OBJECTIVES

Evidence on the perinatal health of mother-infant dyads affected by opioids is limited. Elevated risks of opioid-related harms for people with opioid use disorder (OUD) increase the urgency to identify protective factors for mothers and infants. Our objectives were to determine perinatal outcomes after an OUD diagnosis and associations between opioid agonist treatment and birth outcomes.

METHODS

We conducted a population-based retrospective study among all women with diagnosed OUD before delivery and within the puerperium period in British Columbia, Canada, between 2000 and 2019 from provincial health administrative data. Controlling for demographic and clinical characteristics, we determined associations of opioid agonist treatment on birth weight, gestational age, infant disorders related to gestational age and birth weight, and neonatal abstinence syndrome via logistic regression.

RESULTS

The population included 4574 women and 6720 live births. Incidence of perinatal OUD increased from 166 in 2000 to 513 in 2019. Compared with discontinuing opioid agonist treatment during pregnancy, continuous opioid agonist treatment reduced odds of preterm birth (adjusted odds ratio: 0.6; 95% confidence interval: 0.4–0.8) and low birth weight (adjusted odds ratio: 0.4; 95% confidence interval: 0.2–0.7). Treatment with buprenorphine-naloxone (compared with methadone) reduced odds of each outcome including neonatal abstinence syndrome (adjusted odds ratio: 0.6; 95% confidence interval: 0.4–0.9).

CONCLUSIONS

Perinatal OUD in British Columbia tripled in incidence over a 20-year period. Sustained opioid agonist treatment during pregnancy reduced the risk of adverse birth outcomes, highlighting the need for expanded services, including opioid agonist treatment to support mothers and infants.

What’s Known on this Subject:

Although opioid agonist treatment remains the evidence-based standard for treatment of opioid use disorder, existing evidence on its use in pregnancy and associated neonatal outcomes is limited.

What This Study Adds:

Incidence of perinatal opioid use disorder has tripled over the last 2 decades in British Columbia. Continued engagement in opioid agonist treatment (particularly with buprenorphine, compared with methadone), reduces the risk of several adverse birth outcomes, including neonatal abstinence syndrome.

During a growing crisis in opioid-related morbidity and mortality across North America, rates of opioid use in pregnancy have paralleled the rapid increases observed in the general population.1  National reports estimate 5% of North American women use illicit substances during pregnancy.2,3  Additionally, the rate of infants born with acute opioid withdrawal or neonatal abstinence syndrome (NAS) in the United States has increased to 7.3 per 1000 birth hospitalizations as of 2017 (from 4.0) over the last decade.4 

Opioid agonist treatment is associated with an increased risk of NAS but better neonatal and maternal outcomes compared with that of untreated opioid use disorder (OUD)57 ; however, randomized trials and observational studies investigating the use of perinatal opioid agonist treatment note limitations from small sample sizes, selection bias, and unadjusted confounding from co-occurring substance use and other factors, and conclude that larger scale studies are needed to inform clinical practice.810  Perinatal opioid use may include prescription opioid agonists for pain management, opioid agonist treatment of OUD, and/or illicit opioids, alone or in combination with other prescribed or illicit drugs.11  Polysubstance use (including tobacco) as well as the use of psychotropic medications are reported to increase the risk and severity of NAS as well as the likelihood of other adverse outcomes, including preterm birth.1,1214  Additionally, there is limited evidence on the comparative effectiveness of competing opioid agonist treatment options in pregnancy. A recent Cochrane review of 4 randomized controlled trials reported inconclusive evidence for the efficacy of methadone and buprenorphine for outcomes such as birth weight and NAS.8  In contrast, observational studies and randomized trials have demonstrated the benefits of buprenorphine relative to methadone in reducing the risk of preterm birth and NAS,10,15  warranting further investigation to account for the factors contributing to these differences.

Comprehensive investigations to characterize mother-infant dyads affected by opioids are needed to identify protective factors and inform providers on timely strategies to support mothers and infants. In a setting with universal health care and linkable population-level data, we aimed to describe the perinatal health of women with OUD in pregnancy and their infants in the province of British Columbia from 2000 to 2019. We also aimed to determine the associations between opioid agonist treatment receipt and infant birth outcomes.

We conducted a longitudinal, retrospective study using a provincial-level linkage of 7 health administrative databases. We included the following provincial databases: PharmaNet (drug dispensations),16  the Discharge Abstract Database (hospitalizations),17  Medical Services Plan (physician billing records),18  National Ambulatory Care Reporting System (emergency department visit and ambulatory care),19  British Columbia Vital Statistics (deaths and underlying causes),20  Perinatal Services British Columbia (PSBC) (mother-infant perinatal outcomes and provider-reported maternal substance use),21  and British Columbia corrections (incarceration episodes).22  Databases were linked by using unique individual personal health numbers (deidentified). The details of the databases have been described extensively elsewhere.23 

We identified mother and infant dyads via a case-finding algorithm24,25  (Supplemental Table 4) to identify women who were ever diagnosed with OUD before delivery (including the time period before conception, identified via acute care, physician visits, or opioid agonist treatment receipt) or within the puerperium period (6 weeks after childbirth) with a completed pregnancy between April 1, 2000, and March 31, 2019, in British Columbia. We included all deliveries, including home births, and excluded late terminations or abortions.

We obtained maternal demographic information, including age, parity, gestational age, number of antenatal care visits, prepregnancy BMI,21  area of residence (rural or urban), and incarceration during pregnancy. We included information on the time of first OUD diagnosis (ie, during pregnancy or puerperium period, 1 year, 1 to 5 years, and >5 years before conception) and time of latest receipt of OUD-related care (during pregnancy or puerperium period, before conception [1 year or >1 year], or postdelivery [1 year or >1 year]). We measured cumulative durations of opioid agonist treatment episodes during pregnancy (in months) and opioid agonist treatment regimen type (methadone, buprenorphine/naloxone, slow-release oral morphine (SROM), and injectable opioid agonist treatment).26  Furthermore, we measured nonopioid agonist treatment prescription opioids prescribed to women within the year before pregnancy and during pregnancy. We also measured receipt of selective serotonin reuptake inhibitors (SSRIs), benzodiazepines, and antipsychotics or stimulants (identification codes27  provided in Supplemental Table 5) in pregnancy because use of these psychotropic medications during pregnancy is associated with an increased risk of NAS, preterm birth, and low birth weight.1,14,28  We measured smoking (tobacco), alcohol use, or any prescription, nonprescription, or illicit drug use (recorded by the antenatal care provider as a risk to the pregnancy) in addition to receipt of care for other nonopioid, nonalcohol substance use or tobacco dependence during pregnancy. Related comorbid conditions (ever diagnosed before delivery) included the following: alcohol use disorder, nonopioid and nonalcohol substance use disorder (SUD), HIV, hepatitis C virus, mental health conditions (anxiety, depression, bipolar disorder, schizophrenia and other psychoses, stress and adjustment disorder, personality disorders, attention-deficit/hyperactivity disorder, and developmental disorder), and chronic pain (case definition described in Supplemental Table 4).29,30 

We also included measures of maternal health care use (hospitalizations, emergency department visits, physician visits, and nonopioid agonist treatment drug dispensations) in addition to maternal chronic disease scores, measured within the year before conception. To measure disease severity and complexity, we used the chronic disease score from Clark et al,31  based on drug dispensations received within the year before pregnancy. Finally, we measured pain medications received during labor (anesthesia and analgesics) in addition to prescription opioids prescribed postdelivery.

Perinatal outcomes included birth head circumference (below third percentile or >97th percentile),3234  birth length (below third percentile or >97th percentile),33  Apgar scores,35  preterm birth (<37 weeks’ gestation), low birth weight (<2500 g), length of hospital stay for newborn care, initiation of partial or exclusive breastfeeding before hospital discharge, stillbirth (at least 20 weeks of pregnancy or after attaining a weight of at least 500 g), and infant death (within 12 months of age). We additionally measured fetal growth restrictions and small for gestational age (SGA), infant disorders related to SGA or low birth weight, NAS (International Classifications of Diseases, Ninth Revision, [ICD-9] code 779.5 (World Health Organization) and International Classifications of Diseases, 10th Revision, [ICD-10] code P96.1 (Canada) in perinatal records, hospitalization, physician visit, emergency department visit, or death records within 3 months of birth), and fetus or newborn affected by maternal use of drugs, alcohol, or “drugs of addiction” as well as infant congenital and chromosomal anomalies.1,14,26,36,37  Diagnostic codes38  for perinatal outcomes are detailed in Supplemental Table 6.

We focused on the association between the characteristics of opioid agonist treatment exposure and key birth outcomes among women who received opioid agonist treatment in pregnancy.26,36,37  Key outcomes included preterm birth, low birth weight, infant disorders related to SGA or birth weight, and NAS. We measured the time from the first OUD diagnosis, opioid agonist treatment engagement before pregnancy, duration of latest opioid agonist treatment episode in the third trimester (≤30 days or >30 days), type of opioid agonist treatment received in pregnancy (methadone or buprenorphine/naloxone), daily dosage, and change in opioid agonist treatment dosage in the third trimester. We classified changes in opioid agonist treatment dosage by regimen as follows: consistently low (methadone: ≤40 mg per day; buprenorphine-naloxone: ≤6 mg per day; SROM: ≤350 mg per day; injectable opioid agonist treatment; diacetylmorphine: ≤140 mg per day; hydromorphone: ≤70 mg per day), medium (methadone: 40–85 mg per day; buprenorphine-naloxone: 6–16 mg per day; SROM: 350–750 mg per day; diacetylmorphine: 14–300 mg per day; hydromorphone: 70–150 mg per day), or high (methadone: ≥85 mg per day; buprenorphine-naloxone: ≥16 mg per day; SROM: ≥750 mg per day; diacetylmorphine: ≥300 mg per day; hydromorphone: ≥150 mg per day). We additionally measured episodes increasing from a lower dose to a higher dose only and decreasing from a higher dosage category to a lower category only as well as flexible dosing (ie, daily dose class changed with no specific order and/or direction).25  The thresholds of daily dosage by treatment regimen were determined according to provincial clinical guidelines.3941 

We first presented descriptive statistics of demographic and clinical factors of women with diagnosed OUD during pregnancy stratified by the status of opioid agonist treatment receipt in pregnancy. Second, we presented the annual number of women with OUD in pregnancy and the percentage on opioid agonist treatment during pregnancy from 2000–2001 to 2018–2019 (fiscal year). Third, we described maternal health care use before pregnancy and perinatal outcomes stratified by the status of opioid agonist treatment receipt in pregnancy. Population characteristics (including maternal health care use and perinatal outcomes) were measured among all delivery episodes of care and perinatal outcomes were measured among all live and stillborn infants within these episodes. Fourth, we measured the annual incidence rates of preterm birth, low birth weight, infant disorders related to SGA or low birth weight, and NAS per 1000 live births among all women with OUD from 2000–2001 to 2018–2019.

Finally, we fit generalized linear mixed effect models with a logit link function42  to determine the association between opioid agonist treatment dosing and key perinatal outcomes among all women on opioid agonist treatment in pregnancy. We included all infants born to women with at least 1 opioid agonist treatment dispensation during pregnancy. We compared women who continued treatment in the third trimester to delivery with women who discontinued treatment before the third trimester.1,26  We presented adjusted odds ratios for each of the opioid agonist treatment-related variables described above. Because the treatment-related factors were highly correlated, for each outcome, we fit 6 logistic models with a random intercept for women incorporating each of the 6 opioid agonist treatment factors. We adjusted each model for maternal age, parity, and receipt of psychotropic medications or nonopioid agonist treatment opioids in pregnancy, in addition to alcohol use, other nonopioid, nonalcohol substance use, and smoking during pregnancy (covariates are described in Supplemental Tables 711). We conducted a sensitivity analysis among women who received opioid agonist treatment in pregnancy with a delivery after April 1, 2008 (when the use of specific substances was recorded) to adjust for use of marijuana, cocaine, and heroin in pregnancy (Supplemental Tables 1213).

All analyses were conducted by using SAS Enterprise Guide 7.1 (SAS Institute, Inc, Cary, NC) and R version 3.5.0.

The Providence Health Care Research Ethics Board and the Simon Fraser University Office of Research Ethics determined the study to be exempt from research ethics board review as per Article 2.5 of the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans.

We identified 4574 women diagnosed with OUD before delivery or during the puerperium period (median age: 29), with a total of 6693 deliveries and 6720 live births in British Columbia between April 1, 2000, and March 31, 2019 (Table 1). A total of 1355 (20%) deliveries indicated first OUD diagnosis during pregnancy or the puerperium period. We documented 2824 (42%) of deliveries with opioid agonist treatment engagement in pregnancy and 2684 (37%) of deliveries with prescriptions for either SSRIs, benzodiazepines, or other antipsychotic mediations or stimulants during pregnancy.

TABLE 1

Characteristics of Women With OUD in Pregnancy or the Puerperium Period in British Columbia from 2000–2001 to 2018–2019

CharacteristicsOn Opioid Agonist TreatmentaNot on Opioid Agonist TreatmentTotalb
No. women 2173 2726 4574 
No. deliveries 2824 3869 6693 
Maternal age, median (Q1 and Q3) 29 (25 and 33) 28 (24 and 33) 29 (25 and 33) 
Parity, median, (Q1 and Q3) 1 (0 and 2) 1 (0 and 2) 1 (0 and 2) 
Region    
 Urban 2728 (96.6) 3557 (91.9) 6285 (93.9) 
 Rural 92 (3.3) 310 (8.0) 402 (6.0) 
Incarceratedc 217 (7.7) 144 (3.7) 361 (5.4) 
No. antenatal care visits, median (Q1 and Q3) 8 (4 and 12) 8 (5 and 11) 8 (5 and 11) 
Prepregnancy BMI    
 Underweight (<18.5) 161 (5.7) 162 (4.2) 323 (4.8) 
 Normal wt (18.5–25) 946 (33.5) 1285 (33.2) 2231 (33.3) 
 Overweight (>25) 395 (14.0) 896 (23.2) 1291 (19.3) 
 Unknown 1322 (46.8) 1526 (39.4) 2848 (42.6) 
First diagnosis of OUD    
 During pregnancy or puerperium period 398 (13.9) 978 (24.9) 1355 (20.3) 
 1 y before conception 348 (12.2) 362 (9.2) 704 (10.5) 
 1–5 y before conception 1107 (38.7) 1359 (34.6) 2439 (36.4) 
 >5 y before conception 1007 (35.2) 1227 (31.3) 2195 (32.8) 
Latest indication of OUD    
 During pregnancy or puerperium period 188 (6.7) 742 (19.2) 930 (13.9) 
 1 y before conception — 325 (8.4) 325 (4.86) 
 >1 y before conception — 1460 (37.7) 1460 (21.8) 
 1 y postdelivery 305 (10.8) 68 (1.8) 373 (5.6) 
 >1 y postdelivery 2331 (82.5) 1274 (32.9) 3605 (53.9) 
Opioid agonist treatment engagement during pregnancyd    
 0–3 mo 613 (21.7) — 613 (9.2) 
 3–6 mo 391 (13.8) — 391 (5.8) 
 >6 mo 1820 (64.4) — 1820 (27.2) 
Opioid agonist treatment regimend    
 Methadone 2674 (94.7) — 2674 (40.0) 
 Buprenorphine/naloxone 211 (7.5) — 211 (3.2) 
 SROM or injectable opioid agonist treatment 19 (0.7) — 19 (0.3) 
Opioid agonist treatment initiatione    
 First trimester 2075 (73.5) — 2075 (31.0) 
 Second trimester 347 (12.3) — 347 (5.2) 
 Third trimester 275 (9.7) — 275 (4.1) 
 Puerperium (6 wk after birth) 127 (4.5) — 127 (1.9) 
Nonopioid agonist treatment prescription opioid    
 Within 1 y before conception 968 (34.3) 1485 (38.4) 2453 (36.7) 
 In pregnancy or puerperium period 823 (29.1) 1393 (36.0) 2216 (33.1) 
Other prescription medications in pregnancy    
 Any of the following 1277 (45.2) 1191 (30.8) 2684 (36.9) 
  SSRIs only 450 (15.9) 387 (10.0) 837 (12.5) 
  Benzodiazepines onlyf 234 (8.3) 248 (6.4) 482 (7.2) 
  Antipsychotic or stimulants only 139 (4.9) 101 (2.6) 240 (3.6) 
  Combination of any of the above 454 (16.1) 455 (11.8) 909 (13.6) 
Maternal comorbidityg    
 Alcohol use disorder 756 (26.8) 1144 (29.6) 2299 (34.3) 
 Nonopioid, nonalcohol SUD 2660 (94.2) 3222 (83.3) 6130 (91.6) 
 HIV and AIDS 176 (6.2) 72 (1.9) 248 (3.7) 
 Hepatitis C virus 259 (9.2) 149 (3.9) 408 (6.1) 
 Mental health conditionh 2643 (93.6) 3511 (90.7) 6154 (91.9) 
 Chronic pain 1911 (67.7) 2683 (69.3) 4594 (68.6) 
 Diabetesi 158 (5.6) 338 (8.7) 496 (7.4) 
 Tobacco dependence related health care record during pregnancyj 2161 (76.5) 2467 (63.8) 4628 (69.1) 
 Reported smoking during pregnancyk 1886 (66.8) 1788 (46.2) 3674 (54.9) 
 Reported quitting smoking before pregnancyk 199 (7.0) 563 (14.6) 762 (11.4) 
 Reported substance use as a risk to pregnancyk 2635 (93.3) 1908 (49.3) 4543 (67.9) 
 Reported alcohol use as a risk to pregnancyk 137 (4.9) 283 (7.3) 420 (6.3) 
 Nonopioid and nonalcohol substance use care record during pregnancyl 2134 (75.6) 1286 (33.4) 3420 (51.10) 
CharacteristicsOn Opioid Agonist TreatmentaNot on Opioid Agonist TreatmentTotalb
No. women 2173 2726 4574 
No. deliveries 2824 3869 6693 
Maternal age, median (Q1 and Q3) 29 (25 and 33) 28 (24 and 33) 29 (25 and 33) 
Parity, median, (Q1 and Q3) 1 (0 and 2) 1 (0 and 2) 1 (0 and 2) 
Region    
 Urban 2728 (96.6) 3557 (91.9) 6285 (93.9) 
 Rural 92 (3.3) 310 (8.0) 402 (6.0) 
Incarceratedc 217 (7.7) 144 (3.7) 361 (5.4) 
No. antenatal care visits, median (Q1 and Q3) 8 (4 and 12) 8 (5 and 11) 8 (5 and 11) 
Prepregnancy BMI    
 Underweight (<18.5) 161 (5.7) 162 (4.2) 323 (4.8) 
 Normal wt (18.5–25) 946 (33.5) 1285 (33.2) 2231 (33.3) 
 Overweight (>25) 395 (14.0) 896 (23.2) 1291 (19.3) 
 Unknown 1322 (46.8) 1526 (39.4) 2848 (42.6) 
First diagnosis of OUD    
 During pregnancy or puerperium period 398 (13.9) 978 (24.9) 1355 (20.3) 
 1 y before conception 348 (12.2) 362 (9.2) 704 (10.5) 
 1–5 y before conception 1107 (38.7) 1359 (34.6) 2439 (36.4) 
 >5 y before conception 1007 (35.2) 1227 (31.3) 2195 (32.8) 
Latest indication of OUD    
 During pregnancy or puerperium period 188 (6.7) 742 (19.2) 930 (13.9) 
 1 y before conception — 325 (8.4) 325 (4.86) 
 >1 y before conception — 1460 (37.7) 1460 (21.8) 
 1 y postdelivery 305 (10.8) 68 (1.8) 373 (5.6) 
 >1 y postdelivery 2331 (82.5) 1274 (32.9) 3605 (53.9) 
Opioid agonist treatment engagement during pregnancyd    
 0–3 mo 613 (21.7) — 613 (9.2) 
 3–6 mo 391 (13.8) — 391 (5.8) 
 >6 mo 1820 (64.4) — 1820 (27.2) 
Opioid agonist treatment regimend    
 Methadone 2674 (94.7) — 2674 (40.0) 
 Buprenorphine/naloxone 211 (7.5) — 211 (3.2) 
 SROM or injectable opioid agonist treatment 19 (0.7) — 19 (0.3) 
Opioid agonist treatment initiatione    
 First trimester 2075 (73.5) — 2075 (31.0) 
 Second trimester 347 (12.3) — 347 (5.2) 
 Third trimester 275 (9.7) — 275 (4.1) 
 Puerperium (6 wk after birth) 127 (4.5) — 127 (1.9) 
Nonopioid agonist treatment prescription opioid    
 Within 1 y before conception 968 (34.3) 1485 (38.4) 2453 (36.7) 
 In pregnancy or puerperium period 823 (29.1) 1393 (36.0) 2216 (33.1) 
Other prescription medications in pregnancy    
 Any of the following 1277 (45.2) 1191 (30.8) 2684 (36.9) 
  SSRIs only 450 (15.9) 387 (10.0) 837 (12.5) 
  Benzodiazepines onlyf 234 (8.3) 248 (6.4) 482 (7.2) 
  Antipsychotic or stimulants only 139 (4.9) 101 (2.6) 240 (3.6) 
  Combination of any of the above 454 (16.1) 455 (11.8) 909 (13.6) 
Maternal comorbidityg    
 Alcohol use disorder 756 (26.8) 1144 (29.6) 2299 (34.3) 
 Nonopioid, nonalcohol SUD 2660 (94.2) 3222 (83.3) 6130 (91.6) 
 HIV and AIDS 176 (6.2) 72 (1.9) 248 (3.7) 
 Hepatitis C virus 259 (9.2) 149 (3.9) 408 (6.1) 
 Mental health conditionh 2643 (93.6) 3511 (90.7) 6154 (91.9) 
 Chronic pain 1911 (67.7) 2683 (69.3) 4594 (68.6) 
 Diabetesi 158 (5.6) 338 (8.7) 496 (7.4) 
 Tobacco dependence related health care record during pregnancyj 2161 (76.5) 2467 (63.8) 4628 (69.1) 
 Reported smoking during pregnancyk 1886 (66.8) 1788 (46.2) 3674 (54.9) 
 Reported quitting smoking before pregnancyk 199 (7.0) 563 (14.6) 762 (11.4) 
 Reported substance use as a risk to pregnancyk 2635 (93.3) 1908 (49.3) 4543 (67.9) 
 Reported alcohol use as a risk to pregnancyk 137 (4.9) 283 (7.3) 420 (6.3) 
 Nonopioid and nonalcohol substance use care record during pregnancyl 2134 (75.6) 1286 (33.4) 3420 (51.10) 

OUD was diagnosed before delivery or during puerperium period. —, not applicable.

a

Opioid agonist treatment engagement during pregnancy and puerperium period, continuing opioid agonist treatment episodes, and new initiation included.

b

Percentages derived from total delivery episodes (denominator).

c

Incarcerated during pregnancy or puerperium period.

d

At least 1 dose during pregnancy or puerperium period; cumulative duration of opioid agonist treatment episodes.

e

First opioid agonist treatment exposure during pregnancy or puerperium period; existing and new initiation of opioid agonist treatment episodes were considered.

f

Benzodiazepine dispensation in pregnancy: median days on opioid agonist treatment: 35 (Q1: 10; Q3: 125); not on opioid agonist treatment: 31 (Q1: 10; Q3: 126); total: 34 (Q1: 10; Q3: 125).

g

Diagnosed before delivery, including the time period before conception.

h

Mental health conditions included anxiety, depression, bipolar disorder, schizophrenia and other psychoses, stress and adjustment disorder, personality disorders, attention-deficit/hyperactivity disorder, and developmental disorder.

i

Gestational or preexisting type 1 or type 2 diabetes.

j

Health care record for tobacco dependence or complications related to tobacco use in hospital, emergency department visit, physician billing, drug dispensation, or perinatal care during pregnancy.

k

Antenatal care provider reported smoking, illicit substance use, prescription drug use, or alcohol use during pregnancy as a risk factor to current pregnancy.

l

Any indication of nonopioid, nonalcohol, substance use in physician visit, hospitalizations, or emergency department visit during pregnancy.

We additionally observed a high prevalence of the following maternal comorbidities diagnosed before delivery: other (nonopioid and nonalcohol) SUD (92%), mental health disorders (92%), and chronic pain (69%). We found a slightly higher prevalence of SUD, HIV, hepatitis C virus, and mental health disorders among women who received opioid agonist treatment in pregnancy, compared with that of women who did not receive opioid agonist treatment in pregnancy (Table 1).

The annual incidence of women with OUD in pregnancy has increased over threefold, from 166 cases identified in 2000–2001 to 513 in 2018–2019 (Fig 1A). We highlight consistently low engagement in opioid agonist treatment during pregnancy throughout the study period. As of 2019, 42% of women with OUD had engaged in opioid agonist treatment during pregnancy from 45% in 2000–2001. Additionally, of the 3162 (48%) of deliveries with no history of previous treatment receipt, only 16% initiated treatment during pregnancy (Fig 1B).

FIGURE 1

Long-term trend of the number of women with (A) OUD in pregnancy and (B) history of opioid agonist treatment engagement in British Columbia, 2000–2001 to 2018–2019. During pregnancy includes the puerperium period (6 weeks after birth). OAT, opioid agonist treatment.

FIGURE 1

Long-term trend of the number of women with (A) OUD in pregnancy and (B) history of opioid agonist treatment engagement in British Columbia, 2000–2001 to 2018–2019. During pregnancy includes the puerperium period (6 weeks after birth). OAT, opioid agonist treatment.

Close modal

We documented that 24% of infants were born preterm, 16% had low birth weight, and 29% of infants had a disorder related to small gestational age or low birth weight. A total of 2496 infants (37%) were born with NAS (Table 2).

TABLE 2

Maternal Health Care Use and Perinatal Outcomes Among Women With OUD in Pregnancy in British Columbia from 2000–2001 to 2018–2019

Maternal Factors and Perinatal OutcomesOpioid Agonist TreatmentaNo Opioid Agonist TreatmentTotal
Maternal health care use,b deliveries, N 2824 3869 6693 
 Hospitalization, n (%)    
  None 2162 (76.6) 2626 (67.9) 4788 (71.5) 
  1–3 629 (22.3) 1139 (29.4) 1768 (26.4) 
  >3 33 (1.2) 104 (2.7) 137 (2.0) 
 Emergency department admission, n (%)    
  None 2182 (77.3) 3129 (80.9) 5311 (79.4) 
  1–3 464 (16.4) 519 (13.4) 983 (14.7) 
  >3 178 (6.3) 221 (5.7) 399 (6.0) 
 Physician billing records, median (Q1 and Q3) 45 (13 and 72) 13 (5 and 24) 18 (7 and 47) 
 Nonopioid agonist treatment drug dispensation days, median (Q1 and Q3) 219 (46 and 560) 160 (19 and 471) 181 (30 and 512) 
 Chronic disease score,c median (Q1 and Q3) 2.4 (1.7 and 3.2) 1.9 (1.2 and 2.8) 2.1 (1.2 and 3.0) 
Pain management in labor,dn (%)    
 None 266 (9.4) 404 (10.4) 670 (10.0) 
 Narcotic 628 (22.2) 1247 (32.2) 1875 (28.0) 
 Epidural 1225 (43.4) 1366 (35.3) 2591 (38.7) 
 Entonox 1231 (43.6) 1594 (41.2) 2825 (42.2) 
 Other anestheticse 1095 (38.8) 1567 (40.5) 2662 (39.7) 
 Prescription opioid after deliveryf 446 (15.8) 945 (24.4) 1391 (20.8) 
Perinatal outcomes    
 Pregnancy and/or childbirth complications for maternal drug use, n (%) 859 (30.4) 292 (7.5) 1151 (17.2) 
 Preeclampsia, n (%) 80 (2.8) 102 (2.6) 182 (2.7) 
 Length of hospital stay, delivery, median (Q1 and Q3) 3.6 (2.1 and 9.8) 2.4 (1.4 and 4.7) 3.1 (1.9 and 5.8) 
  Vaginal delivery 4.2 (2.2 and 11.9) 2.0 (1.4 and 3.1) 2.5 (1.5 and 5.2) 
  Cesarean delivery 5.3 (3.5 and 13.0) 3.3 (2.6 and 4.7) 4.0 (3.0 and 6.4) 
Postnatal outcomes, births, N 2854 3932 6786 
 Gestational age, median (Q1 and Q3) 38 (36 and 39) 38 (37 and 39) 38 (37 and 39) 
 Birth head circumference,g,h cm, n (%)    
  Small, below third percentile 453 (15.9) 411 (10.5) 864 (12.7) 
  Large, >97th percentile 59 (2.1) 193 (4.9) 252 (3.7) 
 Birth length,i cm, n (%)    
  Small, below third percentile 546 (19.1) 485 (12.3) 1031 (15.2) 
  Large, >97th percentile 112 (3.9) 369 (9.4) 481 (7.1) 
 Apgar score in 5 min, n (%)    
  Low (0–3) 86 (3.0) 113 (2.9) 199 (3.0) 
  Moderately abnormal (4–6) 135 (4.7) 120 (3.1) 255 (3.8) 
  Reassuring (7–10) 2633 (92.3) 3699 (94.1) 6332 (93.3) 
 Preterm birth (<37 wk), n (%) 805 (28.2) 836 (21.3) 1641 (24.2) 
 Moderate to late preterm (32–36 wk), n (%) 676 (23.7) 701 (17.8) 1377 (20.3) 
 Very preterm (31–28 wk), n (%) 73 (2.6) 83 (2.1) 156 (2.3) 
 Extreme prematurity (<28 wk), n (%) 56 (2) 52 (1.3) 108 (1.6) 
 Low birth wt    
  <1000 g 51 (1.8) 60 (1.5) 111 (1.6) 
  1000–2499 g 531 (18.6) 462 (11.7) 993 (14.6) 
 Intrauterine growth restriction and/or SGA, n (%) 221 (3.3) 165 (2.4) 388 (5.7) 
 Disorder related to small gestational age or low birth wt,in (%) 1061 (15.6) 888 (13.1) 1949 (28.7) 
 NAS,jn (%) 1966 (29) 530 (7.8) 2496 (36.8) 
 Fetus/newborn affected by maternal use of alcohol, n (%) 9 (0.1) 23 (0.3) 32 (0.5) 
 Fetus/newborn affected by maternal use of drug of addiction, n (%) 827 (12.2) 515 (7.6) 1342 (19.8) 
 Congenital and chromosomal anomalies, n (%) 503 (7.4) 534 (7.9) 1037 (15.3) 
 Length of hospital stay,k median, d (Q1 and Q3) 18.2 (6.2 and 32.5) 2.8 (1.5 and 6.7) 5.3 (2.1 and 20.5) 
  Preterm infants, n (%) 24.6 (13.8 and 38.2) 10.6 (3.3 and 22.6) 17.2 (5.8 and 32.6) 
  Term infants, n (%) 15.0 (5.2 and 30.0) 2.3 (1.4 and 4.1) 3.8 (1.9 and 14.6) 
 Initiated breastfeeding at hospital during newborn episode of care,ln (%) 1747 (61.2) 2966 (75.4) 4713 (69.5) 
 Stillbirth, n (%) 25 (0.01) 41 (0.01) 66 (1.0) 
 Infant death,in (%) 55 (1.9) 79 (2.0) 134 (2.0) 
Maternal Factors and Perinatal OutcomesOpioid Agonist TreatmentaNo Opioid Agonist TreatmentTotal
Maternal health care use,b deliveries, N 2824 3869 6693 
 Hospitalization, n (%)    
  None 2162 (76.6) 2626 (67.9) 4788 (71.5) 
  1–3 629 (22.3) 1139 (29.4) 1768 (26.4) 
  >3 33 (1.2) 104 (2.7) 137 (2.0) 
 Emergency department admission, n (%)    
  None 2182 (77.3) 3129 (80.9) 5311 (79.4) 
  1–3 464 (16.4) 519 (13.4) 983 (14.7) 
  >3 178 (6.3) 221 (5.7) 399 (6.0) 
 Physician billing records, median (Q1 and Q3) 45 (13 and 72) 13 (5 and 24) 18 (7 and 47) 
 Nonopioid agonist treatment drug dispensation days, median (Q1 and Q3) 219 (46 and 560) 160 (19 and 471) 181 (30 and 512) 
 Chronic disease score,c median (Q1 and Q3) 2.4 (1.7 and 3.2) 1.9 (1.2 and 2.8) 2.1 (1.2 and 3.0) 
Pain management in labor,dn (%)    
 None 266 (9.4) 404 (10.4) 670 (10.0) 
 Narcotic 628 (22.2) 1247 (32.2) 1875 (28.0) 
 Epidural 1225 (43.4) 1366 (35.3) 2591 (38.7) 
 Entonox 1231 (43.6) 1594 (41.2) 2825 (42.2) 
 Other anestheticse 1095 (38.8) 1567 (40.5) 2662 (39.7) 
 Prescription opioid after deliveryf 446 (15.8) 945 (24.4) 1391 (20.8) 
Perinatal outcomes    
 Pregnancy and/or childbirth complications for maternal drug use, n (%) 859 (30.4) 292 (7.5) 1151 (17.2) 
 Preeclampsia, n (%) 80 (2.8) 102 (2.6) 182 (2.7) 
 Length of hospital stay, delivery, median (Q1 and Q3) 3.6 (2.1 and 9.8) 2.4 (1.4 and 4.7) 3.1 (1.9 and 5.8) 
  Vaginal delivery 4.2 (2.2 and 11.9) 2.0 (1.4 and 3.1) 2.5 (1.5 and 5.2) 
  Cesarean delivery 5.3 (3.5 and 13.0) 3.3 (2.6 and 4.7) 4.0 (3.0 and 6.4) 
Postnatal outcomes, births, N 2854 3932 6786 
 Gestational age, median (Q1 and Q3) 38 (36 and 39) 38 (37 and 39) 38 (37 and 39) 
 Birth head circumference,g,h cm, n (%)    
  Small, below third percentile 453 (15.9) 411 (10.5) 864 (12.7) 
  Large, >97th percentile 59 (2.1) 193 (4.9) 252 (3.7) 
 Birth length,i cm, n (%)    
  Small, below third percentile 546 (19.1) 485 (12.3) 1031 (15.2) 
  Large, >97th percentile 112 (3.9) 369 (9.4) 481 (7.1) 
 Apgar score in 5 min, n (%)    
  Low (0–3) 86 (3.0) 113 (2.9) 199 (3.0) 
  Moderately abnormal (4–6) 135 (4.7) 120 (3.1) 255 (3.8) 
  Reassuring (7–10) 2633 (92.3) 3699 (94.1) 6332 (93.3) 
 Preterm birth (<37 wk), n (%) 805 (28.2) 836 (21.3) 1641 (24.2) 
 Moderate to late preterm (32–36 wk), n (%) 676 (23.7) 701 (17.8) 1377 (20.3) 
 Very preterm (31–28 wk), n (%) 73 (2.6) 83 (2.1) 156 (2.3) 
 Extreme prematurity (<28 wk), n (%) 56 (2) 52 (1.3) 108 (1.6) 
 Low birth wt    
  <1000 g 51 (1.8) 60 (1.5) 111 (1.6) 
  1000–2499 g 531 (18.6) 462 (11.7) 993 (14.6) 
 Intrauterine growth restriction and/or SGA, n (%) 221 (3.3) 165 (2.4) 388 (5.7) 
 Disorder related to small gestational age or low birth wt,in (%) 1061 (15.6) 888 (13.1) 1949 (28.7) 
 NAS,jn (%) 1966 (29) 530 (7.8) 2496 (36.8) 
 Fetus/newborn affected by maternal use of alcohol, n (%) 9 (0.1) 23 (0.3) 32 (0.5) 
 Fetus/newborn affected by maternal use of drug of addiction, n (%) 827 (12.2) 515 (7.6) 1342 (19.8) 
 Congenital and chromosomal anomalies, n (%) 503 (7.4) 534 (7.9) 1037 (15.3) 
 Length of hospital stay,k median, d (Q1 and Q3) 18.2 (6.2 and 32.5) 2.8 (1.5 and 6.7) 5.3 (2.1 and 20.5) 
  Preterm infants, n (%) 24.6 (13.8 and 38.2) 10.6 (3.3 and 22.6) 17.2 (5.8 and 32.6) 
  Term infants, n (%) 15.0 (5.2 and 30.0) 2.3 (1.4 and 4.1) 3.8 (1.9 and 14.6) 
 Initiated breastfeeding at hospital during newborn episode of care,ln (%) 1747 (61.2) 2966 (75.4) 4713 (69.5) 
 Stillbirth, n (%) 25 (0.01) 41 (0.01) 66 (1.0) 
 Infant death,in (%) 55 (1.9) 79 (2.0) 134 (2.0) 
a

Opioid agonist treatment engagement during pregnancy and puerperium period, continuing opioid agonist treatment episodes, and new initiation included.

b

In the past 12 mo before date of conception calculated by using gestational age.

c

Chronic disease score from Clark et al31  based on age, sex, and prescription drug dispensation in the year before conception calculated by using gestational age.

d

Mother received one or more anesthetics/analgesics during labor (first, second, or third stage).

e

General, spinal, pudendal, or unknown anesthetics, transcutaneous electric nerve stimulation, sterile water injections, Tylenol, Talwin, and intrathecal injections.

f

Prescription opioid drug dispensation between delivery and puerperium period.

g

Reflects brain size and is used for screening for potential developmental, nutritional, or health problems.

h

Below third percentile: significantly smaller than average for the age and sex of an infant; >97th percentile: significantly larger than average for age and sex in Canada.

i

Includes outcome occurred within 1-y of age among all live and stillbirth.

j

ICD-9 code 779.5 (World Health Organization) and ICD-10 code P96.1 (Canada) in perinatal, hospitalization, physician visit, emergency department visit, or death records within 3 mo of birth.

k

Length of newborn episode of care and consecutive infant transfer episodes occurred within 24 h of newborn episode discharge.

l

Exclusive or partial breastfeeding was initiated before newborn was discharged from the hospital.

Annual incidence rates of preterm birth, low birth weight, NAS, and other perinatal outcomes associated with perinatal OUD are illustrated in Fig 2. Incidence of preterm birth, disorders related to gestational age or low birth weight, and NAS among mothers with OUD have increased since 2000 by 26%, 30%, and 3%, respectively, whereas low birth weight decreased by 10%, as of 2019. Among mothers with OUD, as of 2019, we reported incidence rates of low birth weight (179 per 1000 live births), preterm birth (287 per 1000) and disorders related to small gestational age or low birth weight (319 per 1000).

FIGURE 2

Annual incidence rate of birth outcomes among women with OUD in pregnancy in British Columbia from 2000–2001 to 2018–2019. The number of live births between 2000–2001 and 2018–2019 is 6720.

FIGURE 2

Annual incidence rate of birth outcomes among women with OUD in pregnancy in British Columbia from 2000–2001 to 2018–2019. The number of live births between 2000–2001 and 2018–2019 is 6720.

Close modal

A total of 2173 women received at least 1 opioid agonist treatment dispensation during pregnancy (Table 1). Among these women, those with a previous history of treatment (whose last treatment episode ended over a year before conception) had a higher odds of preterm birth (adjusted odds ratio: 2.2 [95% confidence interval: 1.5–3.4]) and higher odds of delivering infants with disorders related to SGA or low birth weight (adjusted odds ratio: 1.5 [95% confidence interval: 1.1–2.2]), compared with that of women with no history of opioid agonist treatment before conception (Table 3). Receipt of buprenorphine-naloxone or SROM during pregnancy (compared with methadone) was associated with a lower odds of preterm delivery (adjusted odds ratio: 0.6 [95% confidence interval: 0.3–0.9]) and delivering infants with disorders related to SGA or low birth weight (adjusted odds ratio: 0.6 [95% confidence interval: 0.4–0.9]), and NAS (adjusted odds ratio: 0.6 [95% confidence interval: 0.4–0.9]).

TABLE 3

Clinical Factors Associated With Birth Outcomes Among Women on Opioid Agonist Treatment in Pregnancy in British Columbia from 2000–2001 to 2018–2019

CovariatescPreterm BirthLow Birth WtDisorder Related to Small Gestational Age or Low Birth WtaNASb
aOR (95% CI)PaOR (95% CI)PaOR (95% CI)PaOR (95% CI)P
First OUD diagnosis (reference: during pregnancy or puerperium period)         
 1 y before conception 0.8 (0.5–1.2) .30 2.4 (0.8–7.5) .12 0.7 (0.5–1.0) .07 0.8 (0.6–1.2) .31 
 1–5 y before conception 1.1 (0.8–1.5) .60 1.5 (0.6–3.8) .43 0.8 (0.6–1.1) .13 1.0 (0.7–1.3) .75 
 >5 y before conception 1.3 (1.0–1.8) .09 1.4 (0.5–4.1) .52 1.0 (0.7–1.3) .87 1.1 (0.9–1.5) .33 
Opioid agonist treatment exposure-related covariates         
 Opioid agonist treatment engagement before pregnancyd (reference: no opioid agonist treatment before initiation in pregnancy)         
  Latest receipt ≤12 mo before conception 1.1 (0.9–1.5) .38 1.9 (0.8–4.3) .14 0.9 (0.7–1.1) .27 1.0 (0.8–1.2) .78 
  Latest receipt >12 mo before conception 2.2 (1.5–3.4) <.001 1.9 (0.6–6.6) .29 1.5 (1.1–2.2) .03 1.3 (0.8–1.9) .26 
Opioid agonist treatment engagement during pregnancy         
 Type of opioid agonist treatment (Reference: methadone)         
  Buprenorphine/naloxone or SROM 0.6 (0.3–0.9) .03 0.4 (0.1–2.2) .29 0.6 (0.4–0.9) .02 0.6 (0.4–0.9) .01 
 Opioid agonist treatment receipt in third trimester (reference: no opioid agonist treatment receipt in third trimestere        
  Continued opioid agonist treatment episode during delivery 0.6 (0.4–0.8) <.001 0.4 (0.2–0.7) .01 0.8 (0.6–0.9) .04 4.7 (3.6–6.1) <.001 
  Discontinued opioid agonist treatment episode in third trimester (before delivery) 0.4 (0.3–0.7) .002 0.1 (0.1–0.7) .02 0.5 (0.3–0.8) .01 1.4 (0.9–2.1) .11 
 Duration of last opioid agonist treatment episode in third trimester (reference: no opioid agonist treatment receipt in third trimestere        
  ≤30 d 1.3 (1.0–1.9) .09 1.0 (0.4–2.3) .94 1.2 (0.9–1.7) .18 3.8 (2.8–5.2) <.001 
  >30 d 0.4 (0.3–0.6) <.001 0.2 (0.1–0.5) <.001 0.7 (0.5–0.8) .001 4.4 (3.3–5.7) <.001 
 Opioid agonist treatment dose in third trimester (reference: no opioid agonist treatment receipt in third trimestere        
  Consistently low 0.4 (0.3–0.6) <.001 0.3 (0.1–1.1) .08 0.5 (0.4–0.7) <.001 2.1 (1.6–2.8) <.001 
  Consistently medium 0.5 (0.4–0.7) <.001 0.3 (0.1–0.9) .04 0.7 (0.5–0.9) .01 4.5 (3.3–6.2) <.001 
  Consistently high 0.8 (0.6–1.1) .20 0.6 (0.2–1.9) .37 1.1 (0.8–1.4) .72 5.1 (3.7–7.0) <.001 
  Increased (low to medium, low to high, or medium to high)f 0.4 (0.2–0.8) .01 0.7 (0.1–4.0) .64 0.6 (0.4–1.1) .09 3.0 (1.9–4.9) <.001 
  Decreased (high to medium, high to low, or medium to low)g 0.5 (0.3–0.7) <.001 0.2 (0.1–0.8) .02 0.8 (0.6–1.2) .31 8.1 (5.5–11.9) <.001 
  Flexible dosing 0.5 (0.3–0.7) .001 0.2 (0.1–0.8) .02 0.5 (0.4–0.8) .001 5.1 (3.5–7.5) <.001 
CovariatescPreterm BirthLow Birth WtDisorder Related to Small Gestational Age or Low Birth WtaNASb
aOR (95% CI)PaOR (95% CI)PaOR (95% CI)PaOR (95% CI)P
First OUD diagnosis (reference: during pregnancy or puerperium period)         
 1 y before conception 0.8 (0.5–1.2) .30 2.4 (0.8–7.5) .12 0.7 (0.5–1.0) .07 0.8 (0.6–1.2) .31 
 1–5 y before conception 1.1 (0.8–1.5) .60 1.5 (0.6–3.8) .43 0.8 (0.6–1.1) .13 1.0 (0.7–1.3) .75 
 >5 y before conception 1.3 (1.0–1.8) .09 1.4 (0.5–4.1) .52 1.0 (0.7–1.3) .87 1.1 (0.9–1.5) .33 
Opioid agonist treatment exposure-related covariates         
 Opioid agonist treatment engagement before pregnancyd (reference: no opioid agonist treatment before initiation in pregnancy)         
  Latest receipt ≤12 mo before conception 1.1 (0.9–1.5) .38 1.9 (0.8–4.3) .14 0.9 (0.7–1.1) .27 1.0 (0.8–1.2) .78 
  Latest receipt >12 mo before conception 2.2 (1.5–3.4) <.001 1.9 (0.6–6.6) .29 1.5 (1.1–2.2) .03 1.3 (0.8–1.9) .26 
Opioid agonist treatment engagement during pregnancy         
 Type of opioid agonist treatment (Reference: methadone)         
  Buprenorphine/naloxone or SROM 0.6 (0.3–0.9) .03 0.4 (0.1–2.2) .29 0.6 (0.4–0.9) .02 0.6 (0.4–0.9) .01 
 Opioid agonist treatment receipt in third trimester (reference: no opioid agonist treatment receipt in third trimestere        
  Continued opioid agonist treatment episode during delivery 0.6 (0.4–0.8) <.001 0.4 (0.2–0.7) .01 0.8 (0.6–0.9) .04 4.7 (3.6–6.1) <.001 
  Discontinued opioid agonist treatment episode in third trimester (before delivery) 0.4 (0.3–0.7) .002 0.1 (0.1–0.7) .02 0.5 (0.3–0.8) .01 1.4 (0.9–2.1) .11 
 Duration of last opioid agonist treatment episode in third trimester (reference: no opioid agonist treatment receipt in third trimestere        
  ≤30 d 1.3 (1.0–1.9) .09 1.0 (0.4–2.3) .94 1.2 (0.9–1.7) .18 3.8 (2.8–5.2) <.001 
  >30 d 0.4 (0.3–0.6) <.001 0.2 (0.1–0.5) <.001 0.7 (0.5–0.8) .001 4.4 (3.3–5.7) <.001 
 Opioid agonist treatment dose in third trimester (reference: no opioid agonist treatment receipt in third trimestere        
  Consistently low 0.4 (0.3–0.6) <.001 0.3 (0.1–1.1) .08 0.5 (0.4–0.7) <.001 2.1 (1.6–2.8) <.001 
  Consistently medium 0.5 (0.4–0.7) <.001 0.3 (0.1–0.9) .04 0.7 (0.5–0.9) .01 4.5 (3.3–6.2) <.001 
  Consistently high 0.8 (0.6–1.1) .20 0.6 (0.2–1.9) .37 1.1 (0.8–1.4) .72 5.1 (3.7–7.0) <.001 
  Increased (low to medium, low to high, or medium to high)f 0.4 (0.2–0.8) .01 0.7 (0.1–4.0) .64 0.6 (0.4–1.1) .09 3.0 (1.9–4.9) <.001 
  Decreased (high to medium, high to low, or medium to low)g 0.5 (0.3–0.7) <.001 0.2 (0.1–0.8) .02 0.8 (0.6–1.2) .31 8.1 (5.5–11.9) <.001 
  Flexible dosing 0.5 (0.3–0.7) .001 0.2 (0.1–0.8) .02 0.5 (0.4–0.8) .001 5.1 (3.5–7.5) <.001 

aOR, adjusted odds ratio; CI, confidence interval.

a

Identified before age of 12 mo.

b

ICD-9 code 779.5 (World Health Organization), ICD-10 code P96.1 (Canada) in perinatal, hospitalization, physician visit, emergency department visit, or death records within 3 mo of birth.

c

Because of multicollinearity among the opioid agonist treatment exposure variables for each outcome, we fit 6 separate logistic regression models for each of the 6 sets of covariates characterizing opioid agonist treatment receipt while adjusting for maternal age, parity, receipt of psychotropic medications or nonopioid agonist treatment opioid analgesics in pregnancy, in addition to alcohol use, other nonopioid, nonalcohol substance use, and smoking during pregnancy. See Supplemental Tables 711 for full results on each individual regression model.

d

Opioid agonist treatment receipt in the time period before conception calculated from gestational age.

e

Women with receipt of any opioid agonist treatment in pregnancy before third trimester.

f

Indication of daily dose increased to a higher category at least once, with no indication of decrease.

g

Indication of daily dose decreased to a lower category at least once, with no indication of increase.

Continued opioid agonist treatment during delivery (compared with treatment discontinuation before the third trimester) resulted in increased odds of NAS (adjusted odds ratio: 4.7 [95% confidence interval: 3.6–6.1]) but reduced odds of preterm birth (adjusted odds ratio: 0.6 [95% confidence interval: 0.4–0.8]), low birth weight (adjusted odds ratio: 0.4 [95% confidence interval: 0.2–0.7]) and delivering an infant with disorders related to SGA (adjusted odds ratio: 0.8 [95% confidence interval: 0.6– 0.9]). Similarly, women receiving flexible as well as consistently low and medium treatment doses in the third trimester had an increased odds of NAS but reduced odds of preterm birth, low birth weight, and delivering an infant with disorders related to SGA and birth weight (compared with that of women who discontinued treatment before the third trimester).

Among women who received opioid agonist treatment in pregnancy, coprescription of SSRIs, benzodiazepines, antipsychotics, or stimulants increased odds of preterm birth (adjusted odds ratio: 1.6 [95% confidence interval: 1.2–2.1]) and disorders related to SGA or low birth weight (adjusted odds ratio: 1.4 [95% confidence interval: 1.1–1.8]) after adjusting for treatment duration (Supplemental Tables 811). Other nonopioid, nonalcohol substance use in pregnancy was associated with increased odds of adverse outcomes (Supplemental Tables 813); however, we did not find any independent association of smoking during pregnancy with any of the outcomes.

This report is among the largest and most extensive population-level studies on the association of opioid agonist treatment with birth outcomes. Since 2001, we observed an increase of >200% in the incidence of perinatal OUD in the province. Additionally, among women with OUD in pregnancy, we reported increases of 26% in the incidence of preterm birth and 30% in the incidence of infant disorders related to gestational age and birth weight over the study period. We found that continued opioid agonist treatment engagement to delivery was associated with a reduced odds of several adverse birth outcomes including preterm birth and infant disorders related to gestational age and birth weight; however, as of 2019, nearly 60% of deliveries with maternal OUD did not receive opioid agonist treatment during pregnancy.

With our finding that buprenorphine was associated with a reduced odds of NAS and preterm birth compared with methadone, we corroborate findings from a previous longitudinal cohort study (N = 716)26  and randomized controlled trial (N = 175).15  Furthermore, although we reported fewer adverse outcomes among women receiving flexible as well as low and medium doses of opioid agonist treatment compared with that of women not engaged in treatment in the third trimester, we note that the effect of split dosing regimens should be investigated in future work because there is evidence for lower rates of treatment of NAS with multiple daily dose regimens for methadone compared with single daily dosing.43  Comprehensive comparative effectiveness analyses to account for durations of exposure, dosing regimens, timing of treatment initiation as well as newer forms of opioid agonist treatment are additionally warranted.23,41 

Most importantly however, although our results implicate an increase in NAS with longer durations of opioid agonist treatment exposure, they importantly highlight improved neonatal outcomes and reduced odds of several adverse birth outcomes with a duration of opioid agonist treatment of at least 30 days and for continued engagement to delivery (particularly for buprenorphine-naloxone), presenting key implications for treatment discontinuation.

Our findings have otherwise illustrated a concerningly high prevalence of comorbidities including other (nonopioid) SUDs, mental health disorders, and chronic pain, highlighting key areas of need for integrated care. Over 90% of women in the study population were diagnosed with a mental health disorder before delivery, and we reported 37% were prescribed psychotropic medications during pregnancy. This difference may be explained by the range of mental health conditions included and severity and length of illness as well as clinical guidelines recommending minimized use of psychotropic medications in pregnancy among women with concurrent opioid agonist treatment.41,44  Although psychotropic medications are mainly intended for short-term use,45  we found the median days of dispensation for benzodiazepines to be 34 days. Furthermore, we found that, among women receiving opioid agonist treatment in pregnancy, the use of psychotropic medications was associated with an increased odds of preterm birth and infant disorders related to SGA or low birth weight, signaling key target areas for further research to inform perinatal care for OUD.

For many women with OUD, opioid agonist treatment may not be accessible or desirable. Awareness of safety and use of opioid agonist treatment,44,46  stigma, discrimination, and fear of child services involvement are strong barriers for women to disclose substance use in pregnancy and access addictions treatment.47  There may be a personal desire for abstinence or clinical reasons for opioid agonist treatment not being an appropriate treatment option.41,48  Additionally, many rural and remote regions in British Columbia (as well as other settings) face limited health care resources for addictions treatment and integrated services.49,50 

While the current study provides novel data on the effects of specific factors in the pharmacologic treatment of OUD on maternal and infant outcomes, nonpharmacologic interventions for mother and infant togetherness are additionally important postpartum care standards that support maternal health and long-term child development.7,41,5153 

This study is reported with several limitations. First, we note the potential for interphysician differences related to the diagnosis as well as the clinical presentation of NAS, possible overreporting of NAS diagnoses among women receiving opioid agonist treatment, and possible missed cases of NAS diagnoses among women who did not receive opioid agonist treatment during pregnancy. Second, the PharmaNet database did not include medication dispensations during hospitalization; therefore, NAS case identification did not include receipt of pharmacologic treatment. Third, the study did not include data on drug use severity, which we proxied with measures of time since first OUD diagnosis and history of opioid agonist treatment exposure. Also, although we found no association between smoking during pregnancy and any of the study outcomes for women who received opioid agonist treatment in pregnancy, we did not capture the timing or frequency of maternal smoking. Finally, we did not have data on additional social and environmental factors, which may influence these key outcomes, such as maternal education, socioeconomic status, nutrition, housing instability, and experiences of trauma and violence.5456  Furthermore, it is possible that the buprenorphine/naloxone and methadone comparison may have been confounded by indication and severity of OUD and note the challenges of retention in buprenorphine for women with severe OUD. Nonetheless, this study is among the most comprehensive investigations on the topic conducted to date, offering longitudinal treatment data and physician diagnoses from multiple provincial data sets with individual level linkage, which is rarely found in existing literature.

This study provides key data on the incidence of perinatal OUD and relevant birth outcomes in British Columbia, in addition to opioid agonist treatment engagement and its beneficial effects in pregnancy. The incidence of perinatal OUD has more than tripled in incidence over the past 2 decades, whereas high rates of preterm birth and NAS have persisted among women with OUD. Our findings underscore the need for further research on the effects of medications received in pregnancy, in addition to expanded integrated care services for women with OUD and their children.

FUNDING: Supported by a Health Canada Substance Use and Addictions Program (award 1819-HQ-000036). The funding source was independent of the design of this study and did not have any role during its execution, analyses, interpretation of the data, writing, or decision to submit results.

Ms Piske assisted with conceptualization, conducted literature reviews, wrote the first draft of the article, and revised the manuscript; Ms Homayra assisted with conceptualization, conducted analyses, wrote key methodologic components of the article, and reviewed and provided critical revisions to the manuscript; Ms Min and Mr Zhou assisted with data cleaning, assisted with key methodologic components of the article, and reviewed and provided critical revisions to the manuscript; Drs Marchand, Mead, Ng, and Woolner consulted and advised on key clinical aspects and reviewed and provided critical revisions to the manuscript; Dr Nosyk conceptualized and secured funding for the study and reviewed and provided critical revisions to the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

All inferences, opinions, and conclusions drawn in this study are those of the authors, and do not reflect the opinions or policies of the Data Steward(s).

Deidentified individual data will not be made available. Statistical code available on request: bnosyk@sfu.ca.

     
  • ICD-9

    International Classifications of Diseases, Ninth Revision

  •  
  • ICD-10

    International Classifications of Diseases, 10th Revision

  •  
  • NAS

    neonatal abstinence syndrome

  •  
  • OUD

    opioid use disorder

  •  
  • PSBC

    Perinatal Services British Columbia

  •  
  • SGA

    small for gestational age

  •  
  • SROM

    slow-release oral morphine

  •  
  • SUD

    substance use disorder

  •  
  • SSRI

    selective serotonin reuptake inhibitors

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Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURES: The authors have indicated they have no financial relationships relevant to this article to disclose.

Supplementary data