Annemarie Stroustrup

Epidemiological Characteristics and Resource Use in Neonates With Bronchopulmonary Dysplasia: 1993–2006

OBJECTIVE: To determine the trends in incidence of diagnosis of bronchopulmonary dysplasia (BPD) and associated health services use for the neonatal hospitalization of patients with BPD in an era of changing definitions and management. PATIENTS AND METHODS: All neonatal hospitalization records available through the Nationwide Inpatient Sample, 1993–2006, were analyzed. Multivariable regression analyses were performed for incidence of BPD diagnosis and associated hospital length of stay and charges. Multiple models were constructed to assess the roles of changes in diagnosis of very low birth weight (VLBW) neonates and different modalities of respiratory support used for treatment. RESULTS: The absolute incidence of diagnosis of BPD fell 3.3% annually (P = .0009) between 1993 and 2006 coincident with a 3.5-fold increase in the use of noninvasive respiratory support in patients with BPD. When data were controlled for demographic factors, this significant decrease in incidence persisted at a rate of 4.3% annually (P = .0002). All models demonstrated a rise in hospital length of stay and financial charges for the neonatal hospitalization of patients with BPD. The incidence of BPD adjusted for frequency of prolonged mechanical ventilation also decreased but only by 2.8% annually (P = .0075). CONCLUSIONS: The incidence of diagnosis of BPD decreased significantly between 1993 and 2006. In well-controlled models, birth hospitalization charges for these patients rose during the same period. Less invasive ventilatory support may improve respiratory outcomes of VLBW neonates.

Incidences and sociodemographics of specific congenital heart diseases in the United States of America: an evaluation of hospital discharge diagnoses.

Current estimates of the incidence of congenital heart disease (CHD) are derived from small clinical studies and metaanalyses. For the true incidence of CHD in the United States of America to be estimated, a single large representative population must be analyzed. All the data in this study were derived from the Nationwide Inpatient Sample database. The study determined the overall and lesion-specific incidences of CHD diagnoses among all birth hospitalizations in 2008, stratified by race, gender, socioeconomic status, and hospital geographic location. The study identified 13,093 CHD diagnoses among 1,204,887 birth hospitalizations, yielding an incidence of 10.8 per 1,000, with a predominance of mild lesions and septal defects. Atrial septal defect (ASD) and pulmonic stenosis were more common among females, whereas aortic stenosis, coarctation of the aorta, hypoplastic left heart syndrome, and d-transposition of great arteries were more common among males. No racial difference was observed in the overall CHD incidence. However, isolated patent ductus arteriosus (PDA) and ventricular septal defects (VSDs) were more common among Caucasians, whereas ASDs were more common among Hispanics. The incidences of CHD diagnoses were similar for all socioeconomic classes except the lowest socioeconomic class, which had a significantly lower CHD incidence. There was no geographic or seasonal variation in CHD incidence. This study demonstrated the incidence of echocardiographically confirmed CHD diagnosis to be 10.8 per 1,000 live births, marked by a high proportion of mild cardiac lesions and isolated PDAs. The high incidence of isolated PDAs in this study may be explained by the inclusion of only CHD diagnoses during birth hospitalization.

Impact of hospital-based environmental exposures on neurodevelopmental outcomes of preterm infants.

Purpose of review Over 300 000 infants are hospitalized in a neonatal intensive care unit (NICU) in the United States annually during a developmental period critical to later neurobehavioral function. Environmental exposures during the fetal period and infancy have been shown to impact long-term neurobehavioral outcomes. This review summarizes evidence linking NICU-based environmental exposures to neurodevelopmental outcomes of children born preterm. Recent findings Preterm infants experience multiple exposures important to neurodevelopment during the NICU hospitalization. The physical layout of the NICU, management of light and sound, social interactions with parents and NICU staff, and chemical exposures via medical equipment are important to long-term neurobehavioral outcomes in this highly vulnerable population. Summary Existing research documents NICU-based exposure to neurotoxic chemicals, aberrant light, excess sound, and restricted social interaction. In total, this creates an environment of co-existing excesses (chemicals, light, sound) and deprivation (touch, speech). The full impact of these co-exposures on the long-term neurodevelopment of preterm infants has not been adequately elucidated. Research into the importance of the NICU from an environmental health perspective is in its infancy, but could provide understanding about critical modifiable factors impacting the neurobehavioral health of hundreds of thousands of children each year.

Randomized Controlled Trial of Restrictive Fluid Management in Transient Tachypnea of the Newborn

OBJECTIVE To determine the effect of mild fluid restriction on the hospital course of neonates with transient tachypnea of the newborn (TTN). STUDY DESIGN In this pilot prospective randomized controlled trial of 64 late preterm and term neonates diagnosed with TTN at a single tertiary care hospital in the United States, patients were randomized to receive standard fluid management or mild fluid restriction. The primary outcome was duration of respiratory support. Secondary outcomes were duration of admission to the intensive care unit, time to first enteral feed, and total and composite hospital costs. Results were analyzed by t-test, χ(2) test, Kaplan-Meier estimation, and proportional hazards regression. RESULTS Fluid restriction did not cause adverse events or unsafe dehydration. Fluid management strategy did not affect primary or secondary outcomes in the total study population. Fluid restriction significantly reduced the duration of respiratory support (P = .008) and hospitalization costs (P = .017) in neonates with severe TTN. CONCLUSION Mild fluid restriction appears to be safe in late preterm and term neonates with uncomplicated TTN. Fluid restriction may be of benefit in decreasing the duration of respiratory support and reducing hospitalization costs in term and late preterm neonates with uncomplicated severe TTN.

Antibiotic use in newborns with transient tachypnea of the newborn.

Background: Initiation of empiric antibiotic treatment for possible early-onset sepsis is recommended for late preterm and term neonates with respiratory distress. There is no evidence base to this approach. Objectives: To determine the incidence of adverse infectious events in neonates with transient tachypnea of the newborn (TTN) managed with a risk-factor-based restrictive antibiotic use policy. Methods: This is a single institution retrospective cohort study of neonates with primary diagnosis of TTN between 2004 and 2010. The relationship between antibiotic exposure and infectious outcomes during the neonatal hospitalization was evaluated. An infectious outcome was defined as pneumonia, bacteremia, clinical sepsis, or death. Analysis included t test, χ2 test, and analysis of variance as appropriate. Results: 745 neonates with TTN met inclusion criteria. None of the 494 antibiotic-naive infants, and 212 of the 251 antibiotic-exposed infants had identifiable risk factors for sepsis. No infectious outcomes occurred in infants who did not receive antibiotics. Eight neonates with TTN received full antibiotic treatment for early-onset sepsis. Each was appropriately identified for early receipt of antibiotics based on historical or clinical risk factors for early-onset sepsis. Conclusions: This study suggests that empiric postnatal antibiotic treatment may not be warranted for late preterm and term infants with TTN in the absence of specific infectious risk factors.

Temporal Variation of Birth Prevalence of Congenital Heart Disease in the United States

BACKGROUND This is a longitudinal analysis of the largest and most comprehensive inpatient care database in the United States to determine temporal variation of birth prevalence of congenital heart disease (CHD) diagnosis, adjusting for potentially confounding factors. METHODS We compared all entries of CHD diagnoses in the Nationwide Inpatient Sample (NIS) database in 1998 and 2008 to determine differences in birth prevalence of overall CHD and specific CHD phenotypes stratified by race, gender, socioeconomic status, and geographical location. RESULTS CHD prevalence was 10.2/1000 in 1998 and 10.8/1000 live births in 2008, without significant changes in prevalence (P = .09). Prevalence of isolated patent ductus arteriosus increased from 1.9 to 2.8 per 1000 (P < .001), and this temporal increase remained statistically significant after stratification by race, income status, and geographic location. Prevalence of mild CHD increased from 8.0 to 9.1 per 1000 (P = .01), with most of this increase occurring among Caucasians and the upper socioeconomic class. There was a decrease in prevalence of severe CHD from 1.5 to 0.9 (P = .03), while prevalence of moderate CHD and all other specific CHD phenotypes remained unchanged in both cohorts. CONCLUSIONS We report increased prevalence of isolated patent ductus arteriosus and mild CHD; decreased prevalence of severe CHD; and unchanged prevalence of overall CHD and all other specific CHD phenotype. We speculate that increased prevalence of mild CHD was due to increased case detection because of improvement in echocardiography. Decrease in diagnosis of severe CHD could be due to the impact of pregnancy termination.

Demographics, clinical characteristics and outcomes of neonates diagnosed with fetomaternal haemorrhage

Objective To determine clinical characteristics, demographics and short-term outcomes of neonates diagnosed with fetomaternal haemorrhage (FMH). Design The authors analysed the Nationwide Inpatient Sample, 1993 to 2008. Singleton births diagnosed with FMH were identified by International Classification of Diseases (ICD-9) code 762.3. Descriptive, univariate and multivariable regression analyses were performed to determine the national annual incidence of FMH over time as well as demographics and clinical characteristics of neonates with FMH. Results FMH was identified in 12 116 singleton births. Newborns with FMH required high intensity of care: 26.3% received mechanical ventilation, 22.4% received blood product transfusion and 27.8% underwent central line placement. Preterm birth (OR 3.7), placental abruption (OR 9.8) and umbilical cord anomaly (OR 11.4) were risk factors for FMH. Higher patient income was associated with increased likelihood of FMH diagnosis (OR 1.2), and Whites were more likely to be diagnosed than ethnic minorities (OR 1.9). There was reduced frequency of diagnosis in the Southern USA (OR 0.8 vs the Northeastern USA). Conclusions Diagnosis of FMH is associated with significant morbidity as well as regional, socioeconomic and racial disparity. Further study is needed to distinguish between diagnostic coding bias and true epidemiology of the disease. This is the first report of socioeconomic and racial/ethnic disparities in FMH, which may represent disparities in detection that require national attention.

Congenital malformations in the newborn population: A population study and analysis of the effect of sex and prematurity

BACKGROUND Congenital malformation (CM) is a leading cause of infant mortality. We hypothesized that the current estimates of the prevalence of CM are obsolete because of the increased rate of terminating fetuses with severe CMs and the widespread use of prenatal vitamins. METHODS This population-based cross-sectional study analyzed the effect of sex and prematurity on CM prevalence. All data were derived from birth entries in the 2008 Nationwide Inpatient Sample (NIS) database. Our objectives were to determine the prevalence of CM diagnoses among all birth hospitalizations in 2008 and to analyze the effect of sex and gestational maturity on CM prevalence. RESULTS We identified 29,312 patients with CMs from among 1,014,261 live births, which yielded a CM prevalence of 28.9 per 1000 live births. Associated genetic syndromes were present in 1172 (4%) patients. Among newborns with nonsyndromic CM, 91% of newborns had an isolated CM and 9% of newborns had multiple CMs. The cardiovascular system was the most commonly involved organ system. The risk of CM was significantly higher in preterm newborns for an isolated CM [odds ratio (OR), 1.5; confidence interval (CI), 1.4-1.5]; multiple CMs (OR, 2.1; CI, 2.0-2.3); and overall CMs (OR, 1.4; CI, 1.3-1.5). Males had higher risk of isolated CMs (OR, 1.3; CI, 1.2-1.5). However, there was no sex difference in the risk of overall CM. CONCLUSION We reported up-to-date national estimates of the prevalence of CM, which is important for monitoring trends, determining service planning, and assessing disease burden because of congenital malformations in the United States of America. We also showed a strong association between CM and prematurity. Further study of this association is needed to provide insight into the etiology of these relatively common public health problems.

Impact of physician awareness on diagnosis of fetomaternal hemorrhage.

Background: Fetomaternal hemorrhage (FMH) is a poorly understood condition in which the placenta allows transmission of fetal whole blood to the mother. FMH can cause fetal anemia resulting in critical illness, death or lifelong disability. Ascertainment of the incidence of FMH is limited by reliance on retrospective studies that are dependent on a diagnosis of FMH being made at the time of patient presentation. Objective: To determine whether the diagnosis of FMH is made more frequently after an educational intervention to increase physician awareness of the condition. Methods: This is a retrospective cohort study of all neonates born at our institution from 1988 through 2010. The medical records of all neonates diagnosed with anemia in the first 24 h of life were reviewed. The incidence of FMH as a documented etiology of anemia was compared between infants born before and after our educational intervention. Results: Of 124,738 births during the study period, 572 neonates with neonatal anemia were identified. A total of 23 cases of FMH demonstrated by positive Kleihauer-Betke testing occurred in our cohort. The incidence of diagnosed FMH prior to our intervention was 22 per 1,000 anemic neonates compared to 182 per 1,000 afterwards (p < 0.001), while the incidence of neonatal anemia remained unchanged (p = 0.377). Conclusions: FMH may be a significant cause of neonatal anemia. Diagnosis of FMH is highly dependent on physician awareness of the condition. Incorrect or absent diagnosis of the etiology of neonatal anemia has significant implications for our understanding of the epidemiology of FMH.

Growth and development in children born very low birthweight

Objective To examine the relationships between growth (birth to age 2 years) and developmental outcomes in children born with very low birthweight (VLBW). Design Motor and mental development in children born with VLBW were regressed on anthropometric measurements at birth, 9 months and 2 years using multivariable regression. Setting The Early Childhood Longitudinal Study—Birth Cohort, a longitudinal cohort, community sample, designed to be representative of children born across the USA. Patients 950 children born with VLBW (<1500 g). Main Outcome Measures Motor and cognitive scores on the Bayley Scales at 9 months and 24 months chronological age. Results A high proportion of children exhibited poor growth, with length-for-age z-scores <−2 (ie, stunting) in 21.3% of children at 9 months (adjusted for prematurity) and 34.2% of children at 2 years. Compared with children having z-scores >−2, children with growth shortfalls in head circumference, length and weight had a higher adjusted OR (aOR) of low Bayley motor scores at 9 months and 2 years (aOR ranging from 1.8 to 3.3, all p<0.05), while low Bayley cognitive scores were predicted by 9-month deficits in length and weight (aOR 2.0 and 2.4, respectively, both p<0.01) and 2-year deficits in length and head circumference (aOR 2.9 and 2.8, both p<0.05). Conclusion Anthropometric measures of growth were linked to current and future neurodevelopmental outcomes in children born with VLBW. While careful length measures may be a particularly useful marker, deficits in all anthropometric measures were risk factors for developmental delays.