Original Article
Survey on the Current Status of Perinatal Management among Women with Familial Hypercholesterolemia in Japan
2025 Volume 32 Issue 12 Pages 1523-1535
Details
2025 Volume 32 Issue 12 Pages 1523-1535
Aim: Women with familial hypercholesterolemia (FH) face specific challenges during pregnancy and childbirth, such as treatment restrictions and the absence of guidelines. This study therefore assessed the status of perinatal management and the needs of women with FH.
Methods: We contacted 240 board-certified FH specialists, and these physicians screened eligible patients for the survey. Two internet-based surveys were conducted between August 2023 and March 2024: one for physicians and one for women with FH.
Results: A total of 72 physicians completed the questionnaires. Fifty-seven percent had managed pregnant women with FH, and 64% reported difficulties, including “selecting and adjusting treatment options” and “the absence of guidelines on pregnancy and childbirth for women with FH.” Few physicians referred their patients to obstetricians prior to pregnancy. Eighty-three women with FH completed a questionnaire. Among those who had given birth after being diagnosed with FH, the most common problems reported were “could not be treated,” “obstetricians’ insufficient knowledge of FH,” and “insufficient information about pregnancy and delivery for women with FH.” Half of these women discontinued treatment for over one year. In addition, 78% of women indicated a need for counseling on pregnancy-related matters.
Conclusion: Many physicians have reported challenges in managing pregnant women with FH, and some women have lost years of treatment during pregnancy-related periods. Women with FH should receive advice on planned pregnancy and breastfeeding to balance FH treatment with childbearing and parenting, and obstetricians should actively collaborate with physicians.
See editorial vol. 32: 1484-1485
Familial hypercholesterolemia (FH) is an autosomal dominant disease that causes elevated low-density lipoprotein cholesterol (LDL-C) levels from birth1, 2). The accumulated cholesterol burden leads to an increased prevalence of atherosclerotic cardiovascular disease (ASCVD), leading to intensive early life management to reduce LDL-C levels3). Moreover, some reports suggest that there are sex differences in the treatment of FH, such as a later age at the diagnosis and less strict control of LDL-C levels in women with FH, although there are no sex differences in response to lipid-lowering medications4).
Specific issues arise in women with FH during pregnancy and lactation. First, plasma lipid levels naturally increase during pregnancy as a physiological change. In women with FH, both total cholesterol and LDL-C levels are increased by approximately 30%, which is comparable to or slightly greater than that in women without FH5). Second, statins, a commonly used lipid-lowering medication, are contraindicated in Japan during pregnancy because of their potential effects on the fetus6). Statins have been widely used for the past 40 years to manage hypercholesterolemia, including FH, and the FDA has requested the removal of a warning against statin use during pregnancy7). Third, statin use was contraindicated during lactation6). Consequently, women with FH experience periods when statins cannot be used because of pregnancy and lactation, which may be prolonged depending on the number of pregnancies8).
Considering the long-term health of women, it is essential to properly manage the LDL-C burden during pregnancy and lactation9, 10). In addition to statin suspension during these periods, some women with FH who are trying to conceive may refrain from statin use. Similarly, others may delay resuming statins after breastfeeding, either because they are too busy raising their children or because it is difficult to have the opportunity to visit their physicians.
The frequency of heterozygous FH in Japan is estimated to be 1 in 300 11), suggesting that a significant number of women with FH are of reproductive age. Currently, the Japanese FH guidelines do not include detailed information on lipid management during pregnancy and lactation, leaving physicians to navigate these challenges on a case-by-case basis. Obstetricians should be aware of the unique issues related to the perinatal management of women with FH and collaborate with physicians to enhance the safety of pregnancy and childbirth, while also prioritizing the long-term health of these women.
Since there are no reports on the concerns and needs of Japanese women with FH regarding pregnancy and lactation, in this study, a questionnaire survey was conducted among physicians and women with FH to achieve two aims. The first was to assess the current status of perinatal management for women with FH, and the second was to identify the concerns and needs of Japanese women with FH regarding pregnancy and lactation.
The questionnaire administered to the physicians comprised four sections, all of which are presented in Supplemental Table 1. The first section collected demographic data, including years of experience as a physician, subspecialty, and workplace type. The second section addressed the experience of managing pregnant women with FH, covering topics such as management experience and challenges faced. The third section focused on attitudes toward pregnancy-related information, including whether information was provided, its content, and the timing of its delivery. The final section explored medical coordination with obstetricians, including the availability of coordination, its timing, and associated difficulties.
| 1. Demographic data |
| Q1. How many years of experience do you have as a physician? (Select one) |
| Up to 10 years / 11–20 years / 21–30 years / More than 31 years / Other |
| Q2. What is your subspeciality as a physician? (Select one) |
| General internal medicine / Cardiology / Endocrinology / Neurology / Other |
| Q3. What is your workplace? (Select one) |
| Clinic / General hospital (with obstetricians) / General hospital (without obstetricians) / University hospital / Other |
| 2.Experience managing pregnant women with FH |
| Q4. Do you have experience managing pregnant women with FH? (Select one) |
| Yes / No / Other |
| Q5. Do pregnant women with FH generally seem anxious during their pregnancy? (Select one) |
| Very anxious / Somewhat anxious / Neither / Not very anxious / Not at all anxious |
| Q6. Have you had any problems in managing pregnant women with FH? (Multiple answers allowed) |
|
No problems expe rienced / Selection and coordination of FH treatment during pregnancy / Coordination of obstetric and medical visits / Cooperation with obstetrician/ Absence of guidelines on pregnancy and childbirth for women with FH / Timing of resuming postpartum FH treatment / Inheritance of FH / Other |
| 3. Counseling provided by physicians on pregnancy-related matters |
| Q7. Do you offer counseling on pregnancy-related matters? (Multiple answers allowed) |
|
Not offer / offer at certain times / offer if requested by women with FH / offer if requested by obstetrician / Other |
| Q8. What topics are covered during counseling? (Multiple answers allowed) |
|
Effect of pregnancy on FH / Effect of breastfeeding on FH / Effect of FH on pregnancy / Effect of FH on breastfeeding / FH treatment during pregnancy /Precautions during pregnancy / Mode of delivery / Necessity of resuming postpartum FH treatment / Contraception / Inheritance of FH / Other |
| Q9. Are pregnant women with FH satisfied with your counseling? (Select one) |
| Very satisfied / Satisfied / Neither / Dissatisfied / Very dissatisfied |
| Q10. Do you think your counseling changes your patients’ decision-making regarding pregnancy and childbirth? (Select one) |
| Yes / No / Other |
| Q11. What is the reason why you have not offered counseling? (Multiple answers allowed) |
|
Patients do not ask / Adjusted to drugs that allow the patient to become pregnant / Referred to an obstetrician if necessary / Patients do not want counseling / Absence of guidelines on pregnancy and childbirth for women with FH |
| Q12. Would you like to offer counseling about pregnancy and childbirth in the future? (Select one) |
| Strongly agree / Agree / Somewhat disagree / Disagree |
| Q13. When is the appropriate timing for counseling? (Multiple answers allowed) |
| Senior high school / University / Upon marriage / Upon request / At the first visit / On becoming pregnant / During pregnancy / Other |
| Q14. Who is the most appropriate provider of counseling? (Multiple answers allowed) |
| Physician / Obstetrician / Nurse or midwife / Clinical geneticist / Genetic counselor / Other |
| Q15. What are the appropriate topics for counseling? (Multiple answers allowed) |
|
Effect of pregnancy on FH / Effect of breastfeeding on FH / Effect of FH on pregnancy / Effect of FH on breastfeeding / FH treatment during pregnancy/ Precautions during pregnancy / Mode of delivery / Necessity of resuming postpartum FH treatment/ Contraception / Inheritance of FH / Other |
| 4. Coordination between physicians and obstetricians |
| Q16. What is the current status of coordination with an obstetrician? (Multiple answers allowed) |
|
No coordination / Coordinate before the pregnancy / Coordinate at the time of pregnancy / No affiliated maternity unit / Coordinate if the patient requests it / Coordinate if the obstetrician requests it / Other |
| Q17. Have you ever referred your patient with FH to a maternity unit for a planned pregnancy? (Select one) |
| Yes / No / Other |
| Q18. What information would you like to receive from the obstetrician? (Multiple answers allowed) |
|
Weeks of delivery / Mode of delivery / Birth weight of the baby /Apgar score / Presence or absence of disease in the baby / Breastfeeding status / Other |
The questionnaire administered to women with FH consisted of three sections, all of which are presented in Supplemental Table 2. The first section collected demographic data (e.g. age, educational level, and employment status), background information on FH (e.g. age at the diagnosis, whether genetic testing was performed, anxiety at the diagnosis, frequency of regular physician visits, and current LDL-C level), and personal information on pregnancy and delivery (e.g. past pregnancy experience, delivery history, and desire for children in the near future). The second section included questions about FH management during pregnancy and lactation for women who had experienced pregnancy and delivery after being diagnosed with FH (e.g. duration of medication discontinuation for the first child and FH-related anxiety during pregnancy). The third section addresses pregnancy-related information (e.g. need for information, preferred information provider, and timing and content of information). Data were collected using multiple choice questions for each item.
| 1. Status of women with FH |
| Q1. What is the age at which FH was diagnosed? |
| ( ) years old / I do not remember |
| Q2. Did you have any concerns when you were diagnosed with FH? (Select one) |
| Very anxious / Somewhat anxious / Neither / Not very anxious / Not at all anxious |
| Q3. Have you undergone genetic testing for the diagnosis of FH? |
| Yes, at ( ) years old / Yes, but I don’t remember at what age / No |
| Q4. How often do you visit the doctor about your FH? (Select one) |
| Monthly or more than once a month / Every 2 or 3 months / Once a year / If there is any change / Other |
| Q5. What is your current treatment for FH? (Multiple answers allowed) |
| No treatment / Dietary therapy / Exercise / Drug therapy [drug name ( )] / Lipoprotein apheresis / Other |
| Q6. Approximately what is your current LDL level? (Select one) |
| ＜50 / 50–70 / 70–100 / 100–120 / 120–140 / 140–160 / 160–180 / ＞180 / I do not remember |
| 2. Pregnancy experience |
| Q7. Have you ever been pregnant? (Select one). |
| Yes, ( ) times / No |
| Q8. Do you wish to have a baby now or in the near future? |
| Yes / No / Other |
| 3. For women who wish to give birth in the future |
| Q9. Do you have any concerns about your childbirth for each of the follow items? |
|
Having FH / Having a disease other than FH / Using medication for FH / Insufficient information about pregnancy and delivery in women with FH / Insufficient information about lactation in women with FH / Physicians’ insufficient knowledge of pregnancy and childbirth / Obstetricians’ insufficient knowledge of FH / Inheritance of FH by children / Other |
| Q10. Have you informed your physician of your desire for childbirth? (Select one) |
| Yes / No / Other |
| Q11. Have you discussed your desire for childbirth with your obstetrician? (Select one) |
| Yes / No / Other |
| Q12. Do you know that you can consult with an obstetrician about your pregnancy? (Select one) |
| Yes / No / Yes, and I have seen an obstetrician |
| 4. For women who do not wish to give birth in the future |
| Q13. Reasons (Multiple answers allowed) |
|
No particular reason / Concern about the effect of FH / Concern about other disease / Concern about using medication for FH / Insufficient information about pregnancy and delivery in women with FH / Concern about inheritance of FH by children / Already have a child / Do not have a current partner / My partner does not desire children / My work is more important / I do not like children / Financial reasons / Other |
| 5. For women who have experienced childbirth |
| Q14. How many times have you given birth? |
| ( ) times |
| Q15. Did you breastfeed? (Also, indicate whether you were diagnosed with FH at the time of breastfeeding.) |
| 6. For women who have experienced childbirth after the diagnosis of FH |
| Q16. During your pregnancy, did you have any concerns regarding the following items? |
|
Having FH / Having a disease other than FH / Using medication for FH / Insufficient information about pregnancy and delivery in women with FH / Insufficient information about lactation in women with FH / Physicians’ insufficient knowledge of pregnancy and childbirth / Obstetricians’ insufficient knowledge of FH / Inheritance of FH by children / Other |
| Q17. How was FH treated during your pregnancy? (Multiple answers allowed) |
| Medication was stopped / Dietary therapy / Exercise / Drug therapy [drug name ( ) ] / Lipoprotein apheresis / Other |
| Q18. Did you have any problems with FH during your pregnancy? (Multiple answers allowed) |
|
No particular problems / Failure to take medication for FH / Use of medications for FH / Poorly controlled LDL cholesterol levels / Insufficient information about pregnancy and delivery in women with FH / Insufficient information about lactation in women with FH / Insufficient information about pregnancy and childbirth from physicians / Insufficient information about FH from obstetricians / Inheritanceof FH by children / Other |
| Q19. Did you receive any mental support regarding childbirth? (Multiple answers allowed) |
|
None in particular / Consulted with physician / Consulted with obstetrician / Understanding of partner and family / Information about pregnancy and delivery in women with FH / Information about lactation in women with FH / Other |
| Q20. What information about childbirth did you find most useful? (Select one) |
|
Information about pregnancy and delivery in women with FH / Information about lactation in women with FH / Information about inheritance of FH / Information about general pregnancy and childbirth / Information about general lactation / Other |
| Q21. From whom did you obtain the information in (Q20) above? (Multiple answers allowed) |
| Physician / Obstetrician / Midwife or nurse / Clinical geneticist / Genetic counselor / Other |
| Q22. At the time of childbirth, did you have any desire to breastfeed? (Select one) |
| Yes / Somewhat / Minimal / No |
| Q23. What treatment did you receive for FH during breastfeeding? (Multiple answers allowed) |
|
Did not breastfeed / Shortened the duration of breastfeeding / Medication was stopped / Dietary therapy / Exercise / Drug therapy [drug name ( ) ] / Lipoprotein apheresis / Other |
|
Q24. If you interrupted treatment for FH at the time you planned to become pregnant or because of pregnancy, childbirth, or breastfeeding, please give the approximate length of time: ( ) |
| Q25. To what extent do you feel that having FH was a burden? (Select one) |
| Yes / Somewhat / Neither / Minimal / Not at all |
| 7. Counseling on pregnancy-related matters |
|
Q26. Do you think that information about pregnancy and childbirth should be provided to women with FH? (Select one) |
| Strongly agree / Agree / Somewhat disagree / Disagree |
| Q27. What information do you need? (Multiple answers allowed) |
|
Effect of pregnancy on FH / Effect of breastfeeding on FH / Effect of FH on pregnancy / Effect of FH on breastfeeding / Treatment for FH during pregnancy / Precautions during pregnancy / Mode of delivery / Necessity of resuming postpartum FH treatment / Contraception / Inheritance of FH / Other |
| Q28. What is the best time to provide information about pregnancy and childbirth? (Select one) |
| Senior high school / University / Upon marriage / Upon request / At the first visit / On becoming pregnant / During pregnancy / Other |
| Q29. Do you think your decision-making regarding pregnancy and childbirth will change by receiving such information? (Select one) |
| Strongly agree / Agree / Somewhat disagree / Disagree |
| Q30. From whom would you like to receive information? (Multiple answers allowed) |
| Physician / Obstetrician / Midwife or nurse / Clinical geneticist / Genetic counselor / Other |
| 8. Demographic data of participants |
| Q31. Age: ( ) years |
| Q32. Education: Junior high school / Senior high school / Technical or junior college / College or graduate school / Other |
| Q33. Work: Unemployed / Employed as regular employee / Employed as temporary employee / Other |
| Q34. Place of residence: ( ) |
A document describing the purpose of the study was emailed to the Japan Atherosclerosis Society (JAS) board-certified specialists. A link to an Internet-based survey was then sent to those who confirmed their willingness to participate via email. Responses to the questionnaire were collected anonymously through an online program in August 2023. The participating physicians screened eligible women with FH for the survey and provided them with a brochure explaining the study. Women who agreed to participate accessed the Internet-based survey using the link provided in the brochure and completed the questionnaire. The selection criteria were women 18–60 years old. The data were collected between September 2023 and March 2024. No incentives were offered to the participants, either physicians or women with FH, for their participation.
3-3 Data Analyses, Approval, and EthicsThis survey employed a mixed method design. Descriptive statistics (median, range, and percentage) were calculated for the demographic information. The frequency of responses related to the management of pregnant women with FH, questions about pregnancy-related information provided by physicians, and questions regarding medical coordination with obstetricians was calculated for each response option and expressed as a percentage. This approach was also applied to analyze the results in women with FH. Physicians and women with FH were provided the opportunity to add items that were not included in the questionnaire. Pearson’s correlation analysis was used to examine the relationships between variables related to anxiety level (5-point scale) at the FH diagnosis (2-tailed, p＜0.05).
Statistical analyses were performed using the SPSS software program, version 26.0 (IBM Corp., Armonk, NY, USA), with a 2-sided p＜0.05 considered statistically significant. The study protocol was approved by the Research Ethics Committee of the Japan Atherosclerosis Society (202301) and Medical Research Ethics Committee of Tokyo Medical and Dental University (M2023-063).
A total of 72 physicians completed the questionnaire, with a response rate of 30%. Most respondents (57%) had ≥ 31 years of experience as a physician (Table 1). Endocrinology was the most common subspecialty (46%) followed by cardiology (42%). In addition, 57% of the respondents worked in university hospitals.
| Variable | Respondents (n) | % |
|---|---|---|
| Years of experience as a physician | ||
| ≦10 | 0 | 0 |
| 11-20 | 10 | 13.9 |
| 21-30 | 21 | 29.2 |
| ≧31 | 41 | 56.9 |
| Other | 0 | 0 |
| Subspeciality | ||
| General Internal Medicine | 4 | 5.6 |
| Cardiology | 30 | 41.7 |
| Endocrinology | 33 | 45.8 |
| Neurology | 0 | 0 |
| Other | 5 | 6.9 |
| Type of workplace | ||
| Clinic | 10 | 13.9 |
| General hospital (with obstetricians) | 14 | 19.4 |
| General hospital (without obstetricians) | 5 | 6.9 |
| University hospital | 41 | 56.9 |
| Other | 2 | 2.8 |
Among the respondents, 57% had experience managing pregnant women with FH, and 76% reported that it was challenging. Table 2 presents the percentage of physicians who selected each of the eight listed difficulties. The most commonly reported challenges were the “selection and coordination of treatment” and the “absence of guidelines on pregnancy and childbirth for women with FH,” followed by the “timing of resuming postpartum FH treatment.”
| Items | % |
|---|---|
| No problems experienced | 24.4 |
| Selection and coordination of FH treatment during pregnancy | 53.7 |
| Coordination of obstetric and medical visits | 19.5 |
| Cooperation with obstetricians | 12.2 |
| Absence of guidelines on pregnancy and childbirth for women with FH | 53.7 |
| Timing of resuming postpartum FH treatment | 43.9 |
| Inheritance of FH | 12.2 |
| Others | 4.9 |
Abbreviations: FH: familial hypercholesterolemia Note: Multiple answers allowed.
Sixty-five percent of physicians (n = 47) reported not contacting obstetricians, with “not having an affiliated maternity unit” being the most frequently selected reason (Table 3). In addition, only 3 physicians (4.2%) referred patients with FH to an obstetrician before pregnancy.
| Respondents (n) | % | |
|---|---|---|
| Contact with obstetricians | 25 | |
| Before woman with FH becomes pregnant | 3 | 12 |
| When woman with FH becomes pregnant | 18 | 72 |
| Upon request by woman with FH | 12 | 48 |
| Upon request by obstetrician | 13 | 52 |
| Other | 0 | 0 |
| No contact with obstetricians | 47 | |
| No need | 4 | 8.5 |
| No request by woman with FH | 13 | 27.7 |
| No affiliated maternity unit | 18 | 38.3 |
| Other | 15 | 31.9 |
Note: Multiple answers allowed.
A total of 83 women with FH completed the questionnaire. Participants in their 20s and 30s comprised 58% of the group, 57% had graduated from college or university, and 64% were employed as regular or temporary employees (Table 4-1). The median age at the FH diagnosis was 27 (range, 5–55) years old, and genetic testing was performed in 28% of the participants. At the time of the diagnosis, 65% of the women reported feeling anxious (16% very anxious, 49% somewhat anxious). At the time of this survery, 96% of participants were taking medications, such as rosuvastatin calcium or atorvastatin calcium hydrate. Of these, 35% achieved LDL-C levels of ＜100 mg/dL (Table 4-2). Among the participants, 54% had given birth to at least 1 child; of these, 48% (n = 20) had experienced childbirth after their diagnosis with FH, while 42% expressed no desire to have children.
| Variable | Respondents (n) | % |
|---|---|---|
| Age | ||
| 18-30 | 25 | 30.1 |
| 31-40 | 24 | 29.0 |
| 41-50 | 14 | 16.8 |
| 51-60 | 20 | 24.1 |
| Education | ||
| Junior high school | 2 | 2.4 |
| Senior high school | 18 | 21.7 |
| Technical or junior college | 16 | 19.3 |
| College or graduate school | 47 | 56.6 |
| Work | ||
| Not working | 24 | 28.9 |
| Regular employee | 34 | 41.0 |
| Temporary employee | 19 | 22.9 |
| Other | 6 | 7.2 |
| Prior pregnancy | ||
| Yes | 45 | 54.2 |
| Prior delivery | ||
| Yes | 42 | 50.6 |
| Variable | Median (range) | |
|---|---|---|
| Age at diagnosis of FH | 27 (5-55) | |
| Variable | Respondents (n) | % |
| Genetic testing has been performed | ||
| Yes | 23 | 27.7 |
| Anxiety at diagnosis | ||
| Very anxious | 13 | 15.7 |
| Somewhat anxious | 41 | 49.4 |
| Neither | 8 | 9.6 |
| not anxious | 16 | 19.3 |
| not very anxious | 5 | 6.0 |
| Frequency of regular visits | ||
| ＞1 per month | 8 | 9.6 |
| Once per several months | 72 | 86.7 |
| Once per year | 1 | 1.2 |
| As needed | 0 | 0 |
| Other | 2 | 2.4 |
| Currently on lipid lowering drugs | ||
| Yes | 80 | 96.4 |
| Current LDL-C level | ||
| ＜70 | 8 | 9.6 |
| 71-100 | 21 | 25.3 |
| 101-120 | 23 | 27.7 |
| 121-140 | 14 | 16.9 |
| 141-160 | 2 | 2.4 |
| 161-180 | 5 | 6.0 |
| ＞181 | 8 | 9.6 |
| Don’t know | 2 | 2.4 |
This section analyzes data from 20 women who had given birth after being diagnosed with FH. Forty percent of the participants reported discontinuing treatment, while 35% indicated that they had not received treatment prior to pregnancy. Regarding the duration of treatment discontinuation for their first child (Fig.1), half of the women had been off treatment for more than one year, with a median duration of 17 (range: 0–70) months from preconception to the resumption of FH treatment after lactation. The most frequently reported issues related to FH during pregnancy were: “could not be treated” and “obstetricians’ insufficient knowledge of FH” (both 35%), followed by “insufficient information about FH women’s pregnancy and delivery,” “no experience of trouble,” and “inheritance of FH by children” (all 30%) (Table 5). When asked about the emotional burden of FH during pregnancy and lactation, 70% of participants responded “yes” or “somewhat yes” (Fig.2).
Among women with FH who gave birth after their diagnosis, half had discontinued treatment for more than one year in relation to their first child.
| Women who gave birth after diagnosis of FH (n = 20) | ||
|---|---|---|
| Respondents (n) | % | |
| No difficulties experienced | 6 | 30 |
| Could not be treated | 7 | 35 |
| Taking lipid-lowering drug | 2 | 10 |
| Poor control of LDL-C levels | 4 | 20 |
| Insufficient information on pregnancy and delivery | 6 | 30 |
| Insufficient information on breastfeeding | 5 | 25 |
| Physicians’ insufficient understanding of pregnancy in women with FH | 2 | 10 |
| Obstetricians’ insufficient knowledge of FH | 7 | 35 |
| Inheritance of FH by children | 6 | 30 |
Note: Multiple answers allowed.
Women with FH who gave birth after their diagnosis rated the emotional burden of FH during pregnancy and lactation using a 5-point Likert scale. The graph displays the percentage of participants who selected each option.
We inquired about the counseling provided by physicians regarding pregnancy-related matters and needs among women with FH. A total of 56% of physicians indicated that they offered such counseling, and approximately 78% of women with FH expressed the need for counseling on pregnancy-related matters. Regarding the appropriate timing for counseling, physicians selected “upon marriage” most often, while women with FH selected “at the first visit,” “upon their request,” and “senior high school students” more often (Fig.3-1). Regarding the provider of counseling, both physicians and women with FH selected “physicians” most frequently, and 58% of women with FH selected “obstetricians” (Fig.3-2). Regarding the topics of counseling, both physicians and women with FH selected “FH treatment during pregnancy” and “inheritance of FH by children,” but women with FH also selected “effect of FH on pregnancy” and “effect of FH on breastfeeding” (Fig.3-3).
Physicians and women diagnosed with FH were asked about the appropriate timing for counseling on pregnancy-related matters. The dotted bars represent the percentage of physicians who selected each time point, whereas the black bars represent the percentage of women with FH. Multiple answers were allowed.
Physicians and women diagnosed with FH were asked about appropriate information providers for counseling on pregnancy-related matters. The dotted bars represent the percentage of physicians who selected each provider, whereas the black bars represent the percentage of women with FH. Multiple answers were allowed.
Physicians and women diagnosed with FH were asked about appropriate content for counseling on pregnancy-related matters. The dotted bars represent the percentage of physicians who actually provided these items; the shaded lined bars represent the percentage of physicians who believed they should provide these items; and the black bars represent the percentage of women with FH who desired these items. Multiple answers were allowed.
We analyzed the correlation coefficients for all items asked with particular attention to items related to anxiety at the time of the FH diagnosis. The average anxiety level at the diagnosis was at 2.5 of 5 points (standard deviation = 1.15). Three correlations were obtained: higher levels of anxiety were associated with fewer births, a greater perceived need for pregnancy-related information, and the belief that such information would influence decisions about pregnancy (Table 6).
| Mean | SD | r | p | |
|---|---|---|---|---|
| Necessity of pregnancy-related information | 1.25 | 0.537 | 0.264 | 0.016 |
| Impact of information on reproductive decision-making | 2.53 | 1.001 | 0.341 | 0.002 |
| Number of deliveries | 2.71 | 1.01 | -0.305 | 0.042 |
r, pearsons's correlation coefficient; SD, standard deviation
Our study revealed that approximately 60% of physicians had experience managing pregnant women with FH, and 76% of these physicians reported difficulties in selecting and adjusting treatment options because of the absence of guidelines on pregnancy and lactation for women with FH. Among the participating women with FH, approximately half had given birth; however, 55% of these women were not diagnosed with FH at the time of their pregnancy. Women with FH expressed concerns about the inheritance of FH by their children and the lack of sufficient information regarding pregnancy and breastfeeding for women with FH. In addition, more than half of the women with FH who had given birth reported discontinuing FH treatment for one year or longer in relation to their first child. In fact, there is a chapter on “pregnancy” in the Japanese FH guidelines6), but this needs to be revised to include more specific information.
5-2 Women’s Needs and Pregnancy-Related CounselingAt the time of the FH diagnosis, 65% of women reported feeling anxious. A significant correlation was observed between the level of anxiety and need for pregnancy-related information, highlighting the importance of providing adequate information to these women.
When comparing women diagnosed with FH before pregnancy to those diagnosed after pregnancy, the former group tended to have fewer pregnancies and births (data not shown). While factors such as the age distribution of respondents, attitudes toward childbearing, and severity of FH are also relevant, a diagnosis of FH before conception does not necessarily have a negative impact on subsequent pregnancy and childbearing. However, it is clear that physicians should be mindful of the stress and anxiety that an FH diagnosis can cause. Differences were observed between physicians and women with FH regarding the optimal timing for counseling. Women with FH preferred earlier counseling, such as at their first visit or even during their senior high school years. This preference suggests that they require information at an early stage to help them consider and plan their life goals, including pregnancy and childbirth.
5-3 Reduction of Cumulative Cholesterol BurdenInterruptions in cholesterol management during pregnancy and lactation may increase the cumulative cholesterol burden8). Our study also revealed that some women with FH experienced a significant loss of treatment time during pregnancy-related periods (before and during pregnancy, as well as after breastfeeding). A study from Norway showed that the median (range) duration of pregnancy-related statin discontinuation per pregnancy was 1.3 (0.0–4.7) years12). Similarly, in the present study, the median duration of treatment interruption for the first child was 1.4 years (17 months), although some women experienced longer interruptions. The Japanese FH guidelines recommend discontinuation of lipid-lowering drugs from three months prior to pregnancy through the lactation period. During this time, only bile acid sequestrants, which are not absorbed, and lipoprotein apheresis can be considered safe for use6, 13). However, it is often challenging for women to conceive exactly as planned after a three-month drug-free period14). This makes the timing of resuming FH treatment particularly distressing for women considering their second child. In the past, FH treatment was suggested to be postponed until a woman had completed childbearing. However, this approach is no longer suitable given that many women today have children later in life, and some choose not to have children at all15). In light of these societal changes, women with FH should receive advice on planned pregnancy and breastfeeding, along with options to balance lifelong FH treatment with key life events, such as pregnancy and childrearing. Obstetricians should play a key role in this process by collaborating with midwives in order to provide comprehensive care.
In addition, some women with FH reported that obstetricians’ FH knowledge was insufficient. Women with FH expressed a desire to discuss perinatal care with obstetricians without being concerned about their level of knowledge regarding FH. Therefore, it is recommended that obstetricians and physicians share the medical information and medical history of women with FH, establishing a system of communication and coordination between the maternity unit and the FH women’s attending physicians.
Furthermore, whether interruptions in cholesterol management during pregnancy and lactation increase long-term risks for women with FH and how the mother’s elevated LDL levels affect the fetus require further investigation. In addition, rather than uniformly prohibiting the use of statins during pregnancy, further studies are needed to identify which women with FH may require statin treatment during this period. Most importantly, it is crucial to increase the FH diagnosis rate in women in Japan to ensure that no woman is excluded from these vital discussions.
5-4 Study LimitationsThe participants women with FH in this study may not be representative of all women with FH. The participants regularly visited physicians specializing in FH and were likely to be more interested in this topic. In addition, some women with FH may choose not to have children, making this type of survey less relevant. Likewise, physicians who participated in this study are board-certified specialists of JAS, which aims to research the causes, prevention, and treatment of ASCVD, so selection bias is possible. Nevertheless, the findings of this study remain valuable to clinicians because they highlight that Japanese women with FH feel that they lack sufficient information about pregnancy and breastfeeding.
This study highlights the importance of providing accurate information on women with FH and actively involving obstetricians in perinatal management. Such efforts can empower these women to exercise their right to self-determination regarding their reproductive life.
This work was supported in part by a grant from the Japan Atherosclerosis Research Foundation and JSPS KAKENHI (Grant Number JP23K08860).
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