate analyses using robust Poisson regression and (2) mean number of rehospitalizations between groups using multiple regression negative binomial models.
A total of 119 high-risk, very low birth weight infants were enrolled. Breast milk protected girls but not boys against severe acute lung disease. The interaction between breastfeeding and gender was clinically and statistically significant, even after adjustment for variables that can affect severity of acute lung disease. Disease was most severe in formula-fed girls (versus formula-fed boys).
Breastfeeding decreased the risk for severe acute lung disease in girls but not in boys. These findings suggest that breast milk protection is not universally conferred by passive transfer of humoral immunity (which should be gender indifferent), show that respiratory symptoms may be amenable to nonspecific modulation, and identify nonbreastfed preterm infant girls as an at-risk group for severe acute lung disease.
lower respiratory infection; breast milk; respiratory syncytial virus; prematurity; gender
The proportion of preterm and low-birth-weight infants has been growing steadily for two decades. Most of the more than $10 billion spent on neonatal care in the United States in 2003 was spent on the 12.3% of infants who were born preterm. Research has shown higher initial hospital costs and a higher rate of acute care visits and rehospitalization for preterm and low-birth-weight infants, but only a limited number of studies of the cost of prematurity that follow infants through the first year of life have been conducted.
This study is a secondary analysis of data on a subset of infants drawn from a randomized clinical trial that examined health outcomes and health care costs in women with high-risk pregnancies and their infants. For the current study, a sample of 84 singleton infants was chosen. Forty-three infants (51 %) were full term (37 weeks’ gestation or more) and 41 (49%) were born preterm (less than 37 weeks’ gestation). Fifty-five infants (65.5%) were born at normal birth weights (2,500 g or greater), 24 (28.5%) were born at low birth weights (1,501 to 2,499 g), and five (6%) were born at very low birth weights (less than 1,500 g).
Data on the initial hospital charges and the rates of rehospitalization and acute care visits in the first year of life in relation to gestational age and birth weight were collected. The results clearly demonstrated that the charges for initial hospitalizations increased as birth weights and gestational ages decreased. Low-birth-weight infants were less likely to have unscheduled acute care visits than normal-birth-weight infants.
Interventions to improve prenatal care targeted to women at high risk for delivering preterm or low-birth-weight infants would reduce health care costs and improve health outcomes of infants as well.
Rationale: Benefits of identifying risk factors for bronchopulmonary dysplasia in extremely premature infants include providing prognostic information, identifying infants likely to benefit from preventive strategies, and stratifying infants for clinical trial enrollment.
Objectives: To identify risk factors for bronchopulmonary dysplasia, and the competing outcome of death, by postnatal day; to identify which risk factors improve prediction; and to develop a Web-based estimator using readily available clinical information to predict risk of bronchopulmonary dysplasia or death.
Methods: We assessed infants of 23–30 weeks' gestation born in 17 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and enrolled in the Neonatal Research Network Benchmarking Trial from 2000–2004.
Measurements and Main Results: Bronchopulmonary dysplasia was defined as a categorical variable (none, mild, moderate, or severe). We developed and validated models for bronchopulmonary dysplasia risk at six postnatal ages using gestational age, birth weight, race and ethnicity, sex, respiratory support, and FiO2, and examined the models using a C statistic (area under the curve). A total of 3,636 infants were eligible for this study. Prediction improved with advancing postnatal age, increasing from a C statistic of 0.793 on Day 1 to a maximum of 0.854 on Day 28. On Postnatal Days 1 and 3, gestational age best improved outcome prediction; on Postnatal Days 7, 14, 21, and 28, type of respiratory support did so. A Web-based model providing predicted estimates for bronchopulmonary dysplasia by postnatal day is available at https://neonatal.rti.org.
Conclusions: The probability of bronchopulmonary dysplasia in extremely premature infants can be determined accurately using a limited amount of readily available clinical information.
bronchopulmonary dysplasia; prematurity; low-birth-weight infant
This report presents data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network on care of and morbidity and mortality rates for very low birth weight infants, according to gestational age (GA).
Perinatal/neonatal data were collected for 9575 infants of extremely low GA (22–28 weeks) and very low birth weight (401–1500 g) who were born at network centers between January 1, 2003, and December 31, 2007.
Rates of survival to discharge increased with increasing GA (6% at 22 weeks and 92% at 28 weeks); 1060 infants died at ≤ 12 hours, with most early deaths occurring at 22 and 23 weeks (85% and 43%, respectively). Rates of prenatal steroid use (13% and 53%, respectively), cesarean section (7% and 24%, respectively), and delivery room intubation (19% and 68%, respectively) increased markedly between 22 and 23 weeks. Infants at the lowest GAs were at greatest risk for morbidities. Overall, 93% had respiratory distress syndrome, 46% patent ductus arteriosus, 16% severe intraventricular hemorrhage, 11% necrotizing enterocolitis, and 36% late-onset sepsis. The new severity-based definition of bronchopulmonary dysplasia classified more infants as having bronchopulmonary dysplasia than did the traditional definition of supplemental oxygen use at 36 weeks (68%, compared with 42%). More than one-half of infants with extremely low GAs had undetermined retinopathy status at the time of discharge. Center differences in management and outcomes were identified.
Although the majority of infants with GAs of ≥24 weeks survive, high rates of morbidity among survivors continue to be observed.
extremely low gestation; very low birth weight; morbidity; death
We sought to determine if a center’s approach to care of premature infants at the youngest gestational ages (22–24 weeks’ gestation) is associated with clinical outcomes among infants of older gestational ages (25–27 weeks’ gestation).
Inborn infants of 401 to 1000 g birth weight and 22 0/7 to 27 6/7 weeks’ gestation at birth from 2002 to 2008 were enrolled into a prospectively collected database at 20 centers participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Markers of an aggressive approach to care for 22- to 24-week infants included use of antenatal corticosteroids, cesarean delivery, and resuscitation. The primary outcome was death before postnatal day 120 for infants of 25 to 27 weeks’ gestation. Secondary outcomes were the combined outcomes of death or a number of morbidities associated with prematurity.
Our study included 3631 infants 22 to 24 weeks’ gestation and 5227 infants 25 to 27 weeks’ gestation. Among the 22- to 24-week infants, use of antenatal corticosteroids ranged from 28% to 100%, cesarean delivery from 13% to 65%, and resuscitation from 30% to 100% by center. Centers with higher rates of antenatal corticosteroid use in 22- to 24-week infants had reduced rates of death, death or retinopathy of prematurity, death or late-onset sepsis, death or necrotizing enterocolitis, and death or neurodevelopmental impairment in 25- to 27-week infants.
This study suggests that physicians’ willingness to provide care to extremely low gestation infants as measured by frequency of use of antenatal corticosteroids is associated with improved outcomes for more-mature infants.
low-birth weight infant; NICUs; treatment; patient outcome assessment
Patients with diabetes frequently are hospitalized, and quality of inpatient care for diabetes is of great concern. Rehospitalization after hospital discharge is a frequent adverse outcome experienced by patients with diabetes.
We assessed the frequency of and risk factors for rehospitalization among all Philadelphia residents with diabetes.
Individual histories of hospitalization were ascertained from hospital discharge summaries for Philadelphia residents ages 25–84 who had at least 1 diabetes hospitalization from 1994 through 2001. Logistic regression was used to assess predictors of nonelective rehospitalization within 30 days of discharge, including recording of diabetes diagnosis.
Nonelective rehospitalizations within 30 days of hospital discharge were ascertained for 58,308 (20.0%) of 291,752 discharges. The proportion rehospitalized was 9.4% after a patient’s first diabetes diagnosis hospitalization; after later discharges for which a diabetes diagnosis was not recorded, rehospitalizations occurred in 30.6% of all cases. The absence of a diabetes diagnosis was a highly significant predictor of rehospitalization after adjustment for age, year, gender, race/ethnicity, insurance status, admission type, severity code, length of stay, discharge status, and number of previous hospitalizations.
Failure to record a diabetes diagnoses in administrative hospital discharge data may reflect lack of attention to the critical needs of patients with diabetes who are being treated for other conditions, whereas the attention to patient education and follow-up planning for patients with incident diabetes diagnoses may reduce the risk of rehospitalization.
administrative data; diabetes; diagnosis; readmissions
We sought to determine the incidence of necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) in surviving extremely low-birth-weight (ELBW, <1000 g birth weight) infants and to establish the impact of NEC on outcomes by hospital discharge and at 18 to 22 months adjusted age in a large, contemporary, population-based practice.
Hospital outcome data for all ELBW infants born in the greater Cincinnati region from 1998 to 2009 were extracted from the National Institute of Child Health Neonatal Research Network Database. Neurodevelopmental outcome at 18 to 22 months was assessed using Bayley Scales of Infant Development-II scores for Mental Developmental Index and Psychomotor Developmental Index. Multivariable logistic regression was used and adjusted odds ratios reported to control for confounders.
From 1998 to 2009, ELBW infants accounted for 0.5% of the 352 176 live-born infants in greater Cincinnati. The incidence of NEC was 12%, with a 50% case-fatality rate. Death before discharge, morbid complications of prematurity and neurodevelopmental impairment were all increased among infants diagnosed with NEC. Infants with surgical NEC and SIP had a higher incidence of death, but long-term neurodevelopmental outcomes were not different comparing surviving ELBW infants with medical NEC, surgical NEC and SIP.
Although ELBW infants comprise a very small proportion of live-born infants, those who develop NEC and SIP are at an increased risk for death, morbid complications of prematurity and neurodevelopmental impairment. No significant differences in neurodevelopmental outcomes were observed between the medical and surgical NEC and SIP groups.
necrotizing enterocolitis; extremely low-birth-weight; neurodevelopmental outcome; Bayley scales of infant development
Data are limited on the impact of methicillin-resistant Staphylococcus aureus (MRSA) on morbidity and mortality among very low birth weight (VLBW) infants with S aureus (SA) bacteremia and/or meningitis (B/M).
Neonatal data for VLBW infants (birth weight 401–1500 g) born January 1, 2006, to December 31, 2008, who received care at centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were collected prospectively. Early-onset (≤72 hours after birth) and late-onset (>72 hours) infections were defined by blood or cerebrospinal fluid cultures and antibiotic treatment of ≥5 days (or death <5 days with intent to treat). Outcomes were compared for infants with MRSA versus methicillin-susceptible S aureus (MSSA) B/M.
Of 8444 infants who survived >3 days, 316 (3.7%) had SA B/M. Eighty-eight had MRSA (1% of all infants, 28% of infants with SA); 228 had MSSA (2.7% of all infants, 72% of infants with SA). No infant had both MRSA and MSSA B/M. Ninety-nine percent of MRSA infections were late-onset. The percent of infants with MRSA varied by center (P < .001) with 9 of 20 centers reporting no cases. Need for mechanical ventilation, diagnosis of respiratory distress syndrome, necrotizing enterocolitis, and other morbidities did not differ between infants with MRSA and MSSA. Mortality was high with both MRSA (23 of 88, 26%) and MSSA (55 of 228, 24%).
Few VLBW infants had SA B/M. The 1% with MRSA had morbidity and mortality rates similar to infants with MSSA. Practices should provide equal focus on prevention and management of both MRSA and MSSA infections among VLBW infants.
Staphylococcus aureus; methicillin resistant; infant; newborn
Elevated scores on depression symptom questionnaires predict rehospitalization after acute myocardial infarction (AMI). Whether DSM-IV depressive disorders predict rehospitalization after AMI is unknown.
Methods and Results
Participants (n=766) in an ENRICHD ancillary study were classified by diagnostic interview as having no depression, minor depression, or major depression after AMI. Cardiac rehospitalizations were tracked for up to 42 months. Cox proportional hazards regression was used to model the effect of depressive disorder on time to first cardiac rehospitalization, controlling for mortality risk factors. Logistic regression was used to compare the accuracy with which rehospitalization could be predicted by depression diagnosis or by the Beck Depression Inventory (BDI). Secondary analyses examined the effects of depression on the cumulative number of all-cause rehospitalizations, length of stay, and emergency department visits. Compared to nondepressed patients, those with either major or minor depression were hospitalized sooner (minor: adjusted HR, 2.22; 95% CI, 1.59 to 3.08; P<.001; major: adjusted HR, 2.54; 95% CI, 1.84 to 3.53; P<.001), had more hospitalizations (minor: P<.001; major: P<.001) and emergency department visits (minor: P=.003; major: P<.001), and spent more days in the hospital (minor: P<.001; major: P<.001). The interview and questionnaire methods of assessing depression did not significantly differ in their overall accuracy of predicting rehospitalization.
Depressive disorders increase the risk of rehospitalization after AMI. Future work should focus on developing multivariable models to predict risk of rehospitalization after AMI, and depression should be included in these.
myocardial Infarction; depression; depressive disorder; patient readmission
Inflammation mediated by cytokines may be important in the pathogenesis of bronchopulmonary dysplasia and the competing outcome of death in extremely low birth weight infants.
To develop multi-variable logistic regression models for the outcome of bronchopulmonary dysplasia and/or death at 36w post-menstrual age using clinical and cytokine data from the first 28 days.
1067 extremely low birth weight infants in the Neonatal Research Network of the National Institute of Child Health and Human Development had 25 cytokines measured from blood collected within 4 h of birth and on days 3, 7, 14, and 21. Stepwise regression using peak values of the 25 cytokines and 15 clinical variables identified variables associated with BPD/death. Multi-variable logistic regression was done for bronchopulmonary dysplasia/death using variables selected by stepwise regression. Similar analyses were also done using average cytokine values from days 0–21, days 0–3, and from days 14–21.
Of 1062 infants with available data, 606 infants developed bronchopulmonary dysplasia or died. Combining results from all models, bronchopulmonary dysplasia/death was associated with higher concentrations of interleukins-1β, -6, -8, -10, and interferon-γ and lower concentrations of interleukin-17, RANTES, and tumor necrosis factor-β. Compared to models with only clinical variables, addition of cytokine data improved predictive ability by a statistically significant but clinically modest magnitude.
The overall pattern of cytokines suggests bronchopulmonary dysplasia/death may be associated with impairment in the transition from the innate immune response mediated by neutrophils to the adaptive immune response mediated by T-lymphocytes.
Logistic models; Infant; premature; Predictive value of tests
Spontaneous intestinal perforation (SIP) is associated with the use of postnatal glucocorticoids and indometacin in extremely low birth weight (ELBW) infants. We hypothesized: 1) an association of SIP with the use of antenatal steroids (ANS) and indometacin either as prophylaxis for IVH (P Indo) or for treatment of PDA (Indo/PDA) and 2) an increased risk of death or abnormal neurodevelopmental outcomes in infants with SIP at 18-22 months corrected age.
We retrospectively identified ELBW infants with SIP in the Neonatal Research Network’s generic database. Unadjusted analysis identified the differences in maternal, neonatal and clinical variables between infants with and without SIP. Logistic regression analysis identified the adjusted odds ratio for SIP with reference to ANS, P Indo and Indo/PDA. Neurodevelopmental outcomes were assessed among survivors at 18 to 22 months corrected age.
Indo/PDA was associated with an increased risk of SIP (adjusted OR 1.61; 95% CI 1.25,2.08), while P Indo and ANS were not. SIP was independently associated with an increased risk of death or NDI (adjusted OR−1.85; 95% CI 1.32,2.60) and NDI among survivors (adjusted OR−1.75, 95% CI 1.20,2.55).
Indometacin used for IVH prophylaxis and ANS were not associated with the occurrence of SIP in ELBW infants. Indometacin used for treatment of symptomatic PDA was however associated with an increased risk of SIP. ELBW infants with SIP have an increased risk of poor neurodevelopmental outcomes.
extremely low birth weight infant; intestinal perforation; indometacin; cerebral palsy
To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18–22 months corrected age in extremely low birth weight infants.
Total plasma biirubin and unbound biirubin were measured in 1,101 extremely low birth weight infants at 5±1 day of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18–22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow-up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors.
Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow-up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow-up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants.
In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma and unbound bilirubin and death or adverse neurodevelopmental outcomes at 18–22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants.
Plasma bilirubin; unbound bilirubin; Extremely low birth weight infants; Neurodevelopmental outcomes
Acculturation to U.S. society among minority patients may influence health outcomes beyond race and ethnicity alone. In particular, those who are foreign-born and who do not speak English as their primary language may have greater challenges interacting with the health care system and thus be at greater risk for adverse outcomes.
Methods and Results
We studied patients hospitalized with a principal discharge diagnosis of HF between January 2000 and December 2007 in an integrated delivery system that cares for minority patients. Individuals were defined as having low acculturation if their primary language was not English and their country of birth was outside of the U.S. Multivariable logistic regression and Cox proportional hazards regression were used to determine the independent risk of 30-day rehospitalization and 1-year mortality, respectively. Candidate adjustment variables included demographics (age, gender, race/ethnicity), coexisting illnesses, laboratory values, left ventricular systolic function, and characteristics of the index admission. Of 1,268 patients, 30% (n=379) were Black, 39% (n=498) Hispanic, and 27% (n= 348) White. Eighteen percent (n=228) had low acculturation. After adjustment, low acculturation was associated with a higher risk of readmission at 30 days (OR 1.70; 95% CI 1.07-2.68) but not 1-year all-cause mortality (HR 0.69; 95% CI 0.42-1.14).
Patients with HF who are foreign-born and do not speak English as their primary language have a greater risk of rehospitalization, independent of clinical factors and race/ethnicity. Future studies should evaluate whether culturally concordant interventions focusing on such patients may improve outcomes for this patient population.
heart failure; readmission; survival; risk factors; health disparities
To compare the risk-adjusted incidence of death or neuro-developmental impairment at 18–22 months corrected age, between twin and singleton extremely low birth weight infants.
Twin gestation is independently associated with increased risk of death or adverse neuro-developmental outcomes at 18–22 months corrected age in extremely low birth weight infants.
Retrospective study of inborn extremely low birth weight infants (BW 401– 1000g) admitted to NICHD Neonatal Research Network units between 1997 and 2005, who either died or had follow-up data available at 18–22 months corrected age. Neuro-developmental impairment (NDI), the primary outcome variable, was defined as the presence of any one of the following: moderate or severe cerebral palsy, severe bilateral hearing loss needing amplification, bilateral blindness, Bayley Mental Developmental Index or Psychomotor Developmental Index of less than 70. Death was included with NDI as a composite outcome since it is a competing variable. Results were compared for both twins, twin A, twin B, same sex twins, unlike sex twins and singleton infants. Logistic regression analysis was done to control for demographic and clinical factors that were different among the groups.
The cohort of infants who either died or were assessed for NDI consisted of 7,630 singleton infants and 1,376 twins. Logistic regression adjusting for clinical and socio-demographic risk factors showed an increased risk of death or NDI for twins as a group when compared with the singletons (OR-1.39, 95% CI- 1.19–1.63). On analyzing twin A and B separately as well, risk of death or NDI was increased in both twin A (OR-1.32, 95% CI- 1.09–1.59) and for twin B (OR-1.47, 95% CI- 1.21–1.78), when compared with singleton infants.
Twin gestation in ELBW infants is associated with an independent increased risk of death or NDI at 18–22 months corrected age, compared to ELBW singleton gestation infants. Both first and second born twins are at increased risk of death or NDI when compared to singleton ELBW infants.
twins; neuro-developmental impairment; extremely low birth weight infants
To determine the long-term outcome of neonatal dehydration.
We identified 182 newborns rehospitalized with dehydration (weight loss ≥12% of birth weight and/or serum sodium ≥150 mEq/L) and 419 randomly selected controls from a cohort of 106,627 term and near-term infants ≥2000 g born from 1995 through 1998 in Northern California Kaiser Permanente hospitals. Outcomes data were obtained from electronic records, interviews, questionnaire responses, and neurodevelopmental evaluations performed in a masked fashion.
Follow-up data to the age of at least two years were available for 173/182 children with a history of dehydration (95%) and 372/419 controls (89%) and included formal evaluation at a mean (±SD) age of 5.1±0.12 years for 106 children (58%) and 168 children (40%) respectively. None of the cases developed shock, gangrene, or respiratory failure. Neither crude nor adjusted scores on cognitive tests differed significantly between groups. There was no significant difference between groups in the proportion of children with abnormal neurologic examinations or neurologic diagnoses. Frequencies of parental concerns and reported behavior problems also were not significantly different in the two groups.
Neonatal dehydration in this managed care setting was not associated with adverse neurodevelopmental outcomes in infants born at or near term.
dehydration; neonatal; hypernatremia; neurodevelopmental outcome; breastfeeding
Guidelines for prevention of group B streptococcal (GBS) infection have successfully reduced early onset (EO) GBS disease. Study results suggest that Escherichia coli is an important EO pathogen.
To determine EO infection rates, pathogens, morbidity, and mortality in a national network of neonatal centers.
Infants with EO infection were identified by prospective surveillance at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Network centers. Infection was defined by positive culture results for blood and cerebrospinal fluid obtained from infants aged ≤72 hours plus treatment with antibiotic therapy for ≥5 days. Mother and infant characteristics, treatments, and outcomes were studied. Numbers of cases and total live births (LBs) were used to calculate incidence.
Among 396 586 LBs (2006–2009), 389 infants developed EO infection (0.98 cases per 1000 LBs). Infection rates increased with decreasing birth weight. GBS (43%, 0.41 per 1000 LBs) and E coli (29%, 0.28 per 1000 LBs) were most frequently isolated. Most infants with GBS were term (73%); 81% with E coli were preterm. Mothers of 67% of infected term and 58% of infected preterm infants were screened for GBS, and results were positive for 25% of those mothers. Only 76% of mothers with GBS colonization received intrapartum chemoprophylaxis. Although 77% of infected infants required intensive care, 20% of term infants were treated in the normal newborn nursery. Sixteen percent of infected infants died, most commonly with E coli infection (33%).
In the era of intrapartum chemoprophylaxis to reduce GBS, rates of EO infection have declined but reflect a continued burden of disease. GBS remains the most frequent pathogen in term infants, and E coli the most significant pathogen in preterm infants. Missed opportunities for GBS prevention continue. Prevention of E coli sepsis, especially among preterm infants, remains a challenge.
neonatal sepsis; group B streptococcal disease; Escherichia coli infection
Methods are required to predict prognosis with changes in clinical course. Death or neurodevelopmental impairment in extremely premature neonates can be predicted at birth/admission to the ICU by considering gender, antenatal steroids, multiple birth, birth weight, and gestational age. Predictions may be improved by using additional information available later during the clinical course. Our objective was to develop serial predictions of outcome by using prognostic factors available over the course of NICU hospitalization.
Data on infants with birth weight ≤1.0 kg admitted to 18 large academic tertiary NICUs during 1998–2005 were used to develop multivariable regression models following stepwise variable selection. Models were developed by using all survivors at specific times during hospitalization (in delivery room [n = 8713], 7-day [n = 6996], 28-day [n = 6241], and 36-week postmenstrual age [n = 5118]) to predict death or death/neurodevelopmental impairment at 18 to 22 months.
Prediction of death or neurodevelopmental impairment in extremely premature infants is improved by using information available later during the clinical course. The importance of birth weight declines, whereas the importance of respiratory illness severity increases with advancing postnatal age. The c-statistic in validation models ranged from 0.74 to 0.80 with misclassification rates ranging from 0.28 to 0.30.
Dynamic models of the changing probability of individual outcome can improve outcome predictions in preterm infants. Various current and future scenarios can be modeled by input of different clinical possibilities to develop individual “outcome trajectories” and evaluate impact of possible morbidities on outcome.
logistic models; premature infant; predictive value of tests; prognosis
To determine whether extremely low birth weight (ELBW) infants with bilateral compared to unilateral intraventricular hemorrhage (IVH) have worse neurodevelopmental outcomes at 18–22 months.
166 ELBW infants (<1000 g) admitted to a Cincinnati NICU from 1998–2005 with a head ultrasound showing Grade I–IV IVH and neurodevelopmental assessment at 18–22 months corrected age were included. Multivariable linear and logistic regression models were developed to determine the impact of laterality and grade of IVH and other clinical variables to predict scores on the Bayley Scales of Infant Development, Second Edition, Mental Development Index (MDI) and Psychomotor Development Index (PDI) and the combined outcome of neurodevelopmental impairment (NDI).
Infants with bilateral grade IV IVH had lower adjusted mean Bayley scores compared with infants with unilateral grade IV IVH. For grades I, II, and III IVH, bilaterality of IVH was not associated with lower mean Bayley scores. Infants with grade IV IVH had the highest odds of NDI. The probability of NDI increased with sepsis and postnatal steroid use.
ELBW infants with bilateral compared to those with unilateral grade IV IVH had worse neurodevelopmental outcomes. Infants with grades I–III IVH had similar outcomes whether they had unilateral or bilateral IVH.
premature; sepsis; steroids; Bayley; cognitive; motor
To determine whether delivery room cardiopulmonary resuscitation (DR-CPR) independently predicts morbidities and neurodevelopmental impairment (NI) in extremely low birth weight (ELBW) infants.
Cohort study of infants born with birth weight (BW) 401-1000g and gestational age (GA) 23-30wks. DR-CPR was defined as chest compressions and/or drugs. Logistic regression was used to determine associations between DR-CPR and morbidities, mortality and NI at 18-24 months (Bayley II mental or psychomotor index < 70, cerebral palsy, blindness or deafness). Data are adjusted Odds Ratio (OR) with 95% confidence interval.
Of 8685 infants, 1333(15%) received DR-CPR. DR-CPR infants had lower BW (708±141vs 764±146g, p<0.0001) and GA (25±2 vs 26±2 wks, p<0.0001). DR-CPR infants had more pneumothoraces (OR 1.28, 1.48-2.99), Grade 3-4 intraventricular hemorrhage (OR 1.47, 1.23-1.74), bronchopulmonary dysplasia (OR 1.34, 1.13-1.59), death by 12 hours (OR 3.69, 2.98-4.57) and by 120 days after birth (OR 2.22, 1.93-2.57). NI among survivors (OR 1.23, 1.02-1.49), and death or NI (OR 1.70, 1.46-1.99) were higher for DR-CPR infants. Only 14% of DR-CPR recipients with 5-minute Apgar score<2 survived without NI.
DR-CPR is a prognostic marker for higher mortality and NI for ELBW survivors. New DR-CPR strategies are needed for this population.
cardiac compressions; epinephrine; neurodevelopmental outcomes
Objectives To compare changes in inequalities in sudden infant death syndrome with other causes of infant mortality and stillbirth in Scotland, 1985-2008.
Design Retrospective cohort study.
Setting Scotland 1985-2008, analysed by four epochs of six years.
Participants Singleton births of infants with birth weight >500 g born at 28-43 weeks’ gestation.
Main outcome measures Sudden infant death syndrome, other causes of postneonatal infant death, neonatal death, and stillbirth. Odds ratios expressed as the association across the range of seven categories of Carstairs deprivation score.
Results The association between deprivation and the risk of all cause stillbirth and infant death varied between the four epochs (P=0.04). This was wholly explained by variation in the risk of sudden infant death syndrome (P<0.001 for interaction). Among women living in areas of low deprivation, there was a sharp decline in the rate of sudden infant death syndrome from 1990 to 1993. Among women living in areas of high deprivation, there was a slower decline in sudden infant death syndrome rates between 1992 and 2004. Consequently, the odds ratio for the association between socioeconomic deprivation and sudden infant death syndrome increased from 2.04 (95% confidence interval 1.53 to 2.72) in 1985-90, to 7.52 (4.62 to 12.25) in 1991-6, and 9.50 (5.46 to 16.53) in 1997-2002 but fell to 1.78 (0.87 to 3.65) in 2002-8. The interaction remained significant after adjustment for maternal characteristics.
Conclusion The rate of sudden infant death syndrome declined throughout Scotland in the early 1990s. The decline had a later onset and was slower among women living in areas of high deprivation, probably because of slower uptake of recommended changes in infant sleeping position. The effect was to create a strong independent association between deprivation and sudden infant death syndrome where one did not exist before.
Early infant morbidities may produce adverse outcomes in subsequent life. A low Apgar score is a convenient measure of early infant morbidity. We study determinants of early infant morbidity (sex, plurality, mode of delivery, prior losses, gestational age, prenatal care and birth weight, parity and maternal age, race, maternal education and community development) for the 1998-birth cohort, City of São Paulo, Brazil.
This study identified all deliveries that took place in the City of São Paulo during 1998. Information was extracted from 209,628 birth records. We used multivariate logistic regression to assess the effect of each independent variable on Apgar score less than seven at one minute and Apgar score less than seven at five minutes.
Low birth weight, prematurity and community development were found to be strong predictors of morbidity. Maternal education showed strong negative correlation with both Apgar scores. The negative correlations between maternal schooling and Apgar scores were observed after prenatal care, parity and maternal age were included in the model. Unmeasured proximate factors may thus be the true source of disparity between educational groups. Children of very young adolescent mothers had lower Apgar scores at one minute (but not at five minutes) than those born to mothers 15 to 19. Parity one or higher was associated with decreased odds of low Apgar scores. Cesarean section and operative delivery were associated with higher odds of early infant morbidity.
Education may allow mothers to have better care in the peripartum period. More educated mothers may be more likely to recognize certain morbidities through the pregnancy period and the monitoring of such morbidities yields better infant outcomes. Also, having less than seven prenatal care visits was found to predict early infant morbidity and one way to increase the use of such services is to focus on aspects of care that may lead to easier accessibility and continuity of prenatal care. Physicians should inform mothers about the risks associated with high number of children for a next infant and also about the risks for the infant associated with unnecessary cesarean sections. Special attention should be paid to adolescent mothers, since much of their increased risk is likely to be minimized by counseling.