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Keywords:

  • BMQ;
  • enoxaparin;
  • low-molecular-weight heparin;
  • medication adherence;
  • pregnancy;
  • venous thromboembolism

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Conclusion
  9. Acknowledgements
  10. Disclosure of Conflict of Interests
  11. References
  12. Supporting Information

Summary.  Background: Non-adherence to prescribed medication represents a significant factor associated with treatment failure. Pregnant women identified at risk of venous thromboembolism are increasingly being prescribed low-molecular-weight heparin (LMWH) during pregnancy and the puerperium. It is important to understand women’s views on and adherence to LMWH during pregnancy and the puerperium, so that women gain maximum benefit from the treatment. Objectives: To monitor women’s adherence to enoxaparin, when prescribed during pregnancy and the puerperium, and explore their beliefs about the enoxaparin therapy prescribed. Patients/Methods: A prospective cohort study involving 95 nullparous and multiparous women prescribed enoxaparin for recognized antenatal indications. Adherence to enoxaparin was assessed through self-completion of a diary, additionally verified through laboratory tests. An adapted beliefs about medication questionnaire was administered to women during their pregnancy. Results: Women were highly adherent to enoxaparin: antenatally, mean percentage adherence 97.92%; postnatally, mean percentage adherence 93.37% (paired t-test, P = 0.000). In the cohort of women we followed, their perceived necessity for enoxaparin therapy outweighed any concerns they had regarding enoxaparin antenatally, necessity-concerns differential 2.20. In some women, however, this perceived necessity does decrease postnatally. Conclusions: Our results suggest that most women prescribed enoxaparin are highly adherent to their therapy during the antenatal period and that women’s antenatal beliefs about enoxaparin are able to predict a decrease in postnatal adherence. Our results have important clinical implications, particularly when women are initiated on LMWH just during the postnatal period.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Conclusion
  9. Acknowledgements
  10. Disclosure of Conflict of Interests
  11. References
  12. Supporting Information

Non-adherence to prescribed medication represents a significant factor associated with treatment failure [1], with research suggesting that up to 50% of patients prescribed medications for chronic conditions are not taking them as indicated [2]. Although patients’ beliefs about medicines are often complex and diverse, they can be grouped into two broad categories: (i) perceptions of necessity and (ii) concerns about negative effects [3]. Consequently, patients apply a common-sense approach when deciding whether to use their medication or not, balancing three factors; the illness threat, their perception of the need for therapy, and concerns they may have in relation to their prescribed therapy [2].

Little research has been conducted exploring the issue of medication adherence during pregnancy, even though over the last 30 years, the use of prescription and herbal medicines has increased significantly amongst pregnant women across North America, Europe and Australasia [4–9]. Reports suggest that up to 96.9% of pregnant women use at least one medicine, either prescribed or purchased in a pharmacy, at some stage during their pregnancy [10,11]. A recent study by Sawicki et al. [12] found that in a group of pregnant women taking a prescribed medicine to manage a chronic condition, 59.1% were found to be non-adherent to their medication at some stage during their pregnancy.

While teratogenic risk may well be an important factor influencing non-adherence during the antenatal period, research suggests that women often over-estimate this risk. [13,14]. For example, in the study by Sanz et al. [13], the teratogenic risk of 14 specifically listed medicines was perceived to be higher by pregnant women than the actual risk. This perception can lead to abrupt withdrawal of medication, as has been reported in the field of psychiatry [15,16]. Conversely, the gravid state can also lead to improved medication adherence; in the field of HIV, studies report adherence to highly active anti-retroviral therapy during pregnancy to increase, seen as an attempt by mothers to prevent vertical transmission [17–19]. Adherence to fertility drugs during in-vitro fertilization treatment is also found to be complete, presumably because of a strong desire for a successful pregnancy outcome [20].

Venous thromboembolism (VTE) is a major cause of maternal mortality and morbidity in the western world [21]. The overall incidence of pregnancy-related VTE is reported to be 1–2/1000 pregnancies, an increase in risk of 4–5 fold [22–24], with recent work suggesting that deep vein thrombosis experienced during pregnancy impacts on women’s long term quality of life [25]. The current Royal College of Obstetricians and Gynaecologists guidelines for VTE prevention during pregnancy and the puerperium recommend that all women are assessed for their risk of VTE early during their pregnancy and offered appropriate preventative measures, including low-molecular-weight heparin (LMWH), when applicable [26]. This means that women at high risk of VTE (e.g. a history of VTE) may be prescribed an LMWH for a significant proportion of their pregnancy and for up to 6 weeks postpartum. Together with other indications where women require antenatal LMWH therapy (i.e. treatment of VTE, prophylaxis of women on long-term warfarin switching to LMWH and prevention of fetal loss and placental dysfunction in thrombophillic women) [27], this means that the number of pregnant women being prescribed LMWH is increasing. To date, there have been no published studies that have explored the issue of adherence and women’s views of having to inject LMWH during pregnancy and the postpartum period [28]. It is important to have an insight into this, so that the prescribed treatment can be optimized.

Objectives

  1. Top of page
  2. Abstract
  3. Introduction
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Conclusion
  9. Acknowledgements
  10. Disclosure of Conflict of Interests
  11. References
  12. Supporting Information
  • 1
     To monitor women’s adherence to enoxaparin when prescribed during pregnancy and the puerperium.
  • 2
     To explore women’s views and beliefs about the enoxaparin prescribed.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Conclusion
  9. Acknowledgements
  10. Disclosure of Conflict of Interests
  11. References
  12. Supporting Information

Study setting and recruitment

Nullparous and multiparous women requiring antenatal enoxaparin therapy were eligible for recruitment into the study. Following referral to the hematology clinic, women requiring antenatal enoxaparin therapy were invited to enter a pharmacokinetic study of enoxaparin; the evaluation of adherence and exploration of women’s views formed a sub-study. Women prescribed enoxaparin therapy were reviewed monthly in the hematology clinic during their pregnancy.

Following informed written consent, women were instructed on how to self-inject enoxaparin using prefilled syringes, and given a How to inject Clexane® information booklet (Sanofi-Aventis Ltd, Guildford, Surrey, UK), with designated space for women to document the time(s) at which they injected each day. Where doses were missed, women were asked to record these in the book provided by the principal researcher. This booklet was replaced at each hematology clinic attendance.

Assessment of adherence

Adherence was determined by the self-completion of the aforementioned book. Adherence was additionally verified by the measurement of anti-Xa activity (a biomarker for enoxaparin) at each hematology clinic visit.

Following their last clinic visit (8 weeks post-partum), percentage adherence rates were calculated through both the antenatal and postnatal periods separately. Women were classed as adherent to enoxaparin for the antenatal and/or postnatal period, if they achieved an adherence rate ≥ 80% [29]. The paired t-test was used to compare antenatal adherence rate with the postnatal adherence rate.

Exploring women’s views on enoxaparin

In order to explore women’s views and beliefs about the enoxaparin, the Beliefs about Medication Questionnaire (BMQ) [3] was adapted. This instrument explores patient’s perceived harm and overuse of medication in general and the perceived necessity and concerns associated with medications specifically. To our knowledge, this is the first application of the BMQ in a pregnant population. We therefore adapted the BMQ for application to the cohort of pregnant women prescribed enoxaparin. As the BMQ questionnaire tests beliefs about medicines [(i) perceived harm and (ii) overuse in general and (iii) perceived necessity and (iv) concerns specifically], internal consistency of the adapted BMQ was tested for these four subscales using Cronbach’s alpha, which revealed good internal consistency: perceived harm subscale = 0.772, overuse subscale = 0.782, perceived necessity subscale = 0.774, and concerns subscale = 0.748.

The research team also added a series of questions, which were felt, from clinical experience, to be important issues for pregnant women, for example if women were worried that injecting enoxaparin during their pregnancy might impact on the type of pain relief they could have at delivery.

The final questionnaire (online Data S1) was reviewed by all members of the research team for face and content validity and comprised four sections, with responses to sections 1–3 of the questionnaire requiring the women to indicate their level of agreement with the statements made using a five-point Likert scale (5 = strongly agree, 1 = strongly disagree).

  • 1
     Section 1 explored women’s perceptions regarding harm and overuse of medications in general during pregnancy (12 items).
  • 2
     Section 2 explored women’s perceptions regarding the necessity for and their concerns about medications specifically around enoxaparin in general and repeated again in the context of pregnancy (17 items).
  • 3
     Section 3 contained additional questions related specifically to enoxaparin use in pregnancy (nine items).
  • 4
    Section 4 was an opportunity for women to document any other comments, should they wish.

The questionnaire was given to women at the time they consented to join the study (during the antenatal period) and women were asked to bring the completed questionnaire to one of their subsequent hematology clinic appointments. Women were advised that their responses would be kept confidential and would not be shared with the clinical team.

Analysis of the responses received in the questionnaires

Data from the questionnaires were coded and entered into and analysed using IBM SPSS (version 18; IBM SPSS, Chicago, IL, USA). Descriptive statistics were used to summarize the demographic and clinical characteristics of the cohort of women.

In order to assess women’s beliefs about the enoxaparin prescribed, subscale scores for overuse, harm, necessity and concerns were calculated for the cohort as a whole. We found that women’s adherence to enoxaparin in the study could be classified into two broad groups: women who were equally adherent to enoxaparin through both the antenatal and postnatal periods (optimal adherence group) and women who were adherent to enoxaparin through the antenatal period, but had a 5% or more decrease in adherence through the postnatal period (suboptimal adherence group). The BMQ subscales scores were additionally calculated for these two groups separately and compared using the independent t-test. Furthermore, as first suggested by Clifford and colleagues [30], the necessity-concerns differential was also computed for the cohort of women, and then separately calculated for the two groups and compared. This necessity-concerns differential calculates the difference between the patients’ perceived necessity for treatment and their apparent concerns, and is strongly associated with a patient’s intention to adhere to treatment.

Section 2 of the questionnaire explored the relationship between the general necessity and concern questions of the BMQ and the respective pregnancy-specific repeat questions. Pearson’s correlation was utilized to assess whether each pair of question was correlated and whether women agreed more with the pregnancy specific questions.

The additional questions added to the questionnaire were reported back as % agreement with each statement. Voluntary comments made by women in the questionnaire were themed. Example themed comments are listed in the results section. Significance was set at 0.05.

Ethical approval

The study was approved by the Isle of White, Portsmouth and South East Hampshire Ethics Committee; REC reference number: 09/H0501/5.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Conclusion
  9. Acknowledgements
  10. Disclosure of Conflict of Interests
  11. References
  12. Supporting Information

As part of the wider population pharmacokinetic study, the questionnaire was administered to 103 women. Ninety-five returned a completed questionnaire (response rate = 92.23%). The mean age of the women was 33.03 years (range 18–46); Table 1 lists further background information on these women. The majority of women were prescribed enoxaparin for established indications. There were nine women in the study (‘other’ group) who were prescribed enoxaparin for indications where the evidence base is less well established. In these situations, the lack of an evidence base was discussed with the patient fully and a decision to prescribe antenatal enoxaparin was only taken if the patient wanted to proceed. Forty-nine (51.6%) women were actively being treated for VTE or had suffered from thrombosis in the past. Twenty-five (26.3%) women had a history of recurrent miscarriage.

Table 1.   Information on the women in the study
DemographicNumber (%) n = 95
  1. *The specific indications for the women switched from long-term warfarin to enoxaparin during the index pregnancy were recurrent VTE (x2), symptomatic homozygous FVL (x1), Budd-Chiari (x2), paroxysmal nocturnal hemoglobinuria (x1), valvular atrial fibrillation (x1). **The specific indications for the women in this category include recurrent miscarriages in the absence of anti-phospholipid syndrome (x7), stillbirth in previous pregnancy where post-mortem results indicated perivillous fibrin deposition, placental ageing and dysmaturity (x1), patent foramen ovale (x1).

Ethnicity
 Caucasian54 (56.8)
 African-Caribbean30 (31.6)
 Asian4 (4.2)
 Other7 (7.4)
Indication
 VTE prophylaxis64 (67.4)
 VTE treatment9 (9.5)
 Switched from long-term warfarin*7 (7.3)
 Antiphospholipid syndrome6 (6.3)
 Other**9 (9.5)
Frequency of enoxaparin prescribed
 Once a day80 (84.2)
 Twice a day13 (13.7)
 Once, followed by twice a day2 (2.1)
Prior experience of injecting LMWH during pregnancy
 No70 (73.7)
 Yes25 (26.3)
Obstetric history (as a cohort)
 Gravida340
 Parity96
 Miscarriages131
 Terminations19

Adherence to enoxaparin

A total of 19 308 antenatal doses of enoxaparin were prescribed for the 95 women [mean 203 (range 18–455)], and 4131 postnatal doses [mean 43 (range 0–114)]. The cohort of women was found to adhere highly (> 80%) to the enoxaparin therapy: antenatally, mean percentage adherence 97.92%; postnatally, mean percentage adherence 93.37%. No differences in adherence rates were found between the following subgroups; Caucasian versus African-Caribbean populations, women with a history of recurrent miscarriage compared with those who had no recurrent miscarriage history, and women injecting enoxaparin once a day versus those injecting twice a day.

Adherence to enoxaparin decreased in some women during the postnatal period (paired t-test, t = 5.305, df = 89, P = 0.000). Women could be allocated into two broad categories with respect to their adherence to enoxaparin: (i) women who adhered to enoxaparin antenatally and postnatally with no significant change during the postpartum period (n = 62, 68%) (optimal adherence group), and (ii) women who adhered to enoxaparin antenatally and postnatally, but had at least a 5% drop in adherence during the postnatal phase (n = 29, 32%) (suboptimal adherence group). These subgroups will be referred to later on in the analysis. Four women had no further indication for enoxaparin postnatally.

Established subscales from the BMQ

Table 2 lists the mean scores from the four established subscales (harm, overuse, necessity and concerns) in the BMQ from the women questioned. There was more agreement between the women regarding the specific necessity and concerns questions, compared with the general overuse or harm questions in the instrument, with an overall necessity-concerns differential of 2.20.

Table 2.   Mean BMQ subscale scores
BMQ subscaleMeanSDMin–Max
Overuse10.002.904–17
Harm8.222.634–16
Necessity14.163.615–25
Concerns11.963.665–20

Table 3 lists the differences in the mean BMQ subscale scores when the women’s responses were subdivided by adherence rates:

Table 3.   Differences in the BMQ subscales scores between the two groups
BMQ subscaleGroup** N MeanSDSignificant
  1. *Independent t-test. **Group 1, optimal adherence; Group 2, suboptimal adherence.

Overuse1 262 299.67 10.793.14 2.41NS
Harm1 262 298.01 8.652.69 2.58NS
Necessity1 262 2914.96 13.113.40 3.46< 0.05*
Concerns1 262 2911.78 12.343.72 3.76NS
  • 1
     women who were equally adherent ante- and postnatally (optimal adherence group); and
  • 2
     women who were adherent antenatally, but had a > 5% drop in adherence during the puerperium (suboptimal adherence group).

A significant difference was found between the necessity subscale mean scores of the women in the optimal adherence group and those of the women in the suboptimal adherence group (independent t-test, t = 2.399, df = 89, ≤ 0.05).

The mean necessity-concerns differential for the optimal and suboptimal adherence groups were 3.10 and 0.78, respectively (independent t-test, t = 2.151, df = 89, ≤ 0.05), suggesting that the perceived need for enoxaparin was less in the latter group.

Necessity for and concerns about enoxaparin

In the adapted questionnaire, we asked the original BMQ questions from the necessity and concerns section of the questionnaire, and repeated seven of these questions in the context of pregnancy to assess if women’s responses changed. Table 4 lists the mean responses to these questions, along with the correlation relationship between each pair of questions.

Table 4.   Necessity and concerns responses from the women in general and specific for the context of pregnancy
 MeanSD r*
  1. *Pearson’s correlation. **Significant at the 0.01 level.

Necessity question pairs
 My health at present depends on enoxaparin3.241.070.503**
 My current pregnancy depends on enoxaparin3.520.99
 My life would be impossible without enoxaparin2.240.830.395**
 My current pregnancy would be impossible without enoxaparin2.790.94
 Without enoxaparin I would be very ill2.611.030.726**
 Without taking enoxaparin during this pregnancy I would be very ill2.980.94
 My health in the future depends on enoxaparin2.550.980.091
 Any pregnancies in the future will depend on me taking enoxaparin3.460.99
 Enoxaparin protects me from becoming worse3.441.020.100
 Enoxaparin is protecting my pregnancy3.660.85
Concerns question pairs
 Having to take enoxaparin worries me2.661.090.734**
 Having to take enoxaparin during pregnancy worries me2.741.05
 I sometimes worry about the long-term effects of enoxaparin2.841.160.761**
 I sometimes worry about the long-term effects of enoxaparin on my unborn baby3.061.16

All questions apart from two pairs were well correlated, with more agreement expressed by the women with all the statements, when asked specifically in the context of pregnancy.

Additional questions

In addition to the adapted BMQ questions, additional questions were asked in the questionnaire which the research team felt may be important factors for women prescribed antenatal enoxaparin. Table 5 lists the % agreement of the women to these questions.

Table 5.   Women’s % agreement with the additional statements in the questionnaire
Question% Agreement with statement
General questions about medication use during pregnancy
 Before considering to take a medicine during pregnancy, I like to know about the safety of that medicine for me and my unborn baby96.8
 When deciding on whether to take a medicine whilst I am pregnant, I place a higher priority on the impact the medicine will have on the health of my unborn baby than on any effects the medicine may have on me78.5
 Most medicines are safe when taken during pregnancy if prescribed by a doctor65.2
 Over the counter medicines from a chemist are safer than prescription-only medicines during pregnancy3.2
Specific questions about enoxaparin use during pregnancy
 Having to take enoxaparin throughout pregnancy is not an issue for me, as long as it helps to protect my and my unborn baby’s health91.4
 Having to inject myself with enoxaparin daily is not an issue for me, as long as the health of my unborn baby is protected88.4
 Enoxaparin only works if taken regularly64.2
 The enoxaparin does not cause me any side-effects62.8
 Enoxaparin protects my unborn baby’s health37.2
 I sometimes worry that being on enoxaparin will limit the type of childbirth delivery I can have35.6
 I sometimes worry that being on enoxaparin will limit the type of pain relief I can have at the time of childbirth31.9
 It is difficult for me to take my enoxaparin in exactly the way my doctor has told me21.1
 I sometimes worry that being on enoxaparin during pregnancy will interfere with my ability to breastfeed when my baby is born14.9

Voluntary comments made by women

Of the 95 women who completed the questionnaire, 30 women (31.57%) made comments at the end of the questionnaire, some of which were unrelated to the context of this study (eight women). The remaining relevant comments were themed into three broad categories:

  • 1
     necessity for injecting enoxaparin during pregnancy in order to protect them and/or their unborn baby’s health (13 women);
  • 2
     concerns or perceived harm associated with injecting enoxaparin (seven women); and
  • 3
     suggestions for the future (two women).

Representative comments from each theme follow.

Necessity for enoxaparin

I’m happy to take enoxaparin during pregnancy as a preventative measure. I don’t like doing the injections but it’s manageable, and with my history it’s something I’m prepared to do to ensure a safe arrival of my baby.–3

I am very thankful for enoxaparin and grateful it is available. It is not a problem for me to take if it means I get my babies with me after so many lost babies.–15

As far as I am aware, enoxaparin is to ensure I remain well during pregnancy and do not have a DVT. Therefore it is paramount that my health is taken care of and reviewed. I feel more secure and less worried about my health now I am on this medication. I find the injections uncomfortable but a small price to ensure I have a healthy pregnancy.–56

I don’t have an issue with taking medication during pregnancy, if the unborn baby’s health is not compromised. I believe I am on enoxaparin to prevent blood clots from forming (not that they definitely would appear, but to reduce the risk of them appearing).–73

Definitely gives me piece of mind during pregnancy; without it I would feel very nervous about developing another DVT.–76

Concern or perceived harm

I have no issues injecting if it is safeguarding mine and the babies health but I lack some faith in the safety/side-effects/general effects of the medicine. Published information on Clexane seems to be contradictory.–42

I sometimes worry that in the future they find that enoxaparin has a big side-effect for my baby, for example harmful for the heart or skin.–50

I do worry about the options for pain relief as have been told I need an epidural due to my hypertension too. I worry about bleeding after birth and how the Clexane affects this.–68

Taking enoxaparin worries me...because it’s painful.–89

The problem I have is that I get severe pain for 30 min after the jab, and need to lie down. Early on, I decided I would cope better at night. My husband has to administer the injection as I am terrified of needles. I wish there was another way, other than injection of taking this drug! As I am having an elective C-section, I worry that my blood may cause problems during the operation and that if I stop the Clexane before the C-section, this will cause a problem for our baby. I have suffered with severe bruising around every needle mark, this also causes me concern.–113

Suggestions

I do not have a problem doing injections and was aware of the possibility of the injections before becoming pregnant. However, I think other women might benefit from more time and support around the use of Clexane in their pregnancy.–28

If there was a way to get injections for enoxaparin via an epi-pen type device it would be much more tolerable!–64

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Conclusion
  9. Acknowledgements
  10. Disclosure of Conflict of Interests
  11. References
  12. Supporting Information

This is the first study to explore pregnant women’s views on and adherence to LMWH therapy during pregnancy and the puerperium. We found women to adhere highly to the enoxaparin therapy during both the antenatal (97%) and postnatal (93%) periods, although in a third of women, adherence decreased by > 5% postnatally.

Adherence

The high adherence rate observed in this study is perhaps not surprising. Colwell et al. [31], in the context of extended thromboprophylaxis with LMWH in orthopedic surgery, found that when properly instructed, patients can safely and efficiently self-administer the LMWH at home. This finding was also replicated by Watts et al. [32], who followed a small number of patients who had recently undergone low limb arthroplasty and prescribed LMWH for 6 weeks post-surgery. They found that of the patients who could potentially self-inject at home, 85% were compliant with their prophylactic therapy, and this has been further endorsed by the results of the recently published ETHOS registry [33]. In a recent pilot study with the use of unfractionated heparin for second trimester placental insufficiency, the authors found no increase in maternal anxiety within a high-risk antenatal population attributable to regular self-administration of subcutaneous injections [34]. McLintock et al. [35] are one of the few authors to explore the relationship between adherence to prescribed treatment and outcomes. In their study of high-risk pregnant women with mechanical prosthetic heart valves in-situ, of the women found to suffer from thrombotic complications whilst prescribed enoxaparin treatment, non-compliance and subtherapeutic anti-Xa levels were implicated in each case, with the authors concluding that good compliance with treatment was associated with a low risk of valve thrombosis and good fetal outcomes.

Others, however, have reported problems with self-administration of LMWH. Mengiardi et al. [36] followed 213 non-pregnant patients injecting LMWH in the community and found a self-reported non-compliance rate of 17.1%, with 38.9% of patients stating that self-administration of the injections required some effort. A similar finding was also reported by Spahn [37], who followed 207 patients following knee arthroscopy. Spahn reported problems with self-injection in 34.8% initially and 6.3% over the whole time.

In our study, although some women reported negative experiences when having to inject the enoxaparin, the majority appeared to cope with self-administration.

This study had higher adherence rates compared with the aforementioned studies, with apparently fewer problems. This may be in part due to the stronger beliefs about the necessity for treatment than concerns that the women had regarding the enoxaparin, as demonstrated by the necessity-concerns differential. Another key reason for the high adherence rate may be in part due to the regular monthly follow-up these women had in the hematology clinic. This follow-up provided an opportunity to discuss and check for any problems, and when necessary to reinforce the importance of the LMWH therapy during the antenatal period; this opportunity was lost to a certain degree during the postnatal period.

What is of importance to women?

One issue that came out from the questionnaire, which confirms our previous understanding, is that women like to know the precise teratogenic potential of a prescribed medicine. In this study, 96.8% of women wanted to know to what extent any medicine they took could affect their unborn baby as well as them, with many (78.5%) placing a higher priority on the impact the medicine has on the unborn baby, compared with any impact the medicine may have on them.

Of the women in the study, 91.4% stated that having to inject enoxaparin was not an issue for them, as long as their own and their unborn baby’s health was protected. When this question was repeated, just enquiring about their unborn baby’s health, 88.4% of women stated that having to inject enoxaparin was not an issue for them, as long as their unborn baby’s health was protected, illustrating women’s protective behavior regarding their unborn baby.

These findings suggest that although in the majority of cases, the women were prescribed enoxaparin for maintaining their own health, the fact that the women were pregnant, appeared to make them feel as if the enoxaparin was protecting their unborn baby’s health and maintaining their pregnancy. In some ways, such a belief is not completely wrong, because of the close physical relationship between a mother and child during the gravid period; however, if this belief continues during the postnatal period, then the women’s perceived necessity for enoxaparin may decline and explains in part the reason why postnatally, there was a group of women (suboptimal adherence group) in whom adherence to enoxaparin dropped by > 5% from their respective antenatal adherence rate. The necessity-concerns differential was significantly different between these two groups.

The drop in adherence in some women during the puerperium should perhaps not be surprising, as similar findings are reported in other clinical specialities. For example, in the field of HIV, as previously mentioned, adherence to HAART might increase antenatally, in an attempt by mothers to prevent vertical transmission, and then drop once the baby has been delivered [17–19].

When asked informally in clinic by the principal researcher on why they might have missed doses postnatally, two reasons were most commonly cited; firstly, the challenges of motherhood following birth meant that often they simply forgot because their regular routine had been disrupted (unintentional non-adherence). Others reported that following birth, their perceived necessity for the enoxaparin was less (intentional non-adherence); as their baby had been born successfully, they were less worried if they missed a dose. In their study of medication use in general amongst pregnant women, Sawicki et al. [12] reported the two most commonly cited reasons for women non-adhering to medication during pregnancy were forgetting to take medication and stopping medicine when they were feeling better. Though in Sawicki’s study, the reasons cited are by pregnant patients, clearly they resonate with our study population, as both unintentional and intentional non-adherence behaviors are exhibited by the women.

These finding do have important practice implications. In the current Royal College of Obstetric and Gynaecology guidelines for VTE prevention during pregnancy and the puerperium [26], the threshold for initiating prophylaxis is lower during the puerperium than antenatally. This means that women not eligible for enoxaparin therapy antenatally become eligible postnatally, for example women who have had an emergency Caesarean section (1 week prophylaxis), or women who are asymptomatic heterozygous carriers of Factor V Leiden, will be prescribed LMWH (6 weeks prophylaxis). Given our observations in this study and the fact that one of the reasons women appear to adhere to enoxaparin is that they feel it protects their unborn baby’s health, it might not be too inconceivable that women prescribed prophylaxis cold (i.e. just during the postnatal period) might not adhere to their treatment fully. Healthcare professionals, particularly those in contact with women during the early days following birth, requiring LMWH, should ensure patients have an opportunity to discuss prophylactic LMWH fully and are instructed on how to self-inject competently for those newly starting LMWH therapy and reinforce the necessity of adherence LMWH therapy for those who had already been injecting antenatally, so that women gain maximal benefit postnatally.

Additional questions asked in the questionnaire

The additional questions asked in the questionnaire were questions that the research team thought might be important factors for women injecting LMWH therapy during pregnancy and the puerperium. The key issues that came out from this section included the fact that one-third of women (33.4%) agreed with the statement which said that they sometimes worry that being on enoxaparin will limit the type of childbirth delivery they could have, with a similar number (31.8%) being worried that being on enoxaparin will limit the type of pain relief they could have at the time of childbirth.

Most of the women recruited into this study were asked to complete the questionnaire within a month or two of starting LMWH therapy. In our clinic, discussions about childbirth and options for pain relief are bought to the forefront during the third trimester. Our findings suggest that briefly discussing childbirth and pain relief issues with women on antenatal LMWH early on in their pregnancy might overcome any anxieties that some women may have, particularly as they can be managed.

Study limitations

This study is limited by the fact that the questionnaire was only administered once during the women’s pregnancy. Following the result that postnatal adherence may fall in some women, it would have been interesting to assess how women’s views may have changed as pregnancy progresses and following delivery; this might form the basis of future studies. It must be borne in mind that this study was part of a wider pharmacokinetic modelling study of enoxaparin during the antenatal period. Therefore, the antenatal adherence rates we report might represent an overestimate of the true adherence rate in the real world, due to the fact that women knew enoxaparin (anti-Xa activity) was being monitored. Our clinical experience, however, suggests that women requiring LMWH in this setting are often highly motivated, as they wish for a successful obstetric outcome. Due to the pharmacokinetic nature of the wider study, we had to exclude women from the study who were non-adherent to enoxaparin. During the course of this study, we found this to be the case in three patients and so the questionnaire was not administered to them. It would have been interesting to see what their responses would have been to the questionnaire and assess how they differed from those of the cohort of women who adhered to treatment. Finally, though it was emphasized to the women participating that their responses would remain confidential and not shared with the clinical team, it’s impossible to exclude the fact that some women may have responded with socially acceptable responses.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Conclusion
  9. Acknowledgements
  10. Disclosure of Conflict of Interests
  11. References
  12. Supporting Information

We found women to be highly adherent to LMWH treatment during the antenatal and postnatal period, though in some women adherence did drop postnatally. Women indicated a strong desire to know about what potential effect a medication may have on them and their unborn child, with our results suggesting that women would take a medicine during the antenatal period, even if it caused them pain and discomfort, if they felt it was protecting the health of their unborn baby. In the cohort of women we followed, their perceived necessity for enoxaparin therapy appeared to outweigh any concerns they had antenatally, although in some women this perceived necessity did decrease postnatally. It is important for healthcare professionals to understand women’s beliefs about and experiences with LMWH and reinforce the necessity of adherence to LMWH treatment particularly during the postpartum period, when for some women the risk of an adverse event is greater.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Conclusion
  9. Acknowledgements
  10. Disclosure of Conflict of Interests
  11. References
  12. Supporting Information

The authors acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. The authors would also like to thank all the women who agreed to participate in the study.

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  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Conclusion
  9. Acknowledgements
  10. Disclosure of Conflict of Interests
  11. References
  12. Supporting Information
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Supporting Information

  1. Top of page
  2. Abstract
  3. Introduction
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Conclusion
  9. Acknowledgements
  10. Disclosure of Conflict of Interests
  11. References
  12. Supporting Information

Data S1 Understanding your views on having to take enoxaparin whilst you are pregnant.

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JTH_12020_sm_Supprotinginformation.doc98KSupporting info item

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