Complex patterns of concomitant medication use: A study among Norwegian women using paracetamol during pregnancy

Abstract

BackgroundStudies on medication safety in pregnancy often rely on an oversimplification of medication use into exposed or non-exposed, without considering intensity and timing of use in pregnancy, or concomitant medication use. This study uses paracetamol in pregnancy as the motivating example to introduce a method of clustering medication exposures longitudinally throughout pregnancy. The aim of this study was to use hierarchical cluster analysis (HCA) to better identify clusters of medication exposure throughout pregnancy.MethodsData from the Norwegian Mother and Child Cohort Study was used to identify subclasses of women using paracetamol during pregnancy. HCA with customized distance measure was used to identify clusters of medication exposures in pregnancy among children at 18 months.ResultsThe pregnancies in the study (N = 9 778) were grouped in 5 different clusters depending on their medication exposure profile throughout pregnancy.ConclusionUsing HCA, we identified and described profiles of women exposed to different medications in combination with paracetamol during pregnancy. Identifying these clusters allows researchers to define exposure in ways that better reflects real-world medication usage patterns. This method could be extended to other medications and used as pre-analysis for identifying risks associated with different profiles of exposure.

The French Pregnancy Cohort: Medication use during pregnancy in the French population

“…In the FPC, 91.1% of women took medications in the year before their pregnancy, which is one of the highest prevalence of exposure worldwide [3–5, 14] ( Table 1 , Fig 6 ); women filled on average 10.8 prescriptions (SD 9.6) during this time-window ( Table 1 ). Once the pregnancy was diagnosed, the prevalence of exposure varied between trimesters, 76.4% in the first trimester, 81.1% in the second, and 88.6% in the third ( Table 1 , Fig 6 ); the mean number of filled prescriptions also decreased (3–4 on average) during the gestational period ( Table 1 ).…”

“…The FPC showed that 89.9% of pregnant women had an on-going medication prescription during gestation. Although there is inter-country variation in the prevalence of medication exposure during gestation (86% The Netherlands, 96% Germany, 74%–100% in other French regional cohorts, 68%–100% USA, 46%–100% Finland, 44% Denmark, 56.6% in Quebec) [3–5, 14, 27], partly explained by cultural differences, lifestyles, drug reimbursement plans, definitions of drug exposure within studies, or maternal age or other maternal characteristics, it remains that the FPC highlights the extent of medication exposure during pregnancy in France. Nevertheless, FPC’s prevalence of gestational exposure to medications is comparable to other French cohorts or pregnant women.…”

“…Data from the population-based Quebec Pregnancy Cohort (QPC) has shown that 56% of pregnant women have an on-going medication prescription during gestation [3]. Other estimates have been calculated in The Netherlands (86%) [4], and Norway (61%) [5]. In France however, surveys have suggested that 74%-100% of pregnant women take medications during gestation [6–9].…”

“…Given the limited information on the use of medications during pregnancy at a population level in France; the fact that some medications, such as antidepressants, benzodiazepines and vitamins, are more widely used in France than in other countries; and the fact that some medications are only marketed/used in the French population, it is essential to fully assess prevalence, and trends of drug use during pregnancy in order to have a significant impact on short- and long-term outcomes in this population. In other countries, it has been reported that women using medications during gestation are at an increased risk of induced/planned and spontaneous abortions, prematurity, multiplicity, and post-partum depression [3–5]. Determinants of medication use at the beginning of pregnancy include older maternal age, being on welfare, visiting multiple physicians, and having a history of diabetes, hypertension, depression or asthma [3].…”

Protocol of a prospective and multicentre China Teratology Birth Cohort (CTBC): association of maternal drug exposure during pregnancy with adverse pregnancy outcomes

“…Since the thalidomide disaster occurred in the 1960 s, people have paid increasing attention to the medication safety during pregnancy [ 1 , 2 ]. Drug exposure during pregnancy may cause adverse pregnancy outcomes, including birth defects, spontaneous abortion, foetal growth restriction, stillbirth, premature birth and low birth weight [ 3 – 5 ]. It is estimated that 2–3 % of birth defects are due to drug exposure during pregnancy [ 6 ].…”