Health-related quality of life in pregnancy with uterine fibroid: a cross-sectional study in China

Background: Uterine fibroids (UFs) are the most common benign tumors in women. They are likely to cause numerous clinical symptoms, such as pain, menorrhagia, and other obstetric complications in pregnant women. This study aimed to determine the health-related quality of life (HRQoL) during pregnancy with uterine fibroids (UF) , thus providing a utility-based case value in pregnant women with UF and understanding of whether HRQoL is associated with clinical outcomes in pregnant women with UFs.

This study was conducted in a cross-sectional manner. This study was based on questionnaire surveys completed by sequential out- and in-patients and was conducted in a regional university hospital in Guangzhou, China. The EuroQoL five-dimension-five-level (EQ-5D-5 L) questionnaire was used, and demographic data were collected. An electronic record of the clinical outcomes of pregnant women with UF was retrieved from the hospital’se l e c t r o n i c medical record system. The association between UFand HRQoL was evaluated by ordered regression. Results:Seven-hundred-sixty-seven pregnant women with a mean age (SD) of 32.7 (4.8) years completed 707 questionnaires. Overall, when comparing the UF with non-UF groups, we detected statistical differences in age, body mass index (BMI), gravidity and abortion times, partner’s smoking and alcoholic habits, advanced maternal age, and uterine scars (p < 0.05). Furthermore, pregnant women without UF scored significantly higher than those with UF on the EQ-5D value system (0.84 versus 0.79;p = 0.017). Moreover, pregnant women with UF suffered more health-related problems, especially with respect to self-care (odds ratio [OR] = 3.69,p < 0.01) and usual activity dimensions (OR = 2.11; p = 0.01). Conclusion:We found that UF has a negative impact on the HRQoL of pregnant women with respect to self-care and usual activity dimensions. Also, the EQ-5D score was a better index than the EQ-VAS score for HRQoL when evaluating of the QoL of our population of pregnant women.

Background Uterine fibroids (UFs), also known as uterine myomas, fibromyomas, or leiomyomatas, are the most common benign tumors in women and have clinical morbidity rates of 20 to 40% and prevalence rates of 3 to 12% dur- ing pregnancy. The common causes of UFs are variable factors, such as genetics, endocrine factors and lifestyle factors [ 1–3]. The clinical outcomes range from asymp- tomatic to presentation of pain, menorrhagia, and ob- stetric complications such as infertility, miscarriage, and/ or scarred uterus [ 3, 4]. However, these symptoms can affect the quality of life for pregnant women [ 5]. In a recent study, pregnant women were shown to suf- fer from an increase in the risk of depression [ 6], and depressive symptoms correlate with impairment of HRQoL [ 7]. According to prior studies, pain was shown to be the most common symptom of UF during preg- nancy, and the risk of depression could increase in this © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. * Correspondence: [email protected]; [email protected]; [email protected] †Wai-Kit Ming, Huailiang Wu and Yanxin Wu contributed equally to this work. 1Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Full list of author information is available at the end of the article Ming et al. Health and Quality of Life Outcomes (2019) 17:89 https://doi.org/10.1186/s12955-019-1153-6 situation [ 3, 8]. Some past studies used the EuroQoL Group’s five-dimension questionnaire (EQ-5D) to meas- ure and assess the relationship between pain, depressive symptoms, and quality of life (QoL) [ 7, 9, 10]. Consider- ing that most pregnant women do not have fatal dis- eases, it was suitable to use a generalized questionnaire to assess their HRQoL values. Therefore, as one of the most common instruments for measuring the overall body health state, the EQ-5D is a powerful and popular tool, especially for assessing pain and anxiety/depression symptoms [ 11, 12]. The symptoms and clinical outcomes caused by UFs might correlate with HRQoL; therefore, clinicians can use HRQoL as an index to evaluate the ef- fectiveness of treatment [ 13, 14]. In contrast to traditional clinical outcomes, HRQoL during pregnancies with UFs can be used as an outcome indicator in health policy research, facilitating the im- provement of clinical UF management. Utility data are key factors for cost-utility analysis and quality-adjusted life-year analysis in healthcare-related economics but have not been addressed in the literature; therefore, this study could provide a utility-based case value in preg- nancies with UFs.

We aimed to evaluate several parameters: (1) determine the HRQoL in pregnancies with UFs; (2) provide a utility-based case value in pregnancies with UF; and (3) understand whether HRQoL is associated with the clin- ical outcomes of pregnant women with UFs.

Study design A cross-sectional study was performed as a part of a lon- gitudinal project that studied pregnant women who re- ceived prenatal care during different gestational ages at one of the largest regional university hospitals in south China (The First Affiliated Hospital of the Sun Yat-sen University) from May 2017 to February 2018. Ethical ap- proval was granted by the Institutional Review Board of The First Affiliated Hospital of Sun Yat-sen University (ICE-2017-296). All procedures were conducted in ac- cordance with the Declaration of Helsinki. All partici- pants signed the informed consent documents before participation in this study. Study population All participants came from The First Affiliated Hospital of the Sun Yat-sen University. Eligible participants were included if they were pregnant. Only the first record for each participant was included in this study. Participants were excluded when they had missing personal informa- tion and/or clinical data. Furthermore, if any participants completes more than one EQ5D questionnaire, all add- itional records were excluded, except for the first one. Measurement Patient-evaluated HRQoL is an important index in the assessment of a patient ’s health and functional states [15]. The EuroQoL Group ’s five-dimension question- naire (EQ-5D) with EuroQoL Group ’s visual analog scale questionnaire (EQ-VAS) is a common questionnaire for measuring the quality of life, making cost-efficiency cal- culations, and evaluating economic issues in the public health field. The EuroQoL Group ’s five-dimension five-level questionnaire (EQ-5D-5 L) is a more reliable and sensitive instrument for measuring HRQoL than the EQ-5D-3 L [ 16]. The EQ-5D-5 L instrument contains a descriptive system for assessing a participant ’s health state over five dimensions based on five levels in each di- mension and utilizes a self-determined visual analog scale (VAS). These two parts were used throughout this study. The Chinese version of the EQ-5D-5 L has been shown to be valid and effective and is commonly used to measure HRQoL [ 17, 18]. EQ-VAS can provide a self-reported global measure of overall health and broader dimensions of assessment than EQ-5D although more than half the participants do not accurately evalu- ate themselves when using these types of scoring sys- tems [ 19, 20]. This study might help to identify which of these two independent tools is more suitable for asses- sing pregnant women with UFs and provide detailed HRQoL data for future studies. Participants were administered the EQ-5D question- naire the first time that they visited the hospital for pre- natal care. The EQ-5D assessed five dimensions (mobility, self-care, usual activity, pain/discomfort, and anxiety/depression) and it was based on five problem levels: (1) none; (2) slight; (3) moderate; (4) severe; and (5) extreme/unable. As examples, the self-care dimen- sion asks about the degree of problems experienced when “washing and dressing by yourself ”, and the usual activity dimension asks about the degree of problems in “work, study, housework, family, or leisure activities in daily life ”. The five levels of response were represented by integer values (such as 1 –5 with values of 2 –5 indi- cating health-related problems) [ 16, 17, 19]. Each re- sponse pattern was calculated into a single EQ-5D index value (such as 11,221) through the EQ-5D-5 L Crosswalk Index Value Calculator to produce a final QoL value. The value ranged from − 0.224 to 1 with 1 indicating the best health state of people, whereas 0 represents death. Most patients are in the range from 0 to 1; however, it is still possible to achieve scores < 0, and these negative values correspond with overall health states (both phys- ical and mental) that are considered worse than death [18]. We then measured each dimension and compared Ming et al. Health and Quality of Life Outcomes (2019) 17:89 Page 2 of 11 responses between pregnant women with and without UF. The EQ-VAS was a self-assessment of health state across five dimensions based on five levels of response. It presented as a vertical line with demarcations from 100 (best imaginable health state) to 0 (worst imaginable health state) [ 21]. Respondents were asked to draw a line from the bottom line 0 to the score line based on their opinion of their health states and fill the score in the blank beside. Variables Basic independent covariates of the study population in the models included age, body mass index (BMI), living location, gravidity, parity, abortion, gestational trimester (first, second, or third), and advanced maternal age (in- dicated the age of pregnant women > 35 years old) [ 22]. A meta-analysis showed no significant impact of smok- ing on risk of UFs [ 23]. However, we wanted to detect whether the smoking state of pregnant women could affect the HRQoL in those pregnant women with UF. Furthermore, the partners ’ lifestyle habits, such as smok- ing status and alcohol consumption, were also included in this study. Also, multipara, uterine scar, hepatitis B history, heart disease, and surgical history were included as part of the index for pre-pregnancy conditions. Throughout the study, participants were categorized by gestational trimester in which the first trimester was taken when the pregnant women were at the gestational age of 28 weeks. In generalized situations, we use transvaginal ultrasonography to detect and diagnose uterine fibroids. However, on rare occasions, such as suspected carcin- oma (indicated by elevated cancer biomarker levels), a pathological examination might need to be performed to distinguish the uterine fibroids from uterine carcinoma under the current guideline in our hospital. In this situ- ation, the risk of miscarriage due to the procedure needs to be balanced [ 24]. In this study, we did not have any cases that needed to undergo pathological examinations. Bias The EQ-5D questionnaire was a subjective measurement of pregnant women ’s HRQoL, and self-reported bias may be the main bias in this study. Based on the popula- tion, this study also minimized selection bias but had non-response, volunteer, and ascertainment biases. Statistical methods Data analysis was performed using the STATA/SE 14.0 for Windows. Normally distributed continuous variables were described using the means + standard deviations (SDs), and ranges. Non-normal variables were presented as the median, and categorical variables were described using counts and percentages. The dependent variables were the EQ-5D score utility and EQ5D-VAS. EQ-5D scores were in a skewed distribution; therefore, we used a non-parametric approach to analyze the data. Participants’ demographic data were reported (age, ad- vanced maternal age, BMI, local, gravity, party, abortion, smoking, partner smoking status and alcoholic con- sumption, multipara, surgery history, hepatitis B, and heart disease). The clinical outcomes were retrieved from the hospital electronic medical system after deliv- ery. Since the EQ5D values present a skewed distribu- tion, we divided these values into two groups based for statistical analysis on the median EQ5D values: (1) above the median and (2) below the median [ 25]. Analysis of variance and t- and the chi-squared tests were used to compare continuous and qualitative variables among the three different trimesters. Health quality, as measured by the EQ5D-VAS scores or EQ5D values, and multiple lin- ear regressions was used. Potential confounders were ad- justed. An ordered logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs) is an appropri- ate method to use when examining the effects of inde- pendent risk factors on various dimensions in the EQ5D index when complementary dimensions are taken into account [ 26, 27]. ORs, 95% CIs, and p-values were ob- tained using an ordered logistic regression analysis. All tests were two-sided, and a p-value of 0.05 was consid- ered as statistically significant.

Participants In total, all 767 pregnant women agreed to participate in this study, but of these 60 were excluded due to missing clinical data or personal information. We only reserved the first record as their HRQoL. Therefore, 707 of the included pregnant women provided 707 EQ-5D-5 L valid questionnaires for the analysis. Using electronic medical records, we identified 105 pregnant women with UFs. Of these, 103 were included in the study because two women did not deliver within the period under analysis (Fig. 1). Descriptive data General characteristics of patients Of 707 pregnant women, the ages ranged from 21.3 to 47.4 years, and the mean age was 32.7 ± 4.8 years. Of those, in UF group, 105 women (14.9%) were included and were 35.6 ± 4.8 years on average, while the non-UF group of pregnant women ’ s mean age was 32.3 (4.5) years (Table 1). The mean BMI across those with UFs was 26.4 + 4.0 and was significantly lower (23.5 + 3.9) among those without UFs. Of the 707 eligible pregnant women, most (90.9%) lived locally (living in Guangzhou). The mean values for Ming et al. Health and Quality of Life Outcomes (2019) 17:89 Page 3 of 11 gravidity, parity, and abortion times across the entire population were 2.2 ± 1.1, 0.5 ± 0.5, and 0.6 ± 0.9, respectively. All 707 pregnant women denied smoking during pregnancy. Some women ’s partners (15.4%) were smokers, and 8.1% of the partners consumed alcohol. Fifteen percent of the sample population was multipara, 24.8% had surgical histories, 30.3% were of advanced maternal age, 23.2% had scars on the uterus, 2.1% had hepatitis B, and 0.9% had chronic heart disease. Table 1 shows these risk factors for th e sample population. Signifi- cant differences were found in age between those with and without UFs ( p 0.01), BMI ( p < 0.01), gravidity ( p =0 . 0 3 ) , abortion ( p = 0.01), partner smoking ( p = 0.02), partner alcoholism ( p = 0.03), scarred uterus ( p =0 . 0 3 ) , m u l t i p a r a (p < 0.01), and advanced maternal age (p <0 . 0 1 ) . Outcome data The characteristics of clinical outcomes in pregnant women with UFs Two of the study participants did not deliver at the time point of analysis. Thus, these results only included clin- ical outcomes of 98.15% (103 out of 105) pregnant women with UFs. Among those pregnant women en- rolled in the study (except for the two that had not de- livered), about 44.7% belonged to the below median EQ-5D score group while 55.3% came from the above median EQ-5D score group (Table 2). The mean +S D gestational ages for the below median and above median EQ-5D score groups were 37.8 + 1.7 and 38.0 + 1.6 weeks, respectively. For pregnancy complications, no statistical difference was found between two groups. Main results The EQ-5D and EQ-VAS values assessed using the EQ-5D-5 L The EQ-5D and EQ-VAS value distributions are shown (Figs. 2 and 3). Of the total 707 EQ-5D and EQ-VAS re- cords (707 pregnant women), the mean (SD) EQ-5D in- dices for those with and without UFs were 0.79 ± 0.21 and 0.84 ± 0.18, respectively ( p = 0.017) and the mean of EQ-VAS with and without UFs were 88.0 ± 8.6 and 87.3 ± 9.9, respectively ( p =0 . 4 8 0 ) ( T a b l e3). Besides, the groups also showed differences in age and BMI (both p <0 . 0 1 ) (T able 1). Therefore, age and BMI were adjusted in the Fig. 1 Selection of the study population Table 1 Demographic characteristics UF (n = 105) Non-UF (n = 602) All patients (n = 707) p-value Age (SD) 35.6(4.8) 32.3(4.5) 32.7(4.8) < 0.01 Advanced maternal age 53(50.5%) 161(26.7%) 214(30.3%) < 0.01 BMI (SD) 26.4(4.0) 23.5(3.9) 23.9(4.1) < 0.01 Living location (Guangzhou) 96(91.4%) 547(90.9%) 643(90.9%) 0.85 Gravidity (SD) 2.4(1.2) 2.1(1.1) 2.2(1.1) 0.03 Parity (SD) 0.6 (0.5) 0.5(0.5) 0.5(0.5) 0.57 Abortion (SD) 0.8(0.9) 0.6(0.8) 0.6(0.9) 0.01 Smoking 0(0.0%) 0(0.0%) 0(0.0%) – Partner Smoking 24(22.9%) 85(14.1%) 109(15.4%) 0.02 Partner Alcoholics 14(13.3%) 43(7.1%) 57(8.1%) 0.03 Multipara 5(4.8%) 101(16.8%) 106(15.0%) < 0.01 Surgical history 26(24.8%) 149(24.8%) 175(24.8%) 1.00 Uterine scar 33(31.4%) 131(21.8%) 164(23.2%) 0.03 Hepatitis B 1(1.0%) 14(2.3%) 15(2.1%) 0.37 Heart disease 1(1.0%) 5(0.8%) 6(0.9%) 0.90 UF Uterine fibroids, BMI Body mass index. Bold represented p value < 0.05. Data with SD indicates “mean” value. Data without SD indicates “number” Ming et al. Health and Quality of Life Outcomes (2019) 17:89 Page 4 of 11 analysis. After adjustment, EQ-5D scores were signifi- cantly different between women with and without UFs ( p = 0.007), while the EQ-VAS score showed no statistically significant difference between the two groups (p =0 . 4 8 6 ) . The EQ-5D and EQ5D-VAS scores varied across the different gestational trimesters (Figs. 4 and 5). Pregnant women with UFs scored lower indices on the EQ-5D compared to those without UFs, regardless of the tri- mester. Among those without UFs, the mean EQ5D in- dices were 0.75, 0.88, and 0.82 in the first, second, and third trimesters, respectively. In the first, second, and third trimesters, mean EQ5D indices were 0.56, 0.83, and 0.78, respectively, among those pregnant women with UF. The mean EQ5D-VAS scores were lower among those with UFs compared to those without, ex- cept in the third trimester. Also, women from both groups (non-UF versus UF) presented the greatest EQ-5D indices (0.88 versus 0.83) and EQ5D-VAS scores (88.1 versus 88.0) in the second trimester. Uterine fibroids and other factors contributing to health quality The 707 EQ-5D records were classified based on the presence of UFs in the participant. Table 4 shows that Table 2 Clinical outcomes of pregnant women with uterine fibroids Below median EQ5D score (n = 52) Above median EQ5D score (n = 51) All UF patients (n = 103) p-value Cesarean Section 39(75.0) 31(60.8) 70(68.0) 0.91 Preterm labor 5(9.6) 9(17.6) 14(13.6) 0.67 Precipitate labor 0(0.0) 3(5.9) 3(2.9) 0.11 Placenta adherence 8(15.4) 7(13.7) 15(14.6) 0.34 Nuchal cord around neck 10(19.2) 15(29.4) 25(24.3) 0.19 PROM 11(21.2) 15(29.4) 26(25.2) 0.28 Postpartum hemorrhage 1(1.9) 2(3.9) 3(2.9) 0.44 Amniotic fluid turbidity 6(11.5) 6(11.8) 12(11.7) 0.31 Perineal laceration 7(13.5) 10(19.6) 17(16.5) 0.83 Hypertensive disorders 14(26.9) 9(17.7) 23(22.3) 0.90 Gestation age at birth 37.8(1.4) 38.1(1.9) 37.9(1.7) 0.73 Apgar score - 1 min 9.85(0.5) 9.75(0.63) 9.8(0.57) 0.13 Fetal distress 5(9.6) 12(23.5) 17(16.5) 0.07 PROM Premature rupture of membrane Fig. 2 Distribution of EQ-5D values of all pregnant women Ming et al. Health and Quality of Life Outcomes (2019) 17:89 Page 5 of 11 23.8% of the records for those with UFs also indicated problems with mobility, 20.0% with self-care, 29.5% with usual activity, 52.4% with pain/discomfort, and 35.2% with anxiety/depression. Additionally, 18.9% of the preg- nant women without UFs suffered mobility problems, 7.3% had self-care problems, 16.0% had problems with their usual activities, 45.7% had pain/discomfort prob- lems, and 30.1% had anxiety/depression problems. The

indicate that pain and discomfort during preg- nancy were major problems for pregnant women, while problems with self-care were of the least concern. Be- sides, there were about 13.5% more health-related prob- lems with respect to the usual activity dimension in the UFs group than that in non-UFs group, which was a no- ticeable difference between pregnant women with and without UFs for the five dimensions. For the overall sta- tus, there was a greater proportion of those with UFs who experienced health-related problems (regardless of the dimensions) when compared to those without UFs. An ordered logistic regression analysis was used for each dimension in the EQ-5D (Table 5). Women in their second or third trimesters reported more problems with mobility (OR = 1.77; p < 0.01) and pain/discomfort (OR = 1.46; p < 0.01) than those in their first trimester. UFs were related to self-care problems (OR = 3.69; p < 0.01) and usual activity problems (OR = 2.11; p < 0.01). Fig. 3 Distribution of EQ5D-VAS values of all pregnant women Table 3 EQ-5D Index and EQ-VAS scores with and without UF EQ5D Index ( n = 707) Unadjusted Age adjust Age & BMI adjusted UF group 0.79(0.21) 0.79(0.00) 0.79(0.00) Non-UF group 0.84(0.18) 0.84(0.00) 0.84(0.00) p-value 0.017 0.002 0.007 EQ5D-VAS (n = 707) Unadjusted Age-adjusted Age & BMI adjusted UF group 88.0(8.6) 88.0(0.01) 88.0(0.01) Non-UF group 87.3(9.9) 87.2(0.00) 87.3(0.00) p-value 0.480 0.522 0.486 UF Uterine fibroids, BMI Body mass index Fig. 4 EQ5D index and its 95% confidence interval (CI) on gestational trimesters. a.The first-trimester group contains 30 pregnant women, 27 pregnant women without UFs, and 3 pregnant women with UFs. b.The second-trimester group contains 263 pregnant women, 220 pregnant women without UFs, and 43 pregnant women with UFs. c.The third-trimester group contains 414 pregnant women, 355 pregnant women without UFs, and 59 pregnant women with UFs. d.UFs indicates uterine fibroids Ming et al. Health and Quality of Life Outcomes (2019) 17:89 Page 6 of 11 Pregnant women who were not located locally suffered from more severe pain/discomfort problems during the first trimester (OR = 2.16; p < 0.01). More gravidity was associated with problems regarding usual activity (OR = 1.33; p = 0.01), and less parity was associated with prob- lems with usual activity (OR = 0.56; p = 0.03) and anx- iety/depression (OR = 0.60; p = 0.02).

Key results The major finding of the present study indicated that uterine fibroids could significantly affect HRQoL of pregnant women in two dimensions (self-care and usual activities) when compared to women without UF. Preg- nant women with UFs had a lower EQ-5D index than those without UFs (0.80 versus 0.84) while their average EQ5D-VAS scores were 88.0 versus 87.3. This EQ-VAS

was similar to that found in other research in China in which evaluated health status in a similarly-aged cohort was evaluated [ 28, 29]. Less than 15% of pregnant women rated their health status as 100 (best possible health state) based on the EQ5D-VAS. However, the EQ-VAS scores did not show statistically significant differences between pregnant women with and without UFs, and the different standards of health self-evaluation from each part icipant could cause bias in t h eE Q 5 D - V A Sr e s u l t s ;t h u s ,t h eE Q 5 Di n d e xm i g h tb ea more suitable index than the EQ-VAS for evaluating HRQoL in pregnant women with UFs. Furthermore, preg- nant women showed the greatest EQ-5D indices and EQ5D-VAS scores during their second gestational trimester regardless of UF or non-UF group (Figs. 4 and 5). Figure 2 shows that the EQ-5D value was the lowest in the first ges- tational trimester regardless of UF status. However, this finding was not in agreement with results of some other published studies [30, 31]. This lack of agreement might be caused by the policy of perform ing a full systemic prenatal examination and consultation in the second and third tri- mesters in China in addition to health-care appointments every 2 or 4 weeks, which might improve pregnant women’s the HRQoL. Those with UFs had more health-related prob- lems across a range of five dimensions (mobility, self-care, usual activity, pain/discomf ort, and anxiety/depression) compared to those without (T able 4) .A b o u th a l fo ft h e pregnant women (46.7%) suffered health problems associ- ated with pain and discomfort; this was the greatest propor- tion of the five dimensions. Thus, it is necessary for the public healthcare system to focus on relieving this pain and discomfort when designing policies. Fig. 5 EQ5D-VAS scores and its 95% confidence interval (CI) on gestational trimesters. a. The first-trimester group contains 30 pregnant women, 27 pregnant women without UFs, and 3 pregnant women with UFs. b The second-trimester group contains 263 pregnant women, 220 pregnant women without UFs, and 43 pregnant women with UFs. c The third-trimester group contains 414 pregnant women, 355 pregnant women without UFs, and 59 pregnant women with UFs. d UFs indicates uterine fibroids Table 4 The frequencies of pregnant women that report levels 1 to 5 for the various dimension EQ-5D Dimension Uterine fibroid Total (%) UF (%) Non-UF (%) Mobility Level 1 80(76.2) 488(81.1) 568(80.3) Level 2 20(19.1) 91(15.1) 111(15.7) Level 3 1(1.0) 9(1.5) 10(1.4) Level 4 0(0.0) 3(0.5) 3(0.4) Level 5 4(3.8) 11(1.8) 15(1.4) Self-care Level 1 84(80.0) 558(92.7) 642(90.8) Level 2 17(16.2) 29(4.8) 46(6.5) Level 3 1(1.0) 2(0.3) 3(0.4) Level 4 0(0.0) 1(0.2) 1(0.1) Level 5 3(2.9) 12(2.0) 15(2.1) Usual Activity Level 1 74(70.5) 505(84.0) 579(81.9) Level 2 26(24.8) 75(12.5) 101(14.3) Level 3 2(1.9) 11(1.8) 13(1.8) Level 4 0(0.0) 3(0.5) 3(0.4) Level 5 3(2.9) 8(1.3) 11(1.6) Pain/Discomfort Level 1 50(47.6) 327(54.3) 377(53.3) Level 2 49(46.7) 246(40.9) 295(41.7) Level 3 3(2.9) 15(2.5) 18(2.6) Level 4 0(0.0) 6(1.0) 6(0.9) Level 5 3(2.9) 8(1.3) 11(1.6) Anxiety/ Depression Level 1 68(64.8) 421(69.9) 489(69.2) Level 2 34(32.4) 157(26.1) 191(27.0) Level 3 0(0.0) 11(1.8) 11(1.6) Level 4 1(1.0) 4(0.7) 5(0.7) Level 5 2(1.9) 9(1.5) 11(1.6) Ming et al. Health and Quality of Life Outcomes (2019) 17:89 Page 7 of 11 Besides, the EQ5D indices with respect to mobility and pain/discomfort dimensions fas reported by women without UFs were greater than those with UFs regardless of the trimester, which might be explained by lower levels of physical activities during the second and third trimesters [ 32]. Increased gravidity significantly corre- lated with the rising odds of usual activity problems (Table 5) because pregnant women who have increased gravidity in China mostly had their second child at ad- vanced maternal ages because of the recent start of the Chinese two-child policy and long period of China ’s one-child policy. Under these conditions, pregnant women with advanced maternal ages were more likely to receive more medical care during pregnancy, which might be explain the increase in usual activity problems. In addition, decreased parity (mostly nulliparity) could contribute to the increase in usual activity problems. A previous study had clearly recognized a decrease in par- ity as a risk factor for the incidence of UFs [ 24], possibly because the production of estrogen and progesterone de- clines in parity and has considerable effects on fibroids ’ growth [ 33]. These findings offer additional and detailed evidence for the negative influence of UFs on HRQoL, which is in agreement with other cross-sectional studies. One web-based cross-sectional study investigated the HRQoL across 4848 women aged 18 to 49 years using the Uter- ine Fibroid Symptom-Quality of Life Questionnaire (UFS-QoL) and demonstrated a significant reduction in HRQoL in women with UFs [ 34]. An online cross-sectional study also found that the HRQoL might decrease with UFs and might be significantly impacted by UF-related symptoms [ 35]. Our study shows that UFs in pregnant women might affect the HRQoL scores in the self-care and usual activity dimensions (Table 5). Comparative assessments of pregnant women with and without UFs based on gestational index and chronic condi- tions indicate that some of these independent factors con- tributed considerably to the i ncidence of UFs, while other conditions were in an inverse relation with UFs. Ages and B M I sa r eh i g h e ra m o n gt h o s ew i t hU F st h a nt h o s ew i t h o u t , which can be explained by a greater age indicating more gravidity, abortion, and opportunities for pregnancy during Table 5 Ordered logistic regression analysis for each dimension in the EQ5D Odds ratio 95% CI p-value Mobility Age 0.98 0.93, 1.02 0.35 BMI 1.03 0.98, 1.08 0.26 Local 0.83 0.48, 1.43 0.50 Gestation trimester 1.77 1.21, 2.60 < 0.01 Partner smoking 1.10 0.64, 1.87 0.74 Partner Alcoholics 1.21 0.59,2.51 0.60 Gravidity 1.17 0.95, 1.45 0.15 Parity 0.97 0.60, 1.57 0.90 UF 1.32 0.77, 2.25 0.31 Self-care Age 0.96 0.90, 1.02 0.17 BMI 1.00 0.94, 1.08 0.94 Local 1.15 0.48, 2.76 0.16 Gestation trimester 1.58 0.95, 2.65 0.08 Partner smoking 0.74 0.38, 1.42 0.36 Partner alcoholics 1.79 0.59, 5.37 0.30 Gravidity 0.91 0.64, 1.28 0.59 Parity 0.72 0.35, 1.49 0.38 UF 3.69 1.94, 7.03 < 0.01 Usual activity Age 0.98 0.93, 1.03 0.47 BMI 1.03 0.97, 1.08 0.34 Local 0.74 0.43, 1.29 0.29 Gestation trimester 1.38 0.94, 2.00 0.10 Partner smoking 1.46 0.80, 2.66 0.22 Partner alcoholics 1.16 0.54, 2.49 0.71 Gravidity 1.33 1.07, 1.66 0.01 Parity 0.56 0.33, 0.94 0.03 UF 2.11 1.25, 3.55 < 0.01 Pain/Discomfort Age 0.96 0.93, 1.00 0.06 BMI 1.00 0.96, 1.04 0.96 Local 2.16 1.26, 3.71 < 0.01 Gestation trimester 1.46 1.11 1.93 < 0.01 Partner smoking 1.26 0.82, 1.93 0.29 Partner alcoholics 0.71 0.41, 1.26 0.25 Gravidity 1.07 0.90, 1.29 0.45 Parity 0.75 0.51, 1.10 0.14 UF 1.47 0.94, 2.28 0.09 Anxiety/depression Age 1.00 0.96, 1.04 0.93 BMI 1.01 0.97, 1.06 0.55 Local 1.07 0.65, 1.78 0.78 Gestation trimester 0.90 0.68, 1.21 0.49 Table 5 Ordered logistic regression analysis for each dimension in the EQ5D (Continued) Odds ratio 95% CI p-value Partner smoking 0.85 0.56, 1.31 0.47 Partner alcoholics 0.97 0.53, 1.76 0.91 Gravidity 1.04 0.86, 1.26 0.68 Parity 0.60 0.39, 0.91 0.02 UF 1.18 0.74, 1.89 0.75 Bold represented p-value < 0.05 Ming et al. Health and Quality of Life Outcomes (2019) 17:89 Page 8 of 11 advanced maternal age (T able 1)[ 1, 36]. The incidence of UFs (p < 0.05) will cause higher gravidity and abortion rates according to our data (Table1), and this finding could be ex- plained by the fact that UFs can significantly lead to more infertility [3]; therefore, gravidity and abortion rates will in- crease correspondingly. We were surprised about the self-report smoking status of the pregnant women as none of them smoked. This finding might be due to the family planning policy (one-child policy in the past and two-child policy recently) in China, wh ich might increase mothers ’ concerns about their baby ’s health status although self-report bias is another possible explanation. Also, it seemed that there was no statistical significantly impact be- tween partner smoker/alcohol consumption and pregnant women’s HRQoL state in the different dimensions (T able5). One prior study demonstrated that the rate of Cesarean section has increased from 28.8% in 2008 to 34.9% in 2014 in China [ 37], and this rate was shown to be related to family income, education, health insurance, Chinese health policy, and cultural background, among other factors [ 38]. In pregnant women with UFs, Cesarean section rates reached 67.0%, which was much higher than the rate in the normal population world- wide. Cesarean section may be the most suitable man- agement for pregnant women with other pre-pregnancy conditions [ 39]. These findings are consistent with prior published data [ 35, 40–43]. Although there was no significant correlation between low HRQoL and poor clinical outcomes of pregnant women, further studies need to be done to verify these results. QoL is becoming an increasingly important indi- cator of the effectiveness of the medical intervention, and we should pay greater attention to QoL during preg- nancy in our future practice.

There were some limitations to this study. This was a cross-sectional study, and the data was obtained from an EQ-5D questionnaire in which there was relatively a subjective measurement of pregnant women ’s HRQoL. Thus, self-report bias may be the main bias in this study. This study design also presents limitation with respect to both non-response and volunteer biases. Furthermore, we do not make comparisons against different instru- ment other than the EQ-5D. There are some studies that have used the UFS-QoL to assess the HRQoL in preg- nant women [ 34, 35]. This research could provide HRQoL data for pregnant women who were evaluated using the EQ-5D-5 L, and this information could be use- ful in cost-utility analyses in the healthcare-related eco- nomic area. Additionally, the HRQoL is an important indicator of a patient ’s overall state and plays an increas- ingly important role in evaluation in the clinic although there is no significant difference with respect to clinical outcomes between women with and without UFs in the short-term. Nevertheless, we believe that better quality life-related studies should be performed in order to fur- ther investigate the role of QoL in the clinic and moni- tor long-term effects on QoL. Future studies will need to use a cohort to observe the changes in HRQoL in preg- nant women. Interpretation To our knowledge, this is the first clinical study to use the EQ-5D-5 L to focus on HRQoL during pregnancy in China and detect independent factors that could impact HRQoL in pregnant women with UFs. Also, this study shows that EQ-5D index may be a better index than EQ-VAS for pregnant women with uterine fibroids and possibly for other medical comorbidities or complica- tions. Furthermore, the HRQoL data assessed by the EQ-5D-5 L could be used to perform cost-utility analyses in the future. The clinical outcomes of pregnant women with UFs could still offer insight for the clinical phys- ician when considering the possibility of latent complica- tions in pregnant women with UFs.

In this study, we evaluated the influence of UFs on HRQoL in pregnant women and found that the EQ5D assessment instrument outperformed the EQ-VAS. Our findings dem- onstrated that UFs significantly affected HRQoL in preg- nant women in terms of the self-care and usual activity dimensions. Independent factors, such as living locally, gra- vidity and parity times, and gestational trimester, could have a significant impact on the HRQoL. Finally, whether clinical outcomes may affect HRQoL scores need to be precisely analyzed and requires further research. Abbreviations BMI: Body mass index; CIs: Confidence intervals; EQ-5D: The EuroQoL Group ’s five-dimension questionnaire; EQ-5D-3 L: The EuroQoL Group ’s five- dimension three-level questionnaire; EQ-5D-5 L: The EuroQoL Group ’s five- dimension five-level questionnaire; EQ-VAS: EuroQoL Group ’s visual analog scale questionnaire; HRQoL: Health-related quality of life; ORs: Odds ratios; PROM: Premature rupture of membrane; QoL: Quality of lfe; UFs: Uterine fibroids; UFS-QoL: Uterine Fibroid Symptom-Quality of Life; VAS: Visual analog scale Acknowledgments The authors are grateful to Yunyi Jian, Jingyan Zhai, Yu Cheng, Xianghao Cai, and Bangsheng Jiang for previous support in collecting data. Funding There is no financial support in this study. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Authors’ contributions WM contributed to the idea and design of the whole research process and contributed to the final version of the manuscript. HW contributed to the design and management of the whole study, data analysis, and final version Ming et al. Health and Quality of Life Outcomes (2019) 17:89 Page 9 of 11 of the manuscript. YW contributed to the hypothesis of study and final version of the manuscript. TM, YS, ZW, XH WS, TC, and YW contributed to data collection, data analysis, and final version of the manuscript. WD contributed to data collection and drafting the final version of the manuscript. HC and ZL contributed to data analysis and drafting the final version of the manuscript. ZW contributed to the design of the study, the guidance of research, and discussion of the final version of the manuscript. All authors read and approved the final manuscript. Ethics approval and consent to participate Ethical approval was granted by the Institutional Review Board of The First Affiliated Hospital of Sun Yat-sen University (ICE-2017-296). Consent for publication Not applicable Competing interests The authors declare that they have no competing interests. Publisher’sN o t e Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Author details 1Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 2Pharmacoepidemiology and Pharmacoeconomic, Department of Medicine, Brigham and Women ’s Hospital and Harvard Medical School, Boston, MA, USA. 3School of Medicine, Jinan University, Guangzhou, China. Received: 12 September 2018 Accepted: 1 May 2019

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