Jung et al.

BMC Pregnancy and Childbirth (2015) 15:228

DOI 10.1186/s12884-015-0665-2

RESEARCH ARTICLE Open Access

Body mass index at age 18–20 and later

risk of spontaneous abortion in the Health
Examinees Study (HEXA)
Sun Jae Jung1, Sue Kyung Park1,2,3, Aesun Shin2, Sang-Ah Lee4, Ji-Yeob Choi1, Yun-Chul Hong2, Keun-Young Yoo2,
Jong-Koo Lee5 and Daehee Kang1,2,3*

Abstract
Background: Spontaneous abortion (SA) affects 11.2% of recognized pregnancies in Korea. Many studies have
focused on the increased risk of SA in obese populations, but there are few studies that have focused on underweight
(Body mass index (BMI) <18.5 kg/m2) women, especially in relation to pre-pregnancy BMI. The aim of this study was to
examine the role of pre-pregnancy BMI at age 18–20 in later SA.
Methods: Among the women who were ever pregnant in the Health Examinees Study (HEXA), which was one of the
cohorts studied in the KoGES (Korean Genome and Epidemiology Study) from 2004 to 2012 (N = 80,447), the likelihood
of SA based on pre-pregnancy BMI, classified by the criteria for Asians (Underweight: <18.5 kg/m2; Normal range:
18.5-22.9 kg/m2; Overweight at risk: 23–24.9 kg/m2; Obese I: 25–29.9 kg/m2; Obese II: ≥30 kg/m2), was presented as
odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression models.
Results: Being underweight or obese relative to the normal weight range was associated with a higher likelihood of
SA (OR = 1.10 [95% CI = 1.05–1.15] in underweight women and OR = 1.06 [95% CI = 0.96–1.16] in obese women), and
this effect was much greater in women who experienced recurrent SAs (for three or more SAs: OR = 1.29 [95% CI
1.14–1.46] in underweight women and OR = 1.39 [95% CI 1.09–1.78] in obese women). Obesity was associated with an
increased likelihood of SA at a younger age (≤25 years), whereas underweight was associated with an increased OR of
SA at an older age (≥26 years).
Discussion: As this study was conducted with baseline data of original cohort which focused on other chronic
diseases, recall for previous pregnancy-related information might be less accurate. However, this study shows strength
in its large size and prospective potential.
Conclusions: Pre-pregnancy BMI at ages 18–20 years revealed a U-shaped association with SA, and underweight and
obese women showed increased likelihood for SA during different age periods.

Background Maternal overweight and obesity are related to increased

Spontaneous abortion (SA), or miscarriage, is defined as a risk of stillbirth, neonatal and infant death, large for gesta-
clinically observed pregnancy that is lost or that ends before tional age (LGA), fetal malformations, maternal diabetes,
the 20th week of gestation [1]. According to the Korean na- pregnancy-induced hypertension, pre-eclampsia and a high
tional survey on Fertility, Family Health & Welfare 2012, frequency of Caesarean section [3–6]. In obese women, folli-
SA affects 11.2% of recognized pregnancies, which can be culogenesis, ovulation and conception are more likely to be
viewed as a rather frequent medical phenomenon [2]. impaired, and pregnancy complications frequently occur [7].
In accordance with the known mechanism linking obes-
* Correspondence: dhkang@[Link] ity and SA, there are multiple epidemiologic studies
1
Department of Biomedical Science, Seoul National University College of reporting the association between these two factors [8, 9].
Medicine, Seoul, South Korea
2
Department of Preventive Medicine, Seoul National University College of
Many studies focusing on obese or overweight mothers
Medicine, Seoul, South Korea and their adverse outcomes related to pregnancy have
Full list of author information is available at the end of the article

© 2015 Jung et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
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Jung et al. BMC Pregnancy and Childbirth (2015) 15:228 Page 2 of 8

been published [4–6], but studies on underweight mothers experience of pregnancy, or no information on their par-
are rare [10]. Likewise, an association between pre- ity. Additionally, we excluded the 20,729 women who
pregnancy body mass index (BMI) and adverse pregnancy had missing information on weight or height at ages 18–
outcomes has been assessed in several studies [11, 12], but 20 years. A total of 1,244 women with a first pregnancy
similar studies are uncommon in Asian populations. before age 18 or 20 or with unknown age of first preg-
It is known that bodyweight in early life is associated nancy and 316 women with missing data on spontan-
with morbidity in adult life [13]. In the Nurses’ Health eous abortion were also excluded. Finally, a total of
Study (NHS), women with a BMI greater than 25 kg/m2 80,447 women were included in the final analysis.
at age 18 had an increased risk of premature death, and
this association was only partially explained by adult obes- Measurements
ity [14]. Likewise, there are studies suggesting a crucial ef- The participants were asked about their general charac-
fect of early life BMI on later parity [15, 16]. Another teristics, including occupations, lifestyle factors, socio-
study from NHS with 17 years of follow-up also revealed psychological factors, past medical history, family history
that BMI at age 18 was associated with anovulatory infer- for medical diseases, surgical history, list of medications
tility [17]. As BMI in the early years of life seems to affect and dietary habits. Additionally, the participants were
maternal health, in this study, we aim to evaluate the asso- asked about factors associated with obstetrics and
ciation between underweight, as well as obesity, at age gynecology. Women were also asked whether they had
18–20 and the risk of SA in the Korean population. ever had a SA; if the answer was ‘yes’, then they were
asked at what age the SA had occurred. Additionally,
Methods participants were asked about other factors, such as age
Subject selection at menarche, age at first pregnancy, gestational hyper-
The eligible population was selected from the Health Ex- tension and gestational diabetes.
aminees Study (HEXA). The HEXA comprises a large- Women were asked to recall their weight at age 20
scale genomic community-based prospective cohort of years (surveys from 2004 to 2006) or at age 18 years
170,094 participants and biological samples between 2004 (surveys from 2007 to 2012). From 2004 to 2006, women
and 2012. The HEXA was specifically conducted to evalu- had to report their weight at 20 years, but a correspond-
ate epidemiologic characteristics and genomic risk factors ing question changed to asking the weight at age 18 in-
focusing on major chronic diseases, including cancer, in stead. Therefore, women who participated in the surveys
the Korean population. It is a component of the Korean between 2007 and 2012 reported their recalled weight at
Genome and Epidemiology Study (KoGES). Participating age 18 only. BMI at age 18 or 20 years was calculated
centers were chosen after strict evaluation of the selection using the measured height at the baseline and dividing
criteria and community representativeness of participating the weight by the height squared (kg/m2).
hospitals. Recruited subjects were drawn from the commu-
nity’s adult population, ages 40 to 69 years. Information on Classification of BMI
general lifestyle, including smoking and drinking habits, We modified the BMI criteria of the Steering Committee
physical activity, past medical history, family medical his- of the Regional Office for the Western Pacific Region of
tory, drug use (including health supplements), health the World Health Organization (WHO-WPRO), which
check-ups, psychological factors, diet and reproductive fac- the International Association for the Study of Obesity
tors, was obtained by trained interviewers with a structured and the International Obesity Task Force had suggested
questionnaire. This questionnaire was developed from an to be the proper categorization of obesity in Asians. The
extensive literature review of other questionnaires, includ- criteria defines ‘underweight’, ‘normal range’, ‘overweight
ing the Korea National Health and Nutrition Examination at risk’, ‘obese I’, and ‘obese II’ as a BMI under 18.5 kg/
Survey (KNHANES) [18], which is a representative epide- m2, between 18.5–22.9 kg/m2, between 23–24.9 kg/m2,
miologic study of Korea funded by the Korean Center for between 25–29.9 kg/m2, and 30 kg/m2 or higher, re-
Disease Control (KCDC). The questionnaire was validated spectively [20]. According to these criteria, people who
using back translation with English, and a pilot study was were either ‘obese I’ or ‘obese II’ comprised only 3% of
conducted to evaluate its efficacy and feasibility [19]. Fur- the study population. For this reason, women who were
thermore, anthropometric measures were performed by in either the ‘obese I’ or ‘obese II’ group were placed into
trained interviewers, and laboratory tests for blood and one group (‘obese’). For the reference group, the ‘normal
urine were conducted by central laboratory. More details range’ group was selected.
about the HEXA can be found elsewhere [19].
Of the total participants, 111,600 participants were Statistical analysis
women. Among them, 8,605 women were excluded be- Multivariable logistic regression was applied to compute
cause they had an age other than 40–69 years, no odds ratios (ORs) and 95% confidence intervals (95% CI)
Jung et al. BMC Pregnancy and Childbirth (2015) 15:228 Page 3 of 8

of the association between BMI at ages 18–20 years and In the adjusted logistic regression model, a signifi-
SA. Possible confounders, such as participants’ age at the cantly increased likelihood was observed in women who
survey, income, education, comorbid diseases, exercise, had a BMI lower than 18.5 kg/m2 (OR 1.10, 95% CI
cigarette smoking, alcohol drinking, gestational hyperten- 1.05–1.15); conversely, a significantly reduced likelihood
sion and gestational diabetes, were selected based on a lit- of SA was observed in women who had a BMI between
erature review. Covariates that altered the odds ratio (OR) 23–24.9 kg/m2 (OR 0.94, 95% CI 0.88–0.99) compared
for at least one SA in the underweight population by 10% to the reference group with a BMI between 18.5–22.9
compared to the original model were selected. kg/m2. The association between BMI and total SAs
Initially, the outcome variable was SA; then, we further showed a U-shape pattern when considering all three SA
defined multiple SAs as variables for those who had categories. When we defined multiple SA as women
more than one SA. First, we analyzed the association be- who had at least 3 SA, the likelihood significantly in-
tween pre-pregnancy BMI and women who ever had an creased in both those who had a BMI less than 18.5 kg/
SA. Consequently, women who experienced a SA more m2 and those who had a BMI of 25 kg/m2 or higher at
than twice were classified as the ‘event group’, compared ages 18–20 years (OR 1.29, 95% CI 1.14–1.46 and OR
to those who never had a SA or experienced a SA only 1.39, 95% CI 1.09–1.78, respectively, for three or more
once. Similarly, those who had a SA at least three times SAs) (Table 2).
were defined as the ‘event group’ in a later analysis. Different patterns were observed in groups with differ-
Additionally, we classified these cases by age at first SA ent ages of onset of SA. In women who had their first
to evaluate the effects of BMI across distinct age groups. SA at the age of 25 years or younger, only those with a
Women who experienced SA were divided into 3 groups BMI of 25 kg/m2 or higher at ages 18–20 years showed
(≤25 years, 26–28 years, and >28 years) by tertile distri- a significantly increased likelihood (OR 1.22, 95% CI
bution of age at first SA. Additionally, as both BMI and 1.02–1.45) of SA. In contrast, the likelihood of SA at
spontaneous abortion showed associations with gesta- ages 26 to 28 years decreased in women with a BMI of
tional diabetes [21–23] and gestational hypertension [22, 25 kg/m2 or higher (OR 0.82, 95% CI 0.66–1.01). In re-
24], we performed a stratification analysis on the associ- gard to the likelihood of an SA after the age of 28 years,
ation between BMI and spontaneous abortions accord- only women with a BMI less than 18.5 kg/m2 at ages
ing to these two comorbidities to assess a potential 18–20 years showed a marginally significant increased
effect modifications. likelihood (OR 1.11, 95% CI 1.02–1.21) (Table 3).
For statistical analysis, SAS version 9.3 (SAS Institute In the stratification analysis of smoking status before
Inc., Cary, NC, USA) was used. We set P-values less first pregnancy, there were similar patterns in the likeli-
than 0.05 to indicate significance. hood of SA according to smoking status with various de-
grees of ORs, compared to the reference group (BMI
Ethics 18.5–23 kg/m2). In women who did not smoke before
Written consent was provided by all subjects who agreed pregnancy, the likelihood significantly increased for those
to participate in the HEXA. The statistical analysis of who had a BMI less than 18.5 kg/m2 (OR 1.09, 95% CI
publicly available data was approved by the Institutional 1.05–1.15) and decreased with marginal significance for
Review Board of the Seoul National University Hospital those who had BMIs between 23–24.9 kg/m2 (OR 0.95,
in Seoul, Korea (IRB No.1408-087-604). 95% CI 0.89–1.00). In women who smoked before the first
pregnancy, those who were ‘underweight’ at ages 18–20
Results years had an increased odds ratio (OR 1.31, 95% CI 0.70–
Women who experienced SA were more likely to have 2.44), whereas the odds ratio in those who had a BMI of
more than a high-school education compared to women 25 kg/m2 or over was decreased (OR 0.74, 95% CI 0.15–
without an SA experience (25.2% vs. 23.3%) and had an 3.59), although they were not significant (Table 4).
older age at first pregnancy (≥27 years) than women An additional stratification analysis was conducted
without SA experience (31.9% vs. 29.3%). The proportion with gestational diabetes and gestational hypertension.
of women who had gestational diabetes (GDM) or gesta- In women with gestational hypertension, only women
tional hypertension (GHT) also differed between SA and with BMIs less than 18.5 kg/m2 were associated with a
non-SA groups (GDM: 1.18% with SA vs. 0.91% without higher likelihood of SA (OR 1.22, 95% CI 1.01–1.49). In
SA; GHT: 6.0% with SA vs. 4.7% without SA). The those with gestational diabetes, no significantly increased
proportion of women with babies over 4.0 kg (macro- OR was observed in the groups, compared with the ref-
somia) or under 2.5 kg (microsomia) also differed be- erence group. Among women with no gestational dia-
tween the two groups (macrosomia: 8.2% with SA vs. betes and gestational hypertension, both underweight
7.0% without SA; microsomia: 5.6% with SA vs. 3.8% and obesity were associated with a higher likelihood of
without SA) (Table 1). SA, and women who were in the overweight range
Jung et al. BMC Pregnancy and Childbirth (2015) 15:228 Page 4 of 8

Table 1 General characteristics of the women population with spontaneous abortion (SA) and non-SA at the time of enrollment in
the Health Examinee Study (HEXA), a cohort study of the Korean Genome and Epidemiology Study (KoGES) in the Korea Center for
Disease Control and Prevention (KCDC), 2004-2012
No.=80,447 Spontaneous Abortion
No Yes
N=62,637 N=17,810
N (%) N (%) p-value*
Attained education ≥12 years 14,598 (23.3) 4,484 (25.2) <0.001
Cigarette smoking before the first pregnancy 538 (0.859) 154 (0.865) 0.002
1
Ever consumed alcohol 21,222 (33.9) 6,139 (34.5) <0.001
Regular exercise 32,437 (51.8) 9,211 (51.7) 0.305
Medical history before pregnancy
Hypertension 37 (0.06) 9 (0.05) 0.687
Diabetes 20 (0.02) 3 (0.02) 0.291
Chronic liver disease 154 (0.25) 35 (0.20) 0.266
Tuberculosis 2,067 (3.30) 587 (3.30) 0.878
Thyroid disease 211 (0.34) 73 (0.41) 0.138
Reproductive factors
Menarche age (years) 0.071
≤14 23,559 (37.6) 6,830 (38.4)
15 14,077 (22.5) 3,845 (21.6)
≥16 23,903 (38.2) 6 816 (38.3)
First pregnancy age <0.001
≤23 19,199 (30.7) 5,093 (28.6)
24–26 25,066 (40.0) 7,029 (39.5)
≥27 18,372 (29.3) 5,688 (31.9)
First pregnancy outcome
Stillbirth 393 (0.63) 178 (1.00) <0.001
Extrauterine pregnancy 195 (0.31) 67 (0.38) 0.184
Artificial abortion 7,467 (12.0) 1,466 (8.3)
Number of children <0.001
1 6,358 (10.2) 2,062 (11.8)
2 37,754 (60.8) 9,974 (57.0)
3+ 17,866 (28.8) 5,420 (30.1)
Gestational diabetes 569 (0.91) 211 (1.18) <0.001
Gestational hypertension 2,966 (4.7) 1,065 (6.0) <0.001
Macrosomia (>4.0kg) 4,406 (7.0) 1,646 (8.2) <0.001
Microsomia (<2.5kg) 2,390 (3.8) 995 (5.6) <0.001
*p–value from χ2–test
1
Due to lack of information about age of beginning of drinking, usual drinkers were included in this category

showed significantly decreased likelihoods of SA, which large Korean population. In the analysis of approxi-
were similar to the patterns observed for the entire mately 80,000 women, both high and low BMIs showed
population (Additional file 1: Table S1 and Additional increased likelihoods of SA, resulting in a U-shaped asso-
file 2: Table S2). ciation. In contrast to the expected result, being over-
weight (BMI 23–24.9 kg/m2) showed the lowest OR of
Discussion SA. Our results also showed a similar pattern to the re-
The goal of this study was to evaluate the effect of pre- sults of a study conducted on more than 1 million Asians,
pregnancy BMI on SA as an independent risk factor in a in which a harmful effect due to being underweight and a
Jung et al. BMC Pregnancy and Childbirth (2015) 15:228 Page 5 of 8

Table 2 Logistic regression for having spontaneous abortions (SAs) at age 18–20 from the Health Examinees Study (HEXA), 2004–2012
BMI (kg/m2) Total women Total women with a history of at least Comparison by groups
(N=80,447) One abortion Two abortion Three abortion ≥1 SAs vs. ≥2 SAs vs. ≥3 SAs vs.
No. SA 0–1 SA 0–2 SA
(N=17,180) (N=4,875) (N=1,704)
N N (%) N (%) N (%) OR1 (95% CI) OR1 (95% CI) OR1 (95% CI)
<18.5 13128 3,122 (17.5) 896 (18.38) 335 (19.7) 1.10 (1.05–1.15) 1.14 (1.06–1.23) 1.29 (1.14–1.46)
18.5–22.9 56692 12,462 (70.0) 3,380 (69.3) 1,149 (67.4) 1.00 (ref) 1.00 (ref) 1.00 (ref)
23–24.9 8148 1,675 (9.4) 438 (9.0) 148 (8.7) 0.93 (0.88–0.99) 0.91 (0.82–1.01) 0.88 (0.74–1.04)
≥25 2479 551 (3.1) 161 (3.3) 72 (4.2) 1.06 (0.96–1.16) 1.13 (0.96–1.33) 1.39 (1.09–1.78)
1
Adjusted for age, education, smoking before first pregnancy, drinking status and first pregnancy age

positive effect due to being overweight (22.6–25.0 kg/ m2) both ‘underweight’ and ‘obese’ populations, demon-
on mortality was suggested [25]. strating a U-shaped pattern.
Considering the age at the first SA, it appears that a In regard to the association between BMI and multiple
high BMI or being ‘obese’ at ages 18–20 years seems to recurrent SA, women with a higher BMI were consid-
affect SA at an earlier age, such as 25 years or younger. ered to have a greater likelihood of SA. A study con-
In contrast, lower BMI at ages 18–20 years or being ducted in the Guangzhou Chinese population reported
‘underweight’ influenced SA at a later age (i.e., more significantly increased likelihoods of recurrent SA in
than 25 years). If women had gestational hypertension, participants with a BMI of 24 kg/m2 or higher (OR 1.54;
those with a BMI under 18.5 kg/m2 tended to have 95% CI 1.28–3.49) compared to their counterparts [27].
more SAs. Because this study only compared those with a BMI of
As many studies have focused only on the harm of be- 24 kg/m2 or higher to those with a BMI under 24 kg/
ing obese before pregnancy, the possible association be- m2, it was impossible to evaluate the effect of lower
tween underweight and reproduction has not received BMIs on SA. Another study conducted in the U.K. ana-
much attention. However, our results suggest that lyzed 844 pregnancies of 491 women with recurrent SA.
underweight women at pre-pregnancy ages are at higher In this study, women with a BMI under 19 kg/m2 or
risk for SA compared to normal weight women. over 30 kg/m2 had increased ORs, but neither group
According to the literature review, there is evidence was significant [28].
that an increase in BMI raises the risk of SA in the Given the number of studies regarding the effect of
general population [26], as well as in women who smoking on SA, studies comparing the effect of BMI on
have undergone infertility treatment [8]. However, the both smokers and non-smokers are scarce. Most studies
relationship between lower BMI and SA is far from evaluate the effect of smoking and BMI on SA separately
conclusive, especially in Asians. In a Danish National [29]. A study conducted in Sweden reported that the
Birth Cohort (DNBC), 23,000 women were analyzed, interaction among age, BMI and smoking was not statis-
and women with a pre-pregnancy BMI under 18.5 kg/ tically significant [29]. However, as seen in our results,
m2 or higher than 25 kg/m2 had an increased hazard the likelihood of SA increases in both ‘underweight’ and
ratio (HR) of SA (HR 1.24, 95% CI 0.95–1.63; HR ‘obese’ women, and this association is not linear. Add-
1.14 95% CI 0.98–1.31, respectively) [10]. In compari- itionally, it is well known that as BMI increases, the risk of
son, our results show significantly increased ORs in hypertensive disorders also increases [30]. Interestingly, in

Table 3 Stratification analyses by maternal age for the likelihood for total and recurrent spontaneous abortion (SA) of body mass
index (BMI) at 18–20 years old in the Health Examinee Study (HEXA), 2004-20121
BMI (kg/m2) Maternal age
SA at ≤25 years SA at 26–28 years SA at >28 years
(N=3,980) (N=3,977) (N=4,321)
N (%) OR2 (95% CI) N (%) OR2 (95% CI) N (%) OR2 (95% CI)
<18.5 636 (16.0) 1.07 (0.97–1.17) 768 (19.3) 1.17 (1.08–1.27) 844 (19.5) 1.11 (1.02–1.21)
18.5–22.9 2,765 (69.5) 1.00 (ref) 2,761 (69.4) 1.00 (ref) 2,989 (69.2) 1.00 (ref)
23–24.9 427 (10.7) 1.02 (0.91–1.32) 356 (8.95) 0.92 (0.82–1.03) 376 (8.7) 0.93 (0.83–1.04)
≥25 153 (3.8) 1.22 (1.02–1.45) 92 (2.3) 0.82 (0.66–1.01) 112 (2.6) 0.96 (0.79–1.17)
1
Only included participants who were enrolled between 2007 and 2012 due to lack of information in age at spontaneous abortion
2
Adjusted for age, education, smoking before first pregnancy and drinking status
Jung et al. BMC Pregnancy and Childbirth (2015) 15:228 Page 6 of 8

Table 4 Stratification analyses by smoking before pregnancy for was approximately 0.9 [38]. Although women in the
the likelihood for total and recurrent spontaneous abortion (SA) NHS were aged 25 to 42 years were therefore younger
by body mass index (BMI) at 18–20 years old in the Health than our participants, there is evidence that self-
Examinee Study (HEXA), 2004–2012 reported height and weight data are adequate for asses-
BMI Smokers before pregnancy Never-smokers before pregnancy sing associations in epidemiological studies [39]. In the
(kg/m2)
SA OR1 (95% CI)1 SA OR1 (95% CI)1 stratification analysis of cigarette smoking before preg-
N (%) N (%) nancy, we had an insufficient number of samples to ex-
<18.5 34 (26.0) 1.31 (0.70–2.44) 3,060 (17.5) 1.09 (1.05–1.15) plore the effect of the association of first age of smoking
18.5–22.9 49 (67.1) 1.00 (ref) 12,249 (69.9) 1.00 (ref) and BMI at ages 18–20 years and SA.
This study’s strength is its large size and prospective
23–24.9 3 (4.1) 0.70 (0.12–1.40) 1,666 (9.5) 0.94 (0.89–1.00)
potential. To the best of our knowledge, it is currently
≥25 2 (2.7) 0.74 (0.15–3.59) 545 (3.1) 1.05 (0.95–1.16)
the largest study that has addressed pre-pregnancy BMI
1
Adjusted by age, education, smoking before pregnancy, drinking status and and SA. Additionally, although this study used baseline
first pregnancy age
cohort data with cross-sectional analysis, temporal char-
acteristics are included in the analysis, as women with
women who had gestational hypertension, we observed BMIs at ages 18–20 years were analyzed. Reverse caus-
significantly increased ORs only in the ‘underweight’ ation is the most important problem, in which the loss
population. of weight resulting from particular diseases can falsify
There is abundant evidence supporting the biological the association between lower BMI and health out-
plausibility of the extended risk of higher BMIs and the comes. To clarify this problem, we excluded women
risk of SA. Adolescent or early adult obesity is related to who had pregnancies before the ages of 18–20 years.
increased overall mortality and especially and an in- Furthermore, to provide reliable estimated values for the
creased risk of diabetes and cardiovascular diseases in total effect of BMI on the likelihood of SA in a large
adult life [31]. The association between obesity in youth Korean population, this study also evaluated the rela-
and inflammation leads to vascular damage over time. tionship between low BMI and the likelihood of SA in a
Chronic inflammation may have a key role in SA by more discrete way. This particular outcome could not be
damaging the vessels, which support the utero-feto- appropriately demonstrated in most of the earlier studies
placental complex [32]. conducted in European populations.
In contrast, there are also studies supporting the
mechanism of SA in low BMI women. It has been re-
ported that women with low weights have an increased Conclusions
risk of fetal growth retardation [33], which can be ex- This study revealed that pre-pregnancy BMI at ages 18–
plained by an increased rate of vasoconstriction and de- 20 years was associated with a higher likelihood of SA in
creased serum glucose levels due to poor diet and underweight or obese women, using the Asian BMI clas-
decreased blood pressure, provoking reduced placental sification. This U-shaped association was much stronger
perfusion [34]. Additionally, it has been proposed that for recurrent, consequent SA or in women who had ever
leptin, a hormone secreted by adipose cells, may play a smoked cigarettes before pregnancy. Age at SA and ges-
role in this association. Underweight women usually tational hypertension modified the association of pre-
have low levels of this hormone, which can block ovula- pregnancy BMI with SA. Obese women had a higher
tion [35]. Similarly, maternal underweight caused by a likelihood of SA at earlier maternal ages, whereas under-
shortage of food or eating disorders, such as anorexia or weight women had a higher likelihood of SA at typical
bulimia, is associated with SA [36, 37]. or later ages or with gestational hypertension. Further
There are several limitations to this study. First, as the studies are needed to evaluate the exact cause of the dif-
original HEXA was designed to mainly focus on other ference in age trends and BMI ranges.
chronic diseases, the recall of retrospective, pregnancy-
related information might be less accurate. However, as Additional files
participants were not aware of the main purpose of this
study, there is less chance for recall bias. Additionally, Additional file 1: Table S1. Stratification analyses by gestational
the mean age at enrollment was 52.0 years, and the diabetes (GDM) for the likelihood for total and recurrent spontaneous
abortion (SA) of body mass index (BMI) at 18–20 years old in the Health
women were asked to recall their weight nearly 30 years Examinee Study (HEXA), 2004–2012. (DOC 33 kb)
prior. The results of the Nurses’ Health Study (NHS) in- Additional file 2: Table S2. Stratification analyses by gestational
dicate that participants were able to recall their weight hypertension (GHT) for the likelihood for total and recurrent spontaneous
at the age of 18 years, and the correlation coefficient be- abortion (SA) of body mass index (BMI) at 18–20 years old in the Health
Examinee Study (HEXA), 2004–2012. (DOC 33 kb)
tween recalled and objective measurements for weight
Jung et al. BMC Pregnancy and Childbirth (2015) 15:228 Page 7 of 8

Competing interests 12. Dzakpasu S, Fahey J, Kirby RS, Tough SC, Chalmers B, Heaman MI, et al.
The authors declared that they have no competing interests. Contribution of prepregnancy body mass index and gestational weight
gain to adverse neonatal outcomes: population attributable fractions for
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1
Department of Biomedical Science, Seoul National University College of 21. Ogonowski J, Miazgowski T, Kuczynska M, Krzyzanowska-Swiniarska B,
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National University College of Medicine, Seoul, South Korea. 3Cancer diabetes mellitus. Diabetic medicine : a journal of the British Diabetic
Research Institute, Seoul National University Hospital, Seoul, South Korea. Association. 2009;26(4):334–8.
4
Department of Preventive Medicine, Kangwon National University, Seoul, 22. Shin D, Song WO. Prepregnancy body mass index is an independent risk
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