Estimating the Prevalence of Autism Spectrum Disorder in New South Wales, Australia: A Data Linkage Study of Three Routinely Collected Datasets.

Routinely collected data help estimate the prevalence of autism spectrum disorder (ASD) in jurisdictions without active autism surveillance. We created a population-based cohort of 1,211,834 children born in 2002-2015 in New South Wales, Australia using data linkage. Children with ASD were identified in three datasets - disability services, hospital admissions, and ambulatory mental health data. The prevalence of ASD in the cohort was 1.3% by age 12 and prevalence at age 6 increased an average of 4.1% per year (95% Confidence Interval, 3.3%, 4.8%). Most children with ASD were identified in disability services data (87%), although data linkage identified 1,711 additional cases that were more likely female, older at first contact, and living in major cities and less disadvantaged areas.

Association between cumulative maternal exposures related to inflammation and child attention-deficit/hyperactivity disorder: A cohort study.

BACKGROUND: Preclinical studies suggest synergistic effects of maternal inflammatory exposures on offspring neurodevelopment, but human studies have been limited. OBJECTIVES: To examine the cumulative association and potential interactions between seven maternal exposures related to inflammation and child attention-deficit/hyperactivity disorder (ADHD). METHODS: We conducted a population-based cohort study of children born from July 2001 to December 2011 in New South Wales, Australia, and followed up until December 2014. Seven maternal exposures were identified from birth data and hospital admissions during pregnancy: autoimmune disease, asthma, hospitalization for infection, mood or anxiety disorder, smoking, hypertension, and diabetes. Child ADHD was identified from stimulant prescription records. Multivariable Cox regression assessed the association between individual and cumulative exposures and ADHD and potential interaction between exposures, controlling for potential confounders. RESULTS: The cohort included 908,770 children, one-third (281,724) with one or more maternal exposures. ADHD was identified in 16,297 children (incidence 3.5 per 1000 person-years) with median age of 7 (interquartile range 2) years at first treatment. Each exposure was independently associated with ADHD, and risk increased with additional exposures: one exposure (hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.54, 1.65), two exposures (HR 2.25, 95% CI 2.13, 2.37), and three or more exposures (HR 3.28, 95% CI 2.95, 3.64). Positive interaction was found between smoking and infection. The largest effect size was found for cumulative exposure of asthma, infection, mood or anxiety disorder, and smoking (HR 6.12, 95% CI 3.47, 10.70). CONCLUSIONS: This study identifies cumulative effects of multiple maternal exposures related to inflammation on ADHD, most potentially preventable or modifiable. Future studies should incorporate biomarkers of maternal inflammation and consider gene-environment interactions.

Disparities in Maternal-Infant Drug Testing, Social Work Assessment, and Custody at 5 Hospitals.

OBJECTIVE: To evaluate for disparities in peripartum toxicology testing among maternal-infant dyads across a hospital network and subsequent child protective services (CPS) involvement. METHODS: Retrospective chart review of 59,425 deliveries at 5 hospitals in Massachusetts between 2016 and 2020. We evaluated associations between maternal characteristics, toxicology testing, and child welfare involvement with disproportionality risk ratios and hierarchical logistical regression. RESULTS: Toxicology testing was performed on 1959 (3.3%) dyads. Younger individuals and individuals of color were more likely to be tested for cannabis use or maternal medical complications compared to white non-Hispanic individuals. Among those without a substance use disorder, age <25 (adjusted odds ratio [aOR] 2.81; 95% confidence interval [CI], 2.43-3.26), race and ethnicity (non-Hispanic Black (aOR 1.80; 95% CI, 1.52-2.13), Hispanic (aOR 1.23; 95% CI, 1.05-1.45), mixed race/other (aOR 1.40; 95% CI, 1.04, 1.87), unavailable race (aOR 1.92; 95% CI, 1.32-2.79), and public insurance (Medicaid [aOR 2.61; 95% CI, 2.27-3.00], Medicare [aOR 13.76; 95% CI, 9.99-18.91]) had increased odds of toxicology testing compared to older, white non-Hispanic, and privately insured individuals. The disproportionality ratios in testing were greater than 1.0 for individuals under 25 years old (3.8), Hispanic individuals (1.6), non-Hispanic Black individuals (1.8), individuals of other race (1.2), unavailable race (1.8), and individuals with public insurance (Medicaid 2.6; Medicare 10.6). Among dyads tested, race and ethnicity was not associated with CPS involvement. CONCLUSIONS: Peripartum toxicology testing is disproportionately performed on non-white, younger, and poorer individuals and their infants, with cannabis use and medical complications prompting testing more often for patients of color than for white non-Hispanic individuals.

Cross-sectional survey of antenatal education attendance among nulliparous pregnant women in Sydney, Australia.

BACKGROUND: Antenatal education aims to provide expectant parents with strategies for dealing with pregnancy, childbirth and parenthood and may have the potential to reduce obstetric intervention and fear of childbirth. We aimed to investigate antenatal education attendance, reasons for and barriers to attending, and techniques taught and used to manage labour. METHODS: Antenatal and postnatal surveys were conducted among nulliparous women with a singleton pregnancy at two maternity hospitals in Sydney, Australia in 2018. Classes were classified into psychoprophylaxis, birth and parenting, other, or no classes. Reasons for and barriers to attendance, demographic characteristics, and techniques taught and used in labour were compared by class type, using Pearson's Chi Squared tests of independence. FINDINGS: 724 women were surveyed antenatally. The main reasons for attending classes were to better manage the birth (86 %), feel more secure in baby care (71 %) and as a parent (60 %); although this differed by class type. Reasons for not attending classes included being too busy (33 %) and cost (27 %). Epidural, breathing techniques, massage and nitrous oxide were the most common techniques taught. Women who attended psychoprophylaxis classes used a wider range of pain relief techniques in labour. Women found antenatal classes useful preparation for birth (94 %) and parenting (74 %). Women surveyed postnatally wanted more information on baby care/sleeping and breastfeeding. CONCLUSION: The majority of women found antenatal education useful and utilised techniques taught. Education providers should ensure breastfeeding and infant care information is provided, and barriers to attendance such as times and cost should be addressed.

Association of maternal autoimmune disease and early childhood infections with offspring autism spectrum disorder: A population-based cohort study.

The aim of this study was to examine potential synergistic effects between maternal autoimmune disease and early childhood infections and their association with autism spectrum disorder (ASD) in offspring. Both exposures have been associated with increased risk of ASD in previous studies, but potential synergistic effects remain underexplored. We conducted a population-based cohort study of singleton children born at term gestation (37-41 weeks) in New South Wales, Australia from January 2002 to December 2008. Maternal autoimmune diagnoses and childhood infections before age 2 years were identified from linked maternal and child hospital admissions, and ASD diagnoses by age 9 years were identified from linked disability services data. Multivariable logistic regression assessed the association between each exposure and ASD and additive interaction between exposures, controlling for potential confounders. A total of 18,451 children exposed to maternal autoimmune disease were propensity score matched (1:2) to 36,902 unexposed children. Any maternal autoimmune disease (adjusted odds ratio (aOR) 1.25, 95% confidence interval (CI) 1.07-1.47) and any childhood infection before age 2 years (aOR 1.38, 95% CI 1.15-1.67) were each associated with ASD. However, there was no evidence of additive interaction between the two exposures (relative excess risk due to interaction [RERI] 0.128, 95% CI -0.418-0.675) resulting in increased odds of ASD in offspring. Future studies could examine potential interactions between other sources of maternal immune activation and childhood infection and impact on ASD and other neurodevelopmental disorders.

Length of Stay Among Infants with Neonatal Abstinence Syndrome and Risk of Hospital Readmission.

OBJECTIVES: To assess whether a shorter length of stay (LOS) is associated with a higher risk of readmission among newborns with neonatal abstinence syndrome (NAS) and examine the risk, causes, and characteristics associated with readmissions among newborns with NAS, using a longitudinally linked population-based database. METHODS: Our study sample included full-term singletons with NAS (n = 4,547) and without NAS (n = 327,836), born in Massachusetts during 2011-2017. We used log-binomial regression models to estimate the crude risk ratios (cRRs) and adjusted RRs with 95% confidence intervals (CI) of the association between LOS and readmissions, controlling for maternal age, race/ethnicity, education, marital status, insurance, method of delivery, birthweight, adequacy of prenatal care, smoking, and abnormal conditions of newborn. RESULTS: Compared with infants without NAS, infants with NAS had a non-significantly higher risk of readmission within 2-42 days (2.8% vs. 2.5%; p = 0.17) and a significantly higher risk of readmission within 43-182 days (2.7% vs. 1.8%; p < 0.001). The risk of readmission within 2-42 days was significantly higher among infants with NAS with a LOS of 0-6 days compared to a LOS of 14-20 days (reference group) (aRR: 2.1; 95% CI: 1.2-3.5). No significant differences in readmission rates between 43 and 182 days were observed across LOS categories. CONCLUSIONS: Among infants with NAS, a LOS of 0-6 days was associated with a significantly higher risk of readmission within 2-42 days of discharge compared to a longer LOS.

Birth outcomes by type of attendance at antenatal education: An observational study.

BACKGROUND: Antenatal education aims to prepare expectant parents for pregnancy, birth, and parenthood. Studies have reported antenatal education teaching breathing and relaxation methods for pain relief, termed psychoprophylaxis, is associated with reduction in caesarean section rates compared with general birth and parenting classes. Given the rising rates of caesarean section, we aimed to determine whether there was a difference in mode of birth in women based on the type of antenatal education attended. MATERIALS AND METHODS: A cross-sectional antenatal survey of nulliparous women ≥28 weeks gestation with a singleton pregnancy was conducted in two maternity hospitals in Sydney, Australia in 2018. Women were asked what type of antenatal education they attended and sent a follow-up survey post-birth. Hospital birth data were also obtained. Education was classified into four groups: psychoprophylaxis, birth and parenting, other, or none. RESULTS: Five hundred and five women with birth data were included. A higher proportion of women who attended psychoprophylaxis education had a vaginal birth (instrumental/spontaneous) (79%) compared with women who attended birth and parenting, other or no education (69%, 67%, 60%, respectively P = 0.045). After adjusting for maternal characteristics, birth and hospital factors, the association was attenuated (odds ratio 2.03; 95% CI 0.93-4.43). CONCLUSIONS: Women who attended psychoprophylaxis couple-based education had a trend toward higher rates of vaginal birth. Randomised trials comparing different types of antenatal education are required to determine whether psychoprophylaxis education can reduce caesarean section rates and improve other birth outcomes.

Informed consent is poorly documented when obtaining toxicology testing at delivery in a Massachusetts cohort.

BACKGROUND: Positive toxicology testing at delivery can have enormous consequences for birthing persons and their families, including charges of child abuse or neglect and potential loss of custody for the birthing parent. Therefore state and national guidelines stipulate that, clinicians must obtain consent before toxicology testing at delivery. OBJECTIVE: This study aimed (1) to determine clinician documentation of patient consent for peripartum toxicology testing and (2) to characterize the extent to which patient and hospital characteristics were associated with documented consent. STUDY DESIGN: This was a retrospective cohort of individuals who underwent toxicology testing within 96 hours of delivery between April 2016 and April 2020 at 5 affiliated hospitals across Massachusetts. Medical records were reviewed for documentation of clinician intent to obtain maternal toxicology, testing indication, verbal consent to testing, and child protective services involvement. Hierarchical multivariable logistic regression was used to examine the association between patient and hospital characteristics and documentation of verbal consent. RESULTS: Among 60,718 deliveries, 1562 maternal toxicology tests were obtained. Verbal consent for testing was documented in 466 cases (29.8%). Documented consent was lacking across most demographic groups. Consent was no more likely to be documented when a report was filed with child protective services and less likely in cases where the birthing parent lost custody before discharge (P=.003). In our multivariable model, consent was least likely to be documented when a maternal complication (abruption, hypertension, preterm labor, preterm premature rupture of membranes, or intrauterine fetal demise) was the indication for testing (adjusted odds ratio, 0.46; 95% confidence interval, 0.28-0.76). Verbal consent was twice as likely to be documented in delivery hospitals with established consent policies (adjusted odds ratio, 2.10; 95% confidence interval, 1.01-4.37). CONCLUSION: Consent for toxicology testing at delivery seemed to be infrequently obtained on the basis of clinician documentation. Provider education and hospital policies for obtaining informed consent are needed to protect the rights of birthing individuals.

Assessing Stigma Towards Substance Use in Pregnancy: A Randomized Study Testing the Impact of Stigmatizing Language and Type of Opioid Use on Attitudes Toward Mothers With Opioid Use Disorder.

OBJECTIVE: To examine the extent to which colloquial phrases used to describe opioid-exposed mother-infant dyads affects attitudes toward mothers with opioid use disorder (OUD) to assess the role stigmatizing language may have on the care of mothers with OUD. METHODS: We employed a randomized, cross-sectional, case vignette of an opioid-exposed dyad, varying on 2 factors: (1) language to describe newborn ("substance-exposed newborn" vs "addicted baby") and (2) type of maternal opioid use (injection heroin vs nonmedical use of prescription opioids). Participants were recruited using an online survey platform. Substance-related stigma, punitive-blaming, and supportive scales were constructed to assess attitudes. Two-way analyses of variance were conducted to determine mean scale differences by vignette. Posthoc analyses assessed individual item-level differences. RESULTS: Among 1227 respondents, we found a small statistical difference between language and opioid type factors for the supportive scale only (F = 4.31, η2 = .004, P = 0.038), with greater agreement with supportive statements when describing injection heroin use, compared to prescription opioid use, for the "substance-exposed newborn" vignette only. In posthoc analyses, greater than 85% of respondents agreed the mother was "responsible for her opioid use," her "addiction was caused by poor choices," and that she "put her baby in danger." CONCLUSIONS: We found no major differences in attitudes regardless of vignette received. Overall, respondents supported opportunities for maternal recovery yet blamed women, describing mothers as culpable for causing harm to their newborn, showcasing internally conflicting views. These views could contribute to ongoing stigma and avoidance of care among pregnant women with OUD.

Prevalence of autoimmune disease among pregnant women and women of reproductive age in New South Wales, Australia: a population-based study.

BACKGROUND: Autoimmune diseases disproportionately affect women and have been linked to increased risk of maternal and perinatal mortality and morbidity. Our aim was to determine the prevalence of autoimmune disease among pregnant women and women of reproductive age (WRA), which is not well described. MATERIALS AND METHODS: A population-based study was conducted using data from a survey of general practitioner (GP) encounters and state-wide hospital admissions in New South Wales (NSW). A list of 29 conditions and relevant diagnosis codes was used to identify autoimmune disease. Prevalence estimates and trends were calculated using population denominators for GP encounters for WRA in 2011-2015 and hospital admissions for WRA and pregnant women in 2013-2017. RESULTS: A total 31,065 GP encounters for WRA were identified and 607 (2.0%) reported an autoimmune disease, equivalent to 1.1 GP encounters per 10 WRA each year when extrapolating to NSW population figures. For WRA admitted to hospital, 2.6% had an autoimmune diagnosis recorded each year equivalent to a population prevalence of 0.5%. A total 477,243 births were identified, of which 4230 mothers (0.9%) had at least one autoimmune disease recorded during a 1-year pregnancy lookback period. Autoimmune disease prevalence among both pregnant women and WRA either attending GP or hospital increased, on average, 2-4% per year over the study period. CONCLUSIONS: A small, but potentially growing proportion of reproductive age and pregnant women have a diagnosed autoimmune disease, and this may impact their health outcomes.

Prevalence of autoimmune conditions in pregnant women in a tertiary maternity hospital: A cross-sectional survey and maternity database review.

BACKGROUND: Autoimmune conditions are associated with adverse pregnancy and offspring outcomes; however, the prevalence in pregnant women is not well understood. Estimates based on administrative data alone may underestimate prevalence. METHODS: A cross-sectional survey of women attending a tertiary referral hospital for antenatal care in December 2018-February 2019 and review of the hospital's maternity database of women giving birth from October 2017-June 2018 to estimate autoimmune disease prevalence. RESULTS: A total of 400 women completed surveys (78% response rate) and 41 (10.3%) reported an autoimmune disease, most commonly Hashimoto's thyroiditis (2.8%) and psoriasis (2.5%). From the maternity database, 112 of 2756 women giving birth (4.1%) had a recorded autoimmune disease, most commonly Hashimoto's thyroiditis (1.3%) followed by coeliac disease, Graves' disease, and immune thrombocytopenic purpura (all 0.4%). CONCLUSION: Autoimmune disease prevalence in pregnant women is higher when self-reported and may be more common than previously reported using administrative data.

Methadone and buprenorphine discontinuation among postpartum women with opioid use disorder.

BACKGROUND: The postpartum year is a vulnerable period for women with opioid use disorder, with increased rates of fatal and nonfatal overdose; however, data on the continuation of medications for opioid use disorder on a population level are limited. OBJECTIVE: This study aimed to examine the effect of discontinuing methadone and buprenorphine in women with opioid use disorder in the year following delivery and determine the extent to which maternal and infant characteristics are associated with time to discontinuation of medications for opioid use disorder. STUDY DESIGN: This population-based retrospective cohort study used linked administrative data of 211,096 deliveries in Massachusetts between 2011 and 2014 to examine the adherence to medications for opioid use disorder. Individuals receiving medications for opioid use disorder after delivery were included in the study. Here, demographic, psychosocial, prenatal, and delivery characteristics are described. Kaplan-Meier survival analysis and Cox regression modeling were used to examine factors associated with medication discontinuation. RESULTS: A total of 2314 women who received medications for opioid use disorder at delivery were included in our study. Overall, 1484 women (64.1%) continued receiving medications for opioid use disorder for a full 12 months following delivery. The rate of continued medication use varied from 34% if women started on medications for opioid use disorder the month before delivery to 80% if the medications were used throughout pregnancy. Kaplan-Meier survival curves differed by maternal race and ethnicity (the 12-month continuation probability was .65 for White non-Hispanic women and .51 for non-White women; P<.001) and duration of use of prenatal medications for opioid use disorder (12-month continuation probability was .78 for women with full prenatal engagement and .60 and .44 for those receiving medications for opioid use disorder ≥5 months [but not throughout pregnancy] and ≤4 months prenatally, respectively; P<.001). In all multivariable models, duration of receipt of prenatal medications for opioid use disorder (≤4 months vs throughout pregnancy: adjusted hazard ratio, 3.26; 95% confidence interval, 2.72-3.91) and incarceration (incarceration during pregnancy or after delivery vs none: adjusted hazard ratio, 1.79; 95% confidence interval, 1.52-2.12) were most strongly associated with the discontinuation of medications for opioid use disorder. CONCLUSION: Almost two-thirds of women with opioid use disorder continued using medications for opioid use disorder for a full year after delivery; however, the rates of medication continuation varied significantly by race and ethnicity, degree of use of prenatal medications for opioid use disorder, and incarceration status. Prioritizing medication continuation across the perinatal continuum, enhancing sex-specific and family-friendly recovery supports, and expanding access to medications for opioid use disorder despite being incarcerated can help improve postpartum medication adherence.

Maternal autoimmunity and inflammation are associated with childhood tics and obsessive-compulsive disorder: Transcriptomic data show common enriched innate immune pathways.

Although genetic variation is a major risk factor of neurodevelopmental disorders, environmental factors during pregnancy and early life are also important in disease expression. Animal models demonstrate that maternal inflammation causes fetal neuroinflammation and neurodevelopmental deficits, and brain transcriptomics of neurodevelopmental disorders in humans show upregulated differentially expressed genes are enriched in immune pathways. We prospectively recruited 200 sequentially referred children with tic disorders/obsessive-compulsive disorder (OCD), 100 autoimmune neurological controls, and 100 age-matched healthy controls. A structured interview captured the maternal and family history of autoimmune disease and other pro-inflammatory states. Maternal blood and published Tourette brain transcriptomes were analysed for overlapping enriched pathways. Mothers of children with tics/OCD had a higher rate of autoimmune disease compared with mothers of children with autoimmune neurological conditions (p = 0.054), and mothers of healthy controls (p = 0.0004). Autoimmunity was similarly elevated in first- and second-degree maternal relatives of children with tics/OCD (p < 0.0001 and p = 0.014 respectively). Other pro-inflammatory states were also more common in mothers of children with tics/OCD than controls (p < 0.0001). Upregulated differentially expressed genes in maternal autoimmune disease and Tourette brain transcriptomes were commonly enriched in innate immune processes. Pro-inflammatory states, including autoimmune disease, are more common in the mothers and families of children with tics/OCD. Exploratory transcriptome analysis indicates innate immune signalling may link maternal inflammation and childhood tics/OCD. Targeting inflammation may represent preventative strategies in pregnancy and treatment opportunities for children with neurodevelopmental disorders.

Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: a systematic review.

Inflammation is increasingly recognized as a cause or consequence of common problems of humanity including obesity, stress, depression, pollution and disease states such as autoimmunity, asthma, and infection. Maternal immune activation (MIA), triggered by both acute and systemic chronic inflammation, is hypothesized to be one of the mechanisms implicated in the pathogenesis of neurodevelopmental disorders (NDD). Although there is substantial preclinical evidence to support the MIA hypothesis, the human evidence is disparate. We performed a systematic review on human studies examining associations between maternal inflammatory states and offspring NDDs (autism spectrum disorder- ASD, attention deficit hyperactivity disorder-ADHD, Tourette syndrome-TS). 32 meta-analyses and 26 additional individual studies were identified. Maternal states associated with ASD include obesity, gestational diabetes mellitus, pre-eclampsia, pollution, stress, depression, autoimmune diseases, and infection. Maternal states associated with ADHD include obesity, pre-eclampsia, smoking, low socioeconomic status (SES), stress, autoimmune disease, and asthma. Maternal states associated with TS include low SES, depression, and autoimmune diseases. Diverse maternal inflammatory states in pregnancy are associated with common offspring NDDs. Given the increased prevalence of NDDs, there is urgent need to explore relative and cumulative maternal risk factors and disease mechanisms. Defining preventable risk factors in high-risk pregnancies could mitigate the expression and severity of NDDs.

Association of Maternal Autoimmune Disease With Attention-Deficit/Hyperactivity Disorder in Children.

Importance: Maternal autoimmune disease has been associated with increased risk of neurodevelopmental disorders in offspring, but few studies have assessed the association with attention-deficit/hyperactivity disorder (ADHD). Objective: To examine the association between maternal autoimmune disease and ADHD within a population-based cohort and combine results in a subsequent systematic review and meta-analysis. Design, Setting, and Participants: A cohort study was conducted of singleton children born at term gestation (37-41 weeks) in New South Wales, Australia, from July 1, 2000, to December 31, 2010, and followed up until the end of 2014; and a systematic review evaluated articles from the MEDLINE, Embase, and Web of Science databases to identify all studies published before November 20, 2019. A total of 12 610 children exposed to maternal autoimmune disease were propensity score matched (1:4) to 50 440 unexposed children, for a total cohort of 63 050. A child was considered to have ADHD if they had (1) an authorization or filled prescription for stimulant treatment for ADHD or (2) a hospital diagnosis of ADHD. Children linked to a first ADHD event before 3 years of age were excluded. Data were analyzed from January 13 to April 20, 2020. Exposures: One or more maternal autoimmune diagnoses in linked hospital admission records between July 1, 2000, and December 31, 2012. Thirty-five conditions were considered together and individually. Main Outcomes and Measures: The main outcome was child ADHD identified from stimulant authorization or prescription data and diagnoses in linked hospital admission records. Multivariable Cox regression was used to assess the association between maternal autoimmune disease and ADHD adjusted for child sex. Pooled hazard ratios (HRs) were calculated using random-effects meta-analysis with inverse-variance weights for each exposure reported by 2 or more studies. Results: In the population-based cohort analysis, 831 718 singleton, term infants born to 831 718 mothers (mean [SD] age, 29.8 [5.6] years) were assessed. Of 12 767 infants (1.5%) who were linked to a maternal autoimmune diagnosis, 12 610 were propensity score matched to 50 440 control infants, for a total study cohort of 63 050 infants. In this cohort, any autoimmune disease was associated with ADHD in offspring (HR, 1.30; 95% CI 1.15-1.46), as was type 1 diabetes (HR, 2.23; 95% CI, 1.66-3.00), psoriasis (HR, 1.66; 95% CI, 1.02-2.70), and rheumatic fever or rheumatic carditis (HR, 1.75; 95% CI, 1.06-2.89). Five studies (including the present study) were included in the meta-analysis. Any autoimmune disease (2 studies: HR, 1.20; 95% CI, 1.03-1.38), type 1 diabetes (4 studies: HR, 1.53; 95% CI, 1.27-1.85), hyperthyroidism (3 studies: HR, 1.15; 95% CI, 1.06-1.26), and psoriasis (2 studies: HR, 1.31; 95% CI, 1.10-1.56) were associated with ADHD. Conclusions and Relevance: In this cohort study, maternal autoimmune diseases were associated with increased ADHD among children. These findings suggest possible shared genetic vulnerability between autoimmune disease and ADHD or a potential role for maternal immune activation in the expression of neurodevelopmental disorders in children. Future studies measuring disease activity, modifiers, and medication use are required to better understand the mechanisms underlying this association.

Assessment of Racial and Ethnic Disparities in the Use of Medication to Treat Opioid Use Disorder Among Pregnant Women in Massachusetts.

Importance: Racial and ethnic disparities persist across key health and substance use treatment outcomes for mothers and infants. The use of medications, such as methadone or buprenorphine, for the treatment of opioid use disorder (OUD) has been associated with improvements in the outcomes of mothers and infants; however, only half of all pregnant women with OUD receive these medications. The extent to which maternal race or ethnicity is associated with the use of medication to treat OUD, the duration of the use of medication to treat OUD, and the type of medication used to treat OUD during pregnancy are unknown. Objective: To examine the extent to which maternal race and ethnicity is associated with the use of medications for the treatment of OUD in the year before delivery among pregnant women with OUD. Design, Setting, and Participants: This retrospective cohort study used a linked population-level statewide data set of pregnant women with OUD who delivered a live infant in Massachusetts between October 1, 2011, and December 31, 2015. Of 274 234 total deliveries identified, 5247 deliveries among women with indicators of having OUD were included in the analysis. Maternal race and ethnicity were defined as white non-Hispanic, black non-Hispanic, or Hispanic based on self-reported data on birth certificates. Main Outcomes and Measures: Main outcomes were the receipt of any medication for OUD, the consistency of the use of medication (at least 6 continuous months of use before delivery, inconsistent use, or no use) for the treatment of OUD, and the type of medication (methadone or buprenorphine) used to treat OUD. Multivariable models were adjusted for maternal sociodemographic characteristics, comorbidities, and any significant interactions between the covariates and race and ethnicity. Results: The sample included 5247 pregnant women with OUD who delivered a live infant in Massachusetts during the study period. The mean (SD) maternal age at delivery was 28.7 (5.0) years; 4551 women (86.7%) were white non-Hispanic, 462 women (8.8%) were Hispanic, and 234 women (4.5%) were black non-Hispanic. A total of 3181 white non-Hispanic women (69.9%) received any type of medication for the treatment of OUD in the year before delivery compared with 228 Hispanic women (49.4%) and 108 black non-Hispanic women (46.2%). Compared with white non-Hispanic women, black non-Hispanic and Hispanic women had a substantially lower likelihood (adjusted odds ratio [aOR], 0.37; 95% CI, 0.28-0.49 and aOR, 0.42; 95% CI, 0.35-0.52, respectively) of receiving any medication for the treatment of OUD. Stratification by maternal age identified greater disparities among younger women. Black non-Hispanic and Hispanic women also had a lower likelihood (aOR, 0.24; 95% CI, 0.17-0.35 and aOR, 0.34; 95% CI, 0.27-0.44, respectively) of consistent use of medication for the treatment of OUD compared with white non-Hispanic women. With respect to the type of medication used to treat OUD, black non-Hispanic and Hispanic women had a lower likelihood (aOR, 0.60; 95% CI, 0.40-0.90 and aOR, 0.77; 95% CI, 0.58-1.01, respectively) than white non-Hispanic women of receiving buprenorphine treatment compared with methadone treatment. Conclusions and Relevance: This study found racial and ethnic disparities in the use of medications to treat OUD during pregnancy, with black non-Hispanic and Hispanic women significantly less likely to use medications consistently or at all compared with white non-Hispanic women. Further investigation of patient, clinician, treatment program, and system-level factors associated with these findings is warranted.

Maternal and infant characteristics associated with maternal opioid overdose in the year following delivery.

BACKGROUND AND AIMS: Opioid-related overdose is increasingly linked to pregnancy-associated deaths, but factors associated with postpartum overdose are unknown. We aimed to estimate the strength of the association between maternal and infant characteristics and postpartum opioid-related overdose. DESIGN: Retrospective cohort study using a linked, population-level data set. SETTING: Massachusetts, United States. CONCLUSION: Among women who delivered live infants in Massachusetts, USA between 2012 and 2014, maternal diagnosis of OUD, prior non-fatal overdose, infant diagnosis of NAS and high unscheduled health-care utilization appeared to be positively associated with postpartum opioid overdose. However, more than half of postpartum overdoses in that period were to women without a diagnosis of OUD. Engagement in methadone or buprenorphine treatment in the month prior to delivery was not sufficient to reduce the odds of postpartum overdose. PARTICIPANTS: Women who delivered one or more live births from 2012 to 2014 (n = 174 517). MEASUREMENTS: The primary outcome was opioid-related overdose in the postpartum year. We used multivariable logistic regression to explore the independent associations of maternal (demographics, substance use, pregnancy) and infant [gestational age, birthweight, neonatal abstinence syndrome (NAS)] characteristics with postpartum opioid overdose. Findings were stratified by maternal opioid use disorder (OUD) diagnosis. FINDINGS: There were 189 deliveries to women who experienced ≥ 1 opioid overdose in the first year postpartum (11 of 10 000 deliveries). Among women with postpartum opioid overdose, 46.6% had an OUD diagnosis within 12 months before delivery. In our adjusted model, maternal diagnosis of OUD [adjusted odds ratio (aOR) = 3.61, 95% confidence interval (CI) = 1.73-7.51] and prior non-fatal overdose (aOR = 2.40, 95% CI = 1.11-5.17) were most strongly associated with postpartum overdose. After stratifying by OUD status, infant diagnosis of NAS (OUD+ aOR = 2.03, 95% CI = 1.26-3.27; OUD- aOR = 2.79, 95% CI = 1.12-6.93) and high unscheduled health-care utilization (OUD+ aOR = 2.27, 95% CI = 1.38-3.73; OUD- aOR = 2.11, 95% CI = 1.24-3.58) were positively associated with postpartum overdose in both groups.

Prescription opioid dispensing in Australian children and adolescents: a national population-based study.

BACKGROUND: There are few population-based studies of paediatric opioid use. We aimed to investigate the prevalence of opioid dispensing in Australian children and adolescents. METHODS: In this population-based study, we used data from a random sample of 15% of the children and adolescents who had received any medicines between Feb 1, 2013, and Dec 31, 2017, through the Australian Pharmaceutical Benefits Scheme (PBS). We identified children younger than 18 years who had been dispensed at least one PBS-listed opioid in the study period. We calculated the annual prevalence of children being dispensed one or more opioid presciptions, by age group and by opioid characteristics (such as strength and mode of action), and we assessed trends over time with negative binomial regression. We also identified new treatment episodes and quantified the number of opioid prescriptions dispensed in the ensuing year. FINDINGS: During the study period, 78 320 opioid prescriptions were dispensed to 50 730 Australian children, aged 0-17 years, in our sample. In 2017, 135·4 children per 10 000 were dispensed opioids, representing a slight decrease equal to a change of -2·2% (95% CI -3·5 to -0·8) per annum since 2013. The prevalence of opioid dispensing was greater at older ages: in 2017, 5·7 infants per 10 000 younger than 1 year were dispensed opioids, versus 404·8 adolescents per 10 000 aged 13-17 years, meaning that roughly one in 25 adolescents were dispensed opioids. Weak opioids (ie, codeine and tramadol) accounted for 60·7% of the opioids dispensed, and codeine was the most commonly dispensed opioid, accounting for 39 531 (50·5%) prescriptions dispensed. The prevalence of weak opioid dispensing significantly decreased in all age groups (other than infants younger than 1 year), particularly in those younger than 12 years, for whom weak opioids are not recommended. Dispensing of strong opioids, particularly oxycodone, increased in every age group. Of the 29 073 children who received a new course of treatment, 23 318 (80·2%) children were dispensed only one prescription of opioids in that year. Those dispensed two or more opioids were more likely to be adolescents (vs children younger than 13 years), female, and to have been dispensed several unique medicine types in the 3 previous months (vs those receiving one or fewer types). INTERPRETATION: In 2017, one in 74 Australian children, including one in 25 adolescents, were dispensed an opioid. Dispensing of weak opioids decreased between 2013 and 2017, but codeine is still commonly dispensed in younger children and education to reduce this practice is required. Dispensing of strong opioids increased in all age groups. Children and adolescents must receive appropriate pain management, but further evidence on the risks and benefits of opioid use in this young population is needed. FUNDING: Financial Markets Foundation for Children, National Health and Medical Research Council Centre of Research Excellence in Medicines and Ageing, Australian Government Department of Industry, Innovation and Science, Research Foundation of the Cerebral Palsy Alliance (Australia).

Obstetric Comorbidity and Severe Maternal Morbidity Among Massachusetts Delivery Hospitalizations, 1998-2013.

OBJECTIVES: The rate of severe maternal morbidity in the United States increased approximately 200% during 1993-2014. Few studies have reported on the health of the entire pregnant population, including women at low risk for maternal morbidity. This information might be useful for interventions aimed at primary prevention of pregnancy complications. To better understand this, we sought to describe the distribution of comorbid risk among all delivery hospitalizations in Massachusetts and its association with the distribution of severe maternal morbidity. METHODS: Using an existing algorithm, we assigned an obstetric comorbidity index (OCI) score to delivery hospitalizations contained in the Massachusetts pregnancy to early life longitudinal (PELL) data system during 1998-2013. We identified which hospitalizations included severe maternal morbidity and calculated the rate and frequency of these hospitalizations by OCI score. RESULTS: During 1998-2013, PELL contained 1,185,182 delivery hospitalizations; of these 5325 included severe maternal morbidity. Fifty-eight percent of delivery hospitalizations had an OCI score of zero. The mean OCI score increased from 0.60 in 1998 to 0.82 in 2013. Hospitalizations with an OCI score of zero comprised approximately one-third of all deliveries complicated by severe maternal morbidity, but had the lowest rate of severe maternal morbidity (22.8/10,000 delivery hospitalizations). CONCLUSIONS: The mean OCI score increased during the study period, suggesting that an overall increase in risk factors has occurred in the pregnant population in Massachusetts. Interventions that can make small decreases to the mean OCI score could have a substantial impact on the number of deliveries complicated by severe maternal morbidity. Additionally, all delivery facilities should be prepared for severe complications during low-risk deliveries.