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.

'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.

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.

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.

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.

Risk factors associated with RSV hospitalisation in the first 2†years of life, among different subgroups of children in NSW: a whole-of-population-based cohort study.

BACKGROUND: Data on risk factors for respiratory syncytial virus (RSV)-associated hospitalisation in Australian children may be informative for preventive measures. METHODS: A whole-of-population-based study was conducted to identify comparable risk factors for RSV hospitalisation in different subgroups of children aged <2 years in New South Wales. The cohort was divided into Indigenous children and high-risk and standard risk non-Indigenous children. Data on risk factors were obtained from the Perinatal Data Collection. RSV hospitalisations were ascertained from the Admitted Patient Data Collection. Adjusted HRs were calculated for each subgroup. Population-attributable risk associated with risk factors was estimated. RESULTS: Four factors were associated with increased risk of RSV hospitalisation: maternal smoking during pregnancy, male sex, multiparity and birth during the first half of the RSV season. Increase in relative socioeconomic advantage was associated with decreased risk of hospitalisation. Among high and standard risk non-Indigenous children, the hazard was approximately double for children born to multiparous women compared to those born to primiparous women and among Indigenous children the hazard was approximately double among those born during the first half of the RSV season. Maternal smoking during pregnancy was associated with a 26-45% increased risk across subgroups and accounted for 17% (95% CI 9.3% to 24%) of RSV hospitalisations in Indigenous children, 5% (95% CI 2.5% to 8%) in high-risk and 6% (95% 5% to 7%) in standard risk non-Indigenous children. DISCUSSION: Promoting avoidance of smoking during pregnancy may help in lowering the disease burden, with Indigenous children likely to benefit most.

Outcomes of infants with abdominal wall defects over 18years.

BACKGROUND/PURPOSE: Infants with abdominal wall defects (AWD) are at risk of poor outcomes including prolonged hospitalization, infections and mortality. Our objective was to describe and compare the outcomes of infants admitted with gastroschisis and omphalocele over 18years. METHODS: Population-based study of clinical data and outcomes of live-born infants with AWD admitted to all tertiary-level neonatal intensive care units in New South Wales and Australian Capital Territory from 1992 to 2009. RESULT: There were 502 infants with AWD - 336 gastroschisis, 166 omphalocele. Infants with gastroschisis required a longer duration of total parenteral nutrition (19 vs 4days, p<0.05), longer hospitalization (28 vs 15days, p<0.05) and had a higher rate of systemic infection [23.5% vs 13.3%, OR 1.77 (1.15-2.74), p<0.05] compared to infants with omphalocele. Overall, omphalocele infants had higher mortality rate compared to gastroschisis infants [OR 2.77 (1.53, 5.04), p<0.05]. Gastroschisis mortality rates increased from epoch 1 to epoch 3 (4.2% to 8.8%). CONCLUSION: Compared to infants with omphalocele, infants with gastroschisis required significantly longer hospitalization and parenteral nutrition with higher rates of infection. Infants with omphalocele had higher overall mortality rates. However, there has been an increase in the gastroschisis mortality rates but the cause for this is unclear.

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.

Using hospital discharge data for determining neonatal morbidity and mortality: a validation study.

BACKGROUND: Despite widespread use of neonatal hospital discharge data, there are few published reports on the accuracy of population health data with neonatal diagnostic or procedure codes. The aim of this study was to assess the accuracy of using routinely collected hospital discharge data in identifying neonatal morbidity during the birth admission compared with data from a statewide audit of selected neonatal intensive care (NICU) admissions. METHODS: Validation study of population-based linked hospital discharge/birth data against neonatal intensive care audit data from New South Wales, Australia for 2,432 babies admitted to NICUs, 1994-1996. Sensitivity, specificity and positive predictive values (PPV) with exact binomial confidence intervals were calculated for 12 diagnoses and 6 procedures. RESULTS: Sensitivities ranged from 37.0% for drainage of an air leak to 97.7% for very low birthweight, specificities all exceeded 85% and PPVs ranged from 70.9% to 100%. In-hospital mortality, low birthweight (< or =1500 g), retinopathy of prematurity, respiratory distress syndrome, meconium aspiration, pneumonia, pulmonary hypertension, selected major anomalies, any mechanical ventilation (including CPAP), major surgery and surgery for patent ductus arteriosus or necrotizing enterocolitis were accurately identified with PPVs over 92%. Transient tachypnea of the newborn and drainage of an air leak had the lowest PPVs, 70.9% and 83.6% respectively. CONCLUSION: Although under-ascertained, routinely collected hospital discharge data had high PPVs for most validated items and would be suitable for risk factor analyses of neonatal morbidity. Procedures tended to be more accurately recorded than diagnoses.