1 Department of Food & Nutrition, Hanyang University, 04763 Seoul, Republic of Korea
2 Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, 17104 Yongin, Republic of Korea
3 Departments of Obstetrics and Gynecology, Soonchunhyang University College of Medicine, 14584 Bucheon, Republic of Korea
† These authors contributed equally.
Abstract
Background: The nutritional status of pregnant women has a significant
impact on maternal health, fetal growth, and pregnancy outcomes. The purpose of
this study was to investigate the associations among advanced maternal age,
eating habits, knowledge level, and obstetric outcome in pregnant women.
Methods: We conducted an observational single center study of 168
pregnant women. The participants were divided into three groups by age: group I
(
Keywords
- Education
- Nutrition
- Age
- Pregnancy
Maternal age is the one most important factor that can cause poor health of a newborn [1]. Lately, as the education level and social advancement of women in Korea has increased, the average age at first marriage has increased and the average age of first childbirth has been delayed [2]. According to a report from the Korea National Statistis in 2020, the average age at first marriage for women was 30.6 years and the first childbirth age was 32.3 years [2].
Older age is usually related to higher incidences of maternal hypertension; diabetes; cardiovascular, neurological, renal, and pulmonary complications; and serious blood-losing obstetric problems such as placenta previa and abruption of the placenta [1]. In addition, having a low body mass index (BMI) during pre-pregnancy or the effort of losing weight during pregnancy might cause malnutrition of the fetus and increase the likelihood of a low birth weight infant [3]. Dietary recommendations and education during pregnancy are important, but adequate guidelines and intention are controversial [4]. Actually, poor quality and inadequate amount of dietary intake during pregnancy may cause low body mass index and severe anemia, which can result in maternal death, prematurity and low birth weight of the infant, miscarriage, premature rupture of membranes, and cesarean section [5]. One possible reason is thought to be the lack of understanding, education, and health care during the perinatal period among pregnant women [6].
Currently, Korean government policy includes a pregnancy and childbirth cost support policy and the maternal child health policy. The pregnancy and childbirth policy are a cost support for infertile couples and low-income families, and the maternal child health policy includes support for medical expenses for premature infants and children with congenital dysfunction and support for high-risk pregnant women [7].
In a prospective observational study, we investigated general features, dietary habits, nutritional knowledge and need for education, and understanding of dietary guidelines and practice of them according to age in pregnant women. Second, we investigated obstetric characteristics of pregnant women, eating habits, and nutrition knowledge level and the relationship of these factors to clinical characteristics of infants and pregnancy outcome.
We recruited patients who visited a tertiary center hospital obstetric and gynecologic clinic.
All subjects gave their informed voluntarily consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Institutional Review Board (IRB) (approval number: 2013-01-031).
A total of 168 participants were divided into three groups by age: group I
(
We calculated gestational age starting from the first day of the last
menstruation and performed ultrasonography only in cases of uncertainty. Data
collected included age, height, body weight before pregnancy, educational level,
gestational age, occupation, any medical/surgical complications during pregnancy,
parity, drinking, and smoking. BMI was obtained through height and weight, and
the BMI categories were defined as follows: underweight (BMI
The mini dietary assessment (MDA) [9] consists of 10 questionnaires that can be roughly grouped as questions about foods that are recommended (milk and dairy products, meats, fish, eggs, beans, tofu, vegetables, fruits, etc.), about foods that are not suggested (fried foods, stir-fried foods, simple sugars like ice-cream, salty foods), and about the balance of the diet (regular meals, variety of dietary foods). Different numbers of points are given for the degrees of agreement; 5 points for “strongly doing so” 3 points for “doing so” and 1 point for “not doing so” and the score is summed with a maximum of fifty, with higher points interpreted as a better-quality diet.
We checked nutritional knowledge, interest in nutrition during pregnancy/lactation, what the participants thought about the proper time for nutrition education, and how much they were willing to participate in nutrition education. We used the dietary action guidelines for pregnant women/lactating women of the Korean diet guideline 2012 [10], which is made and distributed by the Ministry of Health and Welfare to modify inappropriate dietary habits that could lead to chronic medical conditions. We gave 3 points for “practicing”, 2 points for “trying to practice”, and 1 point for “not practicing or cannot practice”, and evaluated the practice as “fair” when the sum of points from 5 questionnaires was 12 or higher.
We studied birth weight, length, gestational age, head and chest circumference of the newborn, method of delivery, maternal disease (hypertension and/or gestational diabetes), and maternal hemoglobin and hematocrit before delivery, according to the medical records of the hospital.
We used SPSS version 18.0 (SPSS Inc, Chicago, IL, USA) to analyze the data, and
the results are shown as percentages and mean
The mean age of the participants was 32.33 years. There was no difference in
height between the groups, but body weight increased significantly with age.
Group II and group III women weighed more than those in group I (p =
0.002), and BMI also increased with age (p
Among all subjects, the primipara was 60.7% and the multipara was 39.3%, and the primipara ratio was significantly higher in group I. Regardless of parity, the incidence of hypertension in pregnancy was 2.8% in group I and 8.9% in group III. The incidence of gestational diabetes mellitus was 2.8% in group I and 11.1% in group III. Incidence seemed to increase with the age of the subject, but the relationship was not statistically significant.
In education level, group III had the highest high school graduation rate, and group II had the highest college graduation rate, showing a significant difference between the three groups. Pregnancy itself modified the alcohol consumption and cigarette smoking habits of the subjects; however, there was no difference among the groups (Table 1).
| Variable | Group I | Group II | Group III | Total | p-value | |
| (n = 36) | (n = 87) | (n = 45) | (n = 168) | |||
| Age (years) | 26.83 |
32.10 |
37.16 |
32.33 |
||
| Height (cm) | 160.58 |
161.65 |
159.65 |
160.89 |
0.123 | |
| Pre-pregnant weight (kg) | 51.16 |
56.59 |
59.57 |
56.22 |
0.002 | |
| Pre-pregnancy body mass index (kg/m |
19.85 |
21.62 |
23.32 |
21.70 |
||
| Underweight | 10 (27.8) |
9 (10.3) | 2 (4.4) | 21 (12.5) | ||
| Normal | 22 (61.0) | 56 (64.4) | 22 (48.9) | 100 (59.5) | ||
| Overweight | 2 (5.6) | 12 (13.8) | 10 (22.3) | 24 (14.3) | ||
| Obese | 2 (5.6) | 10 (11.5) | 11 (24.4) | 23 (13.7) | ||
| Parity | Primipara | 29 (80.6) | 57 (65.5) | 16 (35.6) | 102 (60.7) | |
| Multipara | 7 (19.4) | 30 (34.5) | 29 (64.4) | 66 (39.3) | ||
| Prenatal complications | Hypertension | 1 (2.8) | 7 (8.0) | 4 (8.9) | 12 (7.1) | 0.309 |
| Gestational diabetes | 1 (2.8) | 4 (4.6) | 5 (11.1) | 10 (6.0) | 0.104 | |
| Placenta previa, amniotic fluid disease | 1 (2.8) | 7 (8.0) | 4 (8.9) | 12 (7.1) | 0.309 | |
| Education | 11 (30.6) | 22 (25.3) | 25 (55.5) | 58 (34.5) | 0.008 | |
| Junior college | 14 (38.8) | 28 (32.2) | 8 (17.8) | 50 (29.8) | ||
| 11 (30.6) | 37 (42.5) | 12 (26.7) | 60 (35.7) | |||
| Job | Unemployed | 12 (33.3) | 30 (34.5) | 20 (44.4) | 62 (36.9) | 0.002 |
| Specialized job | 2 (5.6) | 27 (31.0) | 5 (11.1) | 34 (20.2) | ||
| Office & service workers | 20 (55.5) | 22 (25.3) | 13 (28.9) | 55 (32.8) | ||
| Others | 2 (5.6) | 8 (9.2) | 7 (15.6) | 17 (10.1) | ||
| Drinking | Current drinker | 2 (5.6) | 0 (0) | 0 (0) | 2 (1.2) | 0.105 |
| Ex-drinker | 12 (33.3) | 39 (44.8) | 15 (33.3) | 66 (39.3) | ||
| Non-drinker | 22 (61.1) | 48 (55.2) | 30 (66.7) | 100 (59.5) | ||
| Smoking | Current smoker | 0 (0) | 0 (0) | 1 (2.2) | 1 (0.6) | 0.508 |
| Ex-smoker | 3 (8.3) | 6 (6.9) | 5 (11.1) | 14 (8.3) | ||
| Non-smoker | 33 (91.7) | 81 (93.1) | 39 (86.7) | 153 (91.1) | ||
| Exercise | 3–5/week | 1 (2.8) | 7 (8.0) | 5 (11.2) | 13 (7.7) | 0.690 |
| 1–2/week | 11 (30.6) | 23 (26.4) | 10 (22.2) | 44 (26.2) | ||
| Never | 24 (66.7) | 57 (65.5) | 30 (66.7) | 111 (66.1) | ||
The dietary assessment is shown in Table 2. The questions about eating less suggested foods such as ice-cream, cake, snacks, and soda (question #9), and about eating a balanced diet (question #10) scored high in the older groups, and there were no differences among groups in the responses to other questions. Reducing salt intake and high-fat meat intake scored 4.23 and 4.07 respectively, which were high scores. The mean score of the overall questionnaire was 33.44. The scores of each group were 32.22 for group I, 33.63 for group II, and 34.04 for group III, and there were no statistically significant differences among the groups (Table 2).
| Group I | Group II | Group III | Total | p-value | |
| (n = 36) | (n = 87) | (n = 45) | (n = 168) | ||
| 1. Consuming more than one serving of milk or dairy products every day. | 3.44 |
3.14 |
3.09 |
3.19 |
0.492 |
| 2. Eating at least 3 to 4 servings of meat, fish, egg, beans, or tofu every day. | 2.72 |
2.33 |
2.11 |
2.36 |
0.073 |
| 3. Eating vegetables and Kim-chi at every meal. | 2.61 |
2.91 |
2.82 |
2.82 |
0.532 |
| 4. Eating one serving of fruit or fruit juice every day. | 3.56 |
3.55 |
3.09 |
3.43 |
0.256 |
| 5. Eating more than one serving of fried or stir-fried food every two days. | 4.11 |
3.67 |
3.76 |
3.79 |
0.221 |
| 6. Eating more than one serving of fatty meat every three days. | 3.72 |
4.08 |
4.33 |
4.07 |
0.066 |
| 7. Adding table salt or sauce to food generally. | 3.83 |
4.36 |
4.29 |
4.23 |
0.094 |
| 8. Having three regular meals a day. | 2.39 |
2.33 |
2.87 |
2.49 |
0.121 |
| 9. Eating ice-cream, cake, snacks, soda between meals every day. | 3.33 |
4.15 |
4.16 |
3.98 |
0.003 |
| 10. Eat a variety of foods (eating a balanced diet). | 2.72 |
3.07 |
3.40 |
3.08 |
0.045 |
| MDA total score | 32.22 |
33.63 |
34.04 |
33.44 |
0.304 |
We evaluated the level of general knowledge during pregnancy. Fifty percent of the subjects in the group I answered “do not know at all or do not know”, while only 24.4% of group III answered in that category. The percentage of subjects who answered that they have average knowledge was 58.9%. 66.1% of subjects said they had attempted to obtain nutrition information during pregnancy, and the rest said that they did not. Nutrition counseling experience during pregnancy was lower in the group I than the other groups. However, among the overall subjects, only 7.7% had nutrition counseling (Table 3).
| Category | Group I | Group II | Group III | Total | p-value | |
| (n = 36) | (n = 87) | (n = 45) | (n = 168) | |||
| Level of knowledge about nutrition in pregnancy | Do not know at all or do not know | 18 (50.0) |
21 (24.2) | 11 (24.4) | 50 (29.8) | 0.025 |
| Normal | 15 (41.7) | 53 (60.8) | 31 (68.9) | 99 (58.9) | ||
| Know a little or know | 3 (8.3) | 13 (14.9) | 3 (6.7) | 19 (11.3) | ||
| Trying to get nutrition information | Making an effort | 27 (75.0) | 55 (63.2) | 29 (64.4) | 111 (66.1) | 0.438 |
| Not making an effort | 9 (25.0) | 32 (36.8) | 16 (35.6) | 57 (33.9) | ||
| Nutrition counseling experience | Yes | 1 (2.8) | 8 (9.2) | 4 (8.9) | 13 (7.7) | 0.441 |
| No | 35 (97.2) | 79 (90.8) | 41 (91.1) | 155 (92.3) | ||
Information sources were mostly blogs or internet cafés (48.2%), followed by friends and neighbors, books and magazines, and medical centers. Of the subjects, 56.5% were aware of the importance of nutrition education before and during the first half of pregnancy. Slightly more than half (57.7%) of the subjects were willing to participate in nutrition education, and the remainder were not (Table 4).
| Category | Frequency | % | |
| Nutrition information source (multiple response analysis) | Public organization | 13 | 9.2 |
| Pregnancy care products portal sites | 6 | 4.3 | |
| On-line community-based blogs or café | 68 | 48.2 | |
| Medical service organizations | 13 | 9.2 | |
| Acquaintances, friends, experienced hands | 21 | 14.9 | |
| Book, magazine, newspaper | 18 | 12.8 | |
| Others | 2 | 1.4 | |
| Reasonable period of nutrition education for pregnant women | Before pregnancy | 95 | 56.5 |
| Early stages of pregnancy | 63 | 37.5 | |
| Second trimester | 3 | 1.8 | |
| Third trimester | 6 | 3.6 | |
| Breastfeeding period | 1 | 0.6 | |
| Nutrition education participation | Will participate | 97 | 57.7 |
| Will not participate | 8 | 4.8 | |
| Do not know | 63 | 37.5 | |
The degree of actual practice of dietary action guidelines for pregnant women/lactating women was processed with the highest score at three points. Group I had lower scores than group II, but the difference was not statistically significant. The mean sum of scores for five questions was 10.86 points, which was lower than 12, meaning that the overall practice of the guidelines was not very successful. In detail, “not drinking alcoholic beverage” scored the highest points at 2.89, and “drinking milk or dairy products every day” was least practiced, with a score of 1.86. One hundred and twenty participants (71.4%) were not aware of the dietary action guidelines for pregnancy, which was much greater than the number who were aware (48 subjects; 28.6%). The percentage who did not know about the guidelines was largest in group I and smallest in group II, but there was no statistically significant difference (Table 5).
| Group I | Group II | Group III | Total | p-value | ||
| (n = 36) | (n = 87) | (n = 45) | (n = 168) | |||
| Practice scores for dietary action guidelines | ||||||
| Drinking more than 3–4 servings of milk or dairy products every day | 1.78 |
1.89 |
1.87 |
1.86 |
0.690 | |
| Eating meat, fish, vegetables, and fruit every day | 1.94 |
2.16 |
2.13 |
2.11 |
0.138 | |
| Preparing the proper amount of clean food | 2.11 |
2.18 |
2.02 |
2.13 |
0.245 | |
| Not drinking alcoholic beverages | 2.94 |
2.84 |
2.93 |
2.89 |
0.276 | |
| Increasing physical activity and exercising every day | 1.92 |
1.93 |
1.96 |
1.93 |
0.962 | |
| Total score | 10.69 |
11.00 |
10.91 |
10.86 |
0.608 | |
| Frequency of awareness of dietary action guidelines | ||||||
| Agree or strongly agree | 7 (19.4) |
30 (34.5) | 11 (24.4) | 48 (28.6) | 0.189 | |
| Strongly disagree | 29 (80.6) | 57 (65.5) | 34 (75.6) | 120 (71.4) | ||
Newborn weight in group 1 was significantly lower than in the other two groups (p = 0.025).
We divided the participants according to their newborns’ birth weight into low birth weight, normal weight, and high birth weight groups. Group I and group III mothers had 50%, and 20.6% low-birth-weight newborns, respectively. Overall, 21.4% of the newborns were born with low birth weight, and birth weight groups was a significant difference (p = 0.015), but there was no difference in gestational age. Head circumference and chest circumference of newborns born to group III mothers were larger than those of newborns born to group I mothers (p = 0.039, p = 0.019), and were in the normal range based on the Korea pediatric developmental standard value (2007) presented in [11].
We found that hemoglobin (Hb) and hematocrit (Hct) measured immediately before delivery dropped by a greater percentage when maternal age was low. Average Hb and Hct levels were higher than the diagnostic values for anemia in pregnant women set by the CDC (Centers for Disease Control) [12], which are 11 g/dL and 33%, respectively. However, when we set the cut-off value for anemia in the second half of pregnancy (by CDC) at 11.0 g/dL, 35.7% of group I, 18.0% of group II, 14.7% of group III, and 19.4% of the total group were categorized as having iron-deficiency anemia by their Hb values. By Hct criteria (Hct less than 33%), 31.6% of the total group of subjects, 50.0% of group I, 28.0% of group II, and 29.4% of group III were anemic. The older groups had experienced a greater number of abortions, but the difference was not statistically significant (Table 6).
| Group I | Group II | Group III | Total | p-value | ||
| (n = 14) | (n = 50) | (n = 34) | (n = 98) | |||
| Birth weight | Mean birth weight (g) | 2409.29 |
2968.00 |
2849.41 |
2847.04 |
0.025 |
| LBW | 7 (50.0) | 7 (14.0) | 7 (20.6) | 21 (21.4) | 0.015 | |
| NBW | 7 (50.0) | 43 (86.0) | 27 (79.4) | 77 (78.6) | ||
| HBW | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||
| Duration of gestation | Mean gestational age in weeks | 35.70 |
37.43 |
36.60 |
36.89 |
0.130 |
| Preterm | 5 (35.7) | 9 (18.0) | 11 (32.4) | 25 (25.5) | 0.213 | |
| Mature | 9 (64.3) | 41 (82.0) | 23 (67.6) | 73 (74.5) | ||
| Post mature | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||
| Mode of delivery | Vaginal delivery | 8 (57.1) | 19 (38.0) | 10 (29.4) | 37 (37.8) | 0.197 |
| Cesarean section | 6 (42.9) | 31 (62.0) | 24 (70.6) | 61 (62.2) | ||
| Birth height (cm) | 45.96 |
48.71 |
48.29 |
48.17 |
0.073 | |
| Head circumference (cm) | 31.82 |
33.77 |
33.43 |
33.37 |
0.039 | |
| Chest circumference (cm) | 29.61 |
32.48 |
31.62 |
31.77 |
0.019 | |
| Hemoglobin status of the pregnant woman (g/dL) | 11.06 |
11.87 |
11.96 |
11.79 |
0.064 | |
| Hematocrit status of the pregnant woman (%) | 32.56 |
34.78 |
35.31 |
34.65 |
0.043 | |
| Abortion experience | 3 (21.4%) | 12 (24.0%) | 12 (35.5%) | 27 (27.6) | 0.313 | |
| Group I: | ||||||
This study detected differences in nutrition knowledge and dietary practices of pregnant women according to age, and evaluated possible differences in birth outcome.
The anthropometric survey of pre-pregnancy outcome of the study subjects showed that the greater the age, the higher the BMI. Our study showed a higher percentage (12.5%) of subjects whose BMI is lower than 18.5 compared to the result (7.0%) of the National Health and Nutrition Examination Survey (2011) [13]. Our results were similar to those of a study that investigated pregnant women in Suwon province [14].
The incidences of hypertension and gestational diabetes tended to increase as maternal age increased, but the associations were not statistically significant. The incidence of prenatal complications, especially hypertension and diabetes, increases in pregnant women age 35 years and older. Ten to twenty percent of chronic hypertension occurs among the older age group (35 and older). Type II diabetes mellitus (DM), gestational DM also increase with age [15]. In this study, the incidence of hypertension in group III was 8.9%, which was a similar result to that of Heo et al. [16] (7.7%) and higher than that found by Jang et al. [13] (4.3%). The incidence of gestational DM was threefold higher in group III than group I. This is consistent with previously reported data in which the incidence of gestational DM was two- to three-fold higher in pregnant women age 35 years and older than in 20- to 25-year-old pregnant women [17]. There has been a report that American multiparae in the older age group have a higher incidence of hypertension and gestational DM. In our study, prenatal complications tended to increase with age, but the relationship was not statistically significant, probably due to the small number of subjects. Therefore, further study is needed.
Pregnancy itself modified alcohol consumption and cigarette smoking habits of the subjects; however, there were no differences among the groups. Alcohol drinking during pregnancy can cause low birth weight, prematurity, and a reduction in the immune system of the newborn. Cigarette smoking can result in aging of the placenta, decreased blood flow through the placenta, fetal growth restriction, and prematurity [18]. Since these social habits can have complex effects on fetal health, it is very important to modify these behaviors.
Result of dietary assessment based on age showed that group III was better at reducing ice-cream, snacks, cake, and sodas, and having more balanced meals than group I (p = 0.003, p = 0.045). Each item compared to salt intake and high fat meat, fried snacks and a score for it was the result of higher intake adjustment I similar to Choi’s study [19]. Group III had generally better evaluations in other questionnaires but the differences among groups were not statistically significant. During pregnancy, the subjects were examined for nutrition-related knowledge, and their training needs were assessed. Group I had a higher percentage of respondents who “do not know at all or do not know” about nutrition knowledge than group III (p = 0.025). Of the total group, 64.5% said they made an effort to obtain more information about nutrition. It may be natural that there are significant differences between the three groups in response to the frequency of intake of sugar-rich foods or the diversity of meals. Considering that group I has a high proportion of primipara, a high proportion of multipara in group III, and a high proportion of comorbid diseases such as gestational diabetes in group III, it is thought that group III have paid more attention to information about diet. Group I went through consultation during pregnancy less frequently than the other groups, but the difference was not statistically significant. Only 7.7% of the total group of subjects had received nutritional education or consultation. This was a very low level compared to the 29.1% who had educational experience in the Yun study [20]. Modifying dietary habits during pregnancy can have tremendous results [21]; therefore, pregnancy is a good opportunity to set the foundation of nutritional knowledge and to establish better habits and make an effort to maintain them [22]. It would be important to attempt proper intervention regarding nutrition in pregnant women, and to improve the accessibility of obstetric care. Especially considering the increase in high-risk pregnancy due to older age, nutritional management is crucial to prevent various complications of pregnancy. More subjects in group I responded that they “do not know” about dietary action guidelines for pregnant women/lactating women, while fewer women in group III answered that they “do not know”. The practice score of the guidelines was also better in group III, but the difference was not statistically significant. All of the criteria, with the exception of cutting alcoholic beverages, were rarely met. This is probably due to poor awareness of the dietary guidelines. In Korea, dietary guidelines for pregnant and lactating women have already been prepared [10]. According to the results of this study, there are differences in educational needs and practice depending on the maternal age, and educational programs and dietary counseling services should be provided reflecting this.
Group II and group III showed better results for birth weight (p =
0.025), head circumference (p = 0.039), and chest circumference
(p = 0.019) of the newborn and maternal hematocrit (p = 0.043)
than group I. The incidence of low birth weight was highest in group I and lowest
in group II (p = 0.015). Group I had shorter gestational age, shorter
birth height, and lower maternal hemoglobin, but the differences were not
statistically significant. In this study, almost one-third (28.6%) of pregnant
women age 29 years and under were underweight, and when pre-pregnant BMI was
below the normal range, they were more likely to have iron deficiency and deliver
a low-birth-weight baby. We should make an effort to improve iron-deficiency
anemia of pregnant women age 29 years and under. It is well known that healthy
weight before pregnancy and proper weight gain during pregnancy play a crucial
role in uterine environment changes, pregnancy outcome, and fetal health [23].
The most important factor in the outcome of pregnancy in the oldest group of
women is age [24]. In a comparison of older (
The limitations of this study are that it did not include a detailed analysis of implementation status and nutrient intake and was performed at a single institution. In addition, it is regrettable that the mini nutritional assessment performed on the subject was not tailored to pregnant women, so it is thought that it needs to be developed in the future. Although the nutritional status of older pregnant women is better, if nutrition knowledge is good and proper eating habits are maintained, a good pregnancy outcome can be expected.
It is obvious that older pregnant women need delicate management in that the disease prevalence rate is higher than that of younger pregnant women. Pregnant women with younger age had a relatively low pre-pregnancy BMI, a higher rate of low birth weight, and low nutritional knowledge. In other words, in order to obtain a good childbirth result, appropriate weight must be considered before pregnancy, and priority management factors must be applied differently depending on the age of the pregnant woman. Nutritional information and service routes to be provided according to the age of the pregnant woman should be diverse and individualized.
MJK and YP conceived and designed the conceptualization; MJK and THK performed the methodology and investigation; MJK, HSL, and HHL contributed data curation and analysis; MJK and HSL wrote the paper; THK and YP reviewed and edited the manuscript. All authors read and approved the final manuscript.
All subjects gave their informed voluntarily consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Institutional Review Board (IRB) (approval number: 2013-01-031).
Thanks to all the peer reviewers for their opinions and suggestions.
This study was supported in part by the Soonchunhyang University Research Fund (grant number: 10210026).
The authors declare no conflict of interest.
