Taiwanese Journal of Obstetrics & Gynecology 58 (2019) 77e81

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Taiwanese Journal of Obstetrics & Gynecology

journal homepage: www.tjog-online.com

Original Article

Uses of dietary supplements and herbal medicines during pregnancy

in women undergoing assisted reproductive technologiese A study of
taiwan birth cohort
Ching-Yi Lin a, b, Yu-Ju Chen b, Shu-Hsin Lee b, c, d, **, Ching-Pyng Kuo c, Maw-Sheng Lee b, e,
Meng-Chih Lee b, f, g, h, *
a
Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan
b
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
c
School of Nursing, Chung Shan Medical University, Taichung, Taiwan
d
Department of Nursing, Chung Shan Medical University Hospital, Taichung, Taiwan
e
Lee Women's Hospital, Taichung, Taiwan
f
Department of Family Medicine, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan
g
Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan
h
College of Management, Chaoyang University of Technology, Taichung, Taiwan

a r t i c l e i n f o a b s t r a c t

Article history: Objective: This study aimed to assess the efficacy of dietary supplements and herbal medicines for the
Accepted 1 November 2018 care of pregnant women undergoing assisted reproductive technologies (ART).
Materials and methods: A total of 366 women undergoing ART and their children from the dataset of
Keywords: Taiwan Birth Cohort Study (TBCS, 2005) were enrolled in this study. Structured questionnaires were
Assisted reproductive technologies (ART) applied to collect the health information at 6-month follow-up after their delivery. The related use
Dietary supplements
patterns were analyzed to investigate the final birth outcomes.
Herbal medicines
Results: Comparing with those of non-ART group, the women undergoing ART consumed more sup-
Pregnancy
Postpartum
plements of multivitamin, fish oil, and calcium than herbal medicines during pregnancy. This study
revealed that the consumptions of multivitamin, calcium pills, Genseng, and Suz-Wu-Tang were asso-
ciated with low birth weight, whereas the intake of Huanglian was associated with birth weight. Besides,
the uses of multivitamin and Suz-Wu-Tang were related to lower gestational age of infants.
Conclusions: Physicians and nurses must educate themselves in dietary supplements and herbal/alter-
native medicines for offering accurate advices for pregnant women to optimize their care. The results
could be of reference for further investigation on longitudinal effects of dietary supplements and herbal
medicines during pregnancy in women undergoing ART continuously followed with TBCS.
© 2018 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction lifetime [5,6]. Due to the effect of women's working career during
their childbearing period, many infertile couples postponed the
The fertility rate in many developed countries and Taiwan has birth of their first child beyond the upper limits of female repro-
been below replacement level. Also, a dramatic decline in birth rate ductive potential. Assisted reproductive technologies (ART) are the
has become an important issue [1e4]. Infertility is a common main strategies used to overcome the burden associated with
condition affecting one out of every six couples during their infertility. However, high costs [6e8] and adverse events [9e14]
associated with ART can be a huge burden to those infertile
couples. As a result, alternative approaches can be considered to
* Corresponding author. Taichung Hospital, Ministry of Health and Welfare, No. prevent potential negative outcomes of mothers and neonates.
199, sec. 1, San-Min Road, Taichung 403, Taiwan. Fax: 886 4 22229517. Health practices regarding specific dietary prescriptions and re-
** Corresponding author. School of Nursing, Chung Shan Medical University, 110,
strictions are very common [15e17]. The approaches of prenatal care
Sec.1, Chien Kuo North Road, Taichung 402, Taiwan. Fax: 886 4 23248173.
E-mail addresses: shl@csmu.edu.tw (S.-H. Lee), mcl@taic.mohw.gov.tw, mcl@ have been made to decrease pregnancy failure and to increase the
csmu.edu.tw (M.-C. Lee). health of fetus/baby [18e24]. Chinese herbal medicines (HM) have

https://doi.org/10.1016/j.tjog.2018.11.015
1028-4559/© 2018 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).
78 C.-Y. Lin et al. / Taiwanese Journal of Obstetrics & Gynecology 58 (2019) 77e81

been used as a complementary therapy of female infertility for thou- correlation. Statistical significances were set at p value < 0.05. All
sands of years in China, Japan, Korea, and other countries [23]. Herbal statistical analyses were performed with the Statistical Package for
medicine use is becoming more popular inpregnant women. However, the Social Sciences version 17.0 (SPSS Inc., Chicago, IL, USA).
the safety and efficacy issues should be considered on the recom-
mendation of their health care providers during pregnancy [21,25]. Results
On the other hand, prior studies indicated that micronutrient
supplements could have potential benefits on mothers’ health, fetal Characteristics of subjects
growth, andbirth outcomes [22,23,26e28]. The use of micro-
nutrient supplements was associated with higher pregnancy rates Baseline characteristics of infertile women were summarized in
not only for women without fertility disorders [29], but also for Table 1 and the characteristics of their babies were summarized in
women with infertility disorders [30e32]. It is very common that Table 2. There were 105 (28.7%) women undergoing ART aged over
pregnant women take various supplements of multivitamins, 35 years old (Table 1). As the preliminary findings of TBCS reported
micronutrients, fish liver oil, fish oil, and calcium micronutrients to [37], ART group (n ¼ 366) was 5 years older than non-ART group
maintain a healthy pregnancy [33e36]. (n ¼ 20868) at the age of delivery (33.2 ± 4.1 v.s. 28.8 ± 4.9 years,
This study focused on the final birth outcomes to those mothers respectively; p < 0.001). Sixty percent of the participants (n ¼ 222)
who had an infertility history from Taiwan Birth Cohort Study hold an educational attainment of college/university or higher
(TBCS) [37]. We aimed to assess the efficacy of dietary supplements (Table 1). Most of the women undergoing ART were still employed
and herbal medicines during pregnancy in the care for women during pregnancy (n ¼ 216, 60.7%).
undergoing ART. A total of 247 (67.5%) women undergoing ART received
Caesarean sections. A total of 95 (26%) women undergoing suffered
Materials and methods from severe nausea/vomiting during pregnancy. About one fifth of
them were ever hospitalized due to various pregnancy related
Study sample symptoms. Their mean body weight was 57.3 ± 2.6 kg before
pregnancy, and 75.5 ± 3.6 kg prior to delivery, then became
The TBCS was designed to investigate multiple aspects of 57.3 ± 2.6 kg at 6-month postpartum. There were 63 (17.2%) women
newborn/mother pairs with the national birth longitudinal cohort reported that they had self-perceived postpartum depression, but
in Taiwan [38]. As a national household probability sampled study, only 6 ever sought treatment.
all babies born between October 2003 and January 2004 in Taiwan Of the infants whose mothers underwent ART, males were
were eligible for the TBCS with no exclusion criteria. In 2005, predominant (n ¼ 209, 57.1%). A total of 121 (33.1%) infants were
24,200 newborn/mother pairs were enrolled in the TBCS study. Of with low birth weight (<2500 g), and 154 (42.1%) infants were
whom, 21,234 pairs have been continuously followed using stan- preterm births (<37 weeks) (Table 2). They had a mean gestational
dardized and structured questionnaires. A total of 366 mothers age of 37.1 ± 2.3 weeks (range: 25e41 weeks). Multiple births
with an infertility history undergoing ART was identified for accounted for 44.3% (n ¼ 162). Those born with various genetic
retrospective analyses [37]. This study was reviewed and approved birth defects accounted for 9.8% (n ¼ 36).
by the Medical Ethics Committee and Data Protection Board in
Taiwan before initiated. Informed consent was received for the Use patterns of dietary supplements and herbal medicines during
parents at each data collection period. pregnancy

Data collection and outcomes As compared with herbal medicine use, there were more
women undergoing ART consumed dietary supplements during
The trained researchers were assigned for home visit and pregnancy (Tables 3 and 4). A total of 291 (79.5%) women under-
follow-up questionnaire at the 6-month follow-up after giving going ART took multivitamin, 85 (23.2%) women took fish oil, and
birth. Participants were asked to report the intake of dietary sup- 196 (53.6%) women took calcium pills, 23 (6.3%) women took fish
plements (including: multivitamin, fish liver oil, fish oil and cal- liver oil (Table 3). However, only 50 (13.7%) women took An-Tai-Yin,
cium pills) and herbal medicines during pregnancy period 50 (13.7%) women took pearl powder, 30 (8.2%) women took
(including: An-Tai-Yin, pearl powder, Huanglian, Szu-Wu-Tang, and Huanglian, 22 (6.0%) women took Ginseng, and 12 (3.6%) women
ginseng [25,39]. The structured questionnaires offered options for took Suz-Wu-Tang. Most of the women in the ART group consumed
frequency of consumption. less than 10 times herbal medicine use during pregnancy. Supple-
The history of pregnancy, miscarriages, induced abortions, ments of multivitamin, fish oil, and calcium pills were significantly
maternal age, spousal factors, educational attainments, household higher in ART group than non-ART group during their pregnancy
incomes, delivery methods, and pregnancy-related illness were period of both first trimester and second trimester (all p values
obtained from the TBSC database or the follow-up interviews. Self- < 0.001; Table 3). The use of Szu-Wu-Tang was significantly less in
reports of female infertility in the current analysis were not women undergoing ART than non-ART group during pregnancy
confirmed by medical review. The infant information was also (3.6% vs. 6.3%, p values < 0.01; Table 4).
collected for analyzing the final birth outcomes such as birth
weight and gestational age. Final birth outcomes under the uses of dietary supplements/herbal
medicines among mothers undergoing ART
Statistical analyses
Table 5 depicts the final birth outcomes for those mothers un-
Baseline characteristics were reported as the mean ± standard dergoing ART and various uses of dietary supplements and herbal
deviation for continuous variables and as percentages for categorical medicines. The Pearson correlation analysis showed that the use of
variables. Student's t test was used to compare continuous variables. multivitamin was negatively correlated with gestational age
Chi-square test was used to analyze for categorical variables. Asso- (r ¼ 0.152, p value < 0.01) and birth weight (r ¼ 0.177, p value <
ciations between the uses of dietary supplements/herbal medicines 0.01). The use of calcium pills was negatively correlated with birth
and the final birth outcomes were analyzed using Pearson's weight of infants (r ¼ 0.110, p value < 0.05).
 C.-Y. Lin et al. / Taiwanese Journal of Obstetrics & Gynecology 58 (2019) 77e81 79

Table 1 birth weight, whereas the intake of Huanglian was positively

Characteristics ofinfertile womenundergoing ART. associated with birth weight. Besides, the uses of multivitamin and
Characteristics Infertile women Suz-Wu-Tang were related to lower gestational age of infants. The
undergoing ART (N ¼ 366) significantly higher uses in multivitamin, fish oil, and calcium pills
Maternal age at delivery (years) 33.2 ± 4.1 among the women undergoing ART were noted in this study. These
20e30 years 96 (26.2%) findings suggest that nutrition intake via dietary supplements
31e35 years 165 (45.1%) attracting increased interest during pregnancy among the mothers
>35 years 105 (28.7%)
with previous infertile experience. Furthermore, those women
Previous pregnancy losses
Spontaneous abortion 77 (21%) undergoing ART might feel more confident to take dietary sup-
Induced abortion 59 (12.3%) plements than herbal medicines, except fish liver oil. Although
Stillbirth 6 (1.6%) prior study showed that fish liver oil may have beneficial impacts
Method of delivery
on pregnant women [40], possible contaminants (such as poly-
Normal spontaneous delivery 119 (32.5%)
Caesarean section 247 (67.5%)
chlorinated biphenyls and mercury) in commercial products of fish
Educational attainment liver oil could be a concern for those pregnant women.
High school or less 144 (39.3%) A higher proportion of ART pregnancies were associated with
College/university or higher 222 (60.7%) obstetrical and perinatal complications, and that children
Employed during pregnancy 216 (60.7%)
conceived through ART may have a higher risk of abnormalities or
Pregnancy associated illness
Severe nausea/vomiting 95 (26%) preterm delivery than spontaneously conceived children [41e43].
Fever and infectious diseases 17 (4.6%) According to a systematic review, better cognitive and/or psycho-
Asthma attacks 4 (1.1%) motor outcomes were reported for supplementations involving
Gestational diabetes 23 (6.3%) multiple micronutrients and n-3 fatty acid. In contrast, null results
Pregnancy-induced hypertension 15 (4.1%)
Pre-eclampsia 6 (1.6%)
of pregnant women on child neurodevelopment were observed
Hospitalized during pregnancy 80 (21.9%) while giving single micronutrient supplementation, such as iron,
Body weight folic acid, vitamin A, and zinc [34,44]. Since multivitamin use was
Pre-pregnancy (kg) 57.6 ± 2.6 associated with higher pregnancy rates for both infertile women
Prior to delivery (kg) 75.5 ± 3.6
and those without infertile disorders, the use of multivitamin may
At 6-month postpartum (kg) 57.3 ± 2.6
Perceived postpartum depression 63 (17.2%) be higher among women planning a pregnancy [29e32]. In the
present study, those pregnant women after receiving ART were
ART: assisted productive technologies.
more likely to take multivitamin than required. More interesting is
that the intake of multivitamin was negatively correlated with
Taking Huanglin was positively correlated with birth weight of gestational age and birth weight of infants. However, we were not
infants (r ¼ 0.112, p < 0.05), whereas Ginseng (r ¼ 0.121) and Suz- able to draw a conclusion.
Wu-Tang (r ¼ 0.118) were negatively correlated with birth weight Previous studies indicated calcium supplements were associ-
of infants (all p value < 0.05). In addition, the use of Suz-Wu-Tang ated with lower risk of preterm birth or serious morbidities [33,45].
was negatively correlated with gestational age (r ¼ 0.113, p Consumption of fish liver oil that contains high levels of vitamins A
value < 0.05) and birth weight (r ¼ 0.118, p value < 0.05). and D has been shown to have a positive effect on the infant size at
birth [40]. There are also epidemiologic evidences that fish oil (a
Discussion rich source of long-chain omega-3 fatty acids) was associated with
mental development of children and improvement of infant size
This study indicated that the consumptions of multivitamin, [35,40,46]. Our study results are not identical with prior studies.
calcium pills, Genseng, and Suz-Wu-Tang were associated with low Regarding the intake of herbal medicine during pregnancy, our
study findings indicated that the consumptions of Genseng and
Table 2 Suz-Wu-Tang were associated with lower birth weight and gesta-
Characteristics of infants whose mothers undergoing ART. tional age of infants. The results were contrary to users’ expecta-
Characteristics Infants (N ¼ 366) tions and beyond our ability to reach a conclusion. Genseng and
Suz-Wu-Tang are very common used herbal medicines among
Male gender 209 (57.1%)
Gestational age (weeks) 37.1 ± 2.3
Chinese women. While the use of these herbal medicines is
<37 weeks 154 (42.1%) believed to be prevalent, little is known about their mechanism
Birth weight (g) 2749 ± 598 specifically during pregnancy. The participants might have been
<2500 g 121 (33.1%) using other natural products or/and medications in addition to
Birth number
those herbal medicines and dietary supplements, which lead to
Singleton 204 (55.7%)
Multiple 162 (44.3%) concerns about possible adverse interactions [47].
Perceived general health conditions of babies Although many consumers assume that herbal medicines are
Very good 185 (50.5%) safe and effective, evaluations of many herbal medicines of defined
Good 122 (33.3%) formulas by well-designed clinical trials or appropriate animal
Fair 57 (15.6%)
Not good 2 (0.5%)
studies are still in luck [48e50]. For example, the compositions of
Genetic birth defects 36 (9.8%) herbs in Sheng-Hua-Tang and Szu-Wu-Tang are different in China
Nervous system 4 (1.1%) and Taiwan, their proportions are not even precisely described
Facial system 6 (1.6%) [25,51]. Despite these herbal medicines have a long history of use in
Cardiovascular system 11 (3%)
treating gynaecological disorders among Chinese women
Digestive system 3 (0.8%)
Urogenital system 7 (1.9%) [23,51,52], those herbal formulas are not regulated to the same
Musculoskeletal system 6 (1.6%) degree as traditional pharmaceutical products and the quality of
Respiratory system 1 (0.3%) their raw materials can vary from batch to batch. It is important to
Chromosomal abnormalities 1 (0.3%) monitor their use, particularly in the case of pregnancy. In the
Others 9 (2.5%)
absence of evidences, knowledge of herbal medicine uses is
80 C.-Y. Lin et al. / Taiwanese Journal of Obstetrics & Gynecology 58 (2019) 77e81

Table 3
Consumption of dietary supplements during pregnancy among women undergoing ART and spontaneous conception (Non-ART).

Dietary supplements ART (n ¼ 366) Non-ART (n ¼ 20868) Pregnancy stages

First trimester Second trimester

ART Non-ART ART Non-ART

Multivitamin 291 (79.5%)*** 12231 (58.6%) 126 (34.4%)*** 4436 (21.3%) 283 (77.3%)*** 11829 (56.7%)
Fish liver oil 23 (6.3%) 1507 (7.2%) 10 (2.7%) 554 (2.7%) 22 (6%) 1387 (6.6%)
Fish oil 85 (23.2%)*** 3297 (15.8%) 27 (7.4%)*** 1093 (5.2%) 83 (22.7%)*** 3210 (15.4%)
Calcium pills 196 (53.6%)*** 8567 (41.1%) 85 (23.3%)*** 1035 (5.0%) 85 (23.3%)*** 3208 (15.4%)

ART: assisted reproductive technologies.

***p < 0.001, ART vs. non-ART.

Table 4
Consumption of herbal medicines during pregnancy among the women undergoing ART and spontaneous conception (Non-ART).

Herbal Medicines Intake during pregnancy Frequency (times)

ART (n ¼ 366) Non-ART (n ¼ 20868) 1e10 11e20 20e40 40e60 61

An-Tai-Yin 50 (13.7%) 2817 (13.5%) 37 (10.1) 5 (1.4) 4 (1.1) 1 (0.3) 3 (0.8)

Pearl powder 50 (13.7%) 2483 (11.9%) 10 (2.7) 9 (2.5) 10 (2.7) 4 (1.1) 17 (4.6)
Huanglian 30 (8.2%) 2212 (10.6%) 8 (2.2) 7 (1.9) 5 (1.4) 4 (1.1) 6 (1.6)
Ginseng 22 (6%) 939 (4.5%) 14 (3.8) 0 (0.0) 3 (0.8) 2 (0.5) 3 (0.8)
Suz-Wu-Tang 13 (3.6%)** 1315 (6.3%) 11 (3.0) 1 (0.0) 1 (0.3) 0 (0.0) 1 (0.3)

ART: assisted reproductive technologies.

**p < 0.01 when compared to non-ART group.

Table 5
Conclusions
The correlation coefficient between the consumptions of dietary supplements/
herbal medicines and the birth outcomes during pregnancy (N ¼ 366). Despite these limitations, it is clear that physicians and nursing
Gestational age Birth weight
staffs must educate themselves in the field of dietary supplements
and herbal/alternative medicines in order to offer accurate advices
Dietary supplements
for pregnant women to optimize their care. It is important for
Multivitamin 0.152** 0.177**
Fish liver oil 0.002 0.022 obstetrician gynecologists to note that many herbal medicines are
Fish oil 0.005 0.005 still not subject to standardized manufacturing or regulation by the
Calcium pills 0.063 0.110* authorities of Taiwan. Thus, variations in therapy and safety can be
Herbal medicines
still a prominent issue. Physicians must be cautious for the safety of
An-Tai-Yin 0.022 0.026
Pearl powder 0.022 0.046
dietary supplements and herbal medicine intake. The results of this
Huanglian 0.084 0.112* study could be of reference for further investigation on longitudinal
Ginseng 0.076 0.121** effects of dietary supplements and herbal medicines during preg-
Suz-Wu-Tang 0.113* 0.118* nancy in women undergoing assisted reproductive technologies
*p < 0.05; **p < 0.01. continuously followed with TBCS.

Conflict of interest statement

particularly important. Even small risks might well outweigh

The authors declare that there are no conflicts of interest.
benefits [50].
The advantage of this study was performed with a large scale
Acknowledgements
national longitudinal study (TBCS) with very high response rate.
The results were of both great representation of practices during
The authors would like to thank the research team of TBCS,
pregnancy of ART subjects and implications for further actions. The
which include interviewers, research scientists, computer techni-
disadvantages of this study included obsolete data collected in
cians and nurses, and all the families who took part in the study.
2000s. However the data could be served as baseline data for
further investigation on the longitudinal effects of dietary supple-
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