Patients’ perspective on aspirin during pregnancy: a survey

ABSTRACT

Objective

To elucidate patients’ knowledge and counseling perspective on aspirin reducing the risk of hypertensive disorders of pregnancy (HDP).

Methods

A quantitative survey was performed including women who are members of the patient orgasnization Dutch HELLP Foundation due to a history of HDP.

Results

Awareness of the risk-reducing effect of aspirin on HDP was present in 51.9% of the 189 women. The majority was informed by their gynecologist (89.8%) and preferred to be informed by a gynecologist (79.4%), at the postpartum checkup (42.3%) or in the consecutive pregnancy (30.7%), both orally and written (62.4%).

Conclusion

Half of the women with a history of HDP were aware of the risk-reducing effect of aspirin in a consecutive pregnancy.

KEYWORDS:

• Aspirin
• gestational hypertension
• HELLP
• placenta
• preeclampsia

Introduction

Gynecologists are becoming increasingly aware of low-dose aspirin as a risk-reducing therapy in pregnancies where there is an increased risk of hypertensive disorders of pregnancy (HDP). It took three decades and about 30 randomized controlled trials before the beneficial effect was accepted.

The first randomized controlled trial which demonstrated the beneficial preventive effect of aspirin in a population at high risk for recurrent HDP and fetal growth restriction was in 1985 [1]. Various randomized controlled trials have been performed thereafter and have been evaluated in several meta-analyses since 1991 confirming the effect [2–4]. A major breakthrough in the acceptance of the beneficial effect of aspirin was achieved by Bujold et al.’s meta-analysis which focussed on the onset of aspirin use and which demonstrated that early start, at least before 16 weeks of gestation, had a beneficial effect [5]. Consequently, in 2010 the UK National Institute for Health and Care Excellence (NICE) recommended aspirin to women at risk of HDP in 2010 [6].

While the etiology of HDP is largely unknown it is considered to probably be multifactorial, including a role for endothelial damage in various organs and “defective deep placentation” [7]. Aspirin might lead to better placentation and therefore reduce the risk of HDP. Awareness among caregivers and women at risk is growing, though not all women at risk are either informed or informed timely.

Now that after nearly three decades of discussion among gynecologists, the beneficial effect of aspirin is agreed upon, the next step is to optimize implementation. Therefore, it is important to know how women at risk for recurrent HDP are informed about the use of aspirin intake during pregnancy, its timing, and their adherence to its use.

This study is designed in close collaboration with the Dutch HELLP Foundation to elucidate women’s perspective of the counseling about aspirin as risk-reducing therapy for HDP.

The aim of this study is to explore if women with a history of HDP are aware of the risk-reducing effect of aspirin in a consecutive pregnancy. We hypothesize that women at risk for HDP are not well-informed by their gynecologists or midwives about using aspirin as risk reducing therapy of HDP in consecutive pregnancies due to the long discussion on its efficacy. Moreover, we want to explore women’s preferences on which caregiver should provide this information, and the timing as to when to receive this information. The attitude toward and adherence to aspirin during pregnancy and to drug use in general during pregnancy is evaluated as well.

Materials and methods

Study population and setting

This quantitative survey was conducted from 30 March 2017 until 6 July 2017. All participants of the Dutch HELLP Foundation were invited by personal e-mail. Participants were made attentive to the invitation by announcements on social media (website and Facebook). The Dutch HELLP Foundation is a patient organization with a focus on women with a history of HDP, including preeclampsia, eclampsia, or hemolysis elevated liver enzymes low platelet syndrome. The foundation provides peer support and medical information and participates in the development of guidelines and medical research since 1994. The survey was conducted in Dutch; thus, only women who can read and write Dutch were included. There were no exclusion criteria.

Method

Participants of the foundation (n = 2000) were invited to fill in an online anonymous survey consisting of 25 non-validated questions. The goal was to obtain a representative sample of at least 100 completed surveys from women who had given birth after 2010, the time period with wide-spread acceptance of aspirin for reducing HDP. The choice for an anonymous survey via the online platform Survey Monkey was made so as to lower social desirability bias.

The survey was designed by gynecologists of our tertiary center together with the Dutch HELLP Foundation. The 25 items (multiple choice with multiple or single answers and open questions) were divided into five categories (see Table 1).

Table 1. Overview of the questions of the survey

Obstetric history
Question	Answers	Nature of question
1. What is your age?		Open question
2. Which of the following complications is applicable to your previous pregnancy/-ies?	a. Preeclampsia b. HELLP syndrome c. Eclampsia d. Combination of pre-eclampsia, HELLP syndrome and/or eclampsia e. Premature delivery before 34 weeks of gestation	Multiple choice, multiple answers possible
3. How many times have you been pregnant?		Open question
4. How many miscarriages have you had (gestation up to 12 weeks)?		Open question
5. In which year(s) did you deliver?		Open question
6. In which year(s) was your pregnancy complicated by pre-eclampsia, HELLP syndrome and/or eclampsia?		Open question
7. Do you have an active desire to have children?		Open question
Women’s knowledge about aspirin as riskreducing therapy
8. Have you been informed about aspirin as risk-reducing medicine for pre-eclampsia and HELLP syndrome in a consecutive pregnancy?		Open question
9. If you were informed about aspirin as risk-reducing medicine, by whom were you informed?	a. Gynecologist b. Midwife c. General practitioner d. Dutch HELLP Foundation e. Other	Multiple choice, one answer possible
Preferences of counseling about aspirin as risk-reducing therapy in timing, method and caregiver informing
10. What is your preference about the timing of informing? Multiple choice, one answer possible.	a. Before the first pregnancy b. During the pregnancy which was complicated by preeclampsia, HELLP syndrome and/or eclampsia c. At the postpartum checkup of the complicated pregnancy d. During clotting analysis e. During a preconception counseling f. At the beginning of the consecutive pregnancy g. No preference	Multiple choice, one answer possible
11. From whom do you prefer receiving the information?	a. Gynecologist b. Midwife c. General practitioner d. Vascular medicine specialist e. No preference	Multiple choice, one answer possible
12. How would you like to be informed?	a. Orally b. Written c. Orally as well as written	Multiple choice, one answer possible
Attitude toward drugs in general, during pregnancy and aspirin during pregnancy
13. What is your attitude about drug use in general?	a. No objection to take drugs b. Neutral c. Prefer not to take medicine	Multiple choice, one answer possible
14. What is your attitude about drug use during pregnancy?	a. Positive, if advised by my gynecologist b. Neutral c. Fear of the health of my unborn baby, even if reassured by my gynecologist	Multiple choice, one answer possible
15. Did you take aspirin during a previous pregnancy?	a. Yes b. No	Multiple choice, one answer possible
If question 15 was answered with “yes,” questions 16–19 were asked.
16. Did you take aspirin daily?	a. Yes b. No c. Don’t know	Multiple choice, one answer possible
17. Have you been advised to take aspirin in the evening?	a. Yes b. No c. Don’t know	Multiple choice, one answer possible
18. Did you experience side effects of the aspirin?	a. Yes b. No c. Don’t know	Multiple choice, one answer possible
19. With the knowledge of aspirin as risk-reducing medicine, would you take aspirin daily in the evening in a consecutive pregnancy?	a. Yes b. No c. Don’t know	Multiple choice, one answer possible
Women’s suggestions on the optimal timing of counseling, counseling daughters of women who have had HDP, and method of counseling
20. Do you think that aspirin should be prescribed to all women with a first pregnancy who have risk factors for developing pre-eclampsia and/or HELLP syndrome?	a. Yes b. No c. Don’t know	Multiple choice, one answer possible
21. Do you think that aspirin should be prescribed to all women with a first pregnancy without risk factors for developing pre-eclampsia and/or HELLP syndrome?	a. Yes b. No c. Don’t know	Multiple choice, one answer possible
22. Daughters of women with a history of pre-eclampsia, HELLP and/or eclampsia are at risk to develop these complications as well. Do you think that they should be informed about aspirin as risk-reducing medicine?	a. Yes b. No c. Don’t know	Multiple choice, one answer possible
23. Do you have any suggestions for the timing of informing about using aspirin as risk-reducing therapy in a consecutive pregnancy?		Open question
24. Do you have any suggestions for the timing of informing daughters of women with a history of pre-eclampsia, HELLP syndrome and/or eclampsia about aspirin as risk-reducing therapy?		Open question
25. Do you have any other suggestions for optimizing the informing process about aspirin as risk-reducing therapy?		Open question

The questions of the survey to participants of the Dutch HELLP Foundation grouped in five themes, depicted in bold. The question, the possible answers, and the nature of the question are listed. Questions are translated to English. The original survey is in Dutch.

Multiple choice questions (n = 22) concerning:

• Obstetric history

• Women’s knowledge about aspirin as risk-reducing therapy

• Preferences with respect to counseling about the use of aspirin as risk-reducing therapy in caregiver informing, timing of the counseling, and method of counseling

• Attitude toward drug use in general, drug use during pregnancy and the use of aspirin during pregnancy

Open questions (n = 3):

• Women’s narrative suggestions concerning the optimal timing of counseling, counseling daughters of women who have had HDP, and suggestions optimizing method of counseling.

Statistical analysis

The results of the survey were analyzed with descriptive statistics. Data are depicted either as means with standard deviations or numbers with percentages as appropriate.

Correlations were analyzed with logistic regression analysis. Knowledge about aspirin was correlated with age (≥30 years or ˂30 years), year of complicated pregnancy (≥2011 or <2011), preterm delivery before <34 weeks gestational age (presence or absence), attitude toward drug use in general (positive, negative, or neutral), attitude toward drug use during pregnancy (positive or negative) and the preference of timing of counseling (during admission of the complicated pregnancy, during postpartum checkup or at the beginning of a consecutive pregnancy).

In addition, preterm delivery <34 weeks was correlated with attitude toward drug use in general (positive, negative, or neutral), attitude toward drug use during pregnancy (positive, negative, or neutral) and the preference of timing of counseling (during admission of the complicated pregnancy, during postpartum checkup or at the beginning of a consecutive pregnancy). SPSS version 26.0 (SPSS Inc., Chicago, IL, USA) was used to perform the statistical analyses. Results were considered significant at the one-sided 5% level. The narrative suggestions on the open questions are grouped in categories and summarized.

Ethical approval

The conducting of an anonymous survey with the present content does not require local research ethics committee approval.

Results

The survey was completed by 189 of 2000 invited participants of the Dutch HELLP Foundation.

Baseline characteristics revealed that the women had given birth between 1978 and 2017, all had HDP and 67.2% had this pregnancy complication after 2010 (Table 2). Preterm delivery occurred in about one-third of the women. More than half of the women responded that they had an active desire to become pregnant again.

Table 2. Baseline characteristics of women with a history of hypertensive disorder of pregnancy

	n = 189
Age (years)	35.8 ± 7.3
Parity	2.1 ± 1.2
Previous* Preeclampsia Eclampsia HELLP Combination of above Preterm delivery	52 (29.6) 9 (5.1) 95 (54.0) 74 (42.1) 61 (32.3)
Year of previous pregnancies** > 2015 2011–2015 2006 – 2010 2000–2005 < 2000	55 (29.1) 135 (71.4) 50 (26.5) 34 (18.0) 43 (22.8)
Year of pregnancy complicated with HDP >2015 2011–2015 2006 – 2010 2000–2005 < 2000	42 (22.2) 85 (45.0) 28 (14.8) 16 (8.5) 18 (9.5)
Number of miscarriages	0.4 ± 0.7
Active desire to have children Yes No Maybe No answer	75 (39.7) 101 (53.4) 8 (4.2) 5 (2.7)

Data are depicted as mean ± SD or numbers (%) as appropriate.

* Total percentage ˃100% because of possible combinations of diagnoses.

** Total percentage ˃100% because some women had more than one previous pregnancy.

HELLP, hemolysis elevated liver enzymes low platelets; HDP, hypertensive disorders of pregnancy.

Women received information about aspirin in 98 out of 189 women, did not receive this information in 83 and did not know if they received information in eight out of 189 women. The information on aspirin was provided by the gynecologist in 88 out of 98 women, midwife in 0, general practitioner in 0, internist in 1, Dutch HELLP Foundation in 2, and researchers in 7 out of 98 women.

Women preferred receiving the information by their gynecologist or midwife at the postpartum checkup of the complicated pregnancy (42.3%) or in the beginning of the consecutive pregnancy (30.7%), and orally as well as written (62.4%) (Table 3).

Table 3. Preferences of counseling concerning women with a history of hypertensive disorder of pregnancy

	n = 189
Would like to receive information by Gynecologist Midwife General practitioner Vascular medicine specialist/internist No preference No answer	150 (79.4) 18 (9.5) 10 (5.3) 4 (2.1) 5 (2.6) 2 (1.0)
Timing of informing Before first pregnancy During pregnancy complicated by HDP Postpartum checkup Outcome clotting analysis Preconception counseling Beginning of consecutive pregnancy No preference/other No answer	1 (0.5) 29 (15.3) 80 (42.3) 2 (1.0) 6 (3.2) 58 (30.7) 11 (5.8) 2 (1.0)
Method of informing Orally Written Orally as well as written No answer	56 (29.6) 11 (5.8) 118 (62.4) 4 (2.1)
Counseling nulliparous women at risk Yes No Don’t know No answer	148 (78.3) 9 (4.8) 26 (13.8) 6 (3.2)
Counseling first grade female family members Yes No Don’t know No answer	159 (84.1) 3 (1.6) 21 (11.1) 6 (3.2)
Counseling nulliparous women not at risk Yes No Don’t know No answer	42 (22.2) 96 (50.8) 45 (23.8) 6 (3.2)

Data are depicted as numbers (%).

HDP, hypertensive disorders of pregnancy.

The majority of the women (45.5%) had a neutral attitude toward drug use in general, while there was a positive attitude about drug use during pregnancy if it was advised by the gynecologist (83.6%). Aspirin use during a previous pregnancy, advice to take it in the evening, and motivation to use aspirin in a consecutive pregnancy are presented in Table 4.

Table 4. Attitude toward drug use in general and aspirin specific outside and during pregnancy

	n = 189
Attitude toward drug use in general No objection Neutral Prefer not to take medicine No answer	37 (19.6) 86 (45.5) 63 (33.3) 3 (1.6)
Attitude toward drug use during pregnancy Positive, if advised by gynecologist Fear of health fetus, even if reassured by gynecologist No answer	158 (83.6) 28 (14.8) 3 (1.6)
Aspirin previous pregnancy Daily intake* Advice intake in evening * Side effects* Motivated for daily aspirin intake in the evening during a possible consecutive pregnancy*	84 (44.4) 78 (92.9) 16 (19.1) 8 (9.5) 75 (89.3)

Data are depicted as numbers (%).

* Percentage of women who used aspirin in previous pregnancy (n = 84). Total percentage ˃100% because of more answers possible.

Knowledge about aspirin as risk-reducing therapy was correlated with a history of preterm delivery (OR = 5.680 (p < 0.001)) and with those 30 years or older (OR = 2.889 (p = 0.01)). No correlation was found between knowledge and the year of the complicated pregnancy, the attitude toward drug use in general, attitude toward drug use during pregnancy, or the preference of timing of counseling.

No correlation was found between a history of preterm delivery and the attitude toward drug use in general, attitude toward drug use during pregnancy, or the preference of timing of counseling.

Narrative suggestions for the best timing of receiving information were made by 131 of the 189 women. Eight women considered it to be optimal during the complicated pregnancy, 52 at the postpartum checkup, 18 at preconception counseling, and 38 of the 131 women at the beginning of a new pregnancy. Additional comments were three months postpartum by one, six months after the complicated pregnancy by six and 12 months by three of the 131 women. The suggestion of informing six to twelfth months after the complicated pregnancy was made by nine women, with the explanation that discussing a consecutive pregnancy is too early at the six weeks postpartum checkup. Finally, five women suggested informing about aspirin use at the first signs of developing HDP.

Narrative suggestions with respect to the best timing of informing daughters of women who have had HDP were made by 106 of the 189 women. Informing as early as possible was suggested by four, in adolescence by 15, when active desire to have children by 32 and in the beginning of a pregnancy by 55 out of the 106 women.

Narrative suggestions for optimizing informing of women at risk for HDP on the use of aspirin were made by 106 of the 189 women. Suggestions for an information brochure were made by 40, training caregivers to create more awareness by them by 30, creating more awareness in general through the media (e.g., via social media, television programs, and fora) by 25, spreading more information by the patient organization Dutch HELLP Foundation by four and other suggestions by seven women.

Discussion

Women at risk for recurrent HDP were not well-informed about using aspirin as risk-reducing therapy for recurrent HDP as we hypothesized. Only half of the women responded that they were aware of using aspirin as risk-reducing therapy for HDP. The majority of these women were informed by their gynecologist with a very small minority being informed through research, the Dutch HELLP Foundation, and/or the internist. From the characteristics of the women, we learned various things. They consisted of women with a mean age of 35.8 ± 7.3 years with a parity of 2.1 ± 1.2 years at the time of responding to the survey. This is in line with the Dutch population. Given the high prevalence of preterm delivery, the women can be considered to be a high-risk population. Knowledge about aspirin as risk-reducing therapy was correlated with a history of preterm delivery and those 30 years or older. The majority of the women had their prior pregnancy complicated with HDP after the acceptance of the beneficial effect of aspirin in 2010 [5].

For the population with mainly preterm preeclampsia, we interpret the findings as showing that the implementation of aspirin lags behind in this study population. Recently, its effect on reducing early-onset preeclampsia has been confirmed in the ASPRE trial [8]. Thus, the beneficial effect of aspirin for preeclampsia has been proven, especially in early-onset preeclampsia [9].

The evaluation of the preference of the counseling resulted in a rank order of first the gynecologist, then the midwife, and finally the general practitioner. The optimal timing of the counseling was considered to be six weeks after birth at the postpartum checkup and at the beginning of the consecutive pregnancy. A few women advised the provision of information six to 12 months after the delivery of the complicated pregnancy. Since six to 12 months postpartum is not a regular checkup date, this should be discussed with the women and offered to them. We must be aware of providing timely advice of aspirin intake in a consecutive pregnancy, since aspirin should be started early in pregnancy, before the second trophoblast invasion, and informing during the consecutive pregnancy might result in a late start. Well-informed women do not advise receiving the information at the onset of HDP complaints as it was only suggested by a small minority (five out of 189 women).

The survey revealed that more than half of the women preferred to be informed orally as well as written. The latter can be explained by the fact that many women after had had HDP experience reduced memory and concentration at the six weeks postpartum checkup and a written explanation would prevent the loss of oral information [10,11]. In addition, an information brochure was suggested by 40 women, training of caregivers to create more awareness by them by 30, creating more awareness in general through different media by 25, and spreading more information by the patients' organization by four. Optimal information about reducing the recurrence of HDP is necessary for decision-making on a consecutive pregnancy. We learned from the suggestion on counseling that almost 80% of the women responded positively to counsel nulliparous women at risk, and almost a quarter to nulliparous women not at risk. Nulliparity is, according to the NICE Guidelines, a moderate risk factor for developing HDP and thus only needed treatment when combined with another risk factor [6]. Informing daughters of women who have had HDP should be done, according to the women, by the mothers, general practitioners, midwives, or gynecologists. Preferences with respect to best timing for informing these daughters were when active desire to have children or at the first pregnancy checkup.

The women’s attitude toward drug use during pregnancy differed from their attitude toward drug use in general. Higher rates of positive attitude are reported during pregnancy if advised by the gynecologist, namely 83.6% versus 19.6%. In a previous study on aspirin adherence in high-risk pregnancies, adherence rates varying from 21.4% to 46.3% were reported [12]. Adequate counseling could result in higher adherence rates during pregnancy. However, 14.8% of the women were not willing to use drugs during pregnancy out of fear for their child, despite reassurance by their gynecologist. Of the women who had used aspirin in a previous pregnancy, 89.3% reported that they would take it daily in the evening in a consecutive pregnancy. This high rate of acceptance of using aspirin might be explained by the low rates of side effects reported, namely 9.5%. Fewer than half of the women had used aspirin in a previous pregnancy. The majority had a daily intake, but fewer than 20% received advice to take aspirin in the evening. Research showed that taking aspirin in the evening leads to greater efficacy and fewer complications [13,14]. Counseling and prescription of aspirin should also include this timing of aspirin intake.

A possible explanation for the correlation between better knowledge and a history of preterm delivery might be that women with a history of preterm delivery usually had a more severe course of disease than women without a history of preterm delivery and therefore might be better informed by caregivers and/or be more open to a risk-reducing therapy such as aspirin. Presently, we do not have an explanation for the correlation between better knowledge and age 30 years or older at the moment of the survey. Knowledge was not correlated with the year of the complicated pregnancy. Thus, women who gave birth after the major breakthrough of Bujold et al. in 2010 were not better informed. This confirms our hypothesis that women are not well enough informed about aspirin as risk-reducing therapy. Better knowledge had no influence on the attitude toward drug use in general or during pregnancy or the preference of the timing of counseling.

A history of preterm birth, and thereby probably a more severe disease course, had no influence on the attitude toward drug use in general or during pregnancy, neither on the preference of the timing of counseling.

With these results in mind, we can conclude that as gynecologists we should improve our counseling of women with a pregnancy complicated by HDP on the use of aspirin in a consecutive pregnancy. Notable is the fact that none of the women were informed by their midwife or general practitioner. Since these caregivers play an important role in the Netherlands in evaluating whether pregnancy checkups should be performed by a midwife or gynecologist, we strive to enhance the knowledge with shared guidelines. Informing the patient should be done by the gynecologist or midwife, preferably at the postpartum checkup, and orally as well as written and repeated after a year when possible. We also suggest distributing an information brochure about aspirin as a risk-reducing therapy for (recurrent) HDP in consecutive pregnancies. In the Netherlands, we will make an information brochure in collaboration with the Dutch HELLP Foundation. The foundation can play an important role in informing a larger group of women at risk who no longer have checkups by a gynecologist or other specialist. They could provide the information brochure advising making a plan with a gynecologist. Patient associations in the United Kingdom (Action-on-pre-eclampsia) and the United States of America (Pre-eclampsia foundation) also inform on their websites about the usage of aspirin as risk-reducing therapy in a consecutive pregnancy [15,16].

The strength of this study is its novelty. Patients’ perspective about aspirin as risk-reducing therapy has to our knowledge not been investigated before. Also, the survey was answered by participants of the Dutch HELLP Foundation which represents the target group of women who have had HDP. Since the majority of the responders delivered after 2010, awareness of the application of aspirin should be present and, as such, the population is representative. Good collaboration with the patient association made it possible to reach the target group. This can also be considered as a limitation of this study, since the participants might not be an optimal reflection of the general population of women who have had HDP. Participants of the Dutch HELLP Foundation form a subgroup of women who are active and mostly well-informed which could cause an overestimation of patients’ knowledge. Also, as we only accessed a population that could read and write Dutch, we miss those who are not able to do so. We are well aware that in case of language barrier we have to strengthen our efforts to inform women of potential hazards of pregnancy and preventive measurements [17].

In conclusion, women at risk for recurrent HDP were not well enough informed about the use of aspirin as a risk-reducing therapy for (recurrent) HDP, confirming our hypothesis. Counseling should be adapted to raise awareness among women at risk and improve the preventive therapy. We advise informing women at risk about using aspirin as risk-reducing therapy at the postpartum checkup and/or in consecutive pregnancies by their gynecologist or midwife, in oral as well as written form. The information needs to include timing of the start and moment of intake. Counseling should be irrespective of the severity of the disease and/or preterm delivery. We want to emphasize the importance of aspirin use in the prevention of HDP in joint guidelines with midwives and general practitioners.

Acknowledgments

First, we would like to express our gratitude toward all participants of the Dutch HELLP Foundation who participated in our study. Furthermore, we want to thank Peter van de Ven, statistical consultant, for his contribution to the statistical analysis.

Disclosure statement

All authors report no conflicts of interest.