Ascertainment of medication use
In the first follow-up questionnaire at gestational week 17,
participants were asked to complete a 6-weeks paper-based medication
diary during gestational weeks 19-24 or 26-31 [22]. Through these
diaries, participants reported on the exact name of the medication used,
daily dose, and specific dates of use. To decrease participant burden,
participants could write down the name of any medication used on a daily
basis on the first page of the diary. A reminder was sent if the diary
was not returned within two weeks after the last day covered by the
diary.
In the Netherlands, most people visit only one or two pharmacies and all
pharmacies use computerized dispensing records. Through the ‘Landelijk
Schakelpunt’, to which 96% of Dutch pharmacies are connected [27],
information on medications dispensed is exchanged between pharmacies,
making their dispensing records virtually complete. For PRIDE Study
participants who provided consent, data on medications dispensed in the
three months before pregnancy until six months after the estimated date
of delivery were requested from the pharmacies the women reported visits
to. From these records, we abstracted data on medications with use in
the 6-weeks covered by the medication diary, including name of the
medication, start and stop dates, frequency of use, and dosage
prescribed.
Medications were coded using the Anatomical Therapeutic Chemical (ATC)
classification system [28]. We excluded vaccines (ATC code J06 and
J07) and vitamins (A11, A12, B03B), as these may not be considered as
medication by the participants. Furthermore, medications that are
predominantly used over-the counter (acetaminophen [N02BE01],
antacids [A02AD01], and xylometazoline [R01AA07]) and
medications not indicated for use during pregnancy (contraceptives
[G03A], fertility medication [G03CA and G03GA], and tranexamic
acid [B02AA02]) were excluded. We classified the medications in
three mutually exclusive categories after the classification of Bakker
et al. [29]: (1) medication for chronic conditions, (2) medications
for occasional and short-time use, and (3) pregnancy-related medication
(Supplemental Table 1). Medications for chronic conditions did not
necessarily have to be taken on a regular or daily basis, but may have
been used on an as-needed basis as well.
Medication adherence
Adherence to prescribed
medications was assessed with three measures. Actual use was defined as
a dispensed medication of which use was reported in the diary. The
definitions of initiation and implementation as described by the ABC
European adherence initiative taxonomy were used [30]. For
medications first dispensed in the diary period (i.e. no use in the
three months preceding the diary period according to the pharmacy
records), we assessed non-initiation and initiation time (difference
between dispensing date and date of first reported use in the diary).
Implementation adherence was calculated as the proportion of days with
at least the correct number of doses taken, with the pharmacy records as
reference standard. Medications that were prescribed on an as-needed
basis were excluded from the analyses on initiation and implementation.