'Joining the Dots: Linking Prenatal Drug Exposure to Childhood and Adolescence' - research protocol of a population cohort study.

INTRODUCTION: Prenatal drug exposure (PDE) is one of the most important causes of child harm, but comprehensive information about the long-term outcomes of the families is difficult to ascertain. The Joining the Dots cohort study uses linked population data to understand the relationship between services, therapeutic interventions and outcomes of children with PDE. METHODS AND ANALYSIS: Information from routinely collected administrative databases was linked for all births registered in New South Wales (NSW), Australia between 1 July 2001 and 31 December 2020 (n=1 834 550). Outcomes for seven mutually exclusive groups of children with varying prenatal exposure to maternal substances of addiction, including smoking, alcohol, prescription/illicit drugs and neonatal abstinence syndrome will be assessed. Key exposure measures include maternal drug use type, maternal social demographics or social determinants of health, and maternal physical and mental health comorbidities. Key outcome measures will include child mortality, academic standardised testing results, rehospitalisation and maternal survival. Data analysis will be conducted using Stata V.18.0. ETHICS AND DISSEMINATION: Approvals were obtained from the NSW Population and Health Services Research Ethics Committee (29 June 2020; 2019/ETH12716) and the Australian Capital Territory Health Human Research Ethics Committee (11 October 2021; 2021-1231, 2021-1232, 2021-1233); and the Aboriginal Health and Medical Research Council (5 July 2022; 1824/21), and all Australian educational sectors: Board of Studies (government schools), Australian Independent Schools and Catholic Education Commission (D2014/120797). Data were released to researchers in September 2022. Results will be presented in peer-reviewed academic journals and at international conferences. Collaborative efforts from similar datasets in other countries are welcome.

Neurodevelopmental outcomes of extremely preterm infants with bronchopulmonary dysplasia (BPD) - A retrospective cohort study.

OBJECTIVE: To investigate the neurodevelopmental outcomes for preterm infants born < 29 weeks gestation with/without bronchopulmonary dysplasia (BPD). STUDY DESIGN: Preterm infants < 29 weeks' gestation born 2007-2018 in New South Wales and the Australian Capital Territory, Australia, were included. Infants who died < 36 weeks' postmenstrual age and those with major congenital anomalies were excluded. Subjects were assessed at 18-42 months corrected age using the Bayley Scales of Infant Development, 3rd edition. RESULTS: 1436 infants without BPD (non-BPD) and 1189 infants with BPD were followed. The BPD group, 69 % infants were discharged without respiratory support (BPD1), 29 % on oxygen (BPD2) and 2 % on pressure support/tracheostomy (BPD3). Moderate neurodevelopmental impairment (NDI) was evident in 5.7 % of non-BPD infants, 11 % BPD1, 15 % BPD2, 15 % BPD3 infants. Severe NDI was seen in 1.7 % non-BPD infants, 3.4 % BPD1, 7.3 % BPD2, 35 % BPD3 infants. After adjusting for confounders, infants with BPD2 (OR 2.24, 99.9 % CI 1.25 to 5.77) or BPD3 (OR 5.99, 99.9 % CI 1.27 to 46.77) were more likely to have moderate-severe NDI compared to non-BPD infants. CONCLUSION: The majority of infants with BPD were discharged home without respiratory support and had better neurocognitive outcomes in early childhood compared to those that required home-based oxygen or respiratory support.

Symptomatic Postnatal Cytomegalovirus Infection in Less than 32-Week Preterm Infants: 13-Year Retrospective Multicenter Case-Control Study.

INTRODUCTION: Reports on the influence of postnatal cytomegalovirus (pCMV) infection in neonatal outcomes of preterm babies vary while guidance on management including screening is lacking. We aim to determine the association between symptomatic pCMV infection and chronic lung disease (CLD) and mortality in preterm infants born less than 32 weeks gestation. METHODS: We used data from the Neonatal Intensive Care Units' (NICUS) population-based prospective data registry of infants in 10 neonatal units in New South Wales and the Australian Capital Territory, Australia. De-identified perinatal and neonatal outcome data for 40,933 infants were examined. We identified 172 infants <32 weeks gestation with symptomatic pCMV infection. Each was matched with one control infant. RESULTS: Infants with symptomatic pCMV infection were 2.7 times more likely to develop CLD (OR 2.7, 95% CI: 1.7-4.5) and spend 25.2 days more in hospital (95% CI: 15.2-35.2). Seventy-five percent (129/172) of infants with symptomatic pCMV were extremely preterm (<28 weeks). The mean age of symptomatic pCMV diagnosis was 62.5 ± 20.5 days or 34.7 ± 3.6 weeks-corrected gestational age. Ganciclovir treatment did not decrease CLD and death. CLD was 5.5 times predictive of death in patients with symptomatic pCMV infection. Symptomatic pCMV infection did not influence mortality nor increase neurologic impairment. CONCLUSION: Symptomatic pCMV is a modifiable factor affecting extreme preterm infants with significant impact on CLD. Prospective study on screening and treatment will help unveil potential benefits in our already at-risk preterm infants.

Variation in hospital morbidities in an Australian neonatal intensive care unit network.

OBJECTIVE: There is an expectation among the public and within the profession that the performance and outcome of neonatal intensive care units (NICUs) should be comparable between centres with a similar setting. This study aims to benchmark and audit performance variation in a regional Australian network of eight NICUs. DESIGN: Cohort study using prospectively collected data. SETTING: All eight perinatal centres in New South Wales and the Australian Capital Territory, Australia. PATIENTS: All live-born infants born between 23+0 and 31+6 weeks gestation admitted to one of the tertiary perinatal centres from 2007 to 2020 (n=12 608). MAIN OUTCOME MEASURES: Early and late confirmed sepsis, intraventricular haemorrhage, medically and surgically treated patent ductus arteriosus, chronic lung disease (CLD), postnatal steroid for CLD, necrotising enterocolitis, retinopathy of prematurity (ROP), surgery for ROP, hospital mortality and home oxygen. RESULTS: NICUs showed variations in maternal and neonatal characteristics and resources. The unadjusted funnel plots for neonatal outcomes showed apparent variation with multiple centres outside the 99.8% control limits of the network values. The hierarchical model-based risk-adjustment accounting for differences in patient characteristics showed that discharged home with oxygen is the only outcome above the 99.8% control limits. CONCLUSIONS: Hierarchical model-based risk-adjusted estimates of morbidity rates plotted on funnel plots provide a robust and straightforward visual graphical tool for presenting variations in outcome performance to detect aberrations in healthcare delivery and guide timely intervention. We propose using hierarchical model-based risk adjustment and funnel plots in real or near real-time to detect aberrations and start timely intervention.

Postnatal Cytomegalovirus Infection: Is it Important? A 10-Year Retrospective Case-control Study of Characteristics and Outcomes in Very Preterm and Very Low Birth Weight Infants.

BACKGROUND: To determine the characteristics and outcomes of postnatal cytomegalovirus (pCMV) infection in preterm infants in a neonatal intensive care unit (NICU). METHODS: A retrospective, matched case-control study in a tertiary NICU. Infants born between January 2009 and December 2019, <32 weeks' gestational age (GA) and/or birth weight (BW) <1500 g with pCMV infection were matched 1:1 with cytomegalovirus-(CMV)-negative infants by year of admission, gender, GA and BW. Primary outcome was death ≤36 weeks' postmenstrual age or bronchopulmonary dysplasia (BPD). Secondary outcomes were length of ventilation (LOV), length of stay (LOS) and neurodevelopmental impairment (NDI) at corrected age 1 and 2 years. RESULTS: Forty-eight pCMV-positive infants (median GA 25.3 weeks, BW 695 g, age 58 days) were identified from 1659 infants (incidence 2.9%). The most common symptoms of pCMV infection were abdominal distension (43.8%), sepsis-like syndrome (29.2%), thrombocytopenia (60.5%) and conjugated hyperbilirubinemia (60.9%). Compared with controls, there were no significant differences in the composite outcome of death or BPD (56.3% vs. 37.5%; P = 0.1) or NDI at 1 and 2 years (51.9% vs. 44%; P = 0.8; 71.4% vs. 50%; P = 0.4). pCMV-positive infants had a significantly longer median LOV (23.5 vs. 12 days)* and LOS (140 vs. 110.5 days)*. Eleven (22.9%) infants received antivirals. Ten improved and 1 died. Two untreated infants died (1 from pCMV infection). CONCLUSIONS: Clinically identifiable pCMV infections are significant and associated with increased respiratory support and prolonged hospital stay in vulnerable infants. pCMV screening and preventive measures against transmission merit consideration.*P < 0.05.

Are we enrolling representative cohorts of premature infants in our clinical trials?

OBJECTIVE: To compare the difference in outcomes in a subset population of infants "eligible but not enrolled; ENE" vs those who were "eligible and enrolled, EE" in The Australian Placental Transfusion Study (APTS). STUDY DESIGN: Population-based multicentre retrospective cohort study. RESULTS: A total of 535 (17.7%) infants were categorized as EE and 2489 (82.3%) ENE. ENE infants were significantly more premature (mean gestation 27.0 vs 28.0 weeks) but otherwise of similar anthropometric measures compared to EE infants. ENE infants had significantly higher incidences of low Apgar scores <7 at 5 min, CLD, IVH and PDA requiring treatment. Using a multivariate adjusted-analysis, ENE were at a greater risk for mortality (OR 1.86; 95% CI, 1.30-2.67, p < 0.001). CONCLUSION: Antenatal consenting may lead to biased population representation, which may affect trial results' generalizability. Retrospective consent or waiver of consent may improve the generalizability of neonatal and emergency clinical trials.

Characteristics and causes of death in children with neonatal abstinence syndrome.

AIM: To determine characteristics of death in children with neonatal abstinence syndrome (NAS). METHODS: A population-based linkage study of children from birth to 13 years of age in New South Wales (NSW), Australia, born 1 July 2000 to 31 December 2011. Infants with an International Statistical Classification of Diseases and Related Problems, Australian modification coding of NAS (P96.1, n = 3842) were compared to infants (n = 1 018 421) without NAS by birth, hospitalisation and death records linkage. RESULTS: Forty-five (1.2%) children with NAS died, compared to 3665 (0.4%) other children. Most deaths (n = 30, 66%) in NAS children occurred between 1 month and 1 year. Risk of death was independently increased in full-term children (hazard ratio 2.34, 95% confidence interval 1.63-3.35; P < 0.001) from lower socio-economic groups (1.23, 1.12-1.35; P < 0.001), most commonly from ill-defined or external causes, including assault and accidents (P < 0.001). CONCLUSIONS: Children with NAS, especially those of term gestation and from lower socio-economic groups, are more likely to die, especially from external causes.

Impact of influenza on hospitalization rates in children with a range of chronic lung diseases.

BACKGROUND: Data on burden of severe influenza in children with a range of chronic lung diseases (CLDs) remain limited. METHOD: We performed a cohort study to estimate burden of influenza-associated hospitalization in children with CLDs using population-based linked data. The cohort comprised all children in New South Wales, Australia, born between 2001 and 2010 and was divided into five groups, children with: (a) severe asthma; (b) bronchopulmonary dysplasia (BPD); (c) cystic fibrosis (CF); (d) other congenital/chronic lung conditions; and (e) children without CLDs. Incidence rates and rate ratios for influenza-associated hospitalization were calculated for 2001-2011. Average cost/episode of hospitalization was estimated using public hospital cost weights. RESULTS: Our cohort comprised 888 157 children; 11 058 (1.2%) had one of the CLDs. The adjusted incidence/1000 child-years of influenza-associated hospitalization in children with CLDs was 3.9 (95% CI: 2.6-5.2) and 0.7 (95% CI: 0.5-0.9) for children without. The rate ratio was 5.4 in children with CLDs compared to children without. The adjusted incidence/1000 child-years (95% CI) in children with severe asthma was 1.1 (0.6-1.6), with BPD was 6.0 (3.7-8.3), with CF was 7.4 (2.6-12.1), and with other congenital/chronic lung conditions was 6.9 (4.9-8.9). The cost/episode (95% CI) of influenza-associated hospitalization was AUD 19 704 (95% CI: 11 715-27 693) for children with CLDs compared to 4557 (95% CI: 4129-4984) for children without. DISCUSSION: This large population-based study suggests a significant healthcare burden associated with influenza in children with a range of CLDs.

Active care of infants born between 22 and 26 weeks of gestation does not follow consensus expert recommendations.

AIM: To determine the relationship between clinical practice and publication of an Australian consensus statement for management of extremely preterm infants in 2006. METHODS: A population-based study using linked data from New South Wales, Australia for births between 22 + 0 and 26 + 6 weeks of gestation between 2000 and 2011. RESULTS: There were 4746 births of whom 2870 were liveborn and 1876 were stillborn. Of the live births, 2041 (71%) were resuscitated, 1914 (67%) were admitted into a neonatal intensive care unit (NICU) and 1310 (46%) survived to hospital discharge. Thirty-nine (2%) stillbirths were resuscitated but none survived. No 22-week infant survived to hospital discharge. Fewer 23-week gestation infants were resuscitated between 2004 (52%) and 2005 (20%) but resuscitation rates increased by 2008 (44%). There was no difference at other gestations. Adjusted odds ratio (OR) for resuscitation was increased by birthweight (OR: 1.01), tertiary hospital birth (OR: 3.4) and Caesarean delivery (OR: 11.3) and decreased by rural residence (OR: 0.4) and male gender (OR: 0.7). CONCLUSION: Expert recommendations may be shaped by clinical practice rather than the converse, especially for 23-week gestation infants. Recommendations should be revised regularly to include clinical practice changes.

Long-term outcomes after group B streptococcus infection: a cohort study.

OBJECTIVE: To describe the risk of death and hospitalisation until adolescence of children after group B streptococcus (GBS) infection during infancy. DESIGN: Population-based cohort study. SETTING: New South Wales, Australia. PATIENTS: All registered live births from 2000 to 2011. INTERVENTIONS: Comparison of long-term outcomes in children with the International Statistical Classification of Diseases and Related Health Problems-10th Revision discharge codes corresponding to GBS infections and those without. MAIN OUTCOME MEASURES: Death and hospitalisation. RESULTS: A total of 1206 (0.1%) children (936 (77.6%)≥37 weeks' gestation) were diagnosed with GBS infection. Over the study period, infection rates decreased from 2.1 (95% CI 1.8 to 2.4) to 0.7 (95% CI 0.5 to 0.9) per 1000 live births. Infants with GBS infection were born at lower gestation (mean 37.6 vs 39.0 weeks), were more likely very low birth weight (<1500 g, OR 9.1(95% CI 7.4 to 11.3)), born premature (OR 3.9(95% CI 3.4 to 4.5)) and have 5 min Apgar scores ≤5 (OR 6.7(95% CI 5.1 to 8.8)). Children with GBS had three times the adjusted odds of death (adjusted OR (AOR) 3.0(95% CI 2.1 to 4.3)) or rehospitalisations (AOR 3.1(95% CI 2.7 to 3.5)). Thirty-six (3.0%) with GBS died, with >50% of deaths occurring <28 days. Children with GBS were hospitalised more frequently (median 2 vs 1), for longer duration (mean 3.7 vs 2.2 days) and were at higher risk for problems with genitourinary (OR 3.1(95% CI 2.8 to 3.5)) and nervous (OR 2.0 (95% CI1.7 to 2.3)) systems. CONCLUSIONS: Despite decreasing GBS rates, the risk of poor health outcomes for GBS-infected children remains elevated, especially during the first 5 years. Survivors continue to be at increased risk of death and chronic conditions requiring hospitalisations, such as cerebral palsy and epilepsy.

Neurodevelopmental outcomes of extremely preterm infants in New South Wales and the Australian Capital Territory.

AIM: This study aimed to provide updated information on gestation-specific neurodevelopmental outcomes of extremely to very preterm infants 23-28 weeks' gestation admitted to neonatal intensive care units (NICUs). METHODS: This was a population-based retrospective cohort study of infants born between 23+0 and 28+6 weeks' gestation and admitted to a network of NICUs between 2007 and 2012 in a well-defined geographic area of New South Wales (NSW) and the Australian Capital Territory (ACT). Primary outcome was moderate to severe neurodevelopmental impairment. RESULTS: Of 2287 infants admitted to NICUs, 1914 (83.7%) survived to discharge, and 1514 (79.8% = 1514/1897) were followed up. Moderate to severe neurodevelopmental impairment was 11% overall, and the incidence decreased with increasing gestational age (GA): 25, 23, 15, 13, 9 and 7% at 23, 24, 25, 26, 27 and 28 weeks, respectively. Male gender, major intraventricular haemorrhage, late-onset sepsis, chronic lung disease and post-natal corticosteroid therapy were found to be independently associated with increased risk of moderate to severe impairment. Compared with an incidence of 16% in the 1998-2004 cohort, there was a significant reduction in moderate to severe neurodevelopmental impairment in the current cohort (unadjusted odds ratio: 0.65, 95% confidence interval: 0.52-0.80). CONCLUSIONS: We report the latest neurodevelopmental outcomes of extremely to very preterm infants in NSW and the ACT. Neurodevelopmental outcome rates based on GA alone may not provide the true estimate as these outcomes can vary based on the presence or absence of other relevant perinatal factors.

Admission temperature and hospital outcomes in extremely preterm infants.

AIM: To evaluate trends in admission temperature and its effect on mortality and short-term morbidities in extremely preterm infants. METHODS: A regional cohort study of infants born at 23-28 weeks' gestation and admitted to the 10 neonatal intensive care units in New South Wales and the Australian Capital Territory between 1994 and 2012. Hypothermia was defined as skin temperature <36°C on admission to the neonatal intensive care unit. The primary outcome was hospital mortality. RESULTS: In total, 6267 infants were included. Mean admission temperatures improved significantly from 35.6°C in 1994 to 36.4°C in 2012 (R < 0.88). The incidence of hypothermia was 29.5 and 13.9% between 1994-2005 and 2006-2012, respectively. In comparison with normothermic infants, hypothermic infants had lower gestational age at birth (26 vs. 27 weeks) and lower birthweight (800 vs. 976 g). In-hospital mortality was higher in hypothermic infants (28.5 vs. 12.9%; odds ratio (OR) 2.69, 95% confidence interval (CI) 2.37-3.06). Severe intraventricular haemorrhage (12.1 vs. 8.5%, OR 1.48, 95% CI 1.25-1.75), necrotising enterocolitis (NEC) (11.0 vs. 7.5%; OR 1.54, 95% CI 1.29-1.83) and severe retinopathy of prematurity (16.5 vs. 8.9%; OR 2.02, 95% CI 1.70-2.39) were significantly higher in hypothermic infants. Multivariate regression analysis showed hypothermia was an independent risk factor for increased mortality (AOR (adjusted odds ratio ) 1.50, 95% CI 1.29-1.74, P < 0.001) and NEC (AOR 1.28, 95% CI 1.05-1.55, P = 0.01). CONCLUSIONS: Admission temperatures improved during the time period. Hypothermia at admission was associated with a significant increase in mortality and NEC.

Association of Age at First Severe Respiratory Syncytial Virus Disease With Subsequent Risk of Severe Asthma: A Population-Based Cohort Study.

OBJECTIVE: In a population-based cohort study, we determined the association between the age at first severe respiratory syncytial virus (RSV) disease and subsequent asthma. METHODS: Incidence rates and rate ratios of the first asthma-associated hospitalization after 2 years of age in children hospitalized for RSV disease at <3 months, 3 to <6 months, 6 to <12 months, and 12-24 months of age were calculated. RESULTS: The incidence of asthma-associated hospitalization per 1000 child-years among children hospitalized for RSV disease at <3 months of age was 0.5 (95% confidence interval [CI], .2-.7); at 3 to <6 months of age, 0.9 (95% CI,.5-1.3); at 6 to <12 months of age, 2.0 (95% CI, 1.4-2.7); and at 12-24 months of age, 1.7 (95% CI, 1.0-2.5). The rate ratio of hospitalization for asthma was 2-7-fold greater among children hospitalized for RSV disease at ages ≥6 months than that among those hospitalized for RSV disease at ages 0 to <6 months. CONCLUSIONS: Although the burden of RSV disease is highest in children aged <6 months, the burden of subsequent asthma is higher in children who develop RSV disease at ages ≥6 months.

Treatment with nitric oxide in the neonatal intensive care unit is associated with increased risk of childhood cancer.

AIM: This study aimed to determine whether neonatal intensive care therapies increase the risk of carcinogenesis in childhood. METHODS: This study used population-based data on 1 072 957 infants born in New South Wales, Australia, between 2000 and 2011 and multivariate logistic regression to examine any associations between therapies used in the neonatal intensive care unit and diagnoses of cancer until mid 2012. RESULTS: A total of 1126 of 1 072 957 (0.1%) children were diagnosed with cancer. Cancer risk was significantly increased by preterm birth (gestation <37 weeks; adjusted odds ratio (aOR) 1.3 (95% confidence interval: 1.0-1.6), birth weight ≥4 kg (aOR 1.4, 1.2-1.6) and caesarean delivery (aOR 1.2, 1.1-1.4). Extremely preterm (<28 weeks of gestation) infants were more likely to develop hepatic tumours (aOR 12.7, 3.3-48.3) than term infants. The only therapy used in the neonatal intensive care that was independently associated with an increased risk of cancer was nitric oxide (aOR 8.6, 4.3-17.4). Eight of the 790 (1%) infants treated with nitric oxide developed cancer (gestation range 30-41 weeks, age of cancer diagnosis: four months-five years). CONCLUSION: Treatment with nitric oxide was associated with a higher risk of childhood cancer. These findings require further research.

Influence of early childhood burns on school performance: an Australian population study.

OBJECTIVES: To determine the influence of burn injuries on childhood performance in national standardised curriculum-based school tests. DESIGN: Birth and health records of 977 children who were hospitalised with a burn injury between 2000 and 2006 in the state of New South Wales, Australia, were linked to performance scores in the National Assessment Program: Literacy and Numeracy test, a compulsory nationwide curriculum-based test (CBT) and compared with children who were not hospitalised for burns and who were matched for birth year, gender, gestation and socioeconomic status. MAIN OUTCOME MEASURES: Test scores in years 3 (ages 8-9), 5 (ages 10-11) and 7 (ages 13-14) in numeracy, writing, reading, spelling, grammar and punctuation. RESULTS: Mean age at first burn injury was 28 months (median: 20, range: 0-140). Children with burns were significantly more likely to have younger mothers (28.5 vs 29.6 years) (P<0.001), be indigenous (OR 2.5 (95% CI 2.1 to 3.1)) (P<0.001) and have siblings (OR 1.2 (95% CI 1.1 to 1.4)) (P<0.001). They were also less likely to meet national minimum standards in most domains of testing until year 5, even after adjustment for parental education levels, parental smoking, maternal age and indigenous status. Each 10% increase in total body surface area burnt was associated with a decrease in year 5 scores by 37.0% in numeracy and 71.9% in writing. CONCLUSIONS: Most childhood burn injuries occur before the start of formal schooling. Children who are hospitalised for burns perform more poorly in CBT even after accounting for family and socioeconomic disadvantage. Rehabilitation of children with burn injuries must address school performance to decrease any long-term negative societal impact of burns.

Variation in hospital mortality in an Australian neonatal intensive care unit network.

BACKGROUND: Studying centre-to-centre (CTC) variation in mortality rates is important because inferences about quality of care can be made permitting changes in practice to improve outcomes. However, comparisons between hospitals can be misleading unless there is adjustment for population characteristics and severity of illness. OBJECTIVE: We sought to report the risk-adjusted CTC variation in mortality among preterm infants born <32 weeks and admitted to all eight tertiary neonatal intensive care units (NICUs) in the New South Wales and the Australian Capital Territory Neonatal Network (NICUS), Australia. METHODS: We analysed routinely collected prospective data for births between 2007 and 2014. Adjusted mortality rates for each NICU were produced using a multiple logistic regression model. Output from this model was used to construct funnel plots. RESULTS: A total of 7212 live born infants <32 weeks gestation were admitted consecutively to network NICUs during the study period. NICUs differed in their patient populations and severity of illness.The overall unadjusted hospital mortality rate for the network was 7.9% (n=572 deaths). This varied from 5.3% in hospital E to 10.4% in hospital C. Adjusted mortality rates showed little CTC variation. No hospital reached the +99.8% control limit level on adjusted funnel plots. CONCLUSION: Characteristics of infants admitted to NICUs differ, and comparing unadjusted mortality rates should be avoided. Logistic regression-derived risk-adjusted mortality rates plotted on funnel plots provide a powerful visual graphical tool for presenting quality performance data. CTC variation is readily identified, permitting hospitals to appraise their practices and start timely intervention.

Association between respiratory syncytial viral disease and the subsequent risk of the first episode of severe asthma in different subgroups of high-risk Australian children: a whole-of-population-based cohort study.

OBJECTIVE: To determine the contribution of respiratory syncytial virus (RSV) to the subsequent development of severe asthma in different subgroups of children at risk of severe RSV disease. SETTINGS: The study was conducted in New South Wales (NSW), Australia. PARTICIPANTS: The study comprised all children born in NSW between 2000 and 2010 with complete follow-up till 31 December 2011. The cohort was divided into three subgroups: (1) non-Indigenous high-risk children: non-Indigenous children born preterm or born with a low birth weight; (2) Indigenous children: children of mothers whose Indigenous status was recorded as Aboriginal and/or Torres Strait Islander and (3) non-Indigenous standard risk children: all other non-Indigenous term children. PRIMARY OUTCOME MEASURE: Risk of development of severe asthma in different subgroups of children who had RSV hospitalisation in the first 2 years of life compared with those who did not. DESIGN: We performed a retrospective cohort analysis using population-based linked administrative data. Extended Cox model was used to determine HR and 95% CI around the HR for first asthma hospitalisation in different subgroups of children. RESULTS: The cohort comprised 847 516 children born between 2000 and 2010. In the adjusted Cox model, the HR of first asthma hospitalisation was higher and comparable across all subgroups of children who had RSV hospitalisation compared with those who did not. The HR (95% CI) was highest in children aged 2-3 years; 4.3 (95% CI 3.8 to 4.9) for high-risk, 4.0 (95% CI 3.3 to 4.8) for Indigenous and 3.9 (95% CI 3.7 to 4.1) for non-Indigenous standard risk children. This risk persisted beyond 7 years of age. CONCLUSION: This large study confirms a comparable increased risk of first asthma hospitalisation following RSV disease in the first 2 years of life across different subgroups children at risk.

Causes of death in very preterm infants cared for in neonatal intensive care units: a population-based retrospective cohort study.

BACKGROUND: While there are good data to describe changing trends in mortality and morbidity rates for preterm populations, there is very little information on the specific causes and pattern of death in terms of age of vulnerability. It is well established that mortality increases with decreasing gestational age but there are limited data on the specific causes that account for this increased mortality. The aim of this study was to establish the common causes of hospital mortality in a regional preterm population admitted to a neonatal intensive care unit (NICU). METHODS: Retrospective analysis of prospectively collected data of the Neonatal Intensive Care Units' (NICUS) Data Collection of all 10 NICUs in the region. Infants <32 weeks gestation without major congenital anomalies admitted from 2007 to 2011 were included. Three authors reviewed all cases to agree upon the immediate cause of death. RESULTS: There were 345 (7.7%) deaths out of 4454 infants. The most common cause of death across all gestational groups was major IVH (cause-specific mortality rate [CMR] 22 per 1000 infants), followed by acute respiratory illnesses [ARI] (CMR 21 per 1000 infants) and sepsis (CMR 12 per 1000 infants). The most common cause of death was different in each gestational group (22-25 weeks [ARI], 26-28 weeks [IVH] and 29-31 weeks [perinatal asphyxia]). Pregnancy induced hypertension, antenatal steroids and chorioamnionitis were all associated with changes in CMRs. Deaths due to ARI or major IVH were more likely to occur at an earlier age (median [quartiles] 1.4 [0.3-4.4] and 3.6 [1.9-6.6] days respectively) in comparison to NEC and miscellaneous causes (25.2 [15.4-37.3] and 25.8 [3.2-68.9] days respectively). CONCLUSIONS: Major IVH and ARI were the most common causes of hospital mortality in this extreme to very preterm population. Perinatal factors have a significant impact on cause-specific mortality. The varying timing of death provides insight into the prolonged vulnerability for diseases such as necrotising enterocolitis in our preterm population.

Neonatal Abstinence Syndrome and High School Performance.

BACKGROUND AND OBJECTIVES: Little is known of the long-term, including school, outcomes of children diagnosed with Neonatal abstinence syndrome (NAS) (International Statistical Classification of Disease and Related Problems [10th Edition], Australian Modification, P96.1). METHODS: Linked analysis of health and curriculum-based test data for all children born in the state of New South Wales (NSW), Australia, between 2000 and 2006. Children with NAS (n = 2234) were compared with a control group matched for gestation, socioeconomic status, and gender (n = 4330, control) and with other NSW children (n = 598 265, population) for results on the National Assessment Program: Literacy and Numeracy, in grades 3, 5, and 7. RESULTS: Mean test scores (range 0-1000) for children with NAS were significantly lower in grade 3 (359 vs control: 410 vs population: 421). The deficit was progressive. By grade 7, children with NAS scored lower than other children in grade 5. The risk of not meeting minimum standards was independently associated with NAS (adjusted odds ratio [aOR], 2.5; 95% confidence interval [CI], 2.2-2.7), indigenous status (aOR, 2.2; 95% CI, 2.2-2.3), male gender (aOR, 1.3; 95% CI, 1.3-1.4), and low parental education (aOR, 1.5; 95% CI, 1.1-1.6), with all Ps < .001. CONCLUSIONS: A neonatal diagnostic code of NAS is strongly associated with poor and deteriorating school performance. Parental education may decrease the risk of failure. Children with NAS and their families must be identified early and provided with support to minimize the consequences of poor educational outcomes.

Risk of neurodevelopmental impairment for outborn extremely preterm infants in an Australian regional network.

OBJECTIVE: To compare neurodevelopmental outcomes at 2-3 years in extremely premature outborn and inborn infants. DESIGN: Population-based retrospective cohort study. SETTING: Geographically defined area of New South Wales (NSW) and the Australian Capital Territory (ACT) served by a network of 10 neonatal intensive care units (NICUs). PATIENTS: All premature infants <29 weeks gestation born between 1998 and 2004 in the setting. INTERVENTION: At 2-3 years, corrected age, 1473 children were assessed with either the Griffiths Mental Developmental Scales (GMDS) or the Bayley Scales of Infant Development (BSID-II). MAIN OUTCOME MEASURE: Moderate/severe functional disability (FD) defined as: developmental delay (GMDS general quotient (GQ) or BSID-II mental developmental index (MDI)) > 2 standard deviations (SD) below the mean; cerebral palsy (CP) requiring aids; sensorineural or conductive deafness (requiring amplification); or bilateral blindness (visual acuity <6/60 in better eye). RESULTS: At 2-3 years, moderate/severe functional disability does not appear to be significantly different between outborn and inborn infants (adjusted OR 0.782; 95% CI 0.424-1.443). However, there were a significant number of outborn infants lost to follow up (23.3% versus 42.9%). CONCLUSION: In this cohort, at 2-3 years follow up neurodevelopmental outcome does not appear to be significantly different between outborn and inborn infants. These results should be interpreted with caution given the limitation of this study.