Reproductive health and knowledge among youth with sickle cell disease

Abstract

Knowledge related to reproductive health in adolescents with sickle cell disease (SCD) is not fully addressed. We evaluated reproductive health and knowledge among adolescent girls with SCD. Seventy-nine adolescents, 13–21 years of age completed a survey on reproductive health and knowledge with menarche age 13.2 (± 1.7) years. Fifty-four percent reported dysmenorrhea and 49% reported SCD pain a week before menstrual cycle. Sixty-two percent reported discussing contraception and pregnancy with medical providers. Adolescents reported late menarche, dysmenorrhea, and pain with menses. Knowledge of overall reproductive health was inadequate. There is an urgent need to improve reproductive education in this population.

Introduction:

Sickle cell disease (SCD) is an autosomal recessive disorder of hemoglobin associated with sickling of red blood cells, hemolytic anemia, and many acute and chronic complications. In the United States, SCD primarily affects individuals of African ancestry, but also often presents in people of Hispanic, Middle Eastern, or Asian Indian descent. SCD is characterized by presence of sickle mutation on the beta globin chain, which results in production of sickle hemoglobin. SCD can be homozygous (HbSS or sickle cell anemia) or present as other SCD genotypes, such as hemoglobin SC disease and sickle beta plus or zero thalassemia. Severity of disease varies within and among the SCD genotypes and clinical manifestation can vary between patients.¹ Hydroxyurea (HU) is the most used disease modifying therapy in SCD. Improved comprehensive care of SCD has resulted in longer life span, with most patients reaching young adult age, making reproductive health issues very important including education related to these therapies in pregnancy planning.^2,3

Females with SCD may have unique challenges as it relates to reproductive health and practices. Females with SCD are at a higher risk for having a child with SCD compared to individuals with sickle trait, as well as higher rates of complications during pregnancy and peripartum period. Furthermore, given the hypercoagulability in this population, there are specific recommendations related to contraceptive choices. Studies have suggested a delayed onset of menarche, normal and variant menstrual patterns and increase in pain crises with menstruation.⁴ There is limited data and gaps in knowledge on the reproductive health and needs of women with SCD and few studies address these concerns in the adolescent population.⁵ The goal of this study was to examine the current state of reproductive health and knowledge in youth with SCD attending our institution for their SCD care.

Materials and Methods:

Children’s National Hospital’s Institutional Review Board (IRB) approved this cross-sectional study. Females with SCD, 13–21 years of age, presenting to the sickle cell clinic from October 2014- June 2017, for their routine hematology visit were approached to complete the survey anonymously. Patients with known endocrine abnormalities or other concerns (such as emotional stress or not able to stay during the visit to complete the survey) from their hematology provider were excluded from the study. Patients who presented for a sick visit to the clinic were also excluded but were eligible for recruitment later when presenting to clinic in a steady state of health (typically 3–6 months). Written consent was obtained from patients 18 years or older and parental consent with adolescent assent were obtained from those under 18 years of age.

Given the lack of a validated questionnaire, a survey focused on SCD was created by the input from a group of experts in adolescent medicine, gynecology, and hematology with expertise in SCD for this study. The survey consisted of 49 questions, comprised of questions on general SCD and reproductive health knowledge, as well as questions on pubertal and menstrual history. Participants completed the questionnaires on paper in the clinic independently, however study staff were available to clarify any questions in the survey. If a patient did not answer a survey question, they were still included in the study. Results for each question reported here only includes patients who responded to that specific question, therefore the number of responses to a specific question could be different from total enrolled participants. For the analysis related to knowledge on reproductive health “strongly agree” and “agree” were considered together to indicate that respondents were aware of that specific information. De-identified data were entered into a secure, password protected database, stored in an Excel file. Descriptive statistical analysis was performed using Stata. Nominal data were represented as frequencies and percentages. When comparison between groups was performed, the two-sample t-test with equal variances was used to establish the significance of the difference. Alpha level used to determine statistical significance was 5%.

Results:

Demographics

Seventy-nine females with SCD or their caregivers consented to participate in the study. Sixty-four (81%) respondents identified themselves as Black. Forty-four (56%) respondents were attending high school at the time of conducting the survey. Seventy (89%) respondents were born in the United States and about one third of the parents were born outside of United States. (Table 1). Fifty- four (68%) reported either taking Hydroxyurea (HU) or being on it at some point.

Table 1.

Demographics of the study population (N=79)

Characteristics	N	Percent
Race
Black	64	86%
African	7	9%
Other	3	3%
Age
13–15	16	20%
16–17	30	38%
18–19	24	30%
20–221	9	11%
Birthplace
United States	70	89%
Africa	5	6%
Other	4	5%
Education
College	17	22%
High School	44	56%
GED	1	1%
Middle School	7	9%
Elementary	2	3%
Not in School	8	10%

^*Numbers represent the number of participants responded

^*Others refer to Non-Black or African

Pain and Menstrual Symptoms

Seventy-three (92%) respondents were post-menarche with the mean ± SD age of menarche at 13.2 ± 1.7 years. Mean age of menarche was not different between the patients who had taken HU compared to those who had not (13.34 vs. 13.31 years; ranges 8–16 and 10–17 years respectively, (P=.05). The average duration of menses was 5 days with a menstrual cycle ranging from 24–35 days. Seventy-eight (99%) patients responded to questions about their symptoms around their menstrual period which inquired about backpain, cramps, headache, irritability, and sickle cell crises pain. Figure 1 shows pain and other symptoms before and during the menstrual cycle. Sixty-four (82%) respondents reported having pain before their menses. Episodes of sickle cell pain crisis a week before and during the menstrual cycle were reported by 38 (49 %) and 33 (43%) respectively.

Figure 1.

Patients (%) reporting pain and other symptoms before and during menstrual cycle.

Knowledge on Reproductive Health

As shown in Figure 2, 68 (92%) respondents were aware of signs of puberty (growth spurt, development of breast and hips, growth of body hair and beginning of menstruation) and 43 (57%) respondents were aware that girls with SCD may experience puberty later than those without SCD. Fifty-seven (76%) respondents were aware that women with SCD can get pregnant and 55 (75%) were also aware that women with SCD may experience more problems during their pregnancy compared to women without SCD. Twenty-seven (46%) respondents could describe complications that women with SCD can experience when asked from the following responses: women with SCD may experience miscarriage, risk for the child to be born with SCD, increased risk for the pregnancy and a possibility of pain crises during pregnancy.

Figure 2.

Responses to questions on knowledge of reproductive health

Fifty-three (68%) respondents denied ever having sexual intercourse. Of the 25 sexually active respondents, 12 (48%) reported using condoms during last intercourse to prevent pregnancy, which was the most common contraceptive used followed by Depo Provera (3) and oral contraceptives (2). Fourteen (19%) of respondents reported using contraception currently or in the past. Indication for using contraception were reported as preventing pregnancy (12), reducing pain symptoms associated with menses (6), to regulate the menstrual cycle (4) and to help with mood symptoms (1).

Fifty-four (68%) respondents reported taking HU. Only about a third (23, 29%) recalled having a discussion on the potential effects of HU on a fetus with a health care provider, 49 (63%) never had that discussion and 6 (8%) were not sure if they ever had that discussion. Thirty-eight (58%) of respondents were not sure if HU was safe in pregnant women with SCD or could be continued if pregnancy was planned.

Discussion

We describe reproductive health and knowledge among young females with SCD at a tertiary care center in the United States. Our study confirmed that there is heightened need for strategies to improve reproductive education in youth with SCD, especially as it relates to contraception, pregnancy planning and medication safety and outcomes related to reproductive health in this population. Pregnancy in SCD can be high risk and often needs combined management and monitoring from both a hematology and obstetric perspective and should ideally be planned.^6,7,8 It is concerning to learn that over one third of respondents reported not receiving information on contraception and pregnancy. Unplanned pregnancy rates historically have remained high and hormonal contraception low in SCD.^8,9 In our cohort many patients reported receiving information about contraception and pregnancy from their hematologist instead of their primary care provider. As hematology visits tend to be more focused on SCD, these discussions are probably not adequately addressed and furthermore, hematologists may not have the expertise to provide this information. Another concerning finding from our survey was that over half of respondents were not aware of current recommendations related to HU and pregnancy or could not recall such discussion. Hydroxyurea (HU) is an FDA approved medication that can be started as early as 9 months of age in children with SCD. Current guidelines recommend holding HU three months before and during pregnancy. Our finding of respondents being unaware of this recommendation could be due to a large proportion of patients starting HU as a child and they may not be aware of discussions related to HU and pregnancy that may have occurred between their parents and the providers when initiating HU therapy. We suggest addressing HU and pregnancy planning along with other reproductive education around puberty again.

Our study also confirmed previously reported findings of delayed menarche in SCD. In the United States, the average age of menarche has been reported to be 12.5 years for Black girls¹⁰ however the mean ± SD age of menarche for girls with SCD in this study was 13.2 (± 1.7) years. Future studies should elucidate characteristics of those with delayed menarche, as this condition may be associated with hypoestrogenic state and could have long term implications for cardiovascular, bone and urogenital health.¹¹ Recently, concerns have been raised about the impact of HU on ovarian reserve, however we did not find any difference in the age of menarche by HU use in our cohort.¹² Increased vaso-occlusive crises have been noted during/around the time of menses and this was also observed in the current study^4,13 Almost half of respondents reported increased frequency of painful crises and other symptoms, such as dysmenorrhea, headaches, and irritability around menses.

Our study showed there is an urgent need to address reproductive health in youth with SCD which was recently confirmed by the Center for Disease Control and Prevention.¹⁴ We propose that adolescents with SCD may benefit from having clinical guidelines and protocols that are developed by multidisciplinary teams that include primary care providers, obstetrics/gynecology, and hematology providers. Clinical guidelines and protocols should include safety of contraceptive use in SCD, care structures to prevent unplanned pregnancy, indications for fertility preservation and SCD treatments and therapies that can affect fertility and optimal treatment during pregnancy.¹⁵

Referral to adolescent medicine or gynecology around the time of puberty for comprehensive evaluation, counseling, and addressing contraception needs, as well as, safety of medications, including HU use (as it relates to pregnancy), is also needed. Patient -provider communications on reproductive health issues such as puberty, contraception, STI risks, as well as sexual function and sexual orientation are important so that necessary and appropriate referrals can be instituted.¹⁶ Communications with adolescents and young adults alone in a private setting is also important. Further research is needed to identify barriers and interventions to improve patient-provider communications. Nurse practitioners can play an important role in education interventions and developing nurse-led models of care to address guidelines and protocols.

There were limitations of this study. We included a convenience sample of patients from one urban pediatric hospital, and we lack use of a non-SCD control population, which may limit generalizability. We were unable to confirm dysmenorrhea and other symptoms reported in our cohort and how they were similar or different compared to adolescents without SCD. There is also concern for recall bias, as participants were asked to report on previous menstrual history ranging from months to years. Another limitation includes the use of a non-validated questionnaire, as a SCD specific survey was unavailable. This led the multidisciplinary team to assemble SCD and adolescent relevant questions in addition to having to utilize standard clinical questions to assess reproductive health and knowledge. We hope that a validated reproductive questionnaire may be developed for future multisite studies to address this area of urgent unmet need. SCD affects primarily those of African ancestry, however association between the country of birth and outcomes were not evaluated in the study. The result of this study adds to the small but growing body of literature on reproductive health in adolescents and young adults with SCD. We hope future studies can build on our findings.

Figure 3.

Source of information on contraception and pregnancy

Highlights.

• Limited data on the reproductive health and needs of women with sickle cell disease

• There is limited knowledge related to reproductive health in adolescent females with sickle cell disease

• There is a need for strategies to improve reproductive education

• Multidisciplinary team approach should be utilized to provide reproductive health education to this population