Effectiveness of Palivizumab against Respiratory Syncytial Virus: Cohort and Case Series Analysis.

OBJECTIVE: To measure the real-world effectiveness of palivizumab immunoprophylaxis against respiratory syncytial virus (RSV)-confirmed infection before age 2 years in a population-cohort of high-risk infants. STUDY DESIGN: Palivizumab is funded for high-risk infants in Western Australia. We used probabilistically linked administrative data encompassing RSV laboratory-confirmed infections, hospital admissions, and palivizumab dispensing records for a cohort of 24 329 high-risk infants admitted to neonatal intensive care units, born 2002-2013 with follow-up to 2015. We used a traditional cohort method with Cox proportional hazards regression and a self-controlled case series analysis to assess effectiveness of palivizumab in reducing RSV-confirmed infection by number of doses. RESULTS: From the cohort of 24 329 infants, 271 (1.1%) received at least 1 dose of palivizumab and 1506 (6.2%) had at least 1 RSV-confirmed infection before age 2 years. Using the traditional cohort approach, we found no protective association of palivizumab receipt with RSV detection (adjusted hazard ratio = 0.99 [95% CI 0.5, 1.9] for 1 dose). However, using a self-controlled case series to eliminate confounding by indication, a protective association was seen with a 74% lower RSV incidence (relative incidence = 0.26; 95% CI 0.11, 0.67) following any dose of palivizumab compared with control (nonexposed) periods. CONCLUSIONS: After accounting for confounding by indication through a self-controlled analysis, palivizumab appeared effective for reducing virologically confirmed RSV in this high-risk cohort.

Risk of Developmental Disorders in Children of Immigrant Mothers: A Population-Based Data Linkage Evaluation.

OBJECTIVES: To evaluate the prevalence and risks of developmental disability (autism spectrum disorder, intellectual disability, and cerebral palsy) in Western Australian children of different groups of foreign-born women. STUDY DESIGN: Western Australian population-based linked data of 764 749 singleton live births from 1980 to 2010 were used to compare disability outcomes among children of foreign-born, Australian-born non-Indigenous, and Indigenous women. The risk of disability was assessed using multinomial logistic regression. RESULTS: Overall, the prevalence of any disability was lowest for the children of foreign-born mothers. From 1980 to 1996 but not from 1997 to 2010, children born to mothers from foreign-born low-income countries had an increased relative risk of autism spectrum disorder with intellectual disability, and children born to foreign-born mothers from upper-middle-income countries had an increased risk of cerebral palsy with intellectual disability. After adjusting for smoking, the relative risks of intellectual disability and cerebral palsy with intellectual disability were markedly decreased in children of Australian-born Indigenous mothers. CONCLUSIONS: Although we did not find among children born to foreign-born women an increased prevalence across all the measured developmental outcomes, we did observe an increased risk of autism spectrum disorder with intellectual disability and cerebral palsy with intellectual disability for mothers of some foreign-born groups. Our findings related to smoking in the Indigenous population underscore its possible role on the causal pathway to intellectual disability. Maternal migration is considered a factor on the causal pathway to intellectual disability. Maternal migration may be either a risk or a protective factor on the causal pathway to developmental disabilities and the direct role of migration is inconclusive in our study.

Distribution of early structural lung changes due to cystic fibrosis detected with chest computed tomography.

OBJECTIVE: To examine the distribution of early structural lung changes in clinically stable infants and young children with cystic fibrosis using chest computed tomography (CT). STUDY DESIGN: This cross-sectional study included 62 children aged 1-6 years with volume-controlled volumetric chest CT scans performed under general anesthesia as part of an early surveillance program. Each lobe was scored for presence and extent of bronchiectasis, mucus plugging, and air trapping using a semiquantitative score. The topographic distribution of structural abnormalities was evaluated by comparing the presence and extent of abnormalities in different lung regions and examining relationships between components. RESULTS: Although bronchiectasis was most common in the right upper lobe, overall changes in lung structure were not more common or more extensive in the upper lobes. Rather, bronchiectasis was more common in the right lung (right lung 0.95, left lung 0.68, P = .003), and mucus plugging (upper 0.41, middle 0.41, lower 0.72, P = .028) and air trapping (upper 0.79, middle 0.48, lower 0.96, P < .001) were more common in the lower lobes. The extents of bronchiectasis (P < .001) and air trapping (P = .011) were greater in the right lung. Scans with bronchiectasis were also more likely to have coexisting mucus plugging (P = .008) and air trapping (P < .001). CONCLUSION: Early structural lung disease is heterogeneously distributed in the lung. Quantitative scoring tools for studies using chest CT as an end point, and mechanistic studies that seek to better understand the pathogenesis of early cystic fibrosis lung disease, should take account of this differential topographic expression of disease early in life.

The long-term effects of breastfeeding on child and adolescent mental health: a pregnancy cohort study followed for 14 years.

OBJECTIVES: To determine whether there was an independent effect of breastfeeding on child and adolescent mental health. STUDY DESIGN: The Western Australian Pregnancy Cohort (Raine) Study recruited 2900 pregnant women and followed the live births for 14 years. Mental health status was assessed by the Child Behaviour Checklist (CBCL) at 2, 6, 8, 10, and 14 years. Maternal pregnancy, postnatal, and infant factors were tested in multivariable random effects models and generalized estimating equations to examine the effects of breastfeeding duration on mental health morbidity. RESULTS: Breastfeeding for less than 6 months compared with 6 months or longer was an independent predictor of mental health problems through childhood and into adolescence. This relationship was supported by the random effects models (increase in total CBCL score: 1.45; 95% confidence interval 0.59, 2.30) and generalized estimating equation models (odds ratio for CBCL morbidity: 1.33; 95% confidence interval 1.09, 1.62) showing increased behavioral problems with shorter breastfeeding duration. CONCLUSION: A shorter duration of breastfeeding may be a predictor of adverse mental health outcomes throughout the developmental trajectory of childhood and early adolescence.

Bronchiectasis in infants and preschool children diagnosed with cystic fibrosis after newborn screening.

OBJECTIVES: To determine the prevalence of bronchiectasis in young children with cystic fibrosis (CF) diagnosed after newborn screening (NBS) and the relationship of bronchiectasis to pulmonary inflammation and infection. STUDY DESIGN: Children were diagnosed with CF after NBS. Computed tomography and bronchoalveolar lavage were performed with anesthesia (n = 96). Scans were analyzed for the presence and extent of abnormalities. RESULTS: The prevalence of bronchiectasis was 22% and increased with age (P = .001). Factors associated with bronchiectasis included absolute neutrophil count (P = .03), neutrophil elastase concentration (P = .001), and Pseudomonas aeruginosa infection (P = .03). CONCLUSIONS: Pulmonary abnormalities are common in infants and young children with CF and relate to neutrophilic inflammation and infection with P. aeruginosa. Current models of care for infants with CF fail to prevent respiratory sequelae. Bronchiectasis is a clinically relevant endpoint that could be used for intervention trials that commence soon after CF is diagnosed after NBS.

Hypertensive diseases of pregnancy and the development of behavioral problems in childhood and adolescence: the Western Australian Pregnancy Cohort Study.

OBJECTIVE: To examine whether maternal gestational hypertension and preeclampsia are associated with behavioral problems in offspring throughout childhood and early adolescence. STUDY DESIGN: We conducted a prospective cohort study of 2804 women in the Western Australian Pregnancy Cohort Study and their children observed at age 2, 5, 8, 10, and 14 years. The Child Behavior Checklist (CBCL) was used to measure problem child behavior with continuous z-scores and clinical cutoff points. Control variables included known biomedical, sociodemographic, and psychological factors. RESULTS: After adjustment, with general linear model analyses children of women with gestational hypertension were shown to be more likely to have higher CBCL z-scores, indicative of poorer behavior, from 8 years on, with the largest difference seen at 14 years. Children of mothers with preeclampsia were more likely to have lower CBCL z-scores, indicative of pro-social behaviors. The multivariable logistic regression analysis showed that gestational hypertension was predictive of clinically significant CBCL T-scores from age 8 to 14 years. This association was significant for externalizing behavior, such as delinquent and aggressive behavior, and for internalizing behavior at age 14 years. Unexpectedly, preeclampsia reduced internalizing morbidity at ages 5 and 8 years. CONCLUSIONS: The opposing effect on child and adolescent behavior of gestational hypertension and preeclampsia warrants further attention.

Predictors of seizure onset in Rett syndrome.

OBJECTIVES: To investigate risk factors for seizure onset in Rett syndrome. STUDY DESIGN: Information on presence and age at onset of seizures, perinatal and developmental history, and genetic status was abstracted on 275 cases in the Australian Rett Syndrome Database. Cox and Weibull regression were used to investigate and provide a model for predicting the effects of genetic and developmental factors on age at seizure onset. RESULTS: Seizures were reported in 81% of 275 cases; the median age of onset was 48 months. Not having gained the ability to walk (P = .003) and developmental problems in the first 10 months of age (P = .04) were associated with an almost 2-fold increased risk of seizures. Cases without a detectable MECP2 mutation had a higher risk of seizure onset up to 4 years of age (P < .001) but a lower risk after 4 years (P = .08). CONCLUSIONS: Seizure onset in Rett syndrome is associated with early developmental factors and with genotype. Information on these factors can be used to predict age at seizure onset after diagnosis.

Rett syndrome in Australia: a review of the epidemiology.

OBJECTIVE: To examine the prevalence, cumulative incidence, and survival in an Australian cohort with Rett syndrome (RTT). STUDY DESIGN: The Australian Rett Syndrome Database is a longitudinal data collection that included 276 verified female cases at the end of 2004. Survival was calculated using the Kaplan-Meier product limit method, and cumulative incidence was determined using the complement of the Kaplan-Meier method. RESULTS: Most cases (88.4%) have had MECP2 mutation testing, with positive results in 73%. The prevalence of RTT was .88 per 10,000 females in 5- to 18-year-olds, and the cumulative incidence was 1.09 per 10,000 females by 12 years of age. The cumulative incidence by the age of 5 years increased from .39 per 10,000 in the 1980 to 1984 cohort to .76 per 10,000 in birth cohorts beyond 1984. Survival was 77.8% at 25 years, compared with 99.96% survival in the Australian female population. Pneumonia (10/25) was the most common cause of death. CONCLUSIONS: The availability of genetic testing has contributed to the changing pattern and timing of RTT diagnosis in Australia. Girls with RTT have worse survival compared with the general female population. When more data are available, it will be possible to evaluate the relationship between survival and specific MECP2 mutations.