Trends and Characteristics of Opioid Use During Pregnancy Between 2010 and 2023: A French Nationwide Drug Utilization Study

ABSTRACT

Background

While opioid use during pregnancy has raised concerns worldwide, population‐based data in Europe remain limited. In France, little is known about opioid use in the context of pregnancy.

Methods

We conducted a nationwide drug utilization study using the French EPI‐MERES Registry, derived from the National Health Data System (SNDS), including pregnancies ≥ 22 weeks from 2010 to 2023. Exposure to weak and strong opioids was assessed before, during and after pregnancy, and according to calendar years. Exposure characteristics included the number of dispensations, prescriber type and oral morphine equivalents. Maternal sociodemographic and clinical characteristics associated with opioid exposure were analysed using multivariable logistic regression models.

Results

Among 9.9 million pregnancies, 548,881 (5.5%) were exposed to weak opioids and 12,501 (0.13%) to strong opioids. Weak opioid exposure increased sharply until 2016 (+120%) before stabilizing; diverging trends were observed thereafter: codeine exposure declined to 3.6% in 2023, whereas tramadol exposure continued to rise (+170% during study period) reaching 2.5%. Opioid exposure substantially decreased after conception and remained low throughout pregnancy. Weak opioid prescriptions were not refilled across trimesters in 85%–95% of exposed pregnancies. Opioid exposure was positively associated with maternal socioeconomic deprivation, chronic diseases and psychiatric disorders, with stronger associations observed for strong opioids.

Conclusion

In France, opioid use in the context of pregnancy is not infrequent and almost exclusively driven by short‐term use of weak opioids. It is strongly associated with maternal vulnerability and low‐income status. Although overall opioid exposure stabilized since 2016, the continuous rise in tramadol use warrants further monitoring.

Significance

Population‐based evidence on opioid use during pregnancy is scarce in Europe and has been lacking in France. This nationwide study provides the first comprehensive analysis of prescription opioid use in pregnancy in France over a 14‐year period, identifying prescribing patterns and populations most likely to be exposed. After a marked increase at the beginning of the study period, overall opioid exposure is stable. In the most recent years, one in 16 pregnant women is exposed to an opioid, almost exclusively a weak opioid, and we observed a sustained rise in tramadol exposure throughout the study period. These findings establish a benchmark for future surveillance.

1. Introduction

Substantial increases in population‐level opioid use, especially in the U.S. during the opioid crisis over the past decades, have led to significant use of opioid analgesics in pregnant women (Desai et al. 2014). The most prevalent maternal indications requiring opioid treatment during pregnancy, including chronic use, appear to be back pain, abdominal pain, migraine and joint pain (Bateman et al. 2014; Straub et al. 2021). To a lesser extent, previous cesarean delivery may also lead to chronic opioid use in pregnant women (Bateman et al. 2016). In addition, predisposing mental health conditions, such as psychiatric comorbidities or substance abuse disorders, have been shown to increase the likelihood of chronic opioid use (Barry et al. 2016; van Rijswijk et al. 2019).

In the United States between 2000 and 2011, studies indicate that between 14% and 22% of pregnant women received at least one opioid prescription during pregnancy, mainly hydrocodone, codeine and oxycodone (Bateman et al. 2014; Desai et al. 2014). This high prevalence is accompanied by a significant rise in maternal opioid use disorders (+131%) between 2010 and 2017 in the U.S., reaching 8.2 per 1000 deliveries (Hirai et al. 2021).

In Europe, although opioid exposure during pregnancy is overall less prevalent, it is around 5%, ranging from 1.5% in Denmark to 13.2% in Iceland, with high variability between countries and temporal trends (Brett et al. 2025; Engeland et al. 2018; Handal et al. 2011; Irvine et al. 2010; Sujan et al. 2019). In contrast to the U.S., codeine and tramadol are the most prevalent prescription opioids in Europe (Brett et al. 2025). Prescription opioids are also frequently co‐prescribed with other psychotropic medications, leading to concerns about combined psychoactive effects (Brett et al. 2025). In France specifically, since the recall of dextropropoxyphen from the market in 2011, tramadol is the most consumed opioid analgesic just over codeine (Chenaf et al. 2019). Like other opioid analgesics, the use of tramadol and codeine has increased over the last decade in the general population, reaching an annual prevalence in 2017 of 8.4% and 6.8%, respectively (Chenaf et al. 2019).

Finally, opioid use in pregnancy has garnered considerable attention due to potential risks for both mothers and their offspring. Studies have reported positive associations with adverse pregnancy outcomes such as preterm birth (Bosworth et al. 2024; Sujan et al. 2019), major birth defects (Bateman et al. 2021; Brogly et al. 2021; Broussard et al. 2011; Sørensen et al. 2022), or neurodevelopmental disorders (Kang et al. 2024), although these risks are debated in the literature.

To date, no population‐based study has described prescription opioid use specifically among pregnant women in France. The aims of this study were, in the context of pregnancy, (i) to describe temporal trends in prescription opioid use at a national level, including the preconceptional and postpartum periods, (ii) to characterize prescription opioid use and (iii) to assess maternal and pregnancy characteristics associated with opioid use.

2. Methods

2.1. Data Source

This comprehensive population‐based study was performed using the National Mother–Child EPI‐MERES Registry, built by the Epi‐Phare team from the French National Health Data System (Système National des Données de Santé, SNDS). The SNDS, covering 99% of the French population and corresponding to about 66 million inhabitants, contains outpatient (drug and medical consultation reimbursements) and inpatient (hospitalization diagnosis codes) information. Indications for outpatient medications are not available in the database. The EPI‐MERES Registry has been previously described (Miranda et al. 2023). It includes all pregnancy episodes in women aged 12–55 years in the SNDS since 2010 and is enriched through yearly updates with additional pregnancies, newborn and child follow‐up. Pregnancy outcomes include both livebirths and non‐livebirths (stillbirths, ectopic pregnancies, therapeutic abortions, elective abortions and spontaneous abortions). The pregnancy outcome dates are defined as the date of delivery or, for miscarriages and pregnancy terminations, the date of diagnosis or procedure. The pregnancy start date was calculated using gestational age (GA) at the end of pregnancy, or, when missing, the date of the last menstrual period entered by the physician at the end of pregnancy. EPI‐MERES contains a wide set of information on maternal (medical history, sociodemographic characteristics), pregnancies (start and end dates, pregnancy outcome, assisted reproduction, ultrasound scans, gestational diabetes and hypertension) and offspring (birth weight, outpatient and inpatient healthcare use, hospital and long‐term diseases diagnosis) characteristics. Comprehensive information on medication exposure by gestation period is available based on reimbursement data. The EPI‐MERES Registry has been previously used to conduct population‐based studies in drug and pregnancy research (Blangis et al. 2024; Lassalle et al. 2023; Meyer et al. 2022; Rios et al. 2024; Tran et al. 2025).

2.2. Study Population

The study included all pregnancies lasting more than 22 weeks and ending between January 1, 2010, and December 31, 2023, in women aged 15–49 years. Pregnancy outcomes were livebirth, stillbirth (defined by the delivery of a dead foetus after a GA of 22 weeks) and medical termination of pregnancy (termination of pregnancy for maternal health or foetal disease). Because weak opioids are systematically recommended for elective abortion in France (Haute Autorité de Santé 2021), pregnancies ending in elective abortion, as well as pregnancies lasting less than 22 weeks, were excluded from the study. Additionally, pregnancies in women without at least one healthcare reimbursement (medication or other type of reimbursement such as medical consultation) in the SNDS in the 24 months before pregnancy were also excluded.

2.3. Drug Exposure

Drug exposures of interest were prescription opioid marketed in France and used in ambulatory care, categorized as weak opioids (codeine, dihydrocodeine, opium powder and tramadol) or strong opioids (morphine, oxycodone, hydrocodone and fentanyl) according to their relative potency compared with morphine (Svendsen et al. 2012). These drugs, alone or in fixed combination, were identified from the dispensed prescriptions, using specific Anatomical Therapeutic Classification (ATC) codes established by the World Health Organization (Table S1). Dihydrocodeine and codeine were considered similar; codeine‐containing drugs used as cough suppressants were not considered in this study.

For each pregnancy, seven mutually exclusive periods of 90 days were defined: early pre‐conceptional period (T‐2, two trimesters before conception: from the 180th to the 91st day before conception), pre‐conceptional period (T‐1, one trimester before conception: from the 90th day to the day before conception), first trimester of pregnancy (T1, from conception to the 90th day), second trimester of pregnancy (T2, from the 91st to the 180th day after conception), third trimester of pregnancy (T3, from the 181st to the end of pregnancy), early postpartum period (T + 1, one trimester after delivery: from the 1st to the 90th day after delivery), late postpartum period (T + 2, two trimesters after delivery: from the 91st to the 180th day after delivery). During each of these trimesters, women were considered exposed if at least one opioid prescription was dispensed between the first and the last day of the trimester. The number of dispensed prescriptions for each trimester of interest was also characterized. Characteristics of opioid prescriptions such as the type of first prescriber and the place of first prescription during pregnancy were assessed, as well as prescription of non‐opioid analgesics and of psychotropic medications.

Furthermore, to assess population‐level exposure to opioids, we calculated the Oral Morphine EQuivalent (OMEQ), taking into account the total amount of opioid dispensed and the equianalgesic potency of the opioid dispensed relative to oral morphine, such as ‘dose of substance (mg) * quantity of units (e.g., number of pills) per reimbursement * equianalgesic conversion factor’ (Nielsen et al. 2016; Svendsen et al. 2011). For this, the quantity (mg) of opioid contained in each drug box was assessed according to the number of tablets in each drug box using reference codes related to each type of packaging (Table S2). OMEQ was expressed as ‘OMEQ per day’, averaged over the duration of each trimester of interest.

2.4. Maternal and Pregnancy Characteristics

Available maternal characteristics included: age at pregnancy start; level of financial resources defined by the solidarity‐based complementary health insurance affiliation (C2S, free healthcare insurance granted to individuals with low income) and allowances received by salaried employees during maternity leave (Blangis et al. 2024); socio‐economic deprivation index related to the place of residence, expressed in quintiles (Rey et al. 2009); history of miscarriage, delivery or surgery during the year before pregnancy; maternal chronic disease (respiratory chronic diseases—including asthma and chronic obstructive pulmonary disease, any systemic inflammatory diseases, psoriasis, inflammatory bowel diseases, ankylosing spondylitis, rheumatoid arthritis, lupus, arterial hypertension, Type 2 diabetes, Type 1 diabetes, epilepsy), psychiatric chronic disorders (depression, bipolar disorder, smoking‐related disorders, history of addiction), active or recent cancer; pain‐related conditions; number of hospitalizations (at least one night stay) during the year before pregnancy; and number of pregnancy‐related or unrelated hospitalizations (at least one night stay) during pregnancy (Table S3). These maternal and pregnancy‐related characteristics were assessed according to opioid exposure anytime during pregnancy, overall and according to the type of opioid.

2.5. Statistical Analysis

Categorical variables were described as absolute numbers (percentages) and continuous variables as means (SD). Maternal and pregnancy‐related characteristics were described according to opioid exposure. Crude numbers and percentages of exposed pregnancies were assessed overall, according to the type of opioid and to the timing of pregnancy (before, during, after), for the whole study period and by predefined calendar subperiods (2010–2013, 2014–2016, 2017–2019, 2020–2023). Multivariate logistic regression analyses were conducted to assess the associations between maternal and pregnancy‐related characteristics, and opioid exposure. Maternal and pregnancy‐related characteristics with a p‐value < 0.1 in the univariate analyses were included in the multivariate models. Crude and adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated. The unit of analysis was the pregnancy, and a woman could account for more than one pregnancy.

The year‐over‐year growth rates of opioid exposure were calculated, as well as the average percentage change (APC) for each calendar subperiods, as follows: $\frac{1}{n}\sum _{i=1}^n\left(\frac{V_i-V_{i-1}}{V_{i-1}}\right)x100$ where $V_i$ is the exposure for the year $i$, $V_{i-1}$ is the exposure for the preceding year, and $n$ is the number of variations between calendar subperiods.

All analyses were performed using SAS Enterprise Guide version 9.4 (SAS Institute, NC, USA) and R software version 4.3.3.

2.6. Ethics

The study was conducted in compliance with the French regulations on accessing and processing of personal data from the SNDS. EPI‐PHARE, a public scientific consortium, has permanent regulatory access to the SNDS database in application of the provisions of Articles R. 1461–12 et seq. of the French Public Health Code and the French Data Protection Authority (CNIL) decision CNIL‐2016‐316. According to regulatory requirements of SNDS data processing, the study was registered on the EPI‐PHARE study register under the reference T‐2024‐11‐499. No individual informed consent is required for studies based on the SNDS. However, general information concerning the SNDS data processing at EPI‐PHARE is available at https://www.epi‐phare.fr/en/regulation‐snds/.

The study followed the reporting recommendations outlined in the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines (Table S4) (von Elm et al. 2008). Study protocol has been registered on the OSF platform under the reference ‘u3dx2’.

3. Results

3.1. Opioid Exposure Overall and According to Pregnancy Trimester

Of 13,937,881 pregnancies in the EPI‐MERES registry during the study period, 9,920,539 were included in the study (Figure 1). Opioid exposure during pregnancy predominantly involved weak opioids (n = 548,881; 5.5%) such as codeine (n = 365,062; 3.7%), tramadol (n = 169,393; 1.7%), and opium powder n whereas strong opioids were used in a minority of pregnancies (n = 12,501; 0.13%) such as morphine (n = 9177; 0.09%), oxycodone (n = 3111; 0.03%) and fentanyl (n = 729; 0.01%).

FIGURE 1.

Flowchart of the study.

Exposure to opioids was stable during the two trimesters before pregnancy and markedly decreased from the first trimester and throughout pregnancy (Figure 2A; Table S5). Codeine exposure decreased from 1.6% during the first trimester to 0.9% during the third trimester of pregnancy. Similarly, tramadol exposure decreased from 1.0% to 0.4% over the course of pregnancy. For all weak opioids, exposure increased after delivery but not fully returned to the preconceptional use. Regarding strong opioids, similar patterns were observed with a decrease in exposure after the start of pregnancy and an increase after delivery (Table S5).

FIGURE 2.

Exposure before, during and after pregnancy for codeine, tramadol and opium powder (A). Whole study period from 2010 to 2023 (B). According to calendar periods. See Table S5 for details and for other types of opioids not presented in the figure due to very low exposure. Postpart, Postpartum; preconcept, Preconceptional.

3.2. Trends Over Time in Opioid Exposure

Between 2010 and 2016, exposure to weak opioids during pregnancy increased by +120% (APC per year 21.6% and 7.0%, in 2010–2013 and 2014–2016, respectively) from 22,379 (2.9%) in 2010 to 45,615 (6.4%) in 2016, before stabilizing afterwards with 37,825 (6.2%) exposed pregnancies in 2023 (Figure 3; Table S6).

FIGURE 3.

Trends of exposure to opioids during pregnancy between 2010 and 2023 at a national level, in France.

Different temporal trends were observed across opioids: exposure to codeine sharply increased by +150% between 2010 and 2016, from 14,027 (1.8%) to 33,030 (4.6%) and declined by −22% thereafter reaching 21,951 (3.6%) in 2023; in contrast, exposure to tramadol steadily increased by +170% over the study period, from 7029 (0.9%) in 2010 to 14,850 (2.5%) in 2023, with positive APC per year throughout, although to a lesser extent at the end of the study period (Table S6). This increasing trend of tramadol exposure was observed for each trimester of pregnancy (Figure 2B; Table S5). For the first postpartum trimester, levels in 2020–2023 slightly exceeded those in the preconceptional period, which was not observed for the other weak opioids. For opium powder, similar to tramadol, exposure consistently increased during the study period by +100% from 2289 (0.3%) exposed pregnancies in 2010 to 3803 (0.6%) in 2023, though it remained much lower than codeine or tramadol.

Regarding strong opioids, although exposure was much lower than for weak opioids, positive APC per year was observed from 2010 to 2016 before stabilization afterwards (Table S7).

During the study period, OMEQ (median, [IQR]) was stable in the preconceptional trimester (1.7 [0.5–3.3] mg/day in 2010–2013 to 1.7 [0.7–4.4] mg/day in 2020–2023), although an increase was observed during the pregnancy trimesters, especially in the third trimester of pregnancy (1.4 [0.6–4.4] mg/day in 2010–2013 to 3.4 [1.1–9.4] mg/day in 2020–2023) (Figure 4; Table S8). An increase in OMEQ through years was similarly observed in the first postpartum trimester, but not in the second postpartum trimester.

FIGURE 4.

Oral Morphine EQuivalent (OMEQ) according to before, during and after pregnancy and to calendar subperiods. See Table S8 for details. Postpart, Postpartum; preconcept, Preconceptional.

3.3. Characteristics of Opioid Prescriptions During Pregnancy

The first opioid prescription during pregnancy mainly originated from an ambulatory setting, regardless of the opioid agent, although variations were observed between opioid agents (Table 1). Prescribers were mostly general practitioners (81.6% and 88.3 for weak and strong opioids, respectively), followed by obstetricians (7.2% and 2.5% for weak and strong opioids, respectively). In 27.9% and 45.8% of the pregnancies exposed to weak and strong opioids, respectively, women were already exposed to an opioid during the preconceptional period. Continuous use throughout the three trimesters of pregnancy remained rare for weak opioids (1.7%) but was substantially higher for strong opioids (17.1%). Opioids were almost systematically used with acetaminophen and infrequently with other non‐opioid analgesics. Co‐medication with psychotropic drugs, likely reflecting underlying maternal conditions, was frequent for weak opioids (14.7%) and for strong opioids (28.6%).

TABLE 1.

Characteristics of the prescriptions of opioid and non‐opioid analgesics, and of other psychotropic drugs, during the whole pregnancy.

	Weak opioids N = 548,881	Codeine N = 365,062	Tramadol N = 169,393	Opium powder N = 50,050	Strong opioids N = 12,501	Morphine N = 9177	Oxycodone N = 3111	Fentanyl N = 729
Opioids
Use of any opioids during preconceptional period	152,967 (27.9)	97,562 (26.7)	53,894 (31.8)	17,283 (34.5)	5726 (45.8)	4001 (43.6)	1550 (49.8)	540 (74.1)
Place of first opioid prescription during pregnancy
Ambulatory	381,990 (69.6)	275,812 (75.6)	89,465 (52.8)	41,260 (82.4)	7942 (63.5)	5844 (63.7)	1854 (59.6)	626 (85.9)
Healthcare facility	166,891 (30.4)	89,250 (24.4)	79,928 (47.2)	8790 (17.6)	4559 (36.5)	3333 (36.3)	1257 (40.4)	103 (14.1)
Type of prescriber for the first opioid prescription during pregnancy (ambulatory only)
General practitioner	311,632 (81.6)	227,894 (82.6)	71,365 (79.8)	32,690 (79.2)	7012 (88.3)	5115 (87.5)	1673 (90.2)	588 (93.9)
Obstetrician gyneacologist	27,522 (7.2)	18,928 (6.9)	6532 (7.3)	3324 (8.1)	201 (2.5)	168 (2.9)	34 (1.8)	2 (0.3)
Surgeon	5320 (1.4)	2576 (0.9)	2184 (2.4)	987 (2.4)	132 (1.7)	96 (1.6)	33 (1.8)	3 (0.5)
Dentist	2006 (0.5)	1464 (0.5)	290 (0.3)	359 (0.9)	4 (0.1)	4 (0.1)	0 (0.0)	0 (0.0)
Rheumatologist	1657 (0.4)	814 (0.3)	706 (0.8)	356 (0.9)	100 (1.3)	78 (1.3)	16 (0.9)	12 (1.9)
Gastroenterologist	1018 (0.3)	524 (0.2)	466 (0.5)	147 (0.4)	75 (0.9)	63 (1.1)	8 (0.4)	6 (1.0)
Other or unknown	32,835 (8.5)	23,612 (8.6)	7922 (8.9)	3397 (8.2)	418 (5.2)	314 (5.3)	87 (4.7)	15 (2.4)
Continuous use during pregnancy (in each trimester)	9111 (1.7)	4609 (1.3)	3278 (1.9)	192 (0.4)	979 (17.1)	550 (6.0)	313 (10.1)	135 (18.5)
Non ‐ opioid analgesics
Acetaminophen (paracetamol)	542,835 (98.9)	364,682 (99.9)	163,704 (96.6)	50,049 (100.0)	11,686 (93.5)	8625 (94.0)	2888 (92.8)	650 (89.2)
Nefopam	12,087 (2.2)	6290 (1.7)	6633 (3.9)	1444 (2.9)	852 (6.8)	643 (7.0)	228 (7.3)	38 (5.2)
Pregabalin	3244 (0.6)	1524 (0.4)	1793 (1.1)	546 (1.1)	447 (3.6)	263 (2.9)	180 (5.8)	66 (9.1)
Gabapentin	973 (0.2)	521 (0.1)	515 (0.3)	154 (0.3)	176 (1.4)	112 (1.2)	71 (2.3)	25 (3.4)
Psychotropic drugs
Psychotropic drugs (any)	80,506 (14.7)	51,197 (14.0)	29,174 (17.2)	9403 (18.8)	3581 (28.6)	2533 (27.6)	982 (31.6)	338 (46.4)
Antidepressants	26,762 (4.9)	16,949 (4.6)	10,232 (6.0)	3126 (6.2)	1657 (13.3)	1134 (12.4)	504 (16.2)	174 (23.9)
Mood‐stabilizing agents	428 (0.1)	264 (0.1)	178 (0.1)	46 (0.1)	23 (0.2)	15 (0.2)	7 (0.2)	2 (0.3)
Aniolytics	60,748 (11.1)	38,748 (10.6)	21,909 (12.9)	7176 (14.3)	2564 (20.5)	1852 (20.2)	664 (21.3)	242 (33.2)
Hypnotics	12,098 (2.2)	7337 (2.0)	5105 (3.0)	1596 (3.2)	719 (5.8)	478 (5.2)	218 (7.0)	96 (13.2)
Antipsychotics	6513 (1.2)	4040 (1.1)	2463 (1.5)	778 (1.6)	314 (2.5)	213 (2.3)	87 (2.8)	43 (5.9)

Note: Hydromorphone prescriptions are not presented in the table due to the very low number of exposed pregnancies (n = 16).

For weak opioids, exposure was mostly based on a single dispensed prescription within the trimester; only 5.8% to 15.0% of exposed pregnancies had prescriptions refilled two or more times during a trimester, depending on the trimester and the type of weak opioid (Figure 5; Table S9). For strong opioids, especially oxycodone and fentanyl, the rate of refilled prescriptions in each trimester ranged from 40.9% to 62.7%.

FIGURE 5.

Number of dispensations in each trimester, before, during and after pregnancy according to the type of opioid. See Table S9 for details. Hydromorphone is not presented in the figure due to the very low number of exposed pregnancies (n = 16). Disp, Dispensation; postpart, Postpartum; preconcept, Preconceptional.

3.4. Maternal and Pregnancy Characteristics Associated With Exposure

Weak opioid exposure was more frequent among women ≥ 40 years (aOR 1.14 [1.12–1.16]) and with a proxy for low income (having the C2S allocation, aOR 1.77, 1.76–1.79) (Table 2). Similar patterns were observed for strong opioid exposure and for any type of opioids, although differences compared to unexposed were more marked for tramadol (Table S10).

TABLE 2.

Maternal and pregnancy characteristics according to opioid exposure during pregnancy.

	Weak opioids			Strong opioids			Unexposed to any opioid
	N = 548,881	Crude OR[95% CI]	aOR[95% CI]	N = 12,501	Crude OR[95% CI]	aOR[95% CI]	N = 9,364,508
Maternal age, years	29.6 (5.6)	—	—	30.4 (5.4)	—	—	29.6 (5.3)
Maternal age, range
< 20	16,438 (3.0)	1.13 [1.11–1.15]	0.79 [0.77–0.80]	208 (1.7)	0.56 [0.49–0.65]	0.36 [0.31–0.41]	256,197 (2.7)
20–29	260,129 (47.4)	1.05 [1.04–1.05]	0.98 [0.97–0.98]	5297 (42.4)	0.84 [0.81–0.87]	0.78 [0.75–0.81]	4,378,101 (46.8)
30–39	250,734 (45.7)	Ref.	Ref.	6392 (51.1)	Ref.	Ref.	4,426,273 (47.3)
40+	21,580 (3.9)	1.25 [1.24–1.27]	1.14 [1.12–1.16]	604 (4.8)	1.38 [1.27–1.50]	1.16 [1.06–1.26]	303,937 (3.2)
Level of financial resources
No C2S and income ≥ median	126,352 (23.0)	Ref.	Ref.	2686 (21.5)	Ref.	Ref.	2,647,767 (28.3)
No C2S and income < median	136,285 (24.8)	1.28 [1.27–1.29]	1.22 [1.21–1.23]	3191 (25.5)	1.41 [1.34–1.48]	1.24 [1.18–1.31]	2,238,079 (23.9)
Allocation C2S	141,431 (25.8)	1.98 [1.96–1.99]	1.77 [1.76–1.79]	2804 (22.4)	1.84 [1.75–1.94]	1.39 [1.31–1.47]	1,500,388 (16.0)
No C2S and no income identified	144,813 (26.4)	1.02 [1.01–1.03]	0.99 [0.98–1.00]	3820 (30.6)	1.26 [1.20–1.33]	1.14 [1.08–1.20]	2,978,274 (31.8)
Socio‐economic deprivation index, quintile
1rst (less deprived)	91,599 (16.9)	Ref.	Ref.	1756 (14.3)	Ref.	Ref.	1,787,965 (19.4)
2nd	101,630 (18.7)	1.10 [1.09–1.11]	1.04 [1.03–1.05]	2485 (20.3)	1.41 [1.32–1.50]	1.30 [1.23–1.39]	1,798,979 (19.5)
3rd	101,975 (18.8)	1.14 [1.13–1.15]	1.02 [1.02–1.03]	2724 (22.2)	1.58 [1.49–1.68]	1.38 [1.30–1.47]	1,752,805 (19.0)
4th	103,711 (19.1)	1.18 [1.17–1.19]	1.03 [1.02–1.04]	2650 (21.6)	1.57 [1.48–1.67]	1.32 [1.24–1.40]	1,714,594 (18.6)
5th (most deprived)	117,288 (21.6)	1.26 [1.25–1.27]	1.01 [1.01–1.02]	2394 (19.5)	1.34 [1.26–1.43]	1.04 [0.98–1.11]	1,813,274 (19.6)
Oversea territories	25,963 (4.8)	1.38 [1.36–1.40]	1.07 [1.05–1.09]	241 (2.0)	0.67 [0.58–0.76]	0.55 [0.48–0.63]	367,263 (4.0)
Maternal health status
Somatic chronic diseases
Having a chronic disease a	64,905 (11.8)	—	—	2261 (18.1)	—	—	656,892 (7.0)
Respiratory chronic diseases	24,670 (4.5)	1.82 [1.80–1.85]	1.51 [1.49–1.53]	877 (7.0)	2.92 [2.73–3.13]	1.82 [1.69–1.95]	235,690 (2.5)
Inflammatory diseases (any)	24,320 (4.4)	—	—	990 (7.9)	—	—	256,489 (2.7)
Psoriasis	15,033 (2.7)	1.41 [1.38–1.43]	1.28 [1.26–1.30]	355 (2.8)	1.46 [1.31–1.62]	1.19 [1.07–1.33]	183,988 (2.0)
Inflammatory bowel diseases	3813 (0.7)	1.56 [1.51–1.61]	1.34 [1.30–1.39]	179 (1.4)	3.24 [2.79–3.76]	1.64 [1.41–1.92]	41,802 (0.4)
Ankylosing spondylitis	3428 (0.6)	4.52 [4.35–4.69]	3.72 [3.57–3.87]	384 (3.1)	22.77 [20.54–25.24]	13.31 [11.80–15.01]	13,014 (0.1)
Rheumatoid arthritis	1725 (0.3)	2.99 [2.84–3.14]	2.06 [1.95–2.18]	104 (0.8)	7.95 [6.55–9.65]	1.75 [1.40–2.20]	9873 (0.1)
Lupus	1194 (0.2)	1.96 [1.85–2.08]	1.42 [1.34–1.51]	61 (0.5)	4.41 [3.42–5.67]	1.67 [1.28–2.18]	10,406 (0.1)
Arterial hypertension	12,059 (2.2)	1.97 [1.93–2.01]	1.62 [1.59–1.66]	400 (3.2)	2.90 [2.63–3.21]	1.72 [1.55–1.91]	105,468 (1.1)
Type 2 diabetes	3862 (0.7)	2.02 [1.95–2.09]	1.23 [1.19–1.27]	97 (0.8)	2.23 [1.83–2.73]	0.71 [0.57–0.87]	32,771 (0.3)
Type 1 diabetes	1834 (0.3)	1.59 [1.51–1.66]	0.86 [0.82–0.90]	61 (0.5)	2.32 [1.80–2.99]	0.45 [0.35–0.59]	19,831 (0.2)
Epilepsy	2435 (0.4)	1.86 [1.79–1.94]	1.28 [1.22–1.33]	111 (0.9)	3.74 [3.10–4.51]	1.27 [1.04–1.54]	22,364 (0.2)
Cancer (active or recent)	4453 (0.8)	1.21 [1.17–1.25]	1.10 [1.06–1.13]	202 (1.6)	2.43 [2.11–2.79]	1.70 [1.47–1.96]	62,910 (0.7)
Psychiatric disorders
Having a psychiatric chronic disorder b	31,796 (5.8)	—	—	1721 (13.8)	—	—	258,022 (2.8)
Depression	13,999 (2.6)	2.43 [2.39–2.48]	1.56 [1.54–1.59]	827 (6.6)	6.89 [6.42–7.40]	2.07 [1.90–2.24]	101,400 (1.1)
Other psychiatric diseases	15,575 (2.8)	1.96 [1.92–1.99]	1.37 [1.34–1.39]	766 (6.1)	4.62 [4.29–4.97]	1.84 [1.70–1.99]	140,178 (1.5)
Bipolar disorder	2222 (0.4)	2.38 [2.28–2.49]	1.40 [1.34–1.47]	128 (1.0)	6.58 [5.52–7.83]	1.30 [1.08–1.57]	16,444 (0.2)
Smoking related disorders	79,431 (14.5)	1.65 [1.64–1.66]	1.40 [1.39–1.41]	2705 (21.6)	2.69 [2.58–2.81]	1.77 [1.69–1.85]	871,465 (9.3)
History of addiction c	11,071 (2.0)	2.08 [2.04–2.12]	1.16 [1.13–1.18]	850 (6.8)	7.36 [6.86–7.89]	2.35 [2.16–2.55]	91,945 (1.0)
Having during the year before pregnancy
Miscarriage or voluntary abortion	33,643 (6.1)	1.15 [1.14–1.17]	1.06 [1.04–1.07]	784 (6.3)	1.18 [1.10–1.27]	0.91 [0.84–0.98]	501,208 (5.4)
Surgery (except delivery)	44,288 (8.1)	1.36 [1.34–1.37]	1.22 [1.20–1.23]	1532 (12.3)	2.16 [2.05–2.28]	1.36 [1.28–1.44]	568,668 (6.1)
Delivery
Vaginal	29,632 (5.4)	Ref.	Ref.	591 (4.7)	Ref.	Ref.	447,228 (4.8)
C‐section	5926 (1.1)	1.17 [1.14–1.21]	1.12 [1.09–1.16]	139 (1.1)	1.38 [1.15–1.66]	1.20 [1.00–1.45]	76,170 (0.8)
Hospitalization
In the year before pregnancy	87,898 (16.0)	1.37 [1.36–1.38]	1.13 [1.12–1.14]	3013 (24.1)	2.28 [2.19–2.37]	1.71 [1.62–1.80]	1,145,803 (12.2)
In pregnancy and related to pregnancy	104,552 (19.0)	1.61 [1.60–1.62]	1.37 [1.36–1.38]	3196 (25.5)	2.35 [2.26–2.45]	1.60 [1.53–1.67]	1194,290 (12.8)
In pregnancy and NOT related to pregnancy	45,592 (8.3)	3.53 [3.49–3.57]	2.84 [2.81–2.88]	3291 (26.3)	13.93 [13.38–14.50]	9.32 [8.92–9.75]	234,220 (2.5)

Note: Crude et adjusted OR compared to unexposed to any opioid. Significant associations are in bold.

^a Any somatic chronic diseases listed in this table, excluding cancer.

^b Any psychiatric disorders, excluding smoking related disorders or history addiction.

^c History of alcohol abuse, opioid abuse or other types of drug addiction.

Weak opioid exposure was associated with several chronic somatic conditions, such as inflammatory bowel disease (aOR 1.34 [1.30–1.39]), ankylosing spondylitis (aOR 3.72 [3.57–3.87]) or hypertension (aOR 1.62 [1.59–1.66]), and with psychiatric disorders, such as depression (aOR 1.56 [1.54–1.59]), bipolar disorder (aOR 1.40 [1.34–1.47]) or other psychiatric disorders (aOR 1.37 [1.34–1.39]) (Tables 2 and S11). For strong opioid exposure, most of the associations were more pronounced, the strongest being for ankylosing spondylitis (aOR 13.31 [11.80–15.01]), history of addiction (aOR 2.35 [2.16–2.55]), depression (aOR 2.07 [1.90–2.24]), respiratory chronic diseases (aOR 1.82 [1.69–1.95]) and rheumatoid arthritis (aOR 1.75 [1.40–2.20]) (Tables 2 and S12).

Healthcare use was consistently higher in exposed groups, including prior surgery, prior delivery by C‐section, hospitalization before pregnancy and pregnancy‐related hospitalization. The strongest association was observed for non–pregnancy‐related hospitalization during pregnancy for both weak opioids (aOR 2.84 [2.81–2.88]), notably regarding tramadol (aOR 4.41 [4.34–4.48]) and strong opioids (aOR 9.32 [8.92–9.75]).

4. Discussion

This nationwide study found that opioid use during pregnancy in France is predominantly driven by weak opioids, with strong opioid use remaining rare. Overall prevalence of exposure to weak opioid remained roughly stable since 2016 at about 6% of pregnancies. Prescribing patterns shifted among weak opioids: codeine use declined whereas tramadol use increased steadily, by +170% over the study period, to reach 2.5% of pregnancies in 2023. Opioid use during pregnancy is mostly short‐term, as most prescriptions are not refilled subsequently within each trimester and is strongly associated with maternal chronic diseases and psychiatric disorders.

Over the last decades, major changes have occurred in pain management, with a widespread use of opioids in non‐cancer pain, which has led to the dramatic opioid epidemic in North America (Brett et al. 2025). In pregnant women in the U.S., prevalence of exposure was reported to be up to 20% of pregnancies in 2010 and has decreased since then, as observed in several countries in recent years (Brett et al. 2025). Although use in pregnancy has been documented in several countries including in Europe, the type of prescribed opioids may differ according to national practices. For instance in the U.S., the most frequently used prescription opioids in pregnant women are codeine and hydrocodone, although strong opioids such as oxycodone were also substantial (Brett et al. 2025). In our study, we found that codeine and tramadol were the two most prevalent opioids before, during and after pregnancy. Since 2016, a shift in exposure trends has occurred with a decrease in codeine use while tramadol use continued to increase. This change might be a ripple effect of the contra‐indication of codeine in breastfeeding women and children under 12 in 2015 by the European Medicines Agency, as well as reclassification of codeine to prescription‐only status in France since 2017 (EMA 2015; Ministere de la Sante 2017).

Our study found that opioid use in pregnancy primarily involves weak opioids and declines sharply from the first trimester, regardless of opioid type, continuing throughout pregnancy. Additionally, about 85%–95% of weak opioid prescriptions were not subsequently refilled each trimester, suggesting short‐term use in pregnancy as well as in preconceptional and postpartum periods, consistent with previous studies from Norway and the U.S. (Handal et al. 2011; Bateman et al. 2014). However, while hydrocodone, codeine and oxycodone are the most used opioids in pregnant women in the U.S., our study found that the most common opioids are tramadol and codeine in this population in France. It also shows exposure levels that are lower—6.2% in 2023—than those observed in the U.S.—10.3% in 2018 in publicly insured population (Brett et al. 2025). Nevertheless, in our study, a different trend was observed for tramadol, with exposure increasing markedly over the study period during pregnancy, especially during the third trimester. Further research is needed to identify risk factors for repeated use during pregnancy and for this tramadol‐driven increase in OMEQ. In contrast to weak opioids, our findings suggest that long‐term use is substantially more common for oxycodone and fentanyl, affecting approximately half of the users.

Our study highlights the high prevalence of socio‐economic deprivation among women using opioids during pregnancy, as well as its association with maternal morbidities and psychiatric disorders. Higher opioid use in pregnant women from most deprived areas has also been found in a Canadian study (Corsi et al. 2020). Similarly to our findings, a study from the U.S. found that women with prescribed opioids were more likely than those not prescribed opioids to have depression, anxiety disorder and to smoking‐related disorders (Patrick et al. 2015). Associations with mental health conditions, including non‐opioid substance use disorder has been reported with opioid use in pregnancy in a Swedish study (Sujan et al. 2019). It is important to note that these associations may be bidirectional or influenced by complex causal pathways, as socioeconomic deprivation and psychiatric disorders can both contribute to and result from opioid use, making interpretation of causality challenging. Finally, except for low‐income status, determinants of opioid use in pregnant women in our study were mostly similar to those in the general population and reflect prescribing of opioids in France (Chenaf et al. 2019).

This study was based on the National Mother–Child EPI‐MERES Registry, which contains comprehensive information on dispensed prescriptions, patients and pregnancies characteristics covering nearly 10 million pregnancies, that is, almost all pregnancies lasting more than 22 weeks occurring in France from 2010 to 2023. Thus, the findings offer a detailed picture of opioid use in the context of pregnancy at the national level and its evolution over a 14‐year period. As such, this study provides important insights in a context of opioid crisis in North America, which also affects pregnant women (Hirai et al. 2021) and the growing use of opioids worldwide. Despite these strengths, this study has some limitations. First, opioid exposure is based on dispensed prescriptions, which may not accurately reflect actual drug ingestion. Moreover, our database precludes identifying the indication for opioid prescription and only indirect inferences using proxies can be made. However, certain pain conditions have been estimated during hospitalizations (Table S13), with similar patterns to those observed in a large U.S. study, identifying back pain as the most commonly associated condition before other pain conditions such as abdominal pain, migraine, joint pain and fibromyalgia (Bateman et al. 2014). Furthermore, in our study, women exposed during pregnancy have more frequent history of hospitalization and surgical procedures in the year before pregnancy, which might indicate reasons for opioid prescription. Second, opioids administered during hospital stays could not be captured. However, except for the delivery stay, hospitalization during pregnancy is not common, as confirmed by our findings, and this is not likely to have significantly underestimated opioid exposure in this study. Third, this study concerned pregnancies lasting more than 22 weeks and did not include elective terminations of pregnancy. A preliminary analysis found that 31.7% of these (803,803 over 2,532,442 during the study period) were exposed to a weak opioid, with a first prescription within the 2 weeks before pregnancy outcome for 90% of them, highlighting a probable use in the context of abortion (Ferrer et al. 2025; Haute Autorité de Santé 2021).

To conclude, although strong opioid use during pregnancy appears rare in France, weak opioid use is not infrequent, with tramadol use steadily increasing over the study period. Exposure is strongly associated with low‐income status and maternal vulnerability. Continued monitoring of opioid use during pregnancy is warranted given the growing concerns regarding the risks of prenatal opioid exposure for the foetus and the mother.

Author Contributions

L.C., S.M., R.D.‐S.: conceptualization and methodology. P.H., H.J.: data curation. L.C.: data analysis. L.C.: writing draft of the manuscript; R.D.‐S., M.Z.: critically review the manuscript. All authors reviewed and approved the final version of the manuscript.

Funding

L.C., hosted at EPI‐PHARE for the realization of this study, was funded by Assistance Publique—Hopitaux de Paris for this study as part of the call for proposals ‘PH Recherche Clinique 2023’. The funder has no role in the conception, the conduct, or the reporting of this study.

Ethics Statement

The study was conducted in compliance with the French regulations on access and processing of personal data from the SNDS. EPI‐PHARE, a public scientific consortium, has permanent regulatory access to the SNDS database in application of the provisions of Articles R. 1461–12 et seq. of the French Public Health Code and the French Data Protection Authority (CNIL) decision CNIL‐2016‐316. According to regulatory requirements of SNDS data processing, the study was registered on the EPI‐PHARE study register under the reference T‐2024‐11‐499. No individual informed consent is required for studies based on the SNDS. However, general information concerning the SNDS data processing at EPI‐PHARE is available at https://www.epi‐phare.fr/en/regulation‐snds/.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Table S1: Types of opioid analysed in the study and related codes.

Table S2: Oral Morphine EQuivalent (OMEQ) conversion table.

Table S3: Codes used to identify medical events, medical history and nonopioid exposures.

Table S4: STROBE checklist.

Table S5: Exposure to opioids before, during and after pregnancy.

Table S6: Evolution of exposure to WEAK opioids during pregnancy, between 2010 and 2023 at a national level, in France.

Table S7: Evolution of exposure to STRONG opioids during pregnancy, between 2010 and 2023 at a national level, in France.

Table S8: Oral Morphine EQquivalent (OMEQ) in mg/day according to each trimester and calendar period.

Table S9: Number of opioid dispensations per trimester.

Table S10: Maternal and pregnancy characteristics according to different types of opioid exposure during pregnancy.

Table S11: Crude et adjusted odds‐ratios for WEAK opioid exposure during pregnancy compared to unexposed to any opioid.

Table S12: Crude et adjusted odds‐ratios for STRONG opioid exposure during pregnancy compared to unexposed to any opioid.

Table S13: Pain‐related conditions identified through inhospital diagnosis codes in the 5 years previous and during pregnancy.

Data Availability Statement

The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database. Consultation by the editorial board or interested researchers may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations. All requests for access must be submitted to the Health data hub. Further information to do this request is available on these websites: https://www.snds.gouv.fr/SNDS/Processus‐D‐acces‐aux‐donnees. https://documentation‐snds.health‐data‐hub.fr/introduction/03‐acces‐snds.html#les‐acces‐sur‐projet.