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.

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.

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.

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.

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.

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.

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.

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.

Eligibility criteria for therapeutic hypothermia: From trials to clinical practice.

AIM: Whole body therapeutic hypothermia (TH) for hypoxic ischaemic encephalopathy was introduced into clinical practice in New South Wales (NSW) and Australian Capital Territory in 2007. State-wide policy adopting the eligibility criteria and practice based on trial-designs was published in 2009. METHODS: The study was conducted by retrospectively reviewing medical records of all TH infants born between 2007 and 2011 in NSW and Australian Capital Territory to examine if eligibility criteria (assessed against evidence-based policy directives) were met. RESULTS: A total of 207 infants received TH, 104 (50%) did not meet the eligibility criteria defined in NSW policy directive. Over the 5-year period, the proportion of infants meeting the eligibility criteria did not change. Seventy percent of infants (73 out of 104) not meeting eligibility criteria did not fulfil the criteria for 'evidence of asphyxia', although half of them met 'moderate or severe encephalopathy criterion'. Adverse events (hypotension, coagulopathy and arrhythmia), were more common in the 'criteria met' group than the 'criteria not met' group (89 vs. 71%, P = 0.001). Similar proportions of infants had TH discontinued before 72 h (criteria met: 32 (31%) vs. criteria not met: 27(26%)). Most frequent reason for early cessation was 'palliation' (19/32, 59%) in criteria met and 'clinical improvement' (16/27, 59%) in criteria not met group. CONCLUSIONS: Many TH infants were treated based on clinician judgement, though not meeting the trial-design policy criteria. Early TH cessation (<72 h) was common. Future studies are warranted on long-term neurodevelopmental outcomes for all infants receiving TH particularly those with early cessation of therapy.

Epidemiological Evidence for a Decreasing Incidence of Neonatal Abstinence Syndrome, 2000-11.

BACKGROUND: This study analyses the incidence of Neonatal Abstinence Syndrome (NAS) in a large geographically defined population in Australia. METHOD: Database linkage analysis of all births between 2000 and 2011 in New South Wales (NSW), Australia. The diagnosis of NAS was derived from hospital coding P96.1, 'Neonatal withdrawal symptoms from maternal use of drugs of addiction'. Temporal trends were studied by comparing epoch 1 (2000-05) with epoch 2 (2006-11). The relationship with changes in maternal factors was further analysed. RESULTS: The NAS was coded in 3842 of 1 022 263 live born infants (0.38%). NAS incidence peaked at 5.07 per 1000 live births in 2002, decreasing to 3.18 in 2011 and was negatively correlated with maternal age (r = -0.7). The rate of NAS in epoch 2 (3.4 per 1000 births, 95% CI 3.28, 3.58) was significantly lower than in epoch 1 (4.1 per 1000 births, 95% CI 3.96, 4.33). Epoch 2 mothers were significantly older (mean 29.8 years vs. 28.3 years), less likely to be multiparous (OR 0.7, 95% CI 0.6, 0.9) or smoke (OR 0.4, 95% CI 0.4, 0.5). They were more likely to engage in antenatal care earlier (mean first visit: 14.1 vs. 18.9 weeks). Most infants (~80%) were born at term (>37 weeks gestation). CONCLUSION: The incidence of NAS as a discharge diagnosis has decreased in our population since 2002. Mothers are also older and engaging earlier in prenatal care. Whether these changes alter NAS presentation and diagnosis or whether pregnant women are using drugs that do not cause typical NAS (e.g. amphetamines) is uncertain and requires further study.

Population-based study shows that resuscitating apparently stillborn extremely preterm babies is associated with poor outcomes.

AIM: This population-based study determined the delivery room management and outcomes of extremely preterm infants born with Apgar scores of 0. METHODS: We linked birth, neonatal intensive care unit (NICU) and death records for babies who were born between 22 + 0 and 27 + 6 weeks of gestation with a one-minute Apgar score of 0, in New South Wales, Australia, between 1998 and 2011. RESULTS: We classified 2173/2262 (96%) of infants with a one-minute Apgar score of 0 as stillborn. Resuscitation was provided for 48/89 (54%) live births and 40/2173 (2%) stillbirths. Cardiac massage was given to 44 infants, including three 22-week stillborn babies. Of the 13 live births admitted to an NICU, 11 survived to hospital discharge. Most (98%) of the 2212 deaths occurred on the first day of life. One baby who was classified as stillborn lived for 51 days. Resuscitation increased the mean (95% confidence interval) duration of survival from 1 (0-2) to 45 (0-104) hours (p < 0.001). No infant with a five-minute Apgar score of 0 survived. CONCLUSION: Clinicians resuscitated extremely preterm infants without a detectable heartbeat, even at 22 weeks of gestation. No infant survived without resuscitation or if their heartbeat was not regained by five minutes.

A population study of respiratory rehospitalisation in very preterm infants in the first 3 years of life.

AIM: Very premature infants consume healthcare resources following discharge from neonatal intensive care units (NICU). This study aimed to evaluate the burden of respiratory related rehospitalisation within the first 3 years post discharge in very premature infants in an Australian population. METHODS: Rehospitalisation of a 4-year cohort of NICU survivors, born less than 32 weeks gestation, was derived from data linkage of three state-wide databases including NSW Neonatal Intensive Care Units' Data Collection, Admitted Patient Data Collection and the Death Registry. Rehospitalisation diagnoses were determined by ICD-10 AM codes. RESULTS: Of the 2939 survivors, 525 (18%) had bronchopulmonary dysplasia (BPD) and 261 BPD infants (50%) were discharged on home oxygen. Almost two-third (1860, 63%) of the survivors are required rehospitalisation, respiratory causes, including 394 respiratory syncytial virus (RSV)-related, accounted for 2668 (48%) of the 5599 rehospitalisations. Significantly more home oxygen BPD survivors had respiratory (70%) and RSV-related (22%) rehospitalisations than the BPD infants not needing home oxygen (58% and 18%, respectively), and the survivors without BPD had the lowest rates (32% and 10%, P < 0.001). Most respiratory (61%) and RSV-related (74%) rehospitalisations occurred during the first 12 months post discharge. No RSV-related fatality occurred. Amongst the total 17 562 hospital days, respiratory and RSV-related admissions accounted for 10 905 (62%) and 3031 (17.2%) days. In multivariable logistic analyses, home oxygen and maternal indigenous status were independently associated with high (3 or more) respiratory and RSV rehospitalisation rates. CONCLUSIONS: Respiratory rehospitalisations are common in very premature survivors. Home oxygen and indigenous status are significant risk factors for respiratory and RSV-related rehospitalisations.

Neurodevelopmental Outcomes of Premature Infants Treated for Patent Ductus Arteriosus: A Population-Based Cohort Study.

OBJECTIVE: To compare neurodevelopmental outcomes of extremely preterm infants diagnosed with patent ductus arteriosus (PDA) who were treated medically or surgically and those who were not diagnosed with PDA or who did not undergo treatment for PDA. STUDY DESIGN: This retrospective population-based cohort study used data from a geographically defined area in New South Wales and the Australian Capital Territory served by a network of 10 neonatal intensive care units. Patients included all preterm infants born at <29 completed weeks of gestation between 1998 and 2004. Moderate/severe functional disability at 2-3 years corrected age was defined as developmental delay, cerebral palsy requiring aids, sensorineural or conductive deafness (requiring bilateral hearing aids or cochlear implant), or bilateral blindness (best visual acuity of <6/60). RESULTS: Follow-up information at age 2-3 years was available for 1473 infants (74.8%). Compared with infants not diagnosed with a PDA or who did not receive PDA treatment for PDA, those with medically treated PDA (aOR, 1.622; 95% CI, 1.199-2.196) and those with surgically treated PDA (aOR, 2.001; 95% CI, 1.126-3.556) were at significantly greater risk for adverse neurodevelopmental outcomes at age 2-3 years. CONCLUSION: Our results demonstrate that treatment for PDA may be associated with a greater risk of adverse neurodevelopmental outcome at age 2-3 years. This was particularly so among infants born at <25 weeks gestation. These results may support permissive tolerance of PDAs; however, reasons for this association remain to be elucidated through carefully designed prospective trials.

Preterm infant outcomes in New South Wales and the Australian Capital Territory.

AIM: This study aimed to provide updated information on gestation-specific hospital outcomes of extreme to very preterm infants admitted to neonatal intensive care units. METHODS: A population-based retrospective cohort study of infants born between 23(+0) and 31(+6) weeks gestation and admitted to a network of neonatal intensive care units between 2007 and 2011 in a well-defined geographic area of New South Wales and the Australian Capital Territory. Main outcome measures were survival and major morbidities prior to hospital discharge. RESULTS: Of 4454 infants included, hospital survival rates based on gestational age alone were 27%, 59%, 76%, 85%, 91% and over 95% at 23, 24, 25, 26, 27 and 28-31 weeks, respectively. Survival rates for each week up to 29 weeks gestation differed by at least 5% when perinatal risk factors including birthweight percentile, exposure to antenatal steroids, birth outside a tertiary hospital and gender were included in the survival estimation. All the major outcome figures were then simplified and displayed in a simple, easy-to-understand preterm outcome table for counselling purposes. CONCLUSION: We report the latest hospital outcomes of extreme to very preterm infants in New South Wales and the Australian Capital Territory. Survival rates based on gestational age alone may not provide the true estimate as the survival for these infants can vary based on the presence or absence of other relevant perinatal factors.

Comparing CRIB-II and SNAPPE-II as mortality predictors for very preterm infants.

AIMS: This article compares the severity of illness scoring systems clinical risk index for babies (CRIB)-II and score for neonatal acute physiology with perinatal extension (SNAPPE)-II for discriminatory ability and goodness of fit in the same cohort of babies of less than 32 weeks gestation and aims to provide validation in the Australian population. METHODS: CRIB-II and SNAPPE-II scores were collected on the same cohort of preterm infants born within a 2-year period, 2003 and 2004. The discriminatory ability of each score was assessed by the area under the receiver operator characteristic curve, and goodness of fit was assessed by the Hosmer-Lemeshow (HL) test. The outcome measure was in-hospital mortality. A multivariate logistic regression model was tested for perinatal variables that might add to the risk of in-hospital mortality. RESULTS: Data for both scores were available for 1607 infants. Both scores had good discriminatory ability (CRIB-II area under the curve 0.913, standard error (SE) 0.014; SNAPPE-II area under the curve 0.907, SE 0.012) and adequate goodness of fit (HL χ2 = 11.384, 8 degrees of freedom, P = 0.183 for CRIB-II; HL χ2 = 4.319, 7 degrees of freedom, P = 0.742 for SNAPPE-II). The multivariate model did not reveal other significant variables. CONCLUSIONS: Both severity of illness scores are ascertained during the first 12 h of life and perform similarly. Both can facilitate risk-adjusted comparisons of mortality and quality of care after the first post-natal 12 h. CRIB-II scores have the advantage of being simpler to collect and calculate.

Population study of neurodevelopmental outcomes of extremely premature infants admitted after office hours.

AIM: The aim of the study was to compare neurodevelopmental outcomes of extremely preterm infants admitted during (OH) and after (AH) office hours. METHODS: A retrospective review of the New South Wales and Australian Capital Territory Neonatal Intensive Care Units' (NICUs) Data Collection of all infants <29 weeks gestation admitted to New South Wales and Australian Capital Territory NICUs between January 1998 and December 2004 was conducted. The primary outcome was moderate/severe functional disability (FD) at 2-3 years follow-up defined as developmental delay (Griffiths Mental Developmental Scales general quotient or Bayley Scales of Infant Development-II mental developmental index >2 standard deviations below the mean), cerebral palsy (unable to walk without aids), deafness (requiring bilateral hearing aids) or blindness (visual acuity <6/60 in the better eye). RESULTS: Mortality and age at follow-up were comparable between the AH and OH groups. Developmental outcome was evaluated in 972 (74.9%) infants admitted during AH and 501 (74.6%) admitted during OH. FD was not significantly different between the AH and OH groups (17.1% vs. 14.8%, adjusted odds ratio 1.131, 95% confidence interval 1.131 (0.839-1.523), P = 0.420). There were no significant differences between AH and OH infants with cerebral palsy (9.6% vs. 7.6%), developmental delay (5.4% vs. 5.0%) or any other component of FD. CONCLUSION: There is little circadian variation in mortality and adverse neurodevelopmental outcomes in an NICU network with the current model of after hours staffing and support, and sharing of NICU workload within a network.

'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.

School performance in children with prenatal drug exposure and out-of-home care in NSW, Australia: a retrospective population-based cohort study.

BACKGROUND: Prenatal drug exposure (PDE) is a global public health problem that is strongly associated with the need for child protection services, including placement into out-of-home care (OOHC). We aimed to assess school outcomes for children with PDE (both with and without neonatal abstinence syndrome [NAS]) and the association of school performance with OOHC. METHODS: Using linked population health, OOHC, and school test data, we compared results on the Australian standardised curriculum-based test, the National Assessment Program-Literacy and Numeracy (NAPLAN), for children with PDE who were born in New South Wales (NSW) between 2001 and 2020 and had completed at least one NAPLAN test between Jan 1, 2008, and June 30, 2021, administered in Year 3 (age 8-9 years), Year 5 (age 10-11 years), Year 7 (age 12-13 years), or Year 9 (age 14-15 years). Linked datasets included NSW Perinatal Data Collection (birth data), NSW Admitted Patient Data Collection (hospital diagnoses), NSW Education Standards Authority (NAPLAN scores), NSW Family and Community Services Dataset-KiDS Data Collection (OOHC information), NSW Mental Health Ambulatory Data Collection, and NSW Registry for Births, Deaths, and Marriages. The primary outcome was scoring above or below the National Minimum Standard (NMS) in any test domain (mathematics, language, writing, and spelling) at each year level, comparing the relative risk of scoring below NMS between children with and without PDE (and with or without NAS within the PDE group), and with and without OOHC contact. The association between OOHC on the likelihood of scoring above NMS was also investigated for PDE and non-PDE cohorts. FINDINGS: The PDE cohort included 3836 children, and the non-PDE cohort included 897 487 children. Within the PDE cohort, 3192 children had a NAS diagnosis and 644 children had no NAS diagnosis. 1755 (45·8%) children with PDE required OOHC compared with 12 880 (1·4%) of 897 487 children without PDE. Children with PDE were more likely than children without PDE to score below NMS in any domain from Year 3 (risk ratio 2·72 [95% CI 2·58-2·76]) to Year 9 (2·36 [2·22-2·50]). Performance was similar regardless of a NAS diagnosis (Year 3: 0·96 [0·84-1·10]; Year 9: 0·98 [0·84-1·15]). The likelihood of scoring above NMS in Year 9 was reduced for children with PDE and without NAS (0·57 [0·45-0·73]) and NAS (0·58 [0·52-0·64]) compared with those without PDE, and also for children who received OOHC (0·60 [0·57-0·64]) compared with those without OOHC, when adjusted for confounders. Among children with PDE, those receiving OOHC had a similar likelihood of scoring above NMS compared with children who did not receive OOHC, from Year 3 (1·01 [0·92-1·11]) to Year 9 (0·90 [0·73-1·10]), when adjusted for confounding factors. By contrast, among children without PDE, those receiving OOHC were less likely to score above NMS than those who did not receive OOHC, from Year 3 (0·78 [0·76-0·80]) to Year 9 (0·58 [0·54-0·61]). INTERPRETATION: Compared with children without PDE, school performance in children with PDE-regardless of whether they were diagnosed with NAS-is poor, and the gap widens with age. The risk of poor performance persists regardless of OOHC status. This finding underscores the need for all children with PDE to receive long-term, culturally sensitive, and proactive support to improve life success. FUNDING: SPHERE Mindgardens Neuroscience Network, Australian Red Cross, Alpha Maxx Healthcare, Centre for Research Excellence for Integrated Health and Social Care, National Health and Medical Research Council, and University of Sydney.

Health Care Needs and Costs for Children Exposed to Prenatal Substance Use to Adulthood.

Importance: Children exposed to substance use during pregnancy have increased health needs but whether these are influenced by engagement in out-of-home care is uncertain. Objective: To evaluate the association between substance use during pregnancy, out-of-home care and hospitalization utilization, and costs from birth up to age 20 years. Design, Setting, and Participants: This was a retrospective cohort study using individual-linked population birth, hospital, and out-of-home care information of all liveborn infants from New South Wales, Australia, between 2001 and 2020 using longitudinal population-based linkage records from administrative databases. Substance use during pregnancy included newborns with neonatal abstinence syndrome (n = 5946) and intrauterine exposure to drugs of addiction (n = 1260) and other substances (eg, tobacco, alcohol, and illicit drugs or misused prescription drugs; n = 202 098). Children not exposed to substance use during pregnancy were those without known exposure to substance use during pregnancy (n = 1 611 351). Data were analyzed from July 2001 to December 2021. Main Outcomes: Main outcomes were hospital readmission, length of stay, and cost burden associated with substance use during pregnancy from birth up to age 20 years. Outcomes were investigated using 2-part and Poisson regression models adjusted for sociodemographic characteristics. Mediation analysis was used to evaluate whether the association of substance use during pregnancy with risk of readmission was mediated through engagement with out-of-home care. Results: Of the 1 820 655 live births, 935 807 (51.4%) were male. The mean (SD) age of mothers was 30.8 (5.5) years. Compared with children who were not exposed to substance use during pregnancy, those who were exposed incurred significantly higher birth hospital costs (adjusted mean difference, A$1585 per child [US$1 = A$1.51]; 95% CI, 1585-1586). If discharged alive, more children with exposure to substance use during pregnancy had at least 1 readmission (90 433/209 304 [43.4%] vs 616 425/1 611 351[38.3%]; adjusted relative risk [RR], 1.06; 95% CI, 1.06-1.07), most commonly for respiratory conditions (RR, 1.11; 95% CI, 1.09-1.12) and mental health/behavioral disorders (RR, 1.36; 95% CI, 1.33-1.41). Excess hospital costs associated with substance use during pregnancy were A$129.0 million in 2019 to 2020. Mediation analyses showed that any out-of-home care contact mediated the association between substance use during pregnancy and risk of inpatient readmission and lower health care cost (decreased by A$25.4 million). For children with neonatal abstinence syndrome, any out-of-home care contact mediated readmission risk by approximately 30%, from adjusted RR, 1.28; 95% CI, 1.19-1.35, to RR, 1.01; 95% CI, 0.98-1.02. Conclusion and Relevance: Children who were exposed to substance use during pregnancy incurred more hospital costs than children who were not exposed up to 20 years of age, but this was reduced in association with any contact with out-of-home care. This provides insights into possible strategies for reducing health and financial burdens associated with exposure to substance use during pregnancy for children.

Causes of death in infants admitted to Australian neonatal intensive care units between 1995 and 2006.

AIM: To compare causes and rates of mortality among infants admitted to 10 Australian neonatal intensive care units (NICUs) between 1995 and 2006. METHODS: De-identified perinatal data from the Neonatal Intensive Care Units' (NICUS) Data Collection for 24 131 infants were examined for causes and rates of death. The study period was divided into two epochs: I (1995-2000, n = 11 185 infants) and II (2001-2006, n = 12 946 infants). RESULTS: A total of 2224 (9.2%) infants died in hospital. Mortality decreased from 10.3% (1152/11 185) in epoch I to 8.3% (1072/12 946) in epoch II (p < 0.001) due to improved survival in term infants. Extreme prematurity also decreased as a primary cause of death (118 (10.2%) vs 76 (7.1%), p = 0.008). No infant >42-week gestation was admitted in epoch II. Congenital abnormalities were the most common cause of death (>20%) in both epochs, mostly in term rather than preterm infants (40.7% vs 13.9%, p < 0.001). Age of death was unchanged between the two epochs (median 4, 1st, 3rd quartiles: 1,16 days). CONCLUSION: Mortality rates have continued to decrease but improvement is predominantly due to improved survival of term infants and prevention of postdate deliveries. Congenital abnormalities continue to be the most common cause of death.