Dispensing of Potentially Harmful Prescription Drugs in 1.8 Million Pregnant Women in France: A Nationwide Study Based on Two Risk Classification Systems

Abstract

Introduction: Nationwide prevalence of potentially harmful drug prescribing during pregnancy is unknown in France, and several risk classification systems (RCS) exist to guide prescribers.

Objective: The aim of this study was to estimate the nationwide prevalence of potentially harmful drug prescribing during pregnancy in France and to describe maternal characteristics associated with this prescription.

Methods: This drug utilisation study, conducted on the French health databases (67 million beneficiaries), included all pregnancies beginning in 2016-2017, regardless of pregnancy outcome. Potentially harmful drug prescribing was defined as at least one reimbursement during pregnancy of Swedish RCS category D drugs, Australian RCS category D/X drugs, or contraindicated drugs in France for drugs not listed in these two RCSs. Maternal characteristics associated with potentially harmful drug prescribing were described using a univariate logistic regression analysis.

Results: Among the 1,844,447 pregnant women identified, the prevalence of potentially harmful drug prescribing was higher according to the Australian RCS (3.9%) than according to the Swedish RCS (2.2%), with good agreement between the two RCSs (Kappa = 0.81 [0.74-0.87]). This prevalence increased to 9.2% and 6.9%, respectively, when considering contraindications in France. Prescribing of teratogenic drugs, including retinoids and valproate, was highest during the first trimester, whereas prescribing of foetotoxic drugs decreased after the first trimester but remained high for nonsteroidal anti-inflammatory drugs (N = 10,021). In women with no chronic diseases, polymedication (five or more drugs) was the strongest maternal characteristic associated with potentially harmful drug prescribing in both RCSs.

Conclusions: Potentially harmful drug prescribing during pregnancy is not uncommon in France. This study supports the comparative analysis of RCS to assess potentially harmful drug prescribing in claims databases.

Fig. 1

Flowchart: definition of the study population and classification of ATC codes according to the two classification systems. Solid lines correspond to the definition of the study population, while dotted lines refer to the attribution of risk categories to ATC classes prescribed to pregnant women exposed to at least one drug during pregnancy. ^aHydatidiform mole or other abnormal products of conception. ^bExcluding homeopathic medicines. ^cFifth-level ATC classes. ^dNine ATC classes corresponding to drug combinations (A02AD01, A06AD10, B01AC30, B05BA10, B05XA31, C03EA01, N01BB52, S01CA01 and S01XA20) are classified in both groups: the Swedish risk category was only applied to French products composed of the same molecules. ^eATC class B02BD02 is classified in both groups, as all types of coagulation factor VIII are listed in the Australian classification system except for turoctocog alfa and human coagulation factor VIII. ^fNumbers do not add up because some ATC classes were assigned different risk categories due, in particular, to the existence of different routes of administration for the same ATC class, corresponding to different risk categories (e.g., tobramycin for inhalation classified as B3, and tobramycin for injection classified as D; see ESM Table 4 for other reasons). ATC anatomical therapeutic chemical, SmPC summary of product characteristics