Prenatal Opioid Exposure and Immune-Related Conditions in Children.

Importance: Prenatal opioid exposure (POE) may alter with fetal development of the immune system, which may influence long-term health and susceptibility to immune-related conditions. Objective: To compare the risk of hospitalization and emergency department presentation for immune-related conditions in children with and without POE. Design, Setting, and Participants: This retrospective, population-based cohort study used linked administrative health records of all children born in Western Australia between January 1, 2003, and December 31, 2018 (N = 401 462). Exposure: Prenatal exposure to prescription opioids (overall and by trimester), neonatal abstinence syndrome diagnosis, and opioid indication (pain or opioid use disorder [OUD]). Main Outcomes and Measures: The main outcome was hospital admissions and emergency department presentations during which a child was diagnosed with an immune-related condition, including infections, conditions associated with an overactive immune system (eg, asthma, eczema, and allergy and anaphylaxis), and autoimmune diseases diagnosed before age 5 years or June 30, 2020. Data were analyzed between August 30, 2022, and February 27, 2023. Results: Neonates with POE (1656 [0.4%]; mean [SD] gestational age, 37.7 [2.1] weeks; 836 females [50.5%]; 820 males [49.5%]) were more likely to be born preterm, have low birth weight for gestational age, and be coexposed to cigarette smoke compared with nonexposed neonates. Perinatal opioid exposure was associated with an increased risk of perinatal infection (adjusted odds ratio [AOR], 1.62; 95% CI, 1.38-1.90) and eczema and dermatitis (AOR, 11.91; 95% CI, 9.84-14.41) compared with nonexposure. Neonatal abstinence syndrome was also associated with both conditions (AOR, 2.91 [95% CI, 2.36-3.57] and 31.11 [95% CI, 24.64-39.28], respectively). Prenatal opioid exposure was also associated with an increased risk of childhood asthma (adjusted hazard ratio [AHR], 1.44; 95% CI, 1.16-1.79), but not allergies and anaphylaxis. It was also associated with an increased risk of childhood eczema and dermatitis, but only in children with POE from opioids used to treat OUD (AHR, 1.47; 95% CI, 1.08-1.99) rather than pain. In contrast, POE from opioids used for pain was associated with an increased risk of infection (AHR, 1.44; 95% CI, 1.32-1.58), but POE to opioids used to treat OUD was not. Autoimmune conditions were rare and were not observed to be associated with POE. Conclusions and Relevance: In this cohort study, POE was associated with an increased risk of infection, eczema and dermatitis, and asthma, but not allergies and anaphylaxis or autoimmune conditions. These findings highlight the importance of further study of opioid-induced immune changes during pregnancy, the potential impact on long-term health in exposed children, and the mechanisms of opioid-induced immune dysregulation.

Impaired vision in children prenatally exposed to methadone: an observational cohort study.

BACKGROUND/OBJECTIVES: To examine prevalence of failed visual assessment at 8-10 years in children born to methadone-maintained opioid dependent (MMOD) mothers and relate this to known in utero substance exposure. SUBJECTS/METHODS: Follow up of observational cohort study of methadone-exposed and comparison children matched for birthweight, gestation and postcode of residence at birth. Participants were 144 children (98 exposed, 46 comparison). Prenatal drug exposure was previously established via comprehensive maternal and neonatal toxicology. Children were invited to attend for visual assessment and casenotes were reviewed. Presence of acuity poorer than 0.2 logMAR, strabismus, nystagmus and/or impaired stereovision constituted a 'fail'. Fail rates were compared between methadone-exposed and comparison children after adjusting for known confounding variables. RESULTS: 33 children attended in person: data were also derived from casenote review for all children. After controlling for maternal reported tobacco use, methadone-exposed children were more likely to have a visual 'fail' outcome, adjusted odds ratio 2.6, 95% CI 1.1-6.2; adjusted relative risk 1.8 (95% CI 1.1-3.4). Visual 'fail' outcome rates did not differ between methadone-exposed children who had (n = 47) or had not (n = 51) received pharmacological treatment for neonatal abstinence/opioid withdrawal syndrome (NAS/NOWS); fail rate 62% vs 53% (95% CI of difference-11-27%). CONCLUSIONS: Children born to MMOD mothers are almost twice as likely as unexposed peers to have significant visual abnormalities at primary school age. Prenatal methadone exposure should be considered in the differential diagnosis of nystagmus. Findings support visual assessment prior to school entry for children with any history of prenatal opioid exposure. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03603301), https://clinicaltrials.gov/ct2/show/NCT03603301 .

Demographics, Birth Parameters, and Social Determinants of Health Among Opioid-Exposed Mother-Infant Dyads Affected by Neonatal Abstinence Syndrome in Pennsylvania, 2018-2019.

OBJECTIVES: To characterize demographics, birth parameters, and social determinants of health among mother-infant dyads affected by neonatal abstinence syndrome (NAS) in Pennsylvania. METHODS: We linked 2018-2019 NAS surveillance data to birth record data using probabilistic methods and then geospatially linked to local social determinants of health data based on residential address. We generated descriptive statistics and used multivariable mixed-effects logistic regression to model the association between maternal characteristics, birth parameters, social determinants of health, and NAS. RESULTS: In adjusted models maternal age > 24, non-Hispanic white race/ethnicity, low educational attainment, Medicaid as payor at delivery, inadequate or no prenatal care, smoking during pregnancy, and low median household income were associated with NAS. We found no significant associations between NAS and county-level measures of clinician supply, number of substance use treatment facilities, or urban/rural designation. CONCLUSIONS FOR PRACTICE: This study characterizes mother-infant dyads affected by NAS using linked non-administrative, population data for Pennsylvania. Results demonstrate a social gradient in NAS and inequity in prenatal care receipt among mothers of infants with NAS. Findings may inform implementation of state-based public health interventions.

Adverse Maternal Experiences and Neonatal Abstinence Syndrome.

OBJECTIVES: To propose a measure for adverse maternal experiences (AMEs) and examine if AMEs are independently associated with delivery of a neonatal abstinence syndrome (NAS) diagnosed infant. METHODS: Using the Pregnancy Risk Assessment Monitoring System (PRAMS) stressful life events questions, we constructed a composite measure of AMEs. We conducted a retrospective analysis of linked Birth Certificate Data, Hospital Discharge Data and PRAMS data for 2012-2018 using the composite measure. Our analytic sample included 6358 singleton deliveries. We calculated prevalence of NAS and AMEs and prevalence odds ratio (POR) for delivery of an NAS-diagnosed infant adjusting for maternal sociodemographic characteristics, pre-pregnancy depression, prescription medicine 12 months prior to pregnancy, and smoking during pregnancy. RESULTS: The overall prevalence of NAS in Delaware during 2012-2018 was 2.2% (95% CI 1.8-2.6); 9.5% (95% CI 8.7-10.2) of women reported AMEs. After adjustment, women with AMEs had 1.1 times greater odds (aPOR 2.1; 95% CI 1.3-3.3) to deliver a NAS-diagnosed infant as compared with women without AMEs. CONCLUSIONS: Although the cross-sectional nature of the study limits drawing any causal inferences, there are co-occurring factors that support plausibility of an association between AMEs and delivering NAS-diagnosed infants. Addressing AMEs, mental health and substance use screening and treatment as part of preconception and prenatal care may mitigate risks.

Outcomes in Subsequent Pregnancies of Individuals With Opioid Use Disorder Treated in Multidisciplinary Clinic in Prior Pregnancy.

BACKGROUND: Untreated opioid misuse in pregnancy is associated with adverse outcomes. Limited information is available on maternal and perinatal outcomes in subsequent pregnancies for individuals initiated on medication for opioid use disorder (MOUD) in a prior pregnancy. OBJECTIVE: Evaluate maternal and neonatal outcomes in subsequent pregnancies for individuals initiated on MOUD in prior pregnancy. METHODS: Historical cohort study including individuals with opioid use disorder with ≥2 pregnancies between 2013 and 2020, received care in our colocated multidisciplinary clinic for >1 pregnancy, and delivered at our institution. Primary outcome was rate of preconception MOUD. Secondary outcomes included rate of neonatal opioid withdrawal syndrome requiring pharmacologic treatment and length of hospital stay. RESULTS: Forty-two individuals with opioid use disorder in their index pregnancies (n = 42) and 46 subsequent pregnancies were identified. Individuals were more likely to receive long-acting reversible contraception in subsequent pregnancies (35% vs 14%, P = 0.04). No differences in tobacco use, gestational age at initiation of prenatal care or delivery was noted. Individuals in their subsequent pregnancies were 6 times more likely to be on MOUD preconception (78% vs 36%; OR, 6.48; [95% CI, 2.52-16.64]) and 67% less likely to have positive illicit urine drug screen upon initiation of care (36% vs 64%; OR, 0.33; 95% [CI, 0.14-0.78]). Neonates had similar rates of neonatal abstinence withdrawal syndrome requiring pharmacological treatment, positive illicit toxicology results, and neonatal length of stay. CONCLUSIONS: Participation in multidisciplinary obstetric and opioid use disorder program increases rate of MOUD in subsequent pregnancy with decrease in illicit drug use.

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.

A retrospective, observational study on medication for opioid use disorder during pregnancy and risk for neonatal abstinence syndrome.

OBJECTIVES: The prevalence of opioid use disorder (OUD) among pregnant women is increasing. Research consistently demonstrates the efficacy of medications for OUD (MOUD); however, researchers have called for additional studies evaluating the safety of MOUD during pregnancy, particularly the relative safety of two commonly used MOUD medications-methadone and buprenorphine. This study aimed to evaluate the consequences of MOUD exposure during pregnancy on risk for neonatal abstinence syndrome (NAS). METHODS: In a clinical sample of infants born to women with OUD, we evaluated the risk of NAS among those exposed to (i) methadone and (ii) buprenorphine compared with those unexposed to MOUD, as well as the risk of NAS among those exposed to (i) methadone compared with those exposed to (ii) buprenorphine. RESULTS: Compared with buprenorphine-exposed infants (n = 37), methadone-exposed infants (n = 27) were at increased risk for NAS (odds ratio [OR] = 4.67, 95% confidence interval [CI]: 1.03, 21.17). Compared with unexposed infants (n = 43), buprenorphine-exposed infants were at decreased risk for NAS (OR = 0.45, 95% CI: 0.14, 1.39) and methadone-exposed infants were at increased risk for NAS (OR = 2.64, 95% CI: 0.79, 8.76), though these associations were not statistically significant. CONCLUSIONS: Our study suggests that when methadone and buprenorphine are equally appropriate options for the treatment of OUD in pregnant women, buprenorphine may add the additional benefit of reduced risk of newborn NAS.

Medications for opioid use disorder (MOUD), such as buprenorphine and methadone, are effective in reducing the significant harms associated with untreated opioid use disorder (OUD) in nonpregnant and pregnant adults. While previous research clearly documents that the risks of MOUD in pregnancy are less than the risks of untreated OUD in pregnancy, researchers have called for additional studies evaluating the safety of MOUD during pregnancy, particularly the relative safety of methadone and buprenorphine. In a clinical sample of infants born to women with OUD, we showed that buprenorphine-exposed infants were at significantly reduced risk for neonatal abstinence syndrome compared with methadone-exposed infants. Our study adds to the growing body of evidence supporting the use of buprenorphine over methadone for the treatment of OUD among pregnant women.

Association Between Neonates With Laryngomalacia and Neonatal Abstinence Syndrome.

OBJECTIVE: Laryngomalacia (LM) is the most common congenital anomaly of the larynx. The cause of LM is still largely unknown, but a neurological mechanism has gained the most acceptance. There have not been any studies examining the prevalence of LM in infants with Neonatal Abstinence Syndrome (NAS). The aim of our study is to determine if infants with NAS are more likely to be diagnosed with LM. METHODS: This study was a population-based inpatient registry analysis. We examined nationwide neonatal discharges in 2016 using the Kids' Inpatient Database (KID). Only patients listed as neonates were included. The International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) codes for neonatal withdrawal symptoms from maternal use of drugs of addiction (P96.1) and diagnoses denoting LM were used. To quantify associations between the LM and NAS groups, prevalence rates and odds ratios (ORs) were used. RESULTS: There were 3 970 065 weighted neonatal discharges in the 2016 KID. Among patients included in our dataset, 0.809% (32 128) had NAS and 0.075% (2974) had LM. There was an increased odds ratio for neonates with NAS and LM (OR of 2.85, 95% CI = 2.24-3.63) compared to infants without NAS. Multiple logistic regression accounting for possible confounders produced an adjusted OR of 1.68 (95% CI = 1.29-2.19). CONCLUSION: Our study found an association between NAS and LM. This suggests that prenatal exposure to opioids or possibly the sequelae of withdrawal symptoms may be risk factors for the development of LM.

Neonatal Outcomes after Combined Opioid and Nicotine Exposure in Utero: A Scoping Review.

BACKGROUND: The majority of women who are pregnant with opioid use disorder (OUD) also smoke tobacco but are rarely offered tobacco cessation counseling. While the effects of exposure to opioids and nicotine in utero are well-understood separately, understanding the impact of the combined exposure to these substances on neonatal outcomes is lacking. METHODS: A scoping review was conducted using PubMed and Scopus databases for studies addressing the combined exposure to opioids and nicotine during pregnancy published between 1 January 1980 and 9 July 2019. A total of 29 papers met the eligibility criteria for inclusion, with nine being identified as clinical trials (three from the MOTHER study) and two as secondary data analysis of clinical trial data. RESULTS: Neonatal outcomes for infants who had a combined exposure to opioids and nicotine in utero indicated a reduction in birth weight and birth length. Findings in infants exposed to both nicotine and opioids were mixed with regard to the duration of neonatal abstinence syndrome (NAS), the likelihood of treatment for NAS, doses of medicine used to treat NAS, and NAS scores when compared with infants who had opioid exposure without nicotine. CONCLUSIONS: The combined exposure to nicotine and opioids during pregnancy may lead to a reduction in neonatal birth weight and birth length and more severe NAS signs, compared with opioid use alone, but more research is necessary to identify the minimum dosage and length of nicotine exposure to accurately predict these outcomes.

Cleft Lip and Palate in Newborns Diagnosed With Neonatal Abstinence Syndrome.

OBJECTIVE: Cleft lip and/or cleft palate (CLP) is the most common major congenital malformation of the head and neck. Previous studies suggested an association between fetal opioid exposure and CLP. This study seeks to evaluate the associations between CLP and neonatal abstinence syndrome (NAS) in the United States. STUDY DESIGN: Population-based inpatient registry analysis. SETTING: Academic medical center. SUBJECTS AND METHODS: Kids' Inpatient Database (2016) was used to identify weighted in-hospital births with diagnoses of CLP or NAS. Demographic information was obtained. RESULTS: Among 3.8 million weighted in-hospital births, prevalence rates of CLP in the NAS and non-NAS populations were 3.13 and 1.35 per 1000, respectively. The odds ratios for patients with NAS developing CLP, isolated cleft palate, isolated cleft lip, and cleft lip and palate when compared with the reference population were 2.33 (95% CI, 1.87-2.91; P < .001), 4.97 (95% CI, 3.84-6.43; P < .001), 1.01 (P = .98), and 0.80 (P = .46). Independent predictors of CLP within the NAS population included median household income for patients' zip code, race, hospital region, payment method, and maternal use of tobacco or other drugs of addiction. The binary logistic regression model accounting for possible confounding variables produced an odds ratio of 1.74 (95% CI, 1.36-2.23; P < .001) for the association between NAS and CLP. CONCLUSION: Our study found an association between NAS and CLP, specifically isolated cleft palate, suggesting that prenatal exposure to opioids may be an environmental risk factor in the development of CLP.

Prenatal opioid exposure - Increasing evidence of harm.

Prenatal opioid exposure adversely impacts upon fetal growth and places the newborn at risk of neonatal opioid withdrawal. The severity and duration of opioid withdrawal cannot be predicted in the individual baby and may be contributed to by other drugs including benzodiazepines and alcohol as well as cigarette smoking. Mitigating factors include breastfeeding, rooming in and absence of maternal polypharmacy. Less well recognised are a variety of other complications associated with prenatal opioid exposure including epigenetic changes, effects on neurophysiological function and structural alterations to the developing brain. The visual system is significantly affected, with changes to both clinical and electrophysiological function persisting at least to mid-childhood. Longer term neurodevelopmental and behavioural outcomes are confounded by multiple factors including poverty, parent-child interaction and small study numbers, but systematic reviews consistently demonstrate poorer outcomes for those children and young people prenatally exposed to opioids. Crucially, manifestation of neonatal withdrawal is not a prerequisite for important long term problems including behavioural, emotional or motor function disorder, sensory or speech disorder, strabismus and nystagmus. A body of evidence supports an independent adverse effect of prenatal opioid exposure upon fetal brain development, mediated via a systemic neuro-inflammatory process. Children prenatally exposed to opioids should remain under appropriate follow up, at least until school entry, as difficulties may only become apparent in mid-childhood. Future studies of the management of opioid use disorder in pregnancy, including maintenance methadone, must include longer term outcomes for the baby.

Comparison of buprenorphine and methadone in the management of maternal opioid use disorder in full term pregnancies.

Objectives To compare pregnancy outcomes with medication assisted treatment using. methadone or buprenorphine in term mothers with opioid use disorder. Methods A cohort of women receiving medication assisted treatment with either methadone or buprenorphine were identified from delivery records over a 10-year period. Women were excluded with delivery <37 weeks, multiple gestations, or a known anomalous fetus. Maternal demographics, medications, mode of delivery, birthweight, newborn length of stay, and neonatal abstinence syndrome were extracted. The study was IRB approved and a p-value of <0.05 was significant. Results There were 260 women, 140 (53.8%) with methadone use and 120 (46.2%) with buprenorphine use. Groups were similar for maternal age, race, parity, homeless rate, tobacco use, mode of delivery and incidence of neonatal abstinence syndrome. The methadone group had a lower mean newborn birthweight (2874±459 g) and a greater incidence of low birth weight (11.4%) than the buprenorphine group (3282±452 g; p<0.001 and 2.5%; p=0.006). The incidence of neonatal abstinence syndrome was similar between groups (97% methadone vs. 92.5% buprenorphine; p=0.08). The methadone group had a longer newborn length of stay (11.4+7.4 days) and more newborn treatment with morphine (44.6%) than the buprenorphine group (8.2+4.4 days; p<0.001 and 24.2%; p<0.001). Maternal methadone use was an independent predictor for a newborn length of hospital stay >7 days (OR 3.61; 95% confidence interval 1.32-9.86; p=0.01). Conclusions Medication assisted treatment favors buprenorphine use when compared to. methadone with an increased birthweight, reduced need for newborn treatment, and a shorter newborn length of stay in term infants.

The Association of Concomitant Maternal Marijuana Use on Health Outcomes for Opioid Exposed Newborns in Massachusetts, 2003-2009.

This population-based study showed that maternal opioid plus marijuana use during pregnancy was associated with increased odds of prematurity and low birth weight but lower odds of neonatal abstinence syndrome and prolonged hospitalization compared with opioid exposure without marijuana use. Further research should evaluate the biologic mechanisms responsible for these outcomes.

Maternal prepregnancy surgery and risk of neonatal abstinence syndrome in future newborns: a longitudinal cohort study.

BACKGROUND: Neonatal abstinence syndrome is increasingly prevalent, and may be related to opioid use disorders caused by postoperative prescriptions for pain control. We assessed the association of maternal prepregnancy surgery with risk of neonatal abstinence syndrome from opioid use disorders in future pregnancies. METHODS: We conducted a longitudinal retrospective cohort study of 2 182 365 deliveries in Quebec, Canada, between 1989 and 2016. The main exposure was maternal prepregnancy surgery. The main outcome measure was neonatal abstinence syndrome in offspring. We adjusted associations for maternal comorbidity and pregnancy characteristics using log-binomial regression models. RESULTS: The prevalence of neonatal abstinence syndrome in the cohort was 10.7 per 10 000 births. Compared with no surgery, prepregnancy surgery was associated with a risk ratio (RR) of neonatal abstinence syndrome of 1.63 (95% confidence interval [CI] 1.49-1.78). Risk was greater for 3 or more prepregnancy surgeries (RR 2.34, 95% CI 2.07-2.63) and age < 15 years at first surgery (1 surgery: RR 2.08, 95% CI 1.71-2.54; 2 or more surgeries: RR 2.79, 95% CI 2.32-3.37). Nearly all surgical specialties increased the risk of neonatal abstinence syndrome, but associations were strongest for cardiothoracic surgery (RR 4.45, 95% CI 2.87-6.91), neurosurgery (RR 3.00, 95% CI 1.56-5.77) and urologic surgery (RR 3.03, 95% CI 2.16-4.26). INTERPRETATION: Prepregnancy surgery is associated with the risk of neonatal abstinence syndrome in future pregnancies. Prescription opioids for postsurgical pain may result in opioid use disorders during future pregnancies, inadvertently increasing the risk of neonatal abstinence syndrome in offspring.

Prevalence of Maternal-Risk Factors Related to Neonatal Abstinence Syndrome in a Commercial Claims Database: 2011-2015.

BACKGROUND: Despite the rising incidence of neonatal abstinence syndrome (NAS), data evaluating trends in maternal risk factors associated with NAS have not been available for recent years, a period characterized by declining opioid prescriptions. The objective of this study was to examine the prevalence of opioid- and non-opioid-related factors associated with NAS, and by mutually exclusive subgroups of deliveries without prescription-opioid use, with prescription-opioid use, and with opioid-use disorder (OUD). METHODS: A cohort of pregnancies resulting in live births in a commercial claims data base in 2011-2015 was identified. Examples of maternal risk factors of interest included antepartum prescription-drug use (e.g., opioids, selective serotonin reuptake inhibitors [SSRIs], antipsychotics) and nonprescription-related factors (e.g., smoking, OUD). RESULTS: A total of 659 cases of NAS among 621,940 deliveries was identified. Among NAS deliveries, prescription opioids were the most commonly used drug-class (39.0%). Adjusted relative risk (RR) for NAS was 5.43 (95% confidence interval [CI] 4.25-6.95), followed by SSRIs (20.9%; RR 3.16, CI 2.43-4.11); OUD was noted in 36.3% of the deliveries (RR 40.74, CI 22.64-73.32). In the subgroup of deliveries without a prescription opioid (33% of overall NAS deliveries), the absolute incidence of NAS was low (0.3 cases/1000 deliveries), and SSRIs were the most commonly used medication class (32.7%; RR 10.21, CI 7.28-14.31). In the subgroup of deliveries with an opioid prescription, the absolute incidence of NAS was 7.7/1000 (29% of all overall NAS deliveries), and 22.7% of these deliveries were exposed to one other psychotropic agent in addition to the opioid, most commonly an SSRI (18.0%). In the subgroup of deliveries with a diagnosis of OUD, the NAS incidence was high (214.3/1000 [36% of all NAS cases]). CONCLUSION: A third of NAS deliveries did not have evidence of prescription opioids. Other psychotropic medications, especially SSRIs, were strong predictors of NAS in this stratum but had no relevance among deliveries with OUD, suggesting varying etiologies and the need for tailored preventive approaches to reduce NAS effectively.

Maternal and neonatal characteristics of a Canadian urban cohort receiving treatment for opioid use disorder during pregnancy.

The epidemic of prescription and non-prescription opioid misuse is of particular importance in pregnancy. The Society of Obstetricians and Gynaecologists of Canada currently recommends opioid replacement therapy with methadone or buprenorphine for opioid-dependent women during pregnancy. This vulnerable segment of the population has been shown to be at increased risk of blood-borne infectious diseases, nutritional insecurity and stress. The objective of this study was to describe an urban cohort of pregnant women on opioid replacement therapy and to evaluate potential effects on the fetus. A retrospective chart review of all women on opioid replacement therapy and their infants who delivered at The Ottawa Hospital General and Civic campuses between January 1, 2013 and March 24, 2017 was conducted. Data were collected on maternal characteristics, pregnancy outcomes, neonatal outcomes and corresponding placental pathology. Maternal comorbidities identified included high rates of infection, tobacco use and illicit substance use, as well as increased rates of placental abruption compared with national averages. Compared with national baseline averages, the mean neonatal birth weight was low, and the incidence of small for gestational age infants and congenital anomalies was high. The incidence of NAS was comparable with estimates from other studies of similar cohorts. Findings support existing literature that calls for a comprehensive interdisciplinary risk reduction approach including dietary, social, domestic, psychological and other supports to care for opioid-dependent women in pregnancy.

Neonatal abstinence syndrome.

Neonatal abstinence syndrome refers to the signs and symptoms attributed to the cessation of prenatal exposure (via placental transfer) to various substances. This Primer focuses on neonatal abstinence syndrome caused by opioid use during pregnancy - neonatal opioid withdrawal syndrome (NOWS). As the global prevalence of opioid use has alarmingly increased, so has the incidence of NOWS. NOWS can manifest with varying severity or not at all, for unknown reasons, but is likely to be associated with multiple factors, both maternal (for example, smoking and additional substance exposures) and neonatal (gestational age, sex and genetics). Care for the infant with NOWS begins with addressing the issues experienced by pregnant women with opioid use disorder. Co-occurring mental illness, economic hardship, intimate partner violence, infectious diseases and limited access to care are common in these women and can result in poor maternal and neonatal outcomes. Although there is no consensus regarding optimal NOWS management, non-pharmacological interventions (such as breastfeeding and rooming-in of the mother and the baby) have become a priority, as they can ameliorate symptoms without the need for further opioid exposure. Untreated NOWS can be associated with morbidity in early infancy, and the long-term consequences of fetal opioid exposure are only beginning to be understood.

Impact of psychiatric medication co-exposure on Neonatal Abstinence Syndrome severity.

BACKGROUND: Among opioid-exposed infants, psychiatric medication co-exposure is common. Our objective was to compare Neonatal Abstinence Syndrome (NAS) outcomes based on individual psychiatric medication co-exposures. METHODS: A retrospective study of 744 opioid-exposed mother-infant dyads from a single institution was performed. Mothers on pharmacotherapy with methadone or buprenorphine at delivery were included. Data were collected on maternal demographics, psychiatric medication use, and NAS outcomes, including any medication treatment, adjunctive medication treatment, length of hospital stay (LOS), and opioid treatment days. The extent to which individual psychiatric medication and polypharmacy exposure were associated with NAS outcomes was assessed using multivariable regression. RESULTS: Fifty-four percent of the mothers were on ≥1 psychiatric medication, with 32% on ≥2 or psychiatric medications (polypharmacy group). In adjusted models, polypharmacy exposure was associated with longer LOS (ß = 4.31 days, 95% CI 2.55-6.06) and opioid treatment days (ß = 3.98 days, 95% CI 2.24-5.72) and more treatment with adjunctive medication for NAS (aOR = 2.49, 95% CI 1.57-3.95). Benzodiazepines were associated with longer LOS (ß = 4.94, 95% CI 2.86-7.03) and opioid treatment days (ß = 4.86, 95% CI 2.61-6.75), and more adjunctive medication treatment (aOR = 2.57, 95% CI 1.49-4.42). Gabapentin was associated with longer LOS (ß = 2.79, 95% CI 0.54-5.03), more NAS medication treatment (aOR = 2.96, 95% CI 1.18-7.42) including more adjunctive medications (aOR = 1.92, 95% CI 1.05-3.53). CONCLUSION: For infants of mothers with OUD who are also on concurrent psychiatric medications, polypharmacy was associated with worse NAS severity. When medically indicated, limiting use of multiple psychiatric medications, particularly benzodiazepines and gabapentin, during pregnancy should be considered to improve NAS outcomes.