Integrative medicine and perinatal outcomes among women giving birth: A national population-based study in South Korea.

Conceptualization: JC. Methodology: JC, SP. Validation: JC, SP, HWL. Formal analysis: JC. Investigation: SK, JC. Resources: JC. Data curation: JC. Writing – Original Draft: SK, JC. Writing – Review & Editing: SK, JC, SP. Visualization: SP.

This study was approved by the Institutional Review Board of Korea University in Seoul, Korea (KUIRB-2020-0298-01), with a waiver for informed consent because the data were obtained from a public database; all personal information was de-identified by the NHIS prior to public release. The principles expressed in the Declaration of Helsinki have been adhered to in this study.

No funding was received for this work.

We conducted a nationwide population-based retrospective cohort study using the Korean National Health Insurance (NHI) Claims database, which includes NHSP data. South Korea has one of the largest NHI systems worldwide, a system that is mandated by law and covers up to 98 % of the entire Korean population. The Korean NHI Claims database records diagnoses on the basis of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes. It has been used to provide reliable estimates of the prevalence of certain diseases in Korea. The National Health Insurance Sharing Service (NHISS) collects various types of information, including sociodemographics, diagnoses, and procedures. We identified 178,809 women who gave birth and their infants in Korea in 2021, and we assessed individual socioeconomic status using the information on visits to medical institutions, income percentile rankings, maternal age, infant sex, delivery mode, complications, and underlying diseases. Maternal data linked to their infants were obtained. The IM group was defined as women who visited both conventional medical institutions at least once and traditional medicine institutions at least 3 times during the 5 years from 2017 to 2021. Similarly, the CM group was defined as women who visited conventional medical institutions at least 3 times during the same period without visiting traditional medicine institutions. Therefore, the IM group was considered the intervention group, and the CM-only group was considered the control group. Variables were selected on the basis of prior knowledge and availability in the NHI database. The Korean NHI cohort database includes individually linked household income decile data. Maternal health conditions related to pregnancy, including hypertension, diabetes mellitus, and chorioamnionitis, within the period from 10 months before childbirth (delivery date-diagnosis date <=300), were identified. Income level was classified into the following four groups: low-income (medical aid and 1–5th deciles), lower middle-income (6–10th deciles), upper middle-income (11–15th deciles), and high-income (16–20 deciles). This study was performed in accordance with the Reporting of Studies Conducted using Observational Routinely Collected Data (RECORD) guidelines (Supplement 1). Data on preterm birth, low weight, cesarean delivery and ART were evaluated. Preterm birth was defined as birth at or before 37 weeks of gestation. Birth weight discordance was defined as a birth weight lower than 2500 g. To identify pregnancy mode variables, we collected data almost 10 months before delivery. Pregnancy outcomes were obtained according to ICD-10 codes, and ART and cesarean delivery data were obtained on the basis of procedure codes. The primary and secondary diagnoses were identified in 989,277 claims in the IM group. The disease data of pregnant women who used IM were collected for 5 years. The diseases related to infertility were recorded after all deliveries. Supplement 2 presents the ICD-10 codes for the outcomes. Demographic information (maternal age, infant sex, and income status), underlying disease information (endometriosis, myeloma of the uterus, premature ovarian failure, polycystic ovarian syndrome, or endometrial polyps), and maternal psychiatric disorder information (organic mood [affective] disorders, current episode of mild or moderate depression, bipolar affective disorder, or current episode of severe depression without psychotic symptoms) were collected and recorded. Maternal health conditions related to pregnancy, including hypertension, diabetes mellitus, and chorioamnionitis, within the period from 10 months before childbirth, were identified. This study was approved by the Institutional Review Board of Korea University. The review board waived patient consent because of the characteristics of this study.

Initially, 178,809 women who gave birth and visited medical institutions in 2021 were included. After excluding 7673 women who gave birth and had fewer than 3 visits to medical institutions, 171,136 women who gave birth were included and divided into two groups, namely, the IM group ( n = 79,234, 46.3 %) and the CM group ( n = 91,902, 53.7 %) ( Fig. 1 ). Table 1 presents the general characteristics of the women. The difference in the sex of the infants was similar between the two groups (boys: 40,738; 51.41 % and girls: 47,038; 51.18 % in the IM group; boys: 38,496; 48.59 % and girls: 44,864; 48.82 % in the CM group). Maternal age (≥35 years) was greater in the IM group (32,513; 41.03 %) than in the CM group (36,168; 39.35 %). Both groups had high rates of cesarean section, and the rate in the IM group (47,240; 60 %) was greater than that in the CM group (30,075; 56.66 %). There was little difference in the number of preterm births (<37 weeks) between the two groups. The CM group had the highest percentage of women with low-income levels (lowest 25 %), whereas the IM group had the highest percentage of women with middle-income levels (50 %). Both groups had a low percentage of women with high-income levels (highest 25 %). Compared with the CM group, the IM group presented higher rates of all complications and underlying diseases. Low birth weight accounted for 2.8 % of all births (4841/171,136). The low-birth weight rate was higher in the IM group (2471; 3.12 %) than in the CM group (2370; 2.58 %). Preeclampsia was more common in the IM group (3018; 3.81 %) than in the CM group (3218; 3.5 %), and diabetes during pregnancy was more common in the IM group (16,321; 20.6 %) than in the CM group (34,443; 20.13 %). Among the women in the IM group, 498 (0.63 %) women had premature ovarian failure, 4465 (5.64 %) women had endometrial polyps and premature ovarian failure, 6313 (7.97 %) women had polyps of the endometrium, 2387 (3.01 %) women had endometriosis, 12,775 (16.12 %) women had myeloma of the uterus, and 7970 (10.06 %) women had polycystic ovarian syndrome (PCOS)In the CM group, 296 (0.32 %) women had premature ovarian failure, 4072 (4.43 %) women had polyps in the endometrium, 1844 (2.01 %) women had endometriosis, 13,236 (14.4 %) women had myoma of the uterus and 6313 (6.87 %) women had PCOS. Fig. 1 Recruitment flowchart. Fig 1 Table 1 General characteristics of the study population, N (%). Table 1 Variables IM CM Total ( n = 79,234; 46.3 %) ( n = 91,902; 53.7 %) ( n = 171,136; 100 %) Infant sex Boy 40,738 (51.41) 47,038 (51.18) 87,776 (51.29) Girl 38,496 (48.59) 44,864 (48.82) 83,360 (48.71) Maternal age <35 years 46,721 (58.97) 55,734 (60.65) 102,455 (59.87) ≥35 years 32,513 (41.03) 36,168 (39.35) 68,681 (40.13) Delivery mode Vaginal 311,994 (40) 39,821 (43.34) 71,821 (42) Cesarean 47,240 (60) 52,075 (56.66) 99,315 (58) Preterm ≥37 weeks 77,475 (97.78) 89,957 (97.88) 167,432 (97.84) <37 weeks 1759 (2.22) 1945 (2.12) 3704 (2.16) Income level High (highest 25 %) 15,242 (20) 17,780 (19.89) 33,022 (19.84) Middle (50 %) 20,726 (29.26) 24,722 (27.64) 25,448 (28.37) Low (lowest 25 %) 22,551 (26.9) 26,284 (29.39) 48,835 (29.34) Very low 18,540 (24.07) 20,611 (23.05) 39,151 (23.52) Complications Low (<2500 g) 2471 (3.12) 2370 (2.58) 4841 (2.83) Preeclampsia 3018 (3.81) 3218 (3.5) 6236 (3.64) Diabetes in pregnancy 16,321 (20.6) 18,122 (19.72) 34,443 (20.13) Underlying disease premature ovarian failure 498 (0.63) 296 (0.32) 794 (0.46) Polyp of endometrium 4465 (5.64) 4072 (4.43) 8537 (4.99) Endometriosis 2387 (3.01) 1844 (2.01) 4231 (2.47) Myoma of the uterus 12,775 (16.12) 13,236 (14.4) 26,011 (15.2) Polycystic ovarian syndrome 7970 (10.06) 6313 (6.87) 14,283 (8.35) CM, conventional medicine; IM, integrative medicine. Recruitment flowchart. General characteristics of the study population, N (%). CM, conventional medicine; IM, integrative medicine. Pregnant women utilizing IM had the highest number of primary diagnoses for the supervision of pregnancy, with 117,215 claims (Z34), followed by female infertility, with 57,667 claims (N97). Diseases of the respiratory system, which included J01, J02, J03, J06, J20, and J30, accounted for six of the top 20 primary diagnoses, making it the most common category, whereas diseases of the genitourinary system, which included N30, N72, N76, and N91, accounted for five of the top 20 primary diagnoses, making it the second most common category ( Table 2 ). Table 2 Pregnant women utilizing integrative medicine have the highest number of primary and secondary diagnoses. Table 2 Diagnosis code Primary diagnosis Secondary diagnosis Other gastroenteritis and colitis of infectious and unspecified origin (A09) 11,166 2981 Candidiasis (B37) 12,767 13,048 Ovarian dysfunction (E28) 3220 8465 Conjunctivitis (H10) 9264 8408 Acute sinusitis (J01) 11,662 8249 Acute pharyngitis (J02) 11,399 6884 Acute tonsillitis (J03) 16,360 8692 Acute laryngitis and tracheitis (J04) 8299 10,308 Acute upper respiratory infections of multiple and unspecified sites (J06) 16,539 9241 Acute bronchitis (J20) 49,932 23,323 Vasomotor and allergic rhinitis (J30) 17,485 55,423 Gastro-esophageal reflux disease (K21) 10,115 11,456 Gastritis and duodenitis (K29) 14,401 69,965 Functional dyspepsia (K30) 1414 12,539 Other functional intestinal disorders (K59) 2804 6691 Allergic contact dermatitis (L23) 14,449 8379 Dorsalgia (M54) 18,343 11,792 Other soft tissue disorder, NEC (M79) 7304 12,602 Cystitis (N30) 11,929 3965 Inflammatory disease of cervix uteri (N72) 16,209 20,168 Other inflammation of vagina and vulva (N76) 27,868 37,227 Absent, scanty and rare menstruation (N91) 9150 1728 Female infertility (N97) 57,667 6770 Other abnormal products of conception (O02) 8986 668 Abdominal and pelvic pain (R10) 7552 8644 Procreative management (Z31) 18,037 3879 Supervision of normal pregnancy (Z34) 117,215 6230 Pregnant women utilizing integrative medicine have the highest number of primary and secondary diagnoses. Functional dyspepsia was the most common secondary diagnosis, with 69,965 claims (K29), and vasomotor and allergic rhinitis (J30) was the second most common secondary diagnosis, with 55,423 claims. For secondary diagnoses, diseases of the respiratory system were the most common, appearing in seven (J01, J02, J03, J04, J06, J20, and J30) of the top 20 secondary diagnoses, followed by diseases of the genitourinary system and diseases of the digestive system, each accounting for three (K21, K29, K30, N72, N76, and N97) of the top 20 secondary diagnoses. We identified the primary and secondary disease codes regarding infertility in 989,277 claims from 79,234 women in the IM group. Among the 989,277 claims, 19,153 claims involved an infertility diagnosis code. Among these claims, considering female infertility (N97) and the subcodes related to female infertility (N970, N971, N972, N973, N974, N978, and N979), 19,153 claims involved these codes as primary diagnoses, and 4756 claims involved these codes as secondary diagnoses ( Table 3 ). The most frequent infertility code as a primary diagnosis was female infertility associated with anovulation (N970), with 9008 claims, followed by female infertility of other origins (N978), with 8977 claims, and female infertility of tubal origin (N971), with 781 claims. As a secondary diagnosis, the most frequent infertility code was female infertility, unspecified (N979), with 2126 claims, followed by female infertility associated with anovulation (N970), with 1656 claims, and female infertility of other origins (N978), with 573 claims. Table 3 Primary and secondary disease codes related to infertility in the IM group. Table 3 Disease code Primary disease code Secondary disease code Female infertility associated with anovulation (N970) 9038 1656 Female infertility of tubal origin (N971) 781 235 Female infertility of uterine origin (N972) 79 48 Female infertility of cervical origin (N973) 13 0 Artificial insemination (N974) 265 107 Female infertility of other origin (N978) 8977 573 Female infertility, unspecified (N979) 0 2126 Primary and secondary disease codes related to infertility in the IM group. Table 4 presents the unadjusted odds ratios (ORs) and p values, as well as the adjusted odds ratios (aORs) and p values, for preterm birth, low birth weight, adverse ART outcomes, and cesarean delivery. The preterm birth (<37 weeks) rate was 2.22 % in the IM group and 2.12 % in the CM group (unadjusted OR, 1.12 [95 % CI, 1.06 to 1.18]; p < 0.0001; adjusted OR, 1.03 [95 % CI, 0.97 to 1.10]; p < 0.0001). The risk of preterm birth was not significantly different between the IM and CM groups. The low-birth weight (<2400 g) rate, which was 3.12 % in the IM group and 2.58 % in the CM group (unadjusted OR, 1.12 [95 % CI, 1.07 to 1.17]; p < 0.0001; adjusted OR, 1.02 [95 % CI, 0.97 to 1.08]; p < 0.0001), was not significantly different after adjustment. The rate of ART outcomes was 60 % in the IM group and 56.66 % in the CM group (unadjusted OR, 1.40 [95 % CI, 1.36 to 1.44]; p < 0.0001; adjusted OR, 1.25 [95 % CI, 1.21 to 1.29]; p < 0.0001), indicating a statistically significant difference. Thus, the risk of ART outcomes was greater in the IM group than in the CM group, even after adjustment for maternal age and underlying disease status. The cesarean delivery rate was 15.03 % in the IM group and 11.2 % in the CM group (unadjusted OR, 1.13 [95 % CI, 1.11 to 1.15]; p < 0.0001; adjusted OR, 1.08 [95 % CI, 1.06 to 1.11]; p < 0.0001), indicating a statistically significant difference. Table 4 Risk of perinatal complication outcomes associated with the use of integrative medicine and only conventional medicine among women who gave birth. Table 4 Outcomes IM group CM group Unadjusted Adjusted * No of event % No of event % OR (95 % CI) OR (95 % CI) Preterm (<37 week) 1759 2.22 1945 2.12 1.12 (1.06,1.18) 1.03 (0.97,1.10) Low weight (<2400 g) 2471 3.12 2370 2.58 1.12 (1.07,1.17) 1.02 (0.97,1.08) Assisted reproductive technology 47,240 60 52,075 56.66 1.40 (1.36,1.44) 1.25 (1.21,1.29) Cesarean delivery 11,908 15.03 10,292 11.2 1.13 (1.11,1.15) 1.08 (1.06,1.11) ⁎ Adjusted OR: maternal age, underlying disease CI, confidence interval; CM, conventional medicine; IM, integrative medicine; OR, odds ratio. Risk of perinatal complication outcomes associated with the use of integrative medicine and only conventional medicine among women who gave birth. Adjusted OR: maternal age, underlying disease CI, confidence interval; CM, conventional medicine; IM, integrative medicine; OR, odds ratio.

The present study investigated the utilization of IM and the associations between IM and perinatal outcomes via data collected from mothers and infants in 2021. To our knowledge, this is the first published study to analyze IM use among a population of women who gave birth in South Korea. In this nationwide cohort study, the combination of IM with CM was associated with improved perinatal outcomes. After adjusting for maternal age and underlying disease status, the risks of preterm birth and low birth weight in the IM group were not significantly different from those in the CM group, whereas the risks of cesarean section and ART outcomes were significantly greater than those in the CM group. Among the claims data, the IM group had the highest health care utilization for respiratory system diseases, followed by genitourinary system diseases. Among infertility-related diagnoses, female fertility associated with anovulation (N970) was the most common primary diagnosis, followed by female infertility of other origins (N978). A previous cohort study has revealed that multiple pregnancies and births in Korea significantly increased after the implementation of an ART health insurance coverage policy. These findings suggest that the development and coverage of policies to support couples experiencing infertility may help address low fertility rates. 18 Previous studies have shown that many infertile patients receive IM treatment, and the use of IM has increased. Women undergoing ART for infertility have been compared with respect to their use of IM and CM. 19 The utilization of IM reported in our study was greater than that reported in the study of Shruti Sehgal et al., who reported that 42 % of 1460 infertility patients in the United States used IM and that 38.5 % of these infertility patients used IM that included only acupuncture. 19 This difference may be attributed to ethnic and cultural variations in the use of IM. 20 Unlike the health care system in most countries, the dual health care system in South Korea, in which both CM and TM are covered by national health insurance, provides easier access to TM. 21 Therefore, the utilization of IM is greater in South Korea. Additionally, a study by Minjung Park et al., which demonstrated the comprehensive effects of IM on stroke, serves as an example of the numerous studies being conducted on IM across various fields in South Korea. Minjung Park et al. reported that IM is associated with a reduced risk of all-cause mortality at 3 months (OR 0.36; 90 % CI 0.13–0.99) and 12 months (OR 0.34; 95 % CI 0.15–0.75) after admission, representing greater health care utilization and higher costs. 22 Many studies have demonstrated that TM interventions improve reproductive function in infertile women, 23 and herbal medicine has also been shown to improve these outcomes. 24 However, our study revealed opposite results regarding the risk of ART outcomes and cesarean section. In our study, the IM group had the highest health care utilization for respiratory system diseases, followed by genitourinary system diseases and infertility-related diagnoses. We believe that dual health care utilization for delivery in infertile women positively contributes to ART and cesarean section. These observations suggest that dual health care utilization may be an important factor for the prognosis of pregnancy in infertile women. Nonetheless, we cannot rule out the possibility that the increased risks of ART outcomes and cesarean section in the IM group may be due to differences in disease severity, as the IM group had a greater proportion of women aged 35 years or older. Despite the growing interest in this area, most previous studies have focused primarily on assessing the effectiveness of IM by examining outcomes, such as birth and miscarriage rates, 23 , 24 with few studies addressing medical utilization issues related to mothers and infants. The present study has several strengths. A major strength is that the NHISS database contains nationwide cohort data, which ensures the applicability of the data to the study when assessing medical practice and health outcomes. Therefore, the major strength of the present study is the large, population-based, and nationwide cohort analyzed to investigate long-term medical utilization outcomes. We also linked the mothers’ data and analyzed potential confounders, including maternal pregnancy complications and general characteristics. The present study also has several limitations. The analysis was performed on the basis of claims data and ICD-10 codes and not the information obtained from medical charts for the diagnosis of diseases. The ICD-10 codes are primarily used for administrative purposes and may not provide detailed clinical information about the patient. There is also the concern of incomplete coding, which could lead to misclassification or underestimation of the severity of outcomes. 25 Therefore, it was impossible to obtain information on disease or disability severity. To address this limitation, we attempted to account for differences in disease severity by examining the proportions of women aged 35 years or older in each group. However, this effort may not have been sufficient to fully account for the severity differences. Furthermore, in our study, IM utilization was not considered a specific TM treatment because it was not covered by health insurance, indicating that findings pertaining to TM utilization could be underestimated. Our findings provide evidence that IM increases the accessibility, necessity and quality of IM treatment, which may contribute to promoting patient needs and changing the approach toward improving women's health outcomes before pregnancy. Although cesarean section and ART were associated with the highest risk in the IM group, health care utilization in the IM group was not associated with more cases of preterm birth or low birth weight than that in the CM group. Thus, the rates of ART and cesarean section were high in the group of women of childbearing age who used IM, but the risk was still low. To improve research on pregnancy and delivery outcomes according to IM health care utilization, advancements in the clinical guidelines for IM, systemic long-term follow-up, and policy support are needed not only to provide evidence for IM but also for the integration of guidelines into the current health care system. Considering the health care structure of Korea, which has a dual medical system, policies that can support couples experiencing infertility through IM should be developed and implemented. Further research is needed to assess the impact of IM utilization on the quality of life and health outcomes of women of childbearing age.

South Korea has a dual health care system, allowing patients to choose between conventional medicine (CM) and traditional medicine (TM). 1 Clinicians and researchers are increasingly using the term integrative medicine (IM) to refer to the combination of TM and CM. 2 Women of childbearing age utilize various CM and TM services to maintain their health during pregnancy. 3 In particular, TM for infertility has recently gained widespread attention, owing to its limited adverse effects, high efficiency, and involvement of various health care and treatment systems, such as acupuncture, pharmacopuncture, moxibustion, and herbal medicine. 4 These treatments have been shown to be effective in improving overall health, endocrine function, and reproductive function in women of childbearing age. 5 Several studies have shown that TM has obvious advantages for and significant curative effects on women of childbearing age with polycystic ovary syndrome (PCOS), endometriosis, and other conditions. 6 , 7 , 8 Thus, TM is widely used to ensure good pregnancy and childbirth outcomes in women of childbearing age in South Korea. However, there are no studies on the use of the dual health care system by women of childbearing age. Additionally, South Korea is facing serious problems related to low fertility and an aging population. The number of births in South Korea has steadily decreased from 438,420 in 2015 to 249,186 in 2022. From 2016 to 2020, the number of births decreased by more than 7 % annually compared with the previous year. In 2017, there was a decrease of 48,472 births or 11.9 % compared with the previous year, marking the highest rate of decline in the past decade. Notably, between 2015 and 2023, the decline in birth rates among women aged 35 years or younger was more pronounced than that among women aged over 35 years. Furthermore, from 2020 to 2022, the birth rate for women aged over 35 years increased, which was in contrast to the overall downward trend. 9 Compared with women under the age of 35, women over the age of 35 have a greater likelihood of infertility. 10 To address the complex issues associated with low birth rates, the Korean government recognized the medical necessity of infertility care and introduced financial support policies and an assisted reproductive technology (ART) insurance mandate for couples experiencing infertility. 11 , 12 A previous cohort study in Korea evaluated the associations of health insurance coverage for ART with pregnancy and birth rates in Korea, revealing that policies that provide financial support for infertility treatment may help address low birth rates in Korea. 13 However, many studies have shown that women with ART-conceived pregnancies are often subject to an increased risk of perinatal and obstetric complications. 14 Perinatal complications are defined as adverse outcomes that occur during pregnancy, childbirth, or the neonatal period, including preterm birth, low birth weight, and the infant being small for gestational age (SGA). Birth characteristics, such as gestational age and birth weight, are included as part of perinatal complications, as they are critical indicators of perinatal health and reflect the immediate risks associated with multifetal pregnancies. ART is responsible for an increasing number of multifetal pregnancies, which significantly contribute to these perinatal complications. 15 Women of childbearing age who wish to undergo ART often use TM for their reproductive health due to the adverse effects of ART. A recent systematic review has reported that the combination of TM with IVF is more likely to increase the live birth rate and clinical pregnancy rate than IVF without adjunctive treatment. 3 These findings indicate that TM may have beneficial effects on pregnancy outcomes in females experiencing infertility. In addition, when ART cannot be offered, acupuncture and herbal medicine can improve patients' conditions to reach a point at which ART can be successful. 16 Although there is an ongoing debate on how to manage infertility before and after ART, previous studies have reported that many patients utilize TM to complement ART to increase their chances of success. 17 However, none of these studies focused on health care utilization for women of childbearing age considering both CM and TM. Whether the dual health care system itself is more beneficial than one health care system is an important issue. In this study, we hypothesized that greater exposure to the dual health care system would be favorably associated with perinatal outcomes and that the most common disease in women who use the dual health care system can be determined. Therefore, we aimed to investigate the health care utilization of mothers who gave birth in 2021 to determine the major diseases they were diagnosed with at the time of their health institution visits and to compare perinatal complications between women who used IM and those who used only CM within the dual health care system.

The authors declare no other conflict of interest.