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Ethnic differences in
drug utilization pattern during
pregnancy: a cross-sectional study
Journal:
The Journal of Maternal-Fetal & Neonatal Medicine
Manuscript ID:
DJMF-2012-0075
Manuscript Type:
Original Paper
Date Submitted by the Author:
29-Jan-2012
Complete List of Authors:
Baraka, Mohamed; Vrije Universiteit Brussel, Pharmacology (FARC)
Steurbaut, Stephane; UZ Brussel and Faculty of Medicine and Pharmacy,
Vrije Universiteit Brussel, Clinical Pharmacology and Pharmacotherapy
Coomans, Danny; Faculty of Medicine and Pharmacy, Vrije Universiteit
Brussel, Biomedical Statistics and Informatics
Dupont, Alain; UZ Brussel and Faculty of Medicine and Pharmacy, Vrije
Universiteit Brussel, Clinical Pharmacology and Pharmacotherapy
Keywords:
Drug utilization, medication, pregnancy, ethnicity, Arab women
URL: http://mc.manuscriptcentral.com/djmf Email: direnzo@unipg.it
The Journal of Maternal-Fetal & Neonatal Medicine
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1
Ethnic differences in drug utilization pattern during
pregnancy: a cross-sectional study
M A Baraka
1*
, S Steurbaut
2
, D Coomans
3
and A G Dupont
2
1
Department of Pharmacology. Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103,
Belgium.
2
Department of Clinical Pharmacology and Pharmacotherapy, UZ Brussel and Faculty of Medicine and Pharmacy,
Vrije Universiteit Brussel, Laarbeeklaan 101, Belgium.
3
Department of Biostatistics and Medical Informatics, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel,
Laarbeeklaan 103, Belgium.
*Corresponding author: Mohamed Abdelhamid Mohamed Baraka
Tel.: +32 488251065; fax: +32-2-4774113
Address: Laarbeeklaan, 103 B-1090 Jette, Brussels, Belgium.
E-mail address: Mohamed.Baraka2020@gmail.com
Running title: Drug exposure in multi-ethnic pregnant women
Key words: Drug utilization, medication, pregnancy, ethnicity, Arab women.
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Abstract
Objective to investigate differences in exposure to medications in a cohort of multi-ethnic pregnant women.
Methods 641 pregnant women of Western, Arab/Turkish and “other origins” participated in this cross-sectional
study using a questionnaire in a university hospital in Brussels, Belgium. Assessment of the drug safety was done
using the food and drug administration (FDA) risk classification system. Data analysis was performed using SPSS.
Results In overall cohort, 83.8% used at least one preparation (including multivitamins) during pregnancy and
37.0% of women used at least one drug (excluding multivitamins). Significantly more Western women (43.7%) used
one or more medications compared to Arab/Turkish women (28.7%;p=0.000). This difference in exposure was most
pronounced for over-the-counter drugs for occasional and pregnancy-related complaints, and was observed for
potentially unsafe drugs or drugs with unknown safety. None of the women reported use of FDA X category drugs.
Conclusions The use of drugs known to be harmful was not observed but a higher prevalence of exposure to
potentially harmful drugs (FDA C/D) was found among Western women who also consumed more over-the-counter
drugs. This highlights the need for cautious prescribing for women in the fertile age in general and for continuous
monitoring of medication use during pregnancy.
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Introduction
Prescribing medications for pregnant women is a challenge for healthcare providers especially since the thalidomide
disaster in the 1960s [1,2]. The use of medications during pregnancy indeed poses a potential risk to both the mother
and the foetus. Despite the lack of evidence on the safety of many medications during pregnancy, many studies have
reported high percentages of drug use during pregnancy [3-5]. Data on medication use during pregnancy appear to
differ between countries due to differences in ethnicity, socio-cultural differences, methods of data collection and
differences in study design [4,6,7]. Drug exposure during pregnancy can also be influenced by the pregnancy stage
and the indication of use (chronic, occasional or pregnancy-related conditions) [7]. Assessment of medication use in
multi-ethnic pregnant women in Europe, where immigration is continuously increasing, has not been given much
attention so far [4]. Therefore, the aims of this study were to investigate possible differences in exposure to
medications (including contraceptives and multivitamins) in a cohort of multi-ethnic pregnant women. We
investigated the pattern of medication use before and during pregnancy in relation to the type of medicines, the
reason for their use and their risk to the foetus. Moreover, we also focused in particular on assessing possible
differences in these patterns of use between Western and immigrant Arab and Turkish women, i.e. the largest non-
Western ethnicity in Belgium and a group of women that has not often been studied.
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Methods
This cross-sectional study was conducted between February and September 2009 in the obstetrics outpatient clinic of
the UZ Brussel, a university hospital and main medical referral centre in Brussels attracting a multi-ethnic
population. After giving written informed consent, the participants completed a questionnaire that was available in
four languages (Dutch, French, English and Arabic) to collect information on ethnicity and details of medication use
before and during pregnancy (including multivitamins and contraceptives). Regardless of age or ethnicity, women
were eligible to participate in the study if they spoke any of the four languages of the questionnaire and had enough
waiting time (around 15 minutes). Among the pregnant women visiting the obstetrics clinic, a random sample of 641
women was invited for participation in the study that was approved by the local Ethical Committee. To maximize the
amount of information collected, women were interviewed in the 2
nd
or the 3
rd
trimester of pregnancy.
Women were classified into three groups according to ethnical origin (Table 1): “Western” (European, Australian
and North American), “Arab/Turkish” (including women originating from all Arab regions and Turkey), and women
from “Other origins” (Asian, African and South American).
All medications (except contraceptives and multivitamins) were classified into three mutually exclusive categories
according to the reason for their use (Table 2): (1) drugs for chronic conditions, (2) drugs for occasional and short-
time use and (3) drugs for pregnancy-related symptoms. Drugs were also classified according to the Anatomical
Therapeutic Chemical (ATC) coding system (WHO ATC) [8], as well as according to the FDA risk classification (A,
B, C, D and X) [9]. Category A: controlled studies show no risk; category B: no evidence of risk in humans; category
C: risk can not be ruled out; category D: positive evidence of risk and category X: contraindicated in pregnancy.
Drugs labelled as A or B and C or D were combined together in two categories for statistical analysis purposes.
Drugs for which no FDA information was available about safety were assigned as U (unknown safety).
The exposure to drugs was investigated per trimester after excluding multivitamins and contraceptives. Trimesters
were defined as: 1
st
trimester (0-14 weeks of gestation), 2
nd
trimester (15-28 weeks) and 3
rd
trimester (29-42 weeks).
Drugs used in more than one trimester were counted in each trimester separately, e.g., drug use that started in the 1
st
trimester and extended to the 2
nd
trimester was considered as exposure in the 1
st
as well as in the 2
nd
trimester.
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Data analysis
The prevalence of the use of contraceptives (analysed separately), medications (with and without multivitamins;
prescription and non-prescription drugs) and multivitamins was determined for the total study population.
Subsequently, differences in these prevalences among the three ethnic subgroups were analyzed using χ
2
tests.
ANOVA test with post hoc Bonferroni correction was used to compare the mean number of medications used among
the three ethnic groups. The percentage of women exposed to certain drug categories was calculated and compared
for the three ethnic groups using the significance test for comparing two proportions that is available online at:
http://math.uc.edu/~brycw/classes/149/wang.htm [10]. Spearman correlation was performed to investigate the
correlation between the exposures to the different drug categories. The level of statistical significance was set as p-
value < 0.05. Data analysis was performed using SPSS (IBM-SPSS v19). The total number of patients differs
according to the availability of data with regard to the different variables analyzed each time.
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Results
Characteristics of the study populations
Of the 641 participants, 334 (52.1%) were Western, 209 (32.6%) Arab/Turkish and 98 (15.3%) were women from
“Other origins”. Women were interviewed once, either in the 2
nd
(244 or 38.1%) or in the 3
rd
trimester (397 or
61.9%), with almost the same distribution mentioned above for each ethnic group within each trimester. The age of
the women ranged from 16 to 48 years with a mean of 30 years. No significant difference was observed in age
categories among the three ethnic groups (p = 0.172: Table 1). A higher percentage of multiparous women was
observed among Arab/Turkish women (75.9%) compared to Western women (50.6%) as shown in Table 1.
Table I to be inserted here.
Patterns of contraceptive use
As shown in Table 1, 295 out of 636 women (46.4%) reported contraceptive use before pregnancy: 181 (61.4%) used
oral contraceptives, 46 (15.6%) used other contraceptive methods such as intrauterine devices (IUDs), implants or
transdermal delivery systems, and 68 (23.0%) women did not report which contraceptive method they used.
Contraception use was continued in 33 women after conception with 21 of them exposed to estrogen/progesterone
based oral contraception. Overall, the use of contraceptives was significantly (p = 0.000) different among the three
ethnic groups. The difference was, however, only significant between the Western (51.8%) and the “Other origins”
group (21.6%). Among the 227 women who reported which kind of contraceptive method they used, Arab/Turkish
women used contraceptive pills (89.5%) more often than Western women (75.6%; p = 0.029). Continuation of
contraceptive use after conception was less prevalent in Western women than in the two other ethnic groups (p =
0.000, Table 1).
Medication use before and during pregnancy
A total of 537 (83.8%) women used at least one preparation (including multivitamins) during pregnancy, and the
total number of preparations used was 1133. After exclusion of multivitamins, more than one third of women (237;
37.0%) used a total of 374 drugs, whereas 505 (78.8%) women used a total of 759 multivitamin preparations. Less
than half (167; 44.6%) of these medications were prescription drugs and 205 (54.8%) over the counter (OTC) drugs.
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About a quarter of the drugs were for chronic use (103; 27.5%), about half were drugs for occasional use (192;
51.3%) and the remaining drugs were for pregnancy related use (78; 20.9%). Only 104 (16.2%) women reported no
use of any medication at all during pregnancy. Two drugs could not be assigned as either prescription or OTC
because women did not report the medication names and, for the same reason, 1 drug could not be classified as being
for chronic, occasional or pregnancy related use.
Table II to be inserted here.
Drug use according to ATC classification
Of the 374 medications used by women, 88 (23.5%) were drugs for the alimentary tract and metabolism including
insulin (A), 81 (21.7%) for the nervous system (N), 68 (18.2%) for the respiratory system (R), 40 (10.7%) anti-
infectives for systemic use (J), 26 (7.0%) systemic hormones excluding sex hormones and insulin (H), 19 (5.1%)
drugs for blood and blood forming organs (B), 17 (4.5%) cardiovascular drugs (C), 15 (4.0%) genitourinary drugs
and sex hormones (G), 12 (3.2%) dermatologicals (D), 6 (1.6%) drugs for sensory organs and 2 (0.5%) drugs for the
musculo-skeletal system (M).
Drug use according to FDA risk classification
Half of the drugs used (86; 49.7%) were classified as safe or reasonably safe (A + B), 95 (25.4%) were potentially
harmful (C + D), and no use (0.0%) of harmful drugs (X) was reported. A quarter (90; 24.1%) of the drugs had no
FDA classification (unknown safety U) and 3 drugs could not be assigned as their names were not reported.
Drug use according to active molecule
The top 10 drugs used were paracetamol (72; 19.3%), followed by the thyroid hormones (18; 4.8%), metoclopramide
(14; 3.7%), salbutamol (9; 2.4%), amoxicillin (8; 2.1%), ranitidine (8; 2.1%), progesterone (8; 2.1%), antacids (8;
2.1%), domperidone (7; 1.9%) and insulin (7; 1.9%). Most of these drugs are considered to be safe but salbutamol,
progesterone and domperidone are potentially harmful (FDA category C).
Out of 759 multivitamin preparations used by women, the most frequently used were folic acid preparations (499;
65.7%) followed by iron preparations (132; 17.4%) and magnesium preparations (51; 6.7%).
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Correlation between exposures to different drug categories
Exposure to OTC drugs significantly correlated with the exposure to occasionally used drugs (r = 0.419; p = 0.000),
pregnancy-related drugs (r = 0.200; p = 0.002) and drugs with unknown safety (r = 0.252; p = 0.000), whereas
exposure to prescription drugs significantly correlated with the exposure to potentially harmful drugs (r = 0.231; p =
0.000) and drugs for chronic conditions (r = 0.464; p = 0.000).
Evolution of drug use before and during pregnancy
As shown in Table 3, the percentage of women exposed to pregnancy related drugs in the 1
st
trimester was five times
that before conception (p = 0.000); in the 2
nd
trimester it was six times higher (p = 0.000) and in the 3
rd
trimester four
times higher than before pregnancy (p = 0.013). No significant difference was detected in any of the three trimesters
in exposure to chronic or occasionally used drugs compared to the preconception use. However, a significant
reduction of the exposure to occasionally used drugs was observed in the 3
rd
trimester compared to the 2
nd
trimester
exposure (p = 0.043). In addition, a trend to lower use of pregnancy related drugs (p = 0.056) and chronic drugs (p =
0.098) was detected in the 3
rd
trimester compared to the 2
nd
trimester without reaching statistical significance.
A significantly higher percentage of women used OTC drugs in the 2
nd
trimester compared to the preconception
period (p = 0.026). Exposure to prescription drugs was higher in both the 1
st
(p = 0.026) and the 2
nd
trimester (p =
0.001) when compared to preconception exposure, and decreased in the 3
rd
trimester when compared to the 2
nd
trimester (p = 0.006). No significant difference was observed between the three pregnancy trimesters in OTC drug
exposure.
The percentage of women exposed to safe or reasonably safe (A + B) or potentially harmful (C + D) drugs did not
vary significantly in any of the pregnancy trimesters when compared to the preconception exposure. However, the
difference was significant for drugs with unknown safety (U) for the 1
st
(p = 0.005), the 2
nd
(p = 0.000) and the 3
rd
trimester (p = 0.037) when compared with the preconception use. The exposure to these drugs increased significantly
from the 1
st
to the 2
nd
trimester (p = 0.009) and then decreased again by 50% in the 3
rd
trimester (p = 0.008). In
general, the total percentage of women exposed to drugs (excluding multivitamins) was significantly higher in both
the 1
st
and the 2
nd
trimester when compared to the preconception exposure.
Table III to be inserted here.
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Ethnic differences in drug exposure
As shown in Table 1, no significant difference was detected among the three ethnic groups in overall medication use
including multivitamins (p = 0.085) or in multivitamin use alone (p = 0.059). However, a significant difference in the
use of medications among the three groups was found when multivitamins were excluded (p = 0.001). Significantly
more Western women used one or more medications other than multivitamins compared to Arab/Turkish women (p
= 0.000) and “Other origins” women (p = 0.033).
The mean number of medications, including multivitamins, used in the population as a whole was significantly
different among the three groups (p = 0.000; Table 4). Pair wise comparisons revealed that the mean number of
medications in Western women (2.02) was significantly higher than in Arab/Turkish (1.50; p = 0.000) and “Other
origins” women (1.48; p = 0.002). Similarly, Western women used on average more drugs other than multivitamins
(0.72) compared to both Arab/Turkish (0.42; p = 0.000) and “Other origins” women (0.46; p = 0.035). The number
of multivitamins used was also significantly higher in Western women (1.29) compared to both Arab/Turkish (1.09;
p = 0.024) and “Other origins” women (1.02; p = 0.022; Table 4). As for the whole group, pair wise comparisons of
women who took at least one medication revealed a significantly higher mean number of medications including
multivitamins in Western women (2.35) compared to Arab/Turkish (1.79; p = 0.000) and "Other origins" women
(1.93; p = 0.028). However, no significant difference was detected when drug use was studied excluding
multivitamins (p = 0.200). Multivitamin use differed significantly among the different ethnic user groups (p = 0.034)
but statistical significance was not reached when pair wise analyses between the three groups were performed.
Table IV to be inserted here.
There were also differences between the ethnic groups when the exposure to medications was investigated in
function of the medication category. As shown in table 5, the percentage of women exposed to chronic drugs was
significantly higher among Western (15.0%) compared to “Other origins” women (6.0%; p = 0.026). The exposure to
pregnancy related drugs was also significantly higher among Western (13.0%) compared to “Other origins” women
(6.0%; p = 0.047). The exposure to occasionally used drugs was significantly higher among Western (26.0%)
compared to Arab/Turkish women (14.0%; p = 0.002). The percentage of women exposed to OTC drugs during
pregnancy was significantly higher among Western women (29.0%) compared to both Arab/Turkish (15.0%; p =
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0.000) and “Other origins” women (18.0%; p = 0.041). No significant difference was observed among the three
ethnic groups in the exposure to prescription drugs, although a trend to more frequent use was observed among
Western women (22.0%) compared to both Arab/Turkish (16.0%; p = 0.058) and “Other origins” women (18.0%; p
= 0.387).
With respect to the safety of the drugs that were used, the percentage of Western women exposed to safe or
reasonably safe (A + B) drugs was significantly higher (28.0%) than that of “Other origins” women (17.0%; p =
0.032). At the same time, significantly more Western women (16.0%) were exposed to potentially unsafe (C + D)
drugs than Arab/Turkish women (7.0%; p = 0.002). Similarly, the percentage of Western women exposed to drugs
with unknown safety (U)
was significantly higher (16.0%) than that of Arab/Turkish women (8.0%; p = 0.004).
Potentially unsafe drugs were mainly anti-asthmatic drugs (salbutamol), corticosteroids (hydrocortisone,
prednisolone, fluticasone and budesonide), codeine, tramadol, miconazole, progesterone, aspirin in low dose as an
antithrombotic agent and in high dose as an analgesic (one woman), nervous system drugs (citalopram, paroxetine
and lorazepam), insulin analogues, domperidone, omeprazole and sulfasalazine. Drugs with an unknown safety
profile were mainly for acid related disorders (alginic acid as well as calcium, magnesium and aluminum based
combinations), laxatives (macrogol, ispaghula and others), antihistaminics (ketotifen, ebastine and dimetindene),
cough suppressants, nasal preparations, diosmin, zopiclone and cinchocaine.
Table V to be inserted here.
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Discussion
The present study demonstrates a high prevalence of medication use throughout pregnancy when the total study
population is considered. More than 80% of women used at least one medication (including multivitamins). This is
similar to the results of a register-based study reported by Bakker et al (2006) and an interview-based study reported
by Kebede et al (2009), who found a prevalence of medication use including multivitamins of 79% and 71.3%,
respectively [7,11]. As in other studies, multivitamins, iron and folic acid preparations were the most frequently used
multivitamin preparations [11,12].
Our finding that 37% of the pregnant women used medications other than multivitamins are also comparable to those
of other studies conducted in Glasgow and Ethiopia who reported a drug use excluding multivitamins of 34.8% and
34.1%, respectively [11,13]. The mean number of medications including multivitamins used by our study population
as a whole (1.77) was concordant with other studies reporting a mean number of 1 to 3 medications [14,15]. Our
study showed that 16.2% of the women reported no use of any medication at all, which is similar to the percentage
found by the European Collaborative Group on Drug Use in Pregnancy who reported that 14% of women did not
take any drug [16].
The most frequently used classes of medications were analgesics followed by antibacterials, antacids, asthma
medications and drugs for gastrointestinal disorders (antispasmodic and antiemetic drugs). This is in line with other
studies also reporting that anti-infectives and analgesics are the most commonly used medications after
multivitamins [11,17,18].
More than half of the drugs used by the pregnant women were OTC drugs. Correlations between exposures to
different drug categories suggest that most of these OTC drugs were for occasional and pregnancy-related use. The
analysis further suggests that OTC drugs are often drugs with unknown safety, whereas the exposure to prescription
drugs was more often associated with potentially harmful drugs that were used for chronic conditions.
The use of contraceptive pills prior to pregnancy was extended to the 1
st
trimester in a considerable number of
women before they recognized they were pregnant. This puts the foetus at a high risk due to the hormonal content of
these pills. Most women do not realize they are pregnant until the 3
rd
week after conception [7].
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As can be expected, pregnancy-related drug use was significantly higher in all trimesters compared to the
preconception use despite a slight decline in the 3
rd
trimester. Such decline was also observed by Pinto Pereira et al
(2010) and may be due to a decrease of the frequency of pregnancy-related complaints in the 3
rd
trimester and/or
women becoming more tolerant to these complaints in this trimester [5]. Our results indicate that the higher use of
drugs during pregnancy compared to the preconception phase is solely due to the increased use in pregnancy- related
medications, which is in line with the observation of Bakker et al (2006) [7]. OTC drugs were more frequently used
in the 2
nd
trimester compared to the preconception period but the pattern of use was not significantly different
between the three trimesters.
Although it is well accepted that rational and safe drug use during pregnancy is essential for maternal health and
foetal development [5], the present study indicates that a considerable number of pregnant women were exposed to
potentially harmful drugs.
While the exposure to these drugs may have been unavoidable and justified in a number of cases, e.g. because being
prescribed for chronic conditions, this was certainly not always the case. Aspirin for example, a drug known to be
associated with potential foetal harm, was given to a woman as an analgesic/antipyretic, whereas paracetamol could
have been used as a safer alternative. As reported by Wen et al (2008), asthma drugs such as salbutamol were also
frequently used by our study population [19]. It is important to control asthma during pregnancy but salbutamol is
known to be associated with an increased risk of congenital malformations [20]. Instead, alternative beta-agonists
such as salmeterol, formoterol, or inhaled corticosteroids such as beclomethasone and budesonide are more
acceptable for asthma therapy in pregnancy [21]. Domperidone was also one of the top 10 drugs used in our study
and has not been classified by the FDA risk classification system. It was used occasionally by many women as an
anti-emetic despite the availability of safer alternatives (FDA category B) such as metoclopramide [9]. Our
observations are in line with a study conducted in the Netherlands reporting that 1.7% of chronically used and 2.3%
of occasionally used drugs were harmful [7]. The zero prevalence of exposure to category X drugs in our study is a
reassuring finding when compared to other studies that reported percentages ranging from 0.2 to 3.9% of exposure to
proven harmful drugs during pregnancy [11,18,19,22]. However, many women were exposed to drugs without FDA
safety labelling. The absence of safety information may be misleading to both the patient and the physician and
creates a false perception of safety. Indeed, non-classified drugs are not necessarily safe for use during pregnancy
and counselling of women concerning their use during pregnancy may be necessary [12]. In our study, these drugs
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were mainly antacids, laxatives, antihistaminics, cough suppressants, nasal preparations and diosmin, which were
used significantly more during pregnancy compared to preconception. Our results indicate that these drugs with
uncertainty about their safety account for the higher use of OTC drugs and those used for pregnancy-related
disorders. Evaluation of the safety of these commonly used drugs with unknown safety is warranted to help women
and their health providers take informed decisions regarding drug use during pregnancy [2]. Educating patients about
the risks of OTC drugs during pregnancy is necessary to reduce the exposure to drugs with unknown safety.
In Belgium, one study on drug use during pregnancy was conducted more than 30 years ago but the impact of
ethnicity on drug use was not investigated [23]. An important finding of our study is the observation that there are
ethnic differences in the use of certain medications during pregnancy. Contraceptive methods were equally utilized
by Western and Arab/Turkish women, but “Other origins” women were less likely to use contraception.
Arab/Turkish women used oral contraceptives more frequently compared to Western women who used relatively
more often IUDs and transdermal patches. There was also a significantly higher postconception exposure to
contraceptive drugs among Arab/Turkish women and among the “Other origins” women compared to Western
women, possibly related to a higher unawareness of the pregnancy. This highlights the need for preconception care
programs to increase the awareness of women towards the proper use of contraceptive drugs. The exposure to oral
contraceptives early in pregnancy could be due to contraceptive failure resulting in an unintended pregnancy [24].
There was a significant difference in the mean number of drugs used (excluding multivitamins) by the three ethnic
groups in total but this difference disappeared when investigated among users only per ethnic group. This indicates
that the difference in drug use was a reflection of the percentage of women exposed rather than the number of drugs
used by each woman using at least one medication. This was also confirmed by the significant differences in the
percentages of women exposed to the different drug categories according to ethnicity. Western women used more
often OTC drugs and medications for occasional use than Arab/Turkish women, and significantly more Western
women were exposed to potentially unsafe drugs than Arab/Turkish women, as well as to drugs with unknown
safety. The finding that Western women used more frequently drugs during their pregnancy than Arab/Turkish and
"Other origins" women, may reflect differences in sociocultural attitudes towards medications worthwhile to further
investigate in order to improve rational drug use among pregnant women.
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Strengths and limitations of our study
Our study was not based on medical records but on data from interviewees. Therefore, it reflects real life drug use
and exposure misclassification can be excluded. The study also provides information about OTC drugs and use of
drugs dispensed to women outside our hospital. Although in such analysis recall bias cannot be excluded, we believe
that interviewing our patients during the antenatal care visits helped in minimizing this bias as poorer recall is higher
in the postnatal period [25]. The FDA risk classification system which we used to evaluate drug safety is a widely
used risk classification system. However, it might be prone to misinterpretation and misapplication, and is now under
review to provide a more reliable and clinically useful model [26,27]. We do not know if the encouraging finding of
zero exposure to category X drugs in our study population is limited to our hospital or reflects a general careful
attitude by pregnant women and their health care providers in Belgium. This merits further investigation.
In conclusion, the present findings demonstrate that the majority of women participating in the study take
medications during their pregnancy but with a general conservative behaviour towards the use of drugs known to be
harmful and with a complete absence of exposure to FDA category X drugs. However, many pregnant women use
OTC drugs for occasional use or for pregnancy-related disorders of which the safety remains uncertain. A clear
difference in drug utilization pattern was found between Western and Arab/Turkish women and a higher prevalence
of exposure to potentially harmful drugs was observed among Western women. This highlights the need for cautious
prescribing during pregnancy as well as for women in the fertile age in general, and for continuous monitoring of
medication use during pregnancy. Further research is warranted to reveal the determinants of the ethnic differences
in drug use during pregnancy.
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Acknowledgement
We thank Prof. Dr. Walter Foulon, head of the Obstetrics department at the UZ Brussel hospital. Our thanks also go
to Dr. Monika Laubach, head of the Obstetrics clinic for helping with the access to data, to the women who
participated in the study and to the midwifery of the hospital’s antenatal clinic for their assistance in distributing and
collecting the questionnaires. We are grateful to the pharmacist Seham Zaitoon for her help in the data entry and to
the Erasmus Mundus organization for funding this research.
Declaration of interest
The authors report no declarations of interest.
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References
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call for public health action. J Womens Health: 14: 104-9.
2. Lee E, Maneno MK, Smith L, Weiss SR, Zuckerman IH, Wutoh AK, Xue Z (2006) National patterns of
medication use during pregnancy. Pharmacoepidemiol Drug Saf: 15: 537-45.
3. Berthier M, Bonneau D, Perault MC, Oriot D, Chabot F, Maillauchaud MC, Magnin G, Vandel B (1993)
Medications exposure during pregnancy: a study in a university hospital. Therapie: 48: 43-6.
4. Checa MA, Peiro R, Pascual J, Cerreras R (2005) Drug intake behavior of immigrants during pregnancy. Eur J
Obstet Gynecol Reprod Biol: 121: 38-45.
5. Pinto Pereira LM, Nayak BS, Abdul-Lateef H, Matmungal V, Mendes K, Persad S, Ramnath G, Bekele I,
Ramasewak S (2010) Drug utilization patterns in pregnant women: A case study at the Mount Hope women’s
hospital in Trinidad, West Indies. West Indian Med J: 59: 561-6.
6. Bonati M, Bortolus R, Marchetti F, Romero M, Tognoni G (1990) Drug use in pregnancy: an overview of
epidemiological (drug utilization) studies. Eur J Clin Pharmacol: 38: 325-8.
7. Bakker MK, Jentink J, Vroom F, Van Den Berg P, De Walle H, De Jong-Van Den Berg L (2006) Drug
prescription patterns before, during and after pregnancy for chronic, occasional and pregnancy-related drugs in
the Netherlands. BJOG: 113: 559-68.
8. WHO Collaborating Center for Drug Statistics Methodology. ATC/DDD Index (2011).
http://www.whocc.no/atc_ddd_index/. Accessed 9 May 2011.
9. Briggs GG, Freeman RK, Yaffe SJ (2008) Drugs in Pregnancy and Lactation: A Reference Guide to Foetal and
Neonatal risk, 8
th
edn, Williams & Wilkins, Baltimore.
10. Comparing two proportions: significance test for comparing two proportions.
http://math.uc.edu/~brycw/classes/149/wang.htm. Accessed 15 July 2011.
11. Kebede B, Gedif T, Getachew A (2009) Assessment of drug use among pregnant women in Addis Ababa,
Ethiopia. Pharmacoepidemiol Drug Saf: 18: 462-8.
12. Henry A, Crowther C (2000) Patterns of medication use during and prior to pregnancy: the MAP study. Aust N
Z J Obstet Gynaecol: 40: 165-72.
13. Rubin PC, Craig GF, Gavin K, Summer D (1986) Prospective survey of use of therapeutic drugs, alcohol, and
cigarettes during pregnancy. Br Med J: 292: 81-3.
14. Rubin JD, Ferenez C, Loffredo C. The Baltimore-Washington infant study group (1993) Use of prescription and
non-prescription drugs in pregnancy. J Clin Epidemiol: 46: 581-9.
15. Donati S, Baglio G, Spinelli A, Grandolfo ME (2000) Drug use in pregnancy among Italian women. Eur J Clin
Pharmacol: 56: 323-8.
16. Collaborative Group on Drug Use in Pregnancy (C.G.D.U.P) (1992) Medication during pregnancy: an
international cooperative study. Int J Gynaecol Obstet: 39: 185-96.
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17. Aviv RI, Chubb K, Lindow SW (1993) The prevalence of maternal medication ingestion in the antenatal period.
S Afr Med J: 83: 657-60.
18. Riley EH, Afflick EF, Jackson RA, Escobar GJ, Brawarsky P, Schreiber M, Haas JS (2005) Correlates of
prescription drug use during pregnancy. J Womens Health: 14: 401-9.
19. Wen SW, Yang T, Krewski D, Yang Q, Nimrod C, Garner P, Fraser W, Olatunbosun O, Walker MC (2008)
Pattern of pregnancy exposure to prescription FDA C, D and X drugs in a Canadian population. J Perinatol: 28:
324-9.
20. Kallen B, Otterblad Olausson P (2007) Use of anti-asthmatic drugs during pregnancy 3. Congenital
malformations in the infants. Eur J Clin Pharmacol: 63: 383-8.
21. Mehta N, Larson L (2011) Pharmacotherapy in pregnancy and lactation. Clin Chest Med: 32: 43-52.
22. Malm H, Martikainen J, Klaukka T, Neuvonen PJ. Prescription of hazardous drugs during pregnancy (2004)
Drug Saf: 27: 899-908.
23. Meire F, Vuylsteek K, Buylaert W, Bogaert M (1979) Drug utilization during pregnancy. Ned Tijdschr
Geneeskd: 123: 703-6.
24. Foster DG, Bley J, Mikanda J, Induni M, Arons A, Baumrind N, Darney PD, Stewart F (2004) Contraceptive
use and risk of unintended pregnancy in California. Contraception: 70: 31-9.
25. Bryant HE, Visser N, Love EJ (1989) Records, recall loss, and recall bias in pregnancy: a comparison of
interview and medical records data of pregnant and postnatal women. Am J Public Health: 79: 78-80.
26. Doering PL, Boothby LA, Cheok M (2002) Review of pregnancy labeling of prescription drugs: Is the current
system adequate to inform risks? Am J Obstet Gynecol: 187: 333-9.
27. Andrade SE, Gurwitz JH, Davis RL, Chan KA, Finkelstein JA, Fortman K, McPhillips H, Raebel MA, Roblin
D, Smith DH, Yood MU, Morse AN, Platt R (2004) Prescription drug use in pregnancy. Am J Obstet Gynecol:
191: 398-407.
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Table I: General characteristics and medication use according to ethnicity [n = 641]
Variables
Total
n (%)
641 (100)
Western (R)
n (%)
334 (52.1)
Arab/Turkish
n (%)
209 (32.6)
Other origins
n (%)
98 (15.3)
p-value
Age
< 26 years
26 – 35 years
> 35 years
[n=641]
117 (18.3)
398 (62.0)
126 (19.7)
[n=334]
55 (16.5)
218 (65.3)
61 (18.3)
[n=209]
37 (17.7)
124 (59.3)
48 (23.0)
[ n=98]
25 (25.5)
56 (57.1)
17 (17.3)
0.172
Parity
Nulliparous
Multiparous
[n=618]
247 (40.0)
371 (60.0)
[n=324]
160 (49.4)
164 (50.6)
[n=199]
48 (24.1)*
151 (75.9)*
[n=95]
39 (41.4)
56 (58.9)
< 0.001
Use of contraceptive method
Yes
No
[n=636]
295 (46.4)
341 (53.6)
[n=332]
172 (51.8)
160 (48.2)
[n=207]
102 (49.3)
105 (50.7)
[ n=97]
21 (21.6)*
76 (78.4)*
0.000
Contraceptive method (users)
Pills
Others
[n=227]
181 (79.7)
46 (20.3)
[n=135]
102 (75.6)
33 (24.4)
[n=76]
68 (89.5)*
8 (10.5)*
[ n=16]
11 (68.8)
5 (31.3)
0.029
Stopped contraceptive after conception
Yes
No
[n=262]
229 (87.4)
33 (12.6)
[n=153]
144 (94.1)
9 (5.9)
[n=90]
74 (82.2)*
16 (17.8)
[ n=19]
11 (57.9)*
8 (42.1)
0.000
Use of medications including multivitamins
Yes
No
[n=641]
537 (83.8)
104 (16.2)
[n=334]
287 (85.9)
47 (14.1)
[n=209]
175 (83.7)
34 (16.3)
[ n=98]
75 (76.5)
23 (23.5)
0.085
Use of medications excluding multivitamins
Yes
No
[n=641]
237 (37.0)
404 (63.0)
[n=334]
146 (43.7)
188 (56.3)
[n=209]
60 (28.7)*
149 (71.3)*
[ n=98]
31 (31.6)*
67 (68.4)*
0.001
Use of multivitamins
Yes
No
[n=641]
505 (78.8)
136 (21.2)
[n=334]
274 (82.0)
60 (18.0)
[n=209]
161 (77.0)
48 (23.0)
[ n=98]
70 (71.4)
28 (28.6)
0.059
n : number of valid data available for each combination of variables may be less than 641 because of missing data in some variables or the
analysis is restricted to users only as in contraceptive use details.
p < 0.05 (overall for the 3 groups) indicates a significant association based on Chi-square test of independence.
*: indicates a significant difference when compared to the Western reference group (R).
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Table II: Categorisation of drugs according to reason for use
Category I: Drugs for chronic
conditions
Category II: Drugs for occasional and
short-time use
Category III: Pregnancy-related drugs
Gastrointestinal bile and liver therapy
(A05)
Drugs used in diabetes (A10)
Antithrombotic agents (B01)
Cardiovascular antihypertensive drugs
(C02)
Lipid modifying agents (C10)
Corticosteroids, dermatological
preparations (D07)
Pituitary and hypothalamic hormones and
analogues (H01)
Corticosteroids for systemic use (H02)
Thyroid therapy (H03)
Anti-infective systemic antivirals (J05)
Anti-inflammatory and antirheumatic
products (M01)
Anti-Parkinson drugs (N04)
Antipsychotics (N05A)
Antidepressants (N06A)
Antiasthmatics (R03)
Stomatological preparations (A01)
Antispasmodic and anticholinergic agents
and propulsives (A03, excl. A03FA01)
Antidiarrhoeals, intestinal anti-
inflammatory/anti-infective agents (A07)
Antihemorrhagics (B02)
Vasoprotectives (C05)
Antifungals for dermatological use (D01)
Antipruritics, including antihistamines,
anesthetics, etc (D04)
Antibiotics and chemotherapeutics for
dermatological use (D06)
Antiseptics and disinfectants (D08)
Antiacne preparations (D10)
Antibacterials for systemic use (J01)
Immune sera and immunoglobulins (J06)
Analgesics and antipyretics (N02B)
Anxiolytics (N05B)
Hypnotics and sedatives (N05C)
Antihistamines for systemic use (R06, excl.
R06AD and R06AE)
Ear, eye, nose and throat preparations (S01,
R01, R02A, R05)
Antacids (A02A)
Antiemetics (A03FA01, R06AE)
Laxatives (A06)
Gynaecological anti-infectives and
antiseptics (G01)
Sex hormones and modulators of the
genital system (G03)
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Table III: Differences in exposure to drugs before and throughout pregnancy
£: number of women for whom information was available (n = 641).
$: number of women for whom information was available (n = 397).
Third trimester drug use: information was only available for 397 women (third trimester interviewee) and proportions for the third trimester were
calculated according to this number.
% women exposed: represents the percentage of women who used drugs from the respective categories; Proportions were calculated as: number of
women exposed to certain kind of drugs / total number in each group.
The bold font p-values: compared to the before conception exposure.
The normal font p-values: compared to the preceding trimester.
First trimester exposure was by default compared to the preceding period.
p < 0.05: indicates a statistically significant difference based on the significant test for comparing two proportions (Two-sided z-test). The test is
available online: http://math.uc.edu/~brycw/classes/149/wang.htm.
Before
conception
Number of
drugs
%
women
exposed
(number
of
women)£
First
trimester
Number
of drugs
%
women
exposed
(number
of
women)£
p-value
Second
trimester
Number
of drugs
%
women
exposed
(number
of
women)£
p-value
Third
trimester
Number
of drugs
%
women
exposed
(number
of
women)$
p-value
Reason of use:
Chronic 64 7.0
(44)
84 9.0
(60)
0.102
78 9.0
(56)
0.697
0.211
33 6.0
(23)
0.098
0.557
Occasional 64 9.0
(58)
80 10.0
(65)
0.507
97 12.0
(78)
0.249
0.070
38 8.0
(33)
0.043
0.623
Pregnancy
related
9 1.0
(8)
31 5.0
(29)
0.000
43 6.0
(40)
0.173
0.000
16 4.0
(14)
0.056
0.013
Prescription or OTC:
OTC 62 9.0
(58)
90 12.0
(74)
0.142
104 13.0
(83)
0.443
0.026
42 9.0
(37)
0.076
0.883
Prescription 74 8.0
(53)
106 12.0
(77)
0.026
113 14.0
(90)
0.281
0.001
44 8.0
(33)
0.006
0.980
FDA risk factor:
A/B 83 12.0
(78)
104 15.0
(93)
0.218
99 14.0
(88)
0.688
0.406
48 11.0
(42)
0.136
0.437
C/D 41 5.0
(34)
62 7.0
(48)
0.110
62 8.0
(49)
0.916
0.089
24 5.0
(21)
0.142
0.992
U 12 2.0
(12)
33 5.0
(30)
0.005
58 8.0
(53)
0.009
0.000
17 4.0
(16)
0.008
0.037
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Table IV: Differences in mean number of preparations used according to ethnicity
n : number of valid data available for each group
p < 0.05 (overall for the 3 groups or pair-wise) indicates a significant difference based on ANOVA test (with Bonferroni post hoc test) and using
the Western group as the reference group (R).
Total
population
p-value
overall test
Western
(R)
Arab/Turkish
p-value Other
origins
p-value
ANOVA test (mean number for the whole group):
Medications including multivitamins
1.77
0.000
2.02
1.50
0.000
1.48
0.002
Medications excluding multivitamins
0.58
0.000
0.72
0.42
0.000
0.46
0.035
Multivitamins
1.18
0.004
1.29
1.09
0.024
1.02
0.022
ANOVA test (mean number for users only in each group):
Medications including multivitamins
2.11
0.000
2.35
1.79
0.000
1.93
0.028
Medications excluding multivitamins
1.58
0.200
1.66
1.45
0.352
1.45
0.683
Multivitamins
1.50
0.034
1.58
1.41
0.059
1.43
0.373
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Table V: Differences in exposure to drugs among the three ethnic groups
Total drug
use
Number of
drugs
Western
women (R)
(n = 334)
Number of
drugs
%
women
exposed
(number
of
women)
Arab/ Turkish
women
(n = 209)
Number of
drugs
%
women
exposed
(number of
women)
p-value
Other origins
women
(n = 98)
Number of
drugs
%
women
exposed
(number
of
women)
p-value
Reason of use:
Chronic 103 69 15.0
(49)
26 10.0
(21)
0.118 8 6.0
(6)
0.026
Occasional 192 120 26.0
(86)
42 14.0
(30)
0.002 30 24.0
(24)
0.801
Pregnancy
related
78 50 13.0
(45)
19 9.0
(18)
0.085 7 6.0
(6)
0.047
Prescription or OTC:
OTC 205 135 29.0
(96)
47 15.0
(32)
0.000 23 18.0
(18)
0.041
Prescription 167 105 22.0
(75)
39 16.0
(33)
0.058 22 18.0
(18)
0.387
FDA risk factor:
A/B 186 113 28.0
(94)
50 22.0
(45)
0.086 23 17.0
(17)
0.032
C/D 95 66 16.0
(52)
19 7.0
(14)
0.002 10 8.0
(8)
0.062
U 90 61 16.0
(54)
18 8.0
(16)
0.004 11 10.0
(10)
0.144
% women exposed: represents the proportion of women who used drugs from the respective categories; Proportions were calculated as: number of
women exposed to certain kind of medications / total number in each group.
The Western group is the reference group (R) that was compared with the Arab/Turkish and with the “Other origins” group.
n : number of valid data available for each group.
The total number of medications is less than 374 because of missing values.
p < 0.05 (overall for the 3 groups) indicates a statistically significant difference based on the significant test for comparing two proportions (Two-
sided z-test). The test is available online: http://math.uc.edu/~brycw/classes/149/wang.htm.
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