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.

Validation of hospital discharge coding for neonatal abstinence syndrome.

AIM: To validate the diagnostic discharge coding of neonatal abstinence syndrome (NAS) (International Classification of Diseases [ICD]-10-AM, P96.1). METHODS: Retrospective record review of infants diagnosed with NAS (P96.1) in a non-tertiary Australian hospital between 2000 and 2016. NAS criteria were predetermined to include the following: (i) maternal opioid use; (ii) infant requiring NAS medication and (iii) at least one score of ≥8 on the Finnegan Neonatal Abstinence Scoring Tool (FNAST). RESULTS: Of the 253 infants coded with P96.1, 82/146 (56%) opioid-exposed infants and 9/107(18%) infants exposed to non-opioid drugs only received withdrawal medication: sensitivity 56.2 (95% confidence interval: 47.7-64.3), specificity 91.6 (84.2-95.8%), positive predictive value (PPV) 90.1 (81.6-95.1%) and negative predictive value (NPV) 60.5 (52.5-68.0%) for all three criteria. Using the criterion of ≥1 FNAST score ≥8 resulted in 58.0 (51.3-64.4%) sensitivity, 63.6 (40.8-82.0%) specificity, 94.4 (88.8-97.4%) PPV and 12.6 (7.3-20.6%) NPV for identifying need for NAS medications. CONCLUSION: A diagnosis of P96.1 is highly specific and predictive but poorly sensitive for identifying opioid-exposed infants requiring medications for withdrawal.

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.

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.

Reasons for Rehospitalization in Children Who Had Neonatal Abstinence Syndrome.

BACKGROUND AND OBJECTIVES: Neonatal abstinence syndrome (NAS) occurs after in utero exposure to opioids, but outcomes after the postnatal period are unclear. Our objectives were to characterize childhood hospitalization after NAS. METHODS: Population-based linkage study of births, hospitalization, and death records of all children registered in New South Wales (NSW), Australia, between 2000 and 2011 to a maximum of 13 years. Infants with an International Statistical Classification of Disease and Related Problems, 10th Edition, Australian Modification, coding of NAS (P96.1, n = 3842) were compared with 1,018,421 live born infants without an NAS diagnosis. RESULTS: Infants with NAS were more likely to be admitted into a nursery (odds ratio 15.6, 95% confidence interval: 14.5-16.8) and be hospitalized longer (10.0 vs 3.0 days). In childhood, they were more likely to be rehospitalized (1.6, 1.5-1.7), die during hospitalization (3.3, 2.1-5.1), and be hospitalized for assaults (15.2, 11.3-20.6), maltreatment (21.0, 14.3-30.9), poisoning (3.6, 2.6-4.8), and mental/behavioral (2.6, 2.1-3.2) and visual (2.9, 2.5-3.5) disorders. Mothers of infants with NAS were more likely to be Indigenous (6.4, 6.0-7.0), have no antenatal care (6.6, 5.9-7.4), and be socioeconomically deprived (1.6, 1.5-1.7). Regression analyses demonstrated that NAS was the most important predictor of admissions for maltreatment (odds ratio 4.5, 95% confidence interval: 3.4-6.1) and mental and behavioral disorders (2.3, 1.9-2.9), even after accounting for prematurity, maternal age, and Indigenous status. CONCLUSIONS: Children with NAS are more likely to be rehospitalized during childhood for maltreatment, trauma, and mental and behavioral disorders even after accounting for prematurity. This continues to adolescence and emphasizes the critical need for continued support of this vulnerable group after resolution of NAS.

Dopamine D2 receptor gene polymorphisms in newborn infants of drug-using women.

OBJECTIVES: To determine the characteristics of dopamine D2 receptor gene (DRD2) polymorphisms in drug-exposed and unexposed neonates and the relationship to neonatal abstinence syndrome (NAS). DESIGN: Retrospective case-control analysis between drug-exposed and unexposed infants between DRD2 polymorphisms, drug exposure and NAS treatment. PATIENTS: Drug-exposed (n=48) and drug-free (n=49) infants born between March 1999 and December 2006. METHODS: Analysis of DNA for the Taq1A, -141Ins/Del and Ser311Cys DRD2 polymorphisms. Drug exposure was determined by antenatal maternal drug and alcohol history. Frequency measures of DRD2 polymorphisms were compared between drug-exposed infants, treatment NAS medication and with control infants. SETTING: Tertiary maternity hospital, Sydney, Australia. MAIN OUTCOME MEASURES: All infants were born in a good condition (25.7% <37 weeks gestation). Opiates (methadone and heroin) were used by 45 (93.8%) of drug-exposed mothers. The A2A2 allele was more common in drug-exposed infants (37 (77.0%) versus 23 (46.9%), p=0.003) but the A1A2 allele was more common in control infants (23 (46.9%) versus 4 (8.3%), p=0.00002). The-ins allele was more common in control (39 (79.6%) versus 20 (41.7%), p=<0.01) and unmedicated drug-exposed (14/25 (56%) versus 5/23 (21.7%), p=0.02) infants. The majority of infants (41 (83.7%) controls versus 41 (85.4%), p=1.000) expressed the least common, Ser polymorphism. CONCLUSIONS: DRD2 polymorphisms are detectable from DNA obtained from stored blood spots. The -ins allele is more common in control and unmedicated drug-exposed infants. Further study is recommended to explore postneonatal outcomes especially in relation to neuropsychiatric behaviours.