Association of Maternal Serum Vitamin A Levels in the First Trimester with the Risk of Adverse Pregnancy Outcomes: A Prospective Cohort Study of Chinese Women

Association of Maternal Serum Vitamin A Levels in the First Trimester with the Risk of Adverse Pregnancy Outcomes: A Prospective Cohort Study of Chinese Women | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association of Maternal Serum Vitamin A Levels in the First Trimester with the Risk of Adverse Pregnancy Outcomes: A Prospective Cohort Study of Chinese Women Qinqin Ren, Yijin Wang, Yang Wang, Hui Yuan, Yao Liu, Yuanhuan Wei, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4935218/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objectives To examine the association of serum vitamin A concentrations in early pregnancy with the risk of adverse pregnancy outcomes in Chinese women. Methods This prospective cohort study was conducted in the Department of Gynecology and Obstetrics at Shenzhen Nanshan People’s Hospital from 2019 to 2020. Serum vitamin A concentrations were measured during the first trimester (the first 6–13 weeks) of pregnancy, and pregnancy outcomes were recorded in the hospital information system. Serum vitamin A concentrations were categorised into the following quintiles: ≤ 0.57 µmol/L, 0.57–0.63 µmol/L, 0.63–0.69 µmol/L, 0.69–0.82 µmol/L, and > 0.82 µmol/L. The participants with serum vitamin A concentrations in the lowest quintile were used as the reference group. Statistical analysis was performed using multivariate logistic regression. Results One thousand and seventy-seven singleton mothers were recruited as participants. After multivariable adjustment, it was found that serum vitamin A concentrations > 0.82 µmol/L and within a safe range were associated with a decreased risk of gestational diabetes mellitus (GDM) (odds ratio [OR]: 0.50; 95% confidence interval [CI]: 0.31–0.81). In addition, compared with participants with serum vitamin A concentrations in the lowest quintile, those of participants with serum vitamin A concentrations in the highest quintile had a decreased risk of low birth weight (LBW) (OR: 0.26; 95% CI: 0.07–0.96). Moreover, after adjustment and compared with participants with serum vitamin A concentrations in the lowest quintile, those with serum vitamin A concentrations in the fourth quintile had a decreased risk of small for gestational age (OR: 0.32; 95% CI: 0.12–0.82). Furthermore, compared with participants with vitamin A concentrations ≤ 0.57 µmol/L, participants with vitamin A concentrations > 0.82 µmol/L had an increased risk of emergency caesarean section (OR: 2.31; 95% CI: 1.26–4.26). Conclusion During the first trimester, maternal serum vitamin A concentrations > 0.82 µmol/L and within a safe range were found to be associated with a reduced risk of GDM and LBW. However, an increase in serum vitamin A concentrations was found to be associated with an increase in the risk of emergency caesarean section. vitamin A adverse pregnancy outcomes gestational diabetes mellitus emergency caesarean section low-birth-weight infant small-for-gestational-age infant Figures Figure 1 Figure 2 1. Background An adverse pregnancy outcome is an event that reduces the chance of having a healthy newborn [ 1 ]. These outcomes encompass all the pathological complications that may occur during pregnancy and childbirth, such as pre-eclampsia, preterm birth, low birth weight (LBW), stillbirth, emergency caesarean section, and gestational diabetes mellitus (GDM). GDM is any degree of glucose intolerance with onset or first detection during pregnancy [ 2 ]. It was reported that the global standardised total prevalence of GDM was 14.0% [ 3 ], being 14.8% in China [ 4 ]. Adverse pregnancy outcomes are a major public health problem, as they increase maternal and neonatal mortality and affect the long-term health of both mothers and children [ 5 ]. In addition, adverse pregnancy outcomes, particularly GDM, are associated with an increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease in women after childbirth [ 4 , 6 – 8 ], and with an increased risk of obesity and T2DM in their offspring [ 9 ]. However, most adverse pregnancy outcomes can be diagnosed only in the mid-to-late stages of pregnancy, leaving insufficient time for prevention [ 10 ]. Therefore, it is important to determine the risk factors for adverse pregnancy outcomes in early pregnancy. Vitamin A is a fat-soluble compound that is essential for normal functioning of the human body. It can be obtained from the diet through consumption of meat containing retinol and its close derivatives, vegetables or dairy products containing provitamin A (carotenoids) or vitamin A-active carotenoids, fortified foods (e.g., cereals or juices), or vitamin supplements [ 11 – 13 ]. During pregnancy, vitamin A is important for cell division, growth, and maturation of the foetal organs and skeletal system. It is also important for the development and maintenance of the foetal immune and visual systems[ 14 , 15 ]. Vitamin A can directly remove reactive oxygen species, thereby protecting cells from oxidative damage[ 16 , 17 ]. Compared with normal pregnant women, pregnant women with T2DM have a lower antioxidant capacity and increased cellular concentrations of oxidative products, given the similarities between the mechanisms of GDM and T2DM, we speculate that oxidative stress may lead to the initiation and development of GDM [ 18 – 20 ]. It has been observed that the activity of superoxide dismutase in pregnant women with GDM is significantly lower than that in normal pregnant women [ 18 , 19 ]. However, few studies have examined the relationship between serum vitamin A concentrations and GDM, and they have drawn inconsistent conclusions. Hekmat et al. [ 21 ] and Suhail et al. [ 22 ] surveyed pregnant women in the third trimester and found that there was a significant decrease in serum vitamin A concentrations in those with GDM. However, Grissa O et al. [ 23 ] found that compared with women without GDM, those with GDM exhibited no significant changes in serum vitamin A concentrations. Retinol-binding protein 4 (RBP4) is secreted mainly by the liver and adipose tissue and was initially identified as a transport protein for vitamin A and other retinoid derivatives in the bloodstream [ 24 , 25 ]. It was also found that serum RBP4 concentrations in women with GDM were higher than those in women without GDM [ 26 ]. So far, only a few prospective studies conducted in China have explored the relationship between maternal serum vitamin A levels in early pregnancy and the incidence of GDM. One study conducted in Beijing found that higher vitamin A levels in early pregnancy (and even normal vitamin A levels) were positively associated with GDM risks [ 27 ]. Another study conducted in Beijing observed the same result, but this finding is contrary to their research hypothesis [ 28 ]. Therefore, it is essential to investigate the correlation between serum vitamin A concentrations and GDM during the first trimester of pregnancy. The nutritional status of the mother affects the development of the foetus. Low concentrations of retinol in umbilical cord blood and maternal serum may reflect poor vitamin A status in the newborn and mother, which may affect foetal growth [ 29 ]. One research observed that greater birth size with higher concentrations of cord retinol [ 30 ]. Additionally, there is a positive correlation between maternal vitamin A concentrations and birth weight after delivery [ 31 ]. However, Fiona Mathews et al. [ 32 ] showed that high retinol concentrations in later pregnancy were associated with lower birth weights in a large group of pregnant white women from the United Kingdom. Samson et al. [ 29 ] showed that vitamin A and zinc deficiencies in the second or third trimesters were not associated with an increased risk of LBW. Overall, the relationship between serum vitamin A concentrations and adverse pregnancy outcomes remains unclear. In addition, most studies that have explored this association were conducted during the second or third trimester or after delivery. Therefore, determination of serum vitamin A concentrations in early pregnancy will clarify whether vitamin A influences the occurrence of adverse pregnancy outcomes. Accordingly, in the present study, we aimed to examine the relationship between serum vitamin A concentrations during the first trimester and the risk of adverse pregnancy outcomes. 2. Materials and Methods 2.1 Participants This prospective cohort study was conducted in the Department of Gynaecology and Obstetrics at Shenzhen Nanshan People’s Hospital, Shenzhen, China, from 2019 to 2020 and investigated the effect of serum vitamin A concentrations in pregnant women on adverse pregnancy outcomes. The inclusion criteria were 1) women aged 18 or older; 2) having a singleton pregnancy; 3) at 6–13 weeks of gestation; and 4) who had registered and plan to deliver in the above-mentioned hospital. Then a total of 1349 pregnant women were recruited in the study. The exclusion criteria were 1) having a multiple pregnancy (n ₌ 7); 2) death of the infant (n ₌ 3); 3) GDM could not be diagnosed (n ₌ 1); 4) having pre-pregnancy diabetes or gestational diabetes diagnosed before 24 weeks (n ₌ 2); 5) having pre-pregnancy hypertension (n ₌ 2); 6) having hepatitis or impaired liver function (n ₌ 58); 7) having nephritis or impaired kidney function (n ₌ 7); 8) lost to follow-up (n ₌ 1); or 9) missing vitamin A laboratory test data or other baseline data (n ₌ 191). After the exclusion of 272 potential participants due to ineligibility, 1077 pregnant women were included as participants. Ethical approval for studying this cohort was obtained from the Ethics Committee of Shenzhen Nanshan People’s Hospital (No. 2019072644), and all participants signed an informed consent form. The study was conducted in accordance with the Declaration of Helsinki developed by the World Medical Association. 2.2 Data collection The baseline data were collected through questionnaire surveys and from the hospital’s medical record system. The collected data comprised the participants’ age, weight, height, educational level, smoking and drinking status during pregnancy, disease history, pregnancy history, family history and other information, and serum vitamin A concentrations and other laboratory data at 6–13 weeks of pregnancy. Pre-pregnancy body mass index (BMI) was calculated from participant-reported pre-pregnancy weight and height. BMI was calculated as weight (kg) divided by the square of height (m). The gender and basic physical characteristics of newborns were obtained from records in the hospital information system. The weight and height of newborns at birth were measured using an infant length and weight measuring instrument, and their head circumference and chest circumference were measured using a tape measure. 2.3 Definition of mother and infant adverse pregnancy outcomes According to the diagnostic criteria established by the International Association of Diabetes and Pregnancy Research Groups, the participants underwent a 75-g oral glucose tolerance test (OGTT) between 24 and 28 weeks of gestation. If the participants’ results met any of the following criteria or any combination thereof, they were diagnosed with GDM: a fasting plasma glucose ≥ 5.1 mmol/L, an OGTT 1-h plasma glucose concentration ≥ 10.0 mmol/L, and an OGTT 2-h plasma glucose concentration ≥ 8.5 mmol /L[ 33 ]. Small for gestational age (SGA) and large for gestational age (LGA) were defined as birth weights below the 10th percentile or above the 90th percentile of the mean weight of other infants of the same gestational age, respectively. Newborns with a birth weight > 4000 g were defined as macrosomic, and those with a birth weight < 2500 g were defined as LBW[ 34 ]. 2.4 Biochemical analysis Serum samples were prepared as follows. Stored serum was thawed at 4°C. A sample (100 µL) was treated with an internal standard solution (100 µL) and methanol (100 µL), and the resulting mixture was vortexed for 2 min. Subsequently, the mixture was treated with hexyl hydride (800 µL), vortexed for 5 min to extract vitamin A, and then centrifuged at 12,000 rpm for 10 min. Next, 650 µL of the supernatant was transferred to another vessel and then taken to dryness under a flow of nitrogen gas. The solid residue was re-dissolved in acetonitrile (100 µL), and the resulting solution was vortexed for 60 s and then centrifuged at 12,000 rpm for 10 min. An aliquot of the supernatant was analysed by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) to determine its concentration of vitamin A. The HPLC-MS/MS method was based on that used in a previous study [ 35 ]. A vitamin A standard and mobile phases (formic acid, ammonium formate, acetonitrile, and methanol) were purchased from Merck. HPLC-MS/MS analysis was performed using an AB ExionLC system coupled with a Triple Quad™ 4500 tandem mass spectrometer (AB Sciex, Framingham, MA). The instruments were controlled using Analyst® software. Chromatographic separation of sample components was performed on a Waters HPLC CORTECS C18 Column (2.1 mm × 50 mm, 2.7 µm). The mobile phases comprised 0.1% formic acid + 0.01 mol/L ammonium formate + water (A) and 0.05% formic acid + methanol (B). The injection volume was 10 µL, and the column temperature was 40°C. Chromatographic separation was performed at a flow rate of 0.6 mL/min using the following gradient elution: 0–0.5 min with A:B = 30:70; 0.5–2.0 min with A:B = 30:70; 2.0–4.5 min with A:B = 0:100; and 4.6–5.6 min with A:B = 30:70. Mass spectrometry was performed using atmospheric pressure chemical ionisation and in multi-reaction monitoring mode. 2.5 Statistical analysis The participants were divided into five groups based on quintiles of serum vitamin A concentrations. Continuous data are expressed as means and standard deviations (SDs) or medians and interquartile ranges (IQRs), depending on their distribution. Categorical variables are expressed as frequencies and percentages. Between-group differences were determined by conducting Kruskal–Wallis tests or one-way analyses of variance for continuous variables and conducting chi-square tests for categorical variables. Correlation analysis was performed to investigate the relationships between serum vitamin A, serum vitamin C, and serum vitamin E concentrations and fasting, OGTT 1-h, and OGTT 2-h plasma glucose concentrations. A multivariate logistic regression model was used to investigate the relationship between vitamin A concentrations and the risk of GDM. Model 1 was not adjusted. Model 2 was adjusted for age and preconception BMI. Model 3 was adjusted for the variables that model 2 was adjusted for plus for education background, parity, smoking status, alcohol consumption, family history of diabetes, and family history of hypertension. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined. The participants were divided into subgroups based on age and BMI with cut-off points of 35 years and 24 kg/m², respectively. The first quintile of serum vitamin A concentrations was used as the reference group for logistical regression analysis. Restricted cubic spline (RCS) regression models with three nodes were used to describe the potential nonlinear relationship between serum vitamin A concentrations and GDM risk. All analyses were performed using SPSS 24.0 software (SPSS Inc., Chicago, IL, USA), wherein a two-sided p -value < 0.05 was considered to indicate a statistically significant difference. Graphs were produced using R version 3.0.3 software (The R Foundation for Statistical Computing, Vienna, Austria). 3. Results 3.1 Baseline characteristics of the participants Table 1 shows the differences in the demographic characteristics and anthropometric measurements of the participants grouped by serum vitamin A concentration quintiles. The participants comprised 1077 singleton pregnant women aged 29.50 (± 4.06) years with a BMI of 20.69 ± 2.56 kg/m 2 (mean ± SD). The median (IQR) concentrations of serum vitamin A were 0.66 (0.58–0.78) µmol/L, and all concentrations were within the safe range for humans. In the quartile 1 to quartile 5 (Q1 to Q5) groups, the median (interquartile range) concentrations of vitamin A (µmol/L) in the first trimester of pregnancy were 0.55 (0.52–0.56), 0.60 (0.59–0.61), 0.67 (0.65–0.68), 0.74 (0.71–0.79), and 0.93 (0.87–1.09) µmol/L, respectively. The Q1 to Q5 groups exhibited statistically significant differences in maternal age ( p = 0.001), 2-h OGTT plasma glucose concentration ( p = 0.005), birth weight ( p = 0.016), and head circumference of newborns ( p = 0.010). In terms of maternal and infant pregnancy outcomes, the Q1 to Q5 groups exhibited significant differences in the incidence of GDM ( p = 0.014), emergency caesarean section ( p = 0.027), and LGA ( p = 0.035). In the Q5 group, the incidence of emergency caesarean section (15.6%) and LGA (13.7%) was the highest, and the incidence of GDM (15.1%) was the lowest. Table 1 Characteristics of participants according to Quintiles of Vitamin A. (N = 1077). Vitamin A levels (µmol/L) P value characteristics Total Quintile 1 Quintile 2 Quintile 3 Quintile 4 Quintile 5 ≤ 0.57 0.57–0.63 0.63–0.69 0.69–0.82 > 0.82 No. of maternal cases 1077 243 206 207 209 212 Maternal age (years) 29.50 ± 4.06 30.45 ± 4.46 29.85 ± 4.02 28.72 ± 3.56 28.94 ± 4.07 29.40 ± 3.84 0.001 Age categories (n (%)) 0.000 \(\:<\) 35 939 (87.2) 190 (78.2) 179 (86.9) 194 (93.7) 187 (89.5) 189 (89.2) \(\:\ge\:\) 35 138 (12.8) 53 (21.8) 27 (13.1) 13 (6.3) 22 (10.5) 23 (10.8) BMI (kg/m 2 ) 20.69 \(\:\:\pm\:\:\) 2.56 20.66 ± 2.38 20.88 ± 2.65 20.40 ± 2.37 20.72 ± 2.70 20.79 ± 2.68 0.391 BMI categories (n (%)) 0.638 \(\:<\) 24 955 (88.7) 216 (88.9) 177 (85.9) 188 (90.8) 186 (89.0) 188 (88.7) \(\:\ge\:\) 24 122 (11.3) 27 (11.1) 29 (14.1) 19 (9.2) 23 (11.0) 24 (11.3) Education background (n (%)) 0.647 Primary 84 (7.8) 17 (7.0) 16 (7.8) 14 (6.8) 22 (10.5) 15 (7.1) Secondary 166 (15.4) 32 (13.2) 28 (13.6) 35 (16.9) 37 (17.7) 34 (16.0) College or above 827 (76.8) 194 (79.8) 162 (78.6) 158 (76.3) 150 (71.8) 163 (76.9) Parity (n (%)) 0.213 Primiparity 649 (60.3) 139 (57.2) 122 (59.2) 139 (67.1) 127 (60.8) 122 (57.5) Multiparity 428 (39.7) 104 (42.8) 84 (40.8) 68 (32.9) 82 (39.2) 90 (42.5) History of miscarriage (n (%)) 278 (25.8) 66 (27.2) 56 (27.2) 45 (21.7) 51 (24.4) 60 (28.3) 0.536 Vitamin A (µmol/L) 0.66 (0.58–0.78) 0.55 (0.52–0.56) 0.60 (0.59–0.61) 0.67 (0.65–0.68) 0.74 (0.71–0.79) 0.93 (0.87–1.09) 0.001 Initial inspection blood pressure SBP (mm Hg) 110.42 ± 10.56 110.10 ± 10.27 111.19 ± 10.99 109.47 ± 10.52 111.29 ± 10.66 109.19 ± 10.99 0.410 DBP (mm Hg) 66.64 ± 7.94 66.79 ± 7.91 66.49 ± 8.04 65.63 ± 7.89 67.12 ± 8.03 66.50 ± 7.98 0.596 OGTT glucose metabolism Fasting plasma glucose (mmol/L) 4.54 ± 0.33 4.56 ± 0.34 4.55 ± 0.35 4.53 ± 0.30 4.57 ± 0.34 4.52 ± 0.31 0.455 1-h post-load glucose (mmol/L) 7.98 ± 1.62 8.06 ± 1.62 8.09 ± 1.79 7.99 ± 1.63 7.99 ± 1.61 7.81 ± 1.46 0.562 2-h post-load glucose (mmol/L) 6.98 ± 1.39 7.15 ± 1.40 7.16 ± 1.43 6.76 ± 1.36 7.06 ± 1.44 6.78 ± 1.30 0.005 Birth weight of newborn (g) 3274.44 ± 452.62 3209.32 ± 439.63 3286.63 ± 484.11 3248.42 ± 421.69 3265.35 ± 445.81 3370.91 ± 459.34 0.016 Birth height of newborn (cm) 49.91 ± 1.85 49.72 ± 1.76 49.93 ± 2.00 49.86 ± 1.65 49.88 ± 2.11 50.18 ± 1.71 0.215 Birth head circumference of newborn (cm) 34.23 ± 1.49 34.12 ± 1.43 34.25 ± 1.72 34.09 ± 1.28 34.10 ± 1.65 34.63 ± 1.29 0.010 Adverse maternal and foetal outcomes GDM 241 (22.4) 67 (27.6) 47 (22.8) 41 (19.8) 54 (25.8) 32 (15.1) 0.014 Emergency caesarean section 108 (10.0) 19 (7.8) 15 (7.3) 23 (11.1) 18 (8.6) 33 (15.6) 0.027 PROM 176 (16.3) 40 (16.5) 32 (15.5) 30 (14.5) 41 (19.6) 33 (15.6) 0.671 Postpartum eclampsia 14 (1.3) 5 (2.1) 4 (1.9) 2 (1.0) 2 (1.0) 1 (0.5) 0.531 Foetal intrauterine distress 60 (5.6) 20 (8.2) 12 (5.8) 9 (4.3) 11 (5.3) 8 (3.8) 0.265 Premature birth 46 (4.3) 12 (4.9) 10 (4.9) 8 (3.9) 10 (4.8) 6 (2.8) 0.785 Macrosomia 31 (2.9) 7 (2.9) 5 (2.4) 5 (2.4) 3 (1.4) 11 (5.2) 0.206 LBW 37 (3.4) 13 (5.3) 6 (2.9) 6 (2.9) 9 (4.3) 3 (1.4) 0.190 SGA 65 (6.0) 20 (8.2) 15 (7.3) 12 (5.8) 6 (2.9) 12 (5.7) 0.172 LGA 105 (9.7) 20 (8.2) 26 (12.6) 18 (8.7) 12 (5.7) 29 (13.7) 0.035 Abbreviations: BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; OGTT: oral glucose tolerance test; GDM: gestational diabetes mellitus; PROM: premature rupture of membranes; LBW: low-birth-weight infants; PTB: preterm birth; SGA: small-for-gestational-age infants; LGA: large-for-gestational-age infants 3.2 Associations between serum vitamin A concentrations during the first trimester and risk of GDM A negative correlation was observed between serum vitamin A concentrations and OGTT 1-h and 2-h plasma glucose concentrations (Table S2). Furthermore, the logistic regression model revealed the relationship between serum vitamin A concentrations in early pregnancy and the risk of GDM (Table 2 ). In model 1, the participants with serum vitamin A concentrations in Q5 (> 0.82 µmol/L) had a lower risk of GDM than those with serum vitamin A concentrations in Q1 (≤ 0.57 µmol/L) (OR: 0.47; 95% CI: 0.29–0.75). In models 2 and 3, after adjusting for confounding factors, the correlation between serum vitamin A concentrations and GDM remained significant (OR: 0.51; 95% CI: 0.31–0.82 and OR: 0.50; 95% CI: 0.31–0.81, respectively). The RCS regression models depicted in Fig. 2 A showed a linear association between serum vitamin A concentrations and a decreased risk of GDM in a non-excess serum vitamin A concentration range ( p = 0.036). Table 2 Odds ratios (95% confidence intervals) for the occurrence of GDM according to the vitamin A levels at the first trimester. Vitamin A levels (µmol/L) Quintile 1 Quintile 2 Quintile 3 Quintile 4 Quintile 5 P trend ≤ 0.57 0.57–0.63 0.63–0.69 0.69–0.82 > 0.82 GDM Case/N 67/243 47/206 41/207 54/209 32/212 Model 1 1.00 0.78 (0.51, 1.19) 0.65 (0.42, 1.01) 0.91 (0.60, 1.39) 0.47 ** (0.29, 0.75) 0.006 Model 2 1.00 0.82 (0.53, 1.28) 0.79 (0.50, 1.24) 1.03 (0.67, 1.59) 0.51 ** (0.31, 0.82) 0.018 Model 3 1.00 0.81 (0.52, 1.27) 0.78 (0.49, 1.25) 1.02 (0.66, 1.59) 0.50 ** (0.31, 0.81) 0.015 * p < 0.05, ** p < 0.01; Abbreviations: GDM: gestational diabetes mellitus; Model 1: without adjustment. Model 2 adjusted for age, BMI; Model 3 adjusted for the variables in Model 1 plus education background, smoking status, alcohol status, parity, history of miscarriage, nation, history of diabetes, history of hypertension. The ORs (95% CIs) associated with serum vitamin A concentrations and GDM in participants classified by BMI or age are shown in Fig. 1 . In the BMI ≥ 24 kg/m 2 group, high serum vitamin A concentrations were associated with a low risk of GDM ( p -trend = 0.035). This trend was not observed in the BMI < 24 kg/m 2 group. In the aged ≥ 35 group, high serum vitamin A concentrations were associated with a low risk of GDM ( p -trend = 0.027). This trend was not observed in the aged < 35 group. 3.3 Association between serum vitamin A concentrations in early pregnancy and risk of other adverse pregnancy outcomes Table 3 shows the relationship between serum vitamin A concentrations in early pregnancy and some adverse pregnancy outcomes. After adjustment for age and BMI, the risk of foetal distress in utero decreased in the Q5 group as serum vitamin A concentrations increased (OR: 0.41; 95% CI: 0.18–0.96). Compared with the Q1 group, the Q5 group had an increased risk of emergency caesarean section in model 1 (OR: 2.17; 95% CI: 1.20–3.95, p -trend = 0.003). The same trend existed after adjustment for potential confounding factors, i.e., in model 2 (OR: 2.26; 95% CI: 1.24–4.13, p -trend = 0.003) and model 3 (OR: 2.31; 95% CI: 1.26–4.26, p -trend = 0.002). Furthermore, high serum concentrations of vitamin A were associated with a decreased risk of LBW. Compared with the Q1 group, the Q5 group had a lower risk of LBW (OR: 0.26; 95% CI: 0.07–0.96). However, there was not a marked increase in the risk of LBW from Q1 to Q5 ( p -trend = 0.099). After adjustment, the Q4 group had a lower risk of SGA than the Q1 group (OR: 0.32; 95% CI: 0.12–0.82). In model 2, group Q5 had a higher risk of LGA than group Q1 (OR: 1.92; 95% CI: 1.04–3.54). The risk of SGA in the Q4 group was significantly lower than that in the Q1 group (OR: 0.33; 95% CI: 0.13–0.84), and this trend persisted after adjustment for potential confounding factors, i.e., in model 3 (OR: 0.32; 95% CI: 0.12–0.82). However, there was no significant association between serum vitamin A concentrations and the risks of other adverse pregnancy outcomes (Table S3, Figure S1 ). The results of the RCS analysis demonstrated that increased serum concentrations of vitamin A were associated with an increased risk of emergency caesarean section (Fig. 2 B), a decreased risk of intrauterine foetal distress (Fig. 2 C), and a decreased risk of SGA (Fig. 2 D). Table 3 ORs (95% CIs) for adverse pregnancy outcomes according to the Vitamin A levels at the first trimester. Vitamin A levels (µmol/L) Quintile 1 Quintile 2 Quintile 3 Quintile 4 Quintile 5 P trend ≤ 0.57 0.57–0.63 0.63–0.69 0.69–0.82 > 0.82 Foetal distress in utero Case/N 20/243 12/206 9/207 11/209 8/212 Model 1 1.00 0.69 (0.33–1.45) 0.51 (0.23–1.14) 0.62 (0.29–1.33) 0.44 (0.19, 1.01) 0.068 Model 2 1.00 0.67 (0.32, 1.40) 0.47 (0.21, 1.05) 0.58 (0.27, 1.26) 0.41 * (0.18, 0.96) 0.054 Model 3 1.00 0.71 (0.33, 1.51) 0.47 (0.21, 1.08) 0.60 (0.28, 1.31) 0.44 (0.19, 1.04) 0.073 Emergency caesarean section Case/N 19/243 15/206 23/207 18/209 33/212 Model 1 1.00 0.93 (0.46, 1.87) 1.47 (0.78, 2.79) 1.11 (0.57, 2.18) 2.17 * (1.20, 3.95) 0.003 Model 2 1.00 0.94 (0.46, 1.91) 1.58 (0.82, 3.01) 1.15 (0.59, 2.27) 2.26 ** (1.24, 4.13) 0.003 Model 3 1.00 0.95 (0.46, 1.93) 1.53 (0.79, 2.96) 1.18 (0.60, 2.34) 2.31 ** (1.26, 4.26) 0.002 LBW Case/N 13/243 6/206 6/207 9/209 3/212 Model 1 1.00 0.53 (0.20, 1.42) 0.53 (0.20, 1.42) 0.80 (0.33, 1.90) 0.25 * (0.07, 0.90) 0.070 Model 2 1.00 0.57 (0.21, 1.53) 0.57 (0.21, 1.55) 0.84 (0.35, 2.03) 0.27 * (0.08, 0.97) 0.088 Model 3 1.00 0.52 (0.19, 1.45) 0.59 (0.21, 1.65) 0.88 (0.35, 2.17) 0.26 * (0.07, 0.96) 0.099 SGA Case/N 20/243 15/206 12/207 6/209 12/212 Model 1 1.00 0.88 (0.44, 1.76) 0.69 (0.33, 1.44) 0.33 * (0.13, 0.84) 0.67 (0.32, 1.40) 0.156 Model 2 1.00 0.88 (0.44, 1.79) 0.64 (0.30, 1.36) 0.32 * (0.13, 0.82) 0.65 (0.31, 1.37) 0.137 Model 3 1.00 0.90 (0.44, 1.84) 0.64 (0.30, 1.37) 0.32 * (0.12, 0.82) 0.70 (0.33, 1.48) 0.185 LGA Case/N 20/243 26/206 18/207 12/209 29/212 Model 1 1.00 1.61 (0.87, 2.98) 1.06 (0.55, 2.07) 0.68 (0.32, 1.43) 1.77 (0.97, 3.23) 0.217 Model 2 1.00 1.66 (0.89, 3.11) 1.22 (0.62, 2.42) 0.72 (0.34, 1.53) 1.92 * (1.04, 3.54) 0.152 Model 3 1.00 1.65 (0.88, 3.10) 1.29 (0.65, 2.57) 0.72 (0.34, 1.53) 1.79 (0.96, 3.33) 0.256 * p < 0.05, ** p < 0.01; Model 1: without adjustment. Model 2 adjusted for age, BMI; Model 3 adjusted for the variables in Model 1 plus education background, smoking status, alcohol status, parity, history of miscarriage, nation, history of diabetes, history of hypertension. Abbreviations: LBW: low-birth-weight infants; SGA: small-for-gestational-age infants; LGA: large-for-gestational-age infants. 4. Discussion In this prospective cohort study, the associations between maternal serum vitamin A concentrations in early pregnancy and adverse pregnancy outcomes were determined. None of the participants had excessive serum vitamin A concentrations. Increased serum vitamin A concentrations were found to be significantly associated with decreased risks of GDM, LBW, and SGA and an increased risk of emergency caesarean delivery. Consistent with the aforementioned findings, serum vitamin A concentration as a continuous variable was negatively correlated with OGTT 1-h and 2-h plasma glucose concentrations. In model 2, serum vitamin A concentrations in the Q5 group were significantly associated with a decreased risk of intrauterine foetal distress and a significantly increased risk of LGA. No significant association was observed between serum vitamin A concentrations and other adverse pregnancy outcomes. Vitamin A is a fat-soluble vitamin and is an essential micronutrient for the human body, vitamin A also plays a key role in the development of pregnant women and foetuses [ 11 ]. Moreover, vitamin A has antioxidant properties, and previous research has shown that oxidative stress may lead to the development of GDM [ 36 ]. Therefore, we evaluated the association of maternal serum vitamin A concentrations in early pregnancy with the occurrence of GDM and other adverse pregnancy outcomes. Only a few studies have assessed the relationship between vitamin A (in terms of food intake or physical conditions) and the risk of GDM, and they have reported inconsistent results. Our findings are similar to those of a recent case–control study in China (Table S1 ), which found that serum vitamin A concentrations were lower in the group with GDM than in the group without GDM [ 37 ]. However, it is difficult to determine a causal relationship between serum vitamin A concentrations and GDM based on the aforementioned results because the testing of serum vitamin A concentrations and diagnosis of GDM were performed in pregnant women at 24–28 weeks. A case–control study conducted in Iran of pregnant women at 30–32 weeks showed that retinol concentrations in the GDM group were significantly lower than those in the control group [ 21 ]. However, a previous retrospective cohort study in China showed that serum vitamin A concentrations in the GDM group were higher than those in the non-GDM group in the first trimester [ 38 ]. In addition, a multiple logistic regression analysis in this study did not find that vitamin A was an independent influencing factor for GDM, which is inconsistent with the findings in the present study [ 38 ]. Similarly, another recent Chinese prospective cohort study found that increases in serum vitamin A concentrations in early pregnancy led to increases in the risk of GDM, which is inconsistent with the findings in the present study[ 28 ]. However, unlike the present study, despite the fact that vitamin A is stored and metabolised in the liver, the aforementioned two studies did not exclude pregnant women with hepatitis or impaired liver function. Furthermore, it was previously found that women with GDM may experience mild liver dysfunction [ 39 ], potentially leading to higher serum concentrations of vitamin A in the GDM group than in the non-GDM group. The present study found that participants aged 35 or older or with a BMI of 24 kg/m² or higher had higher serum vitamin A concentrations and a lower risk of GDM than other participants. Women of advanced maternal age (AMA) are those who will be aged 35 or older at their estimated date of delivery [ 40 ]. Some studies have demonstrated that AMA is associated with the occurrence of GDM [ 41 , 42 ]. In addition, the risk of GDM is higher in women with obesity than in those with a normal BMI[ 43 , 44 ]. Vitamin A plays a key role in reducing the risk of GDM in women of AMA and women with obesity. Therefore, it is important to monitor serum vitamin A concentrations in these two populations of women during the first trimester to reduce the incidence of GDM. A deficiency of vitamin A is harmful to the mother and foetus, while an excess of vitamin A can have toxic and teratogenic effects early in pregnancy [ 45 , 46 ]. A prospective cohort study conducted in Chengdu, China, showed that dietary intake of vitamin A during the first trimester was associated with the development of GDM, it also showed that a higher dietary intake of vitamin A than the recommended nutrient intake reduced the risk of GDM [ 47 ]. Another case–control study in a Chinese population examined dietary nutrition patterns and assessed their association with GDM risk, it found that a vitamin nutrition pattern diet (a diet rich in vitamin A, carotene, vitamin B2, vitamin B6, vitamin C, dietary fibre, folate, calcium, and potassium) was associated with a reduced risk of GDM [ 48 ]. In practice, pregnant women should be directed to eat a moderate amount of foods rich in vitamin A, because vitamin A may improve the pregnancy outcomes of mothers and babies. The present study did not perform surveys of dietary intake of vitamin A, but it did determine circulating concentrations of vitamin A, which may be more reliable. Some studies have found that women with GDM have an increased risk of adverse perinatal outcomes, such as macrosomia and LGA, and that GDM is a risk factor for emergency caesarean section [ 49 , 50 ]. Dittakarn et al. [ 51 ] found that the incidence of emergency caesarean delivery was significantly greater in pregnant women with GDM than in normal pregnant women. In the present study, high serum vitamin A concentrations were associated with a decreased risk of GDM but with an increased risk of emergency caesarean section and LGA. The mechanism underlying the association between high serum vitamin A concentrations and emergency caesarean delivery is unknown and must be examined in future work. Maternal vitamin A status plays a crucial role in the normal development of the foetus and neonate [ 52 ]. A low intake of vitamin A has been linked to LBW and SGA [ 53 , 54 ]. In the present study, although there was no significant difference in the incidence of LBW across the five quintiles based on serum vitamin A concentrations, a logistic regression analysis revealed that high vitamin A concentrations were associated with a decreased risk of LBW. A previous study conducted in China found that infant umbilical cord blood vitamin A concentrations were significantly and positively correlated with birth weight [ 55 ]. However, this study did not measure serum vitamin A concentrations in pregnant mothers. Additionally, a cluster-randomised placebo-controlled trial conducted in rural northwestern Bangladesh found that prenatal vitamin A or β-carotene supplementation did not result in a decrease in the incidence of LBW [ 56 ]. The heterogeneous nature of results from previous studies may be attributable to variations in study design and populations. Furthermore, a retrospective cohort study by Catov et al. suggested that regular periconceptional multivitamin use was associated with a reduced risk of non-overweight women having SGA newborns [ 57 ], but did not analyse the effects of serum concentrations of vitamin A on SGA. The findings of the present study indicate that high serum concentrations of vitamin A (0.69–0.82 µmol/L) were associated with a decreased incidence of SGA (OR: 0.32, 95% CI: 0.12–0.82). This study has several limitations. First, we lacked detailed information on dietary patterns and physical activity during pregnancy, although we controlled for some covariates, the effects of unmeasured or unknown residual confounders might not have been eliminated. Second, this study was conducted in a hospital in Shenzhen. Thus, although pregnant women from all areas of China may give birth at this hospital, it remains to be verified that our findings are generalisable to the whole population of China. Third, we measured only serum vitamin A concentrations, measurement of markers of oxidative stress and other antioxidant concentrations may enhance our understanding of the balance of factors affecting oxidative stress status and adverse pregnancy outcomes in women with GDM. 5. Conclusions This prospective cohort study conducted in China showed that increased maternal serum vitamin A concentrations during early pregnancy were significantly associated with a reduced risk of GDM, LBW, and SGA. However, high serum concentrations of vitamin A were significantly associated with a high risk of emergency caesarean section. Therefore, it appears that monitoring of vitamin A concentrations should be a key part of the clinical care of pregnant women to optimise their pregnancy outcomes. Abbreviations GDM Gestational diabetes mellitus T2DM Type 2 diabetes mellitus ROS Reactive oxygen species SOD Superoxide dismutase RBP4 Retinol binding protein 4 BMI Body mass index SGA Small for gestational age infants LGA Large for gestational age infants LBW Low–birth–weight infants RCS Restricted cubic spline SBP systolic blood pressure DBP diastolic blood pressure OGTT oral glucose tolerance test PROM premature rupture of membranes PTB preterm birth. Declarations Acknowledgments We thank the mothers and children who participated in this study and all the clinical staff at Shenzhen Nanshan People’s Hospital for their support and contribution. Authors’ contributions Guifang Deng, Qinqin Ren and Yijin Wang conceived and designed the study. Yang Wang and Yao Liu assisted with study design. Hui Yuan, Yuanhuan Wei, Ruifang Sun and Ping Tian collected the data. Qinqin Ren contributed to statistical analysis and wrote the manuscript. Hongguang Yang and Yao Liu provided statistical advice and assisted with data analysis. Guifang Deng and Jianjun Yang reviewed and edited the manuscript. All authors read and approved the final manuscript. Funding This work was supported by grants from the National Natural Science Foundation of China [grant number 82103821], the Major Technological Project of Shenzhen Nanshan District Health System [grant number NSZD2023024], and the Key Project of Shenzhen Nanshan District of Science and Technology [grant number NS2024005]. Availability of data and materials To protect the privacy of pregnant women, the datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate Participants written informed consent forms at the beginning of the study. The protocol for this study was approved by the Ethics Committee of the Shenzhen Nanshan People’s Hospital (No. 2019072644) and all methods were performed in accordance with the relevant guidelines and regulations (Declaration of Helsinki). Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Author details [1] Department of Public Health, School of Public Health, Ningxia Medical University, Yinchuan, People’s Republic of China 2 Department of Clinical Nutrition, Shenzhen Nanshan People’s Hospital, No. 89 Taoyuan Road, Shenzhen, Guangdong 518052, P.R. China. 3 Department of Children Healthcare, Shenzhen Nanshan People’s Hospital, No. 89 Taoyuan Road, Shenzhen, Guangdong 518052, P.R. China. References Liu C, Luo D, Wang Q, Ma Y, Ping L, Wu T, et al. Serum homocysteine and folate concentrations in early pregnancy and subsequent events of adverse pregnancy outcome: the Sichuan Homocysteine study. 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Deng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsUlEQVRIiWNgGAWjYDACZiCuKGCQY2NvP0CCljMGDMZ8PGcSSLAJqCVxnoSDAXGqddvZn0kcMDic3ibBkMDwo2IbYS1mh3nMQFpy26QbDzD2nLlNlBY26Q8gLTIHEpgZ24jSAnUYm0SCAbFaGMAOSyBFC4+xxQGDdMM2YCAfJM4v548/vHGgwlpevr394IMfFURoAQIWCQaGZjDrAFHqgYD5AwNDHbGKR8EoGAWjYCQCAJ0/PLikMXENAAAAAElFTkSuQmCC","orcid":"","institution":"Shenzhen Nanshan People’s Hospital","correspondingAuthor":true,"prefix":"","firstName":"Guifang","middleName":"","lastName":"Deng","suffix":""}],"badges":[],"createdAt":"2024-08-19 01:55:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4935218/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4935218/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":66630963,"identity":"d98f8dd5-8fed-4347-ac77-238a7978a18b","added_by":"auto","created_at":"2024-10-15 04:51:53","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":738292,"visible":true,"origin":"","legend":"\u003cp\u003eORs (95%CIs) for serum vitamin A levels associated with GDM according to different BMI ang age values.\u003c/p\u003e\n\u003cp\u003eThe model adjusted education background, smoking status, alcohol status, parity, gravidity, history of miscarriage, nation, history of diabetes, history of hypertension.\u003c/p\u003e","description":"","filename":"Figure1.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4935218/v1/72d1f50981550196a6501dea.jpg"},{"id":66630962,"identity":"8204a538-8efb-43ed-83a4-7eacec4a5a79","added_by":"auto","created_at":"2024-10-15 04:51:53","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":961527,"visible":true,"origin":"","legend":"\u003cp\u003eRCS regression analysis of serum vitamin A levels with GDM and other adverse maternal and foetal outcomes.\u003c/p\u003e\n\u003cp\u003e(A) GDM: gestational diabetes mellitus, (B) Emergency caesarean section, (C) Foetal distress in utero. (D) SGA: small for gestational age infants. The median of vitamin A 0.66 µmol/L was selected as the reference levels. The lines indicate estimated ORs, and the light blue-shaded areas represent 95%CI.\u003c/p\u003e","description":"","filename":"Figure2.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4935218/v1/681dcff92d886456cb834176.jpg"},{"id":73282280,"identity":"04866847-b546-426d-9cd9-d1cb18c68528","added_by":"auto","created_at":"2025-01-08 12:47:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2585290,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4935218/v1/b71fb39d-cd7f-4ab2-b61e-00afd45b7720.pdf"},{"id":66630961,"identity":"ac110864-2aab-4e7c-b6b0-b88f31e37079","added_by":"auto","created_at":"2024-10-15 04:51:53","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":283016,"visible":true,"origin":"","legend":"","description":"","filename":"file.docx","url":"https://assets-eu.researchsquare.com/files/rs-4935218/v1/ffb427deb82b050e33cd33ce.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association of Maternal Serum Vitamin A Levels in the First Trimester with the Risk of Adverse Pregnancy Outcomes: A Prospective Cohort Study of Chinese Women","fulltext":[{"header":"1. Background","content":"\u003cp\u003eAn adverse pregnancy outcome is an event that reduces the chance of having a healthy newborn [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. These outcomes encompass all the pathological complications that may occur during pregnancy and childbirth, such as pre-eclampsia, preterm birth, low birth weight (LBW), stillbirth, emergency caesarean section, and gestational diabetes mellitus (GDM). GDM is any degree of glucose intolerance with onset or first detection during pregnancy [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. It was reported that the global standardised total prevalence of GDM was 14.0% [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], being 14.8% in China [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Adverse pregnancy outcomes are a major public health problem, as they increase maternal and neonatal mortality and affect the long-term health of both mothers and children [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In addition, adverse pregnancy outcomes, particularly GDM, are associated with an increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease in women after childbirth [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], and with an increased risk of obesity and T2DM in their offspring [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, most adverse pregnancy outcomes can be diagnosed only in the mid-to-late stages of pregnancy, leaving insufficient time for prevention [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Therefore, it is important to determine the risk factors for adverse pregnancy outcomes in early pregnancy.\u003c/p\u003e \u003cp\u003eVitamin A is a fat-soluble compound that is essential for normal functioning of the human body. It can be obtained from the diet through consumption of meat containing retinol and its close derivatives, vegetables or dairy products containing provitamin A (carotenoids) or vitamin A-active carotenoids, fortified foods (e.g., cereals or juices), or vitamin supplements [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. During pregnancy, vitamin A is important for cell division, growth, and maturation of the foetal organs and skeletal system. It is also important for the development and maintenance of the foetal immune and visual systems[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Vitamin A can directly remove reactive oxygen species, thereby protecting cells from oxidative damage[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Compared with normal pregnant women, pregnant women with T2DM have a lower antioxidant capacity and increased cellular concentrations of oxidative products, given the similarities between the mechanisms of GDM and T2DM, we speculate that oxidative stress may lead to the initiation and development of GDM [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. It has been observed that the activity of superoxide dismutase in pregnant women with GDM is significantly lower than that in normal pregnant women [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, few studies have examined the relationship between serum vitamin A concentrations and GDM, and they have drawn inconsistent conclusions. Hekmat et al. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and Suhail et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] surveyed pregnant women in the third trimester and found that there was a significant decrease in serum vitamin A concentrations in those with GDM. However, Grissa O et al. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] found that compared with women without GDM, those with GDM exhibited no significant changes in serum vitamin A concentrations. Retinol-binding protein 4 (RBP4) is secreted mainly by the liver and adipose tissue and was initially identified as a transport protein for vitamin A and other retinoid derivatives in the bloodstream [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. It was also found that serum RBP4 concentrations in women with GDM were higher than those in women without GDM [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. So far, only a few prospective studies conducted in China have explored the relationship between maternal serum vitamin A levels in early pregnancy and the incidence of GDM. One study conducted in Beijing found that higher vitamin A levels in early pregnancy (and even normal vitamin A levels) were positively associated with GDM risks [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Another study conducted in Beijing observed the same result, but this finding is contrary to their research hypothesis [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Therefore, it is essential to investigate the correlation between serum vitamin A concentrations and GDM during the first trimester of pregnancy.\u003c/p\u003e \u003cp\u003eThe nutritional status of the mother affects the development of the foetus. Low concentrations of retinol in umbilical cord blood and maternal serum may reflect poor vitamin A status in the newborn and mother, which may affect foetal growth [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. One research observed that greater birth size with higher concentrations of cord retinol [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Additionally, there is a positive correlation between maternal vitamin A concentrations and birth weight after delivery [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. However, Fiona Mathews et al. [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] showed that high retinol concentrations in later pregnancy were associated with lower birth weights in a large group of pregnant white women from the United Kingdom. Samson et al. [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] showed that vitamin A and zinc deficiencies in the second or third trimesters were not associated with an increased risk of LBW. Overall, the relationship between serum vitamin A concentrations and adverse pregnancy outcomes remains unclear. In addition, most studies that have explored this association were conducted during the second or third trimester or after delivery. Therefore, determination of serum vitamin A concentrations in early pregnancy will clarify whether vitamin A influences the occurrence of adverse pregnancy outcomes. Accordingly, in the present study, we aimed to examine the relationship between serum vitamin A concentrations during the first trimester and the risk of adverse pregnancy outcomes.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Participants\u003c/h2\u003e \u003cp\u003eThis prospective cohort study was conducted in the Department of Gynaecology and Obstetrics at Shenzhen Nanshan People\u0026rsquo;s Hospital, Shenzhen, China, from 2019 to 2020 and investigated the effect of serum vitamin A concentrations in pregnant women on adverse pregnancy outcomes. The inclusion criteria were 1) women aged 18 or older; 2) having a singleton pregnancy; 3) at 6\u0026ndash;13 weeks of gestation; and 4) who had registered and plan to deliver in the above-mentioned hospital. Then a total of 1349 pregnant women were recruited in the study. The exclusion criteria were 1) having a multiple pregnancy (n ₌ 7); 2) death of the infant (n ₌ 3); 3) GDM could not be diagnosed (n ₌ 1); 4) having pre-pregnancy diabetes or gestational diabetes diagnosed before 24 weeks (n ₌ 2); 5) having pre-pregnancy hypertension (n ₌ 2); 6) having hepatitis or impaired liver function (n ₌ 58); 7) having nephritis or impaired kidney function (n ₌ 7); 8) lost to follow-up (n ₌ 1); or 9) missing vitamin A laboratory test data or other baseline data (n ₌ 191). After the exclusion of 272 potential participants due to ineligibility, 1077 pregnant women were included as participants. Ethical approval for studying this cohort was obtained from the Ethics Committee of Shenzhen Nanshan People\u0026rsquo;s Hospital (No. 2019072644), and all participants signed an informed consent form. The study was conducted in accordance with the Declaration of Helsinki developed by the World Medical Association.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Data collection\u003c/h2\u003e \u003cp\u003eThe baseline data were collected through questionnaire surveys and from the hospital\u0026rsquo;s medical record system. The collected data comprised the participants\u0026rsquo; age, weight, height, educational level, smoking and drinking status during pregnancy, disease history, pregnancy history, family history and other information, and serum vitamin A concentrations and other laboratory data at 6\u0026ndash;13 weeks of pregnancy. Pre-pregnancy body mass index (BMI) was calculated from participant-reported pre-pregnancy weight and height. BMI was calculated as weight (kg) divided by the square of height (m). The gender and basic physical characteristics of newborns were obtained from records in the hospital information system. The weight and height of newborns at birth were measured using an infant length and weight measuring instrument, and their head circumference and chest circumference were measured using a tape measure.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Definition of mother and infant adverse pregnancy outcomes\u003c/h2\u003e \u003cp\u003eAccording to the diagnostic criteria established by the International Association of Diabetes and Pregnancy Research Groups, the participants underwent a 75-g oral glucose tolerance test (OGTT) between 24 and 28 weeks of gestation. If the participants\u0026rsquo; results met any of the following criteria or any combination thereof, they were diagnosed with GDM: a fasting plasma glucose\u0026thinsp;\u0026ge;\u0026thinsp;5.1 mmol/L, an OGTT 1-h plasma glucose concentration\u0026thinsp;\u0026ge;\u0026thinsp;10.0 mmol/L, and an OGTT 2-h plasma glucose concentration\u0026thinsp;\u0026ge;\u0026thinsp;8.5 mmol /L[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Small for gestational age (SGA) and large for gestational age (LGA) were defined as birth weights below the 10th percentile or above the 90th percentile of the mean weight of other infants of the same gestational age, respectively. Newborns with a birth weight\u0026thinsp;\u0026gt;\u0026thinsp;4000 g were defined as macrosomic, and those with a birth weight\u0026thinsp;\u0026lt;\u0026thinsp;2500 g were defined as LBW[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Biochemical analysis\u003c/h2\u003e \u003cp\u003eSerum samples were prepared as follows. Stored serum was thawed at 4\u0026deg;C. A sample (100 \u0026micro;L) was treated with an internal standard solution (100 \u0026micro;L) and methanol (100 \u0026micro;L), and the resulting mixture was vortexed for 2 min. Subsequently, the mixture was treated with hexyl hydride (800 \u0026micro;L), vortexed for 5 min to extract vitamin A, and then centrifuged at 12,000 rpm for 10 min. Next, 650 \u0026micro;L of the supernatant was transferred to another vessel and then taken to dryness under a flow of nitrogen gas. The solid residue was re-dissolved in acetonitrile (100 \u0026micro;L), and the resulting solution was vortexed for 60 s and then centrifuged at 12,000 rpm for 10 min. An aliquot of the supernatant was analysed by high-performance liquid chromatography\u0026ndash;tandem mass spectrometry (HPLC-MS/MS) to determine its concentration of vitamin A.\u003c/p\u003e \u003cp\u003eThe HPLC-MS/MS method was based on that used in a previous study [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. A vitamin A standard and mobile phases (formic acid, ammonium formate, acetonitrile, and methanol) were purchased from Merck. HPLC-MS/MS analysis was performed using an AB ExionLC system coupled with a Triple Quad\u0026trade; 4500 tandem mass spectrometer (AB Sciex, Framingham, MA). The instruments were controlled using Analyst\u0026reg; software. Chromatographic separation of sample components was performed on a Waters HPLC CORTECS C18 Column (2.1 mm \u0026times; 50 mm, 2.7 \u0026micro;m). The mobile phases comprised 0.1% formic acid\u0026thinsp;+\u0026thinsp;0.01 mol/L ammonium formate\u0026thinsp;+\u0026thinsp;water (A) and 0.05% formic acid\u0026thinsp;+\u0026thinsp;methanol (B). The injection volume was 10 \u0026micro;L, and the column temperature was 40\u0026deg;C. Chromatographic separation was performed at a flow rate of 0.6 mL/min using the following gradient elution: 0\u0026ndash;0.5 min with A:B\u0026thinsp;=\u0026thinsp;30:70; 0.5\u0026ndash;2.0 min with A:B\u0026thinsp;=\u0026thinsp;30:70; 2.0\u0026ndash;4.5 min with A:B\u0026thinsp;=\u0026thinsp;0:100; and 4.6\u0026ndash;5.6 min with A:B\u0026thinsp;=\u0026thinsp;30:70. Mass spectrometry was performed using atmospheric pressure chemical ionisation and in multi-reaction monitoring mode.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Statistical analysis\u003c/h2\u003e \u003cp\u003eThe participants were divided into five groups based on quintiles of serum vitamin A concentrations. Continuous data are expressed as means and standard deviations (SDs) or medians and interquartile ranges (IQRs), depending on their distribution. Categorical variables are expressed as frequencies and percentages. Between-group differences were determined by conducting Kruskal\u0026ndash;Wallis tests or one-way analyses of variance for continuous variables and conducting chi-square tests for categorical variables. Correlation analysis was performed to investigate the relationships between serum vitamin A, serum vitamin C, and serum vitamin E concentrations and fasting, OGTT 1-h, and OGTT 2-h plasma glucose concentrations. A multivariate logistic regression model was used to investigate the relationship between vitamin A concentrations and the risk of GDM. Model 1 was not adjusted. Model 2 was adjusted for age and preconception BMI. Model 3 was adjusted for the variables that model 2 was adjusted for plus for education background, parity, smoking status, alcohol consumption, family history of diabetes, and family history of hypertension. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined. The participants were divided into subgroups based on age and BMI with cut-off points of 35 years and 24 kg/m\u0026sup2;, respectively. The first quintile of serum vitamin A concentrations was used as the reference group for logistical regression analysis. Restricted cubic spline (RCS) regression models with three nodes were used to describe the potential nonlinear relationship between serum vitamin A concentrations and GDM risk. All analyses were performed using SPSS 24.0 software (SPSS Inc., Chicago, IL, USA), wherein a two-sided \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to indicate a statistically significant difference. Graphs were produced using R version 3.0.3 software (The R Foundation for Statistical Computing, Vienna, Austria).\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Baseline characteristics of the participants\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the differences in the demographic characteristics and anthropometric measurements of the participants grouped by serum vitamin A concentration quintiles. The participants comprised 1077 singleton pregnant women aged 29.50 (\u0026plusmn;\u0026thinsp;4.06) years with a BMI of 20.69\u0026thinsp;\u0026plusmn;\u0026thinsp;2.56 kg/m\u003csup\u003e2\u003c/sup\u003e (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD). The median (IQR) concentrations of serum vitamin A were 0.66 (0.58\u0026ndash;0.78) \u0026micro;mol/L, and all concentrations were within the safe range for humans. In the quartile 1 to quartile 5 (Q1 to Q5) groups, the median (interquartile range) concentrations of vitamin A (\u0026micro;mol/L) in the first trimester of pregnancy were 0.55 (0.52\u0026ndash;0.56), 0.60 (0.59\u0026ndash;0.61), 0.67 (0.65\u0026ndash;0.68), 0.74 (0.71\u0026ndash;0.79), and 0.93 (0.87\u0026ndash;1.09) \u0026micro;mol/L, respectively. The Q1 to Q5 groups exhibited statistically significant differences in maternal age (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), 2-h OGTT plasma glucose concentration (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005), birth weight (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016), and head circumference of newborns (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.010). In terms of maternal and infant pregnancy outcomes, the Q1 to Q5 groups exhibited significant differences in the incidence of GDM (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014), emergency caesarean section (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.027), and LGA (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.035). In the Q5 group, the incidence of emergency caesarean section (15.6%) and LGA (13.7%) was the highest, and the incidence of GDM (15.1%) was the lowest.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of participants according to Quintiles of Vitamin A. (N\u0026thinsp;=\u0026thinsp;1077).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c7\" namest=\"c3\"\u003e \u003cp\u003eVitamin A levels (\u0026micro;mol/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003echaracteristics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eQuintile 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eQuintile 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQuintile 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQuintile 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eQuintile 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.57\u0026ndash;0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.63\u0026ndash;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.69\u0026ndash;0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo. of maternal cases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1077\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e206\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age\u0026nbsp;(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.50\u0026thinsp;\u0026plusmn;\u0026thinsp;4.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.45\u0026thinsp;\u0026plusmn;\u0026thinsp;4.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.85\u0026thinsp;\u0026plusmn;\u0026thinsp;4.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28.72\u0026thinsp;\u0026plusmn;\u0026thinsp;3.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e28.94\u0026thinsp;\u0026plusmn;\u0026thinsp;4.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e29.40\u0026thinsp;\u0026plusmn;\u0026thinsp;3.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge categories (n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\u0026lt;\\)\u003c/span\u003e\u003c/span\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e939 (87.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e190 (78.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e179 (86.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e194 (93.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e187 (89.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e189 (89.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\ge\\:\\)\u003c/span\u003e\u003c/span\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e138 (12.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (21.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (13.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22 (10.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e23 (10.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.69\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\:\\pm\\:\\:\\)\u003c/span\u003e\u003c/span\u003e2.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.66\u0026thinsp;\u0026plusmn;\u0026thinsp;2.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.88\u0026thinsp;\u0026plusmn;\u0026thinsp;2.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20.40\u0026thinsp;\u0026plusmn;\u0026thinsp;2.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20.72\u0026thinsp;\u0026plusmn;\u0026thinsp;2.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e20.79\u0026thinsp;\u0026plusmn;\u0026thinsp;2.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.391\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI categories (n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.638\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\u0026lt;\\)\u003c/span\u003e\u003c/span\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e955 (88.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e216 (88.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e177 (85.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e188 (90.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e186 (89.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e188 (88.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\ge\\:\\)\u003c/span\u003e\u003c/span\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e122 (11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19 (9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23 (11.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e24 (11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEducation background (n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.647\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22 (10.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e166 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (13.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (13.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e37 (17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e34 (16.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCollege or above\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e827 (76.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e194 (79.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e162 (78.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e158 (76.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e150 (71.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e163 (76.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity (n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.213\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimiparity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e649 (60.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e139 (57.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e122 (59.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e139 (67.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e127 (60.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e122 (57.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiparity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e428 (39.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104 (42.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84 (40.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e68 (32.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e82 (39.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e90 (42.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of miscarriage (n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e278 (25.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 (27.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56 (27.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e45 (21.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e51 (24.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e60 (28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.536\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin A (\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.66 (0.58\u0026ndash;0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.55 (0.52\u0026ndash;0.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.60 (0.59\u0026ndash;0.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.67 (0.65\u0026ndash;0.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.74 (0.71\u0026ndash;0.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.93 (0.87\u0026ndash;1.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInitial inspection blood pressure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e110.42\u0026thinsp;\u0026plusmn;\u0026thinsp;10.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110.10\u0026thinsp;\u0026plusmn;\u0026thinsp;10.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e111.19\u0026thinsp;\u0026plusmn;\u0026thinsp;10.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e109.47\u0026thinsp;\u0026plusmn;\u0026thinsp;10.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e111.29\u0026thinsp;\u0026plusmn;\u0026thinsp;10.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e109.19\u0026thinsp;\u0026plusmn;\u0026thinsp;10.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.410\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.64\u0026thinsp;\u0026plusmn;\u0026thinsp;7.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.79\u0026thinsp;\u0026plusmn;\u0026thinsp;7.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66.49\u0026thinsp;\u0026plusmn;\u0026thinsp;8.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65.63\u0026thinsp;\u0026plusmn;\u0026thinsp;7.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e67.12\u0026thinsp;\u0026plusmn;\u0026thinsp;8.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e66.50\u0026thinsp;\u0026plusmn;\u0026thinsp;7.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.596\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOGTT glucose metabolism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFasting plasma glucose (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.455\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-h post-load glucose (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.98\u0026thinsp;\u0026plusmn;\u0026thinsp;1.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.06\u0026thinsp;\u0026plusmn;\u0026thinsp;1.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.09\u0026thinsp;\u0026plusmn;\u0026thinsp;1.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.99\u0026thinsp;\u0026plusmn;\u0026thinsp;1.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.99\u0026thinsp;\u0026plusmn;\u0026thinsp;1.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.81\u0026thinsp;\u0026plusmn;\u0026thinsp;1.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.562\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2-h post-load glucose (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.98\u0026thinsp;\u0026plusmn;\u0026thinsp;1.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.15\u0026thinsp;\u0026plusmn;\u0026thinsp;1.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.16\u0026thinsp;\u0026plusmn;\u0026thinsp;1.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.76\u0026thinsp;\u0026plusmn;\u0026thinsp;1.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.06\u0026thinsp;\u0026plusmn;\u0026thinsp;1.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.78\u0026thinsp;\u0026plusmn;\u0026thinsp;1.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth\u0026nbsp;weight\u0026nbsp;of\u0026nbsp;newborn (g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3274.44\u0026thinsp;\u0026plusmn;\u0026thinsp;452.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3209.32\u0026thinsp;\u0026plusmn;\u0026thinsp;439.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3286.63\u0026thinsp;\u0026plusmn;\u0026thinsp;484.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3248.42\u0026thinsp;\u0026plusmn;\u0026thinsp;421.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3265.35\u0026thinsp;\u0026plusmn;\u0026thinsp;445.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3370.91\u0026thinsp;\u0026plusmn;\u0026thinsp;459.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth\u0026nbsp;height\u0026nbsp;of\u0026nbsp;newborn (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.72\u0026thinsp;\u0026plusmn;\u0026thinsp;1.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49.93\u0026thinsp;\u0026plusmn;\u0026thinsp;2.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49.86\u0026thinsp;\u0026plusmn;\u0026thinsp;1.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e49.88\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e50.18\u0026thinsp;\u0026plusmn;\u0026thinsp;1.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.215\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth\u0026nbsp;head circumference\u0026nbsp;of\u0026nbsp;newborn (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34.23\u0026thinsp;\u0026plusmn;\u0026thinsp;1.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.12\u0026thinsp;\u0026plusmn;\u0026thinsp;1.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.25\u0026thinsp;\u0026plusmn;\u0026thinsp;1.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34.09\u0026thinsp;\u0026plusmn;\u0026thinsp;1.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e34.10\u0026thinsp;\u0026plusmn;\u0026thinsp;1.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e34.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003eAdverse maternal and foetal outcomes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGDM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e241 (22.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67 (27.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47 (22.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41 (19.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e54 (25.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e32 (15.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmergency caesarean section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e108 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18 (8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e33 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePROM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e176 (16.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (16.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32 (15.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30 (14.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e41 (19.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e33 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.671\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostpartum eclampsia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.531\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFoetal intrauterine distress\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.265\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePremature birth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.785\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMacrosomia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.206\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLBW\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.190\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.172\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e105 (9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (12.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18 (8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e29 (13.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eAbbreviations: BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; OGTT: oral glucose tolerance test; GDM: gestational diabetes mellitus; PROM: premature rupture of membranes; LBW: low-birth-weight infants; PTB: preterm birth; SGA: small-for-gestational-age infants; LGA: large-for-gestational-age infants\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Associations between serum vitamin A concentrations during the first trimester and risk of GDM\u003c/h2\u003e \u003cp\u003eA negative correlation was observed between serum vitamin A concentrations and OGTT 1-h and 2-h plasma glucose concentrations (Table S2). Furthermore, the logistic regression model revealed the relationship between serum vitamin A concentrations in early pregnancy and the risk of GDM (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In model 1, the participants with serum vitamin A concentrations in Q5 (\u0026gt;\u0026thinsp;0.82 \u0026micro;mol/L) had a lower risk of GDM than those with serum vitamin A concentrations in Q1 (\u0026le;\u0026thinsp;0.57 \u0026micro;mol/L) (OR: 0.47; 95% CI: 0.29\u0026ndash;0.75). In models 2 and 3, after adjusting for confounding factors, the correlation between serum vitamin A concentrations and GDM remained significant (OR: 0.51; 95% CI: 0.31\u0026ndash;0.82 and OR: 0.50; 95% CI: 0.31\u0026ndash;0.81, respectively). The RCS regression models depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003eA showed a linear association between serum vitamin A concentrations and a decreased risk of GDM in a non-excess serum vitamin A concentration range (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.036).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOdds ratios (95% confidence intervals) for the occurrence of GDM according to the vitamin A levels at the first trimester.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eVitamin A levels (\u0026micro;mol/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQuintile 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eQuintile 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eQuintile 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQuintile 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQuintile 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP trend\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.57\u0026ndash;0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.63\u0026ndash;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.69\u0026ndash;0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGDM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCase/N\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67/243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47/206\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41/207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e54/209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32/212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.78 (0.51, 1.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.65 (0.42, 1.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.91 (0.60, 1.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.47\u003csup\u003e**\u003c/sup\u003e (0.29, 0.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.82 (0.53, 1.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.79 (0.50, 1.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.03 (0.67, 1.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.51\u003csup\u003e**\u003c/sup\u003e (0.31, 0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.81 (0.52, 1.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.78 (0.49, 1.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.02 (0.66, 1.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.50\u003csup\u003e**\u003c/sup\u003e (0.31, 0.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e* p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, ** p\u0026thinsp;\u0026lt;\u0026thinsp;0.01; Abbreviations: GDM: gestational diabetes mellitus;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eModel 1: without adjustment. Model 2 adjusted for age, BMI; Model 3 adjusted for the variables in Model 1 plus education background, smoking status, alcohol status, parity, history of miscarriage, nation, history of diabetes, history of hypertension.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe ORs (95% CIs) associated with serum vitamin A concentrations and GDM in participants classified by BMI or age are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e. In the BMI\u0026thinsp;\u0026ge;\u0026thinsp;24 kg/m\u003csup\u003e2\u003c/sup\u003e group, high serum vitamin A concentrations were associated with a low risk of GDM (\u003cem\u003ep\u003c/em\u003e-trend\u0026thinsp;=\u0026thinsp;0.035). This trend was not observed in the BMI\u0026thinsp;\u0026lt;\u0026thinsp;24 kg/m\u003csup\u003e2\u003c/sup\u003e group. In the aged\u0026thinsp;\u0026ge;\u0026thinsp;35 group, high serum vitamin A concentrations were associated with a low risk of GDM (\u003cem\u003ep\u003c/em\u003e-trend\u0026thinsp;=\u0026thinsp;0.027). This trend was not observed in the aged\u0026thinsp;\u0026lt;\u0026thinsp;35 group.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e3.3 Association between serum vitamin A concentrations in early pregnancy and risk of other adverse pregnancy outcomes\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the relationship between serum vitamin A concentrations in early pregnancy and some adverse pregnancy outcomes. After adjustment for age and BMI, the risk of foetal distress in utero decreased in the Q5 group as serum vitamin A concentrations increased (OR: 0.41; 95% CI: 0.18\u0026ndash;0.96). Compared with the Q1 group, the Q5 group had an increased risk of emergency caesarean section in model 1 (OR: 2.17; 95% CI: 1.20\u0026ndash;3.95, \u003cem\u003ep\u003c/em\u003e-trend\u0026thinsp;=\u0026thinsp;0.003). The same trend existed after adjustment for potential confounding factors, i.e., in model 2 (OR: 2.26; 95% CI: 1.24\u0026ndash;4.13, \u003cem\u003ep\u003c/em\u003e-trend\u0026thinsp;=\u0026thinsp;0.003) and model 3 (OR: 2.31; 95% CI: 1.26\u0026ndash;4.26, \u003cem\u003ep\u003c/em\u003e-trend\u0026thinsp;=\u0026thinsp;0.002). Furthermore, high serum concentrations of vitamin A were associated with a decreased risk of LBW. Compared with the Q1 group, the Q5 group had a lower risk of LBW (OR: 0.26; 95% CI: 0.07\u0026ndash;0.96). However, there was not a marked increase in the risk of LBW from Q1 to Q5 (\u003cem\u003ep\u003c/em\u003e-trend\u0026thinsp;=\u0026thinsp;0.099). After adjustment, the Q4 group had a lower risk of SGA than the Q1 group (OR: 0.32; 95% CI: 0.12\u0026ndash;0.82). In model 2, group Q5 had a higher risk of LGA than group Q1 (OR: 1.92; 95% CI: 1.04\u0026ndash;3.54). The risk of SGA in the Q4 group was significantly lower than that in the Q1 group (OR: 0.33; 95% CI: 0.13\u0026ndash;0.84), and this trend persisted after adjustment for potential confounding factors, i.e., in model 3 (OR: 0.32; 95% CI: 0.12\u0026ndash;0.82). However, there was no significant association between serum vitamin A concentrations and the risks of other adverse pregnancy outcomes (Table S3, Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). The results of the RCS analysis demonstrated that increased serum concentrations of vitamin A were associated with an increased risk of emergency caesarean section (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003eB), a decreased risk of intrauterine foetal distress (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003eC), and a decreased risk of SGA (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003eD).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eORs (95% CIs) for adverse pregnancy outcomes according to the Vitamin A levels at the first trimester.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eVitamin A levels (\u0026micro;mol/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQuintile 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eQuintile 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eQuintile 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQuintile 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQuintile 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e trend\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.57\u0026ndash;0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.63\u0026ndash;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.69\u0026ndash;0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFoetal distress in utero\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCase/N\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20/243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12/206\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9/207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11/209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8/212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.69 (0.33\u0026ndash;1.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.51 (0.23\u0026ndash;1.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.62 (0.29\u0026ndash;1.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.44 (0.19, 1.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.67 (0.32, 1.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.47 (0.21, 1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.58 (0.27, 1.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.41\u003csup\u003e*\u003c/sup\u003e (0.18, 0.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.71 (0.33, 1.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.47 (0.21, 1.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.60 (0.28, 1.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.44 (0.19, 1.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.073\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmergency caesarean section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCase/N\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19/243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15/206\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23/207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18/209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e33/212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.93 (0.46, 1.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.47 (0.78, 2.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.11 (0.57, 2.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.17\u003csup\u003e*\u003c/sup\u003e (1.20, 3.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.94 (0.46, 1.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.58 (0.82, 3.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.15 (0.59, 2.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.26\u003csup\u003e**\u003c/sup\u003e (1.24, 4.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.95 (0.46, 1.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.53 (0.79, 2.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.18 (0.60, 2.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.31\u003csup\u003e**\u003c/sup\u003e (1.26, 4.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLBW\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCase/N\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13/243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6/206\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6/207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9/209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3/212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.53 (0.20, 1.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.53 (0.20, 1.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.80 (0.33, 1.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.25\u003csup\u003e*\u003c/sup\u003e (0.07, 0.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.070\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.57 (0.21, 1.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.57 (0.21, 1.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.84 (0.35, 2.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.27\u003csup\u003e*\u003c/sup\u003e (0.08, 0.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.088\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.52 (0.19, 1.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.59 (0.21, 1.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.88 (0.35, 2.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.26\u003csup\u003e*\u003c/sup\u003e (0.07, 0.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.099\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCase/N\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20/243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15/206\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12/207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6/209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12/212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.88 (0.44, 1.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.69 (0.33, 1.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.33\u003csup\u003e*\u003c/sup\u003e (0.13, 0.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.67 (0.32, 1.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.156\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.88 (0.44, 1.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.64 (0.30, 1.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.32\u003csup\u003e*\u003c/sup\u003e (0.13, 0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.65 (0.31, 1.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.137\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.90 (0.44, 1.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.64 (0.30, 1.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.32\u003csup\u003e*\u003c/sup\u003e (0.12, 0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.70 (0.33, 1.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.185\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCase/N\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20/243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26/206\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18/207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12/209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29/212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.61 (0.87, 2.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.06 (0.55, 2.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.68 (0.32, 1.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.77 (0.97, 3.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.217\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.66 (0.89, 3.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.22 (0.62, 2.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.72 (0.34, 1.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.92\u003csup\u003e*\u003c/sup\u003e (1.04, 3.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.152\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.65 (0.88, 3.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.29 (0.65, 2.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.72 (0.34, 1.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.79 (0.96, 3.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.256\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e* \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, ** \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eModel 1: without adjustment. Model 2 adjusted for age, BMI; Model 3 adjusted for the variables in Model 1 plus education background, smoking status, alcohol status, parity, history of miscarriage, nation, history of diabetes, history of hypertension. Abbreviations: LBW: low-birth-weight infants; SGA: small-for-gestational-age infants; LGA: large-for-gestational-age infants.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn this prospective cohort study, the associations between maternal serum vitamin A concentrations in early pregnancy and adverse pregnancy outcomes were determined. None of the participants had excessive serum vitamin A concentrations. Increased serum vitamin A concentrations were found to be significantly associated with decreased risks of GDM, LBW, and SGA and an increased risk of emergency caesarean delivery. Consistent with the aforementioned findings, serum vitamin A concentration as a continuous variable was negatively correlated with OGTT 1-h and 2-h plasma glucose concentrations. In model 2, serum vitamin A concentrations in the Q5 group were significantly associated with a decreased risk of intrauterine foetal distress and a significantly increased risk of LGA. No significant association was observed between serum vitamin A concentrations and other adverse pregnancy outcomes.\u003c/p\u003e \u003cp\u003eVitamin A is a fat-soluble vitamin and is an essential micronutrient for the human body, vitamin A also plays a key role in the development of pregnant women and foetuses [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Moreover, vitamin A has antioxidant properties, and previous research has shown that oxidative stress may lead to the development of GDM [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Therefore, we evaluated the association of maternal serum vitamin A concentrations in early pregnancy with the occurrence of GDM and other adverse pregnancy outcomes. Only a few studies have assessed the relationship between vitamin A (in terms of food intake or physical conditions) and the risk of GDM, and they have reported inconsistent results. Our findings are similar to those of a recent case\u0026ndash;control study in China (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e), which found that serum vitamin A concentrations were lower in the group with GDM than in the group without GDM [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. However, it is difficult to determine a causal relationship between serum vitamin A concentrations and GDM based on the aforementioned results because the testing of serum vitamin A concentrations and diagnosis of GDM were performed in pregnant women at 24\u0026ndash;28 weeks. A case\u0026ndash;control study conducted in Iran of pregnant women at 30\u0026ndash;32 weeks showed that retinol concentrations in the GDM group were significantly lower than those in the control group [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, a previous retrospective cohort study in China showed that serum vitamin A concentrations in the GDM group were higher than those in the non-GDM group in the first trimester [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. In addition, a multiple logistic regression analysis in this study did not find that vitamin A was an independent influencing factor for GDM, which is inconsistent with the findings in the present study [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Similarly, another recent Chinese prospective cohort study found that increases in serum vitamin A concentrations in early pregnancy led to increases in the risk of GDM, which is inconsistent with the findings in the present study[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. However, unlike the present study, despite the fact that vitamin A is stored and metabolised in the liver, the aforementioned two studies did not exclude pregnant women with hepatitis or impaired liver function. Furthermore, it was previously found that women with GDM may experience mild liver dysfunction [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e], potentially leading to higher serum concentrations of vitamin A in the GDM group than in the non-GDM group.\u003c/p\u003e \u003cp\u003eThe present study found that participants aged 35 or older or with a BMI of 24 kg/m\u0026sup2; or higher had higher serum vitamin A concentrations and a lower risk of GDM than other participants. Women of advanced maternal age (AMA) are those who will be aged 35 or older at their estimated date of delivery [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Some studies have demonstrated that AMA is associated with the occurrence of GDM [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. In addition, the risk of GDM is higher in women with obesity than in those with a normal BMI[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Vitamin A plays a key role in reducing the risk of GDM in women of AMA and women with obesity. Therefore, it is important to monitor serum vitamin A concentrations in these two populations of women during the first trimester to reduce the incidence of GDM.\u003c/p\u003e \u003cp\u003eA deficiency of vitamin A is harmful to the mother and foetus, while an excess of vitamin A can have toxic and teratogenic effects early in pregnancy [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. A prospective cohort study conducted in Chengdu, China, showed that dietary intake of vitamin A during the first trimester was associated with the development of GDM, it also showed that a higher dietary intake of vitamin A than the recommended nutrient intake reduced the risk of GDM [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. Another case\u0026ndash;control study in a Chinese population examined dietary nutrition patterns and assessed their association with GDM risk, it found that a vitamin nutrition pattern diet (a diet rich in vitamin A, carotene, vitamin B2, vitamin B6, vitamin C, dietary fibre, folate, calcium, and potassium) was associated with a reduced risk of GDM [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. In practice, pregnant women should be directed to eat a moderate amount of foods rich in vitamin A, because vitamin A may improve the pregnancy outcomes of mothers and babies. The present study did not perform surveys of dietary intake of vitamin A, but it did determine circulating concentrations of vitamin A, which may be more reliable.\u003c/p\u003e \u003cp\u003eSome studies have found that women with GDM have an increased risk of adverse perinatal outcomes, such as macrosomia and LGA, and that GDM is a risk factor for emergency caesarean section [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Dittakarn et al. [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e] found that the incidence of emergency caesarean delivery was significantly greater in pregnant women with GDM than in normal pregnant women. In the present study, high serum vitamin A concentrations were associated with a decreased risk of GDM but with an increased risk of emergency caesarean section and LGA. The mechanism underlying the association between high serum vitamin A concentrations and emergency caesarean delivery is unknown and must be examined in future work.\u003c/p\u003e \u003cp\u003eMaternal vitamin A status plays a crucial role in the normal development of the foetus and neonate [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. A low intake of vitamin A has been linked to LBW and SGA [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. In the present study, although there was no significant difference in the incidence of LBW across the five quintiles based on serum vitamin A concentrations, a logistic regression analysis revealed that high vitamin A concentrations were associated with a decreased risk of LBW. A previous study conducted in China found that infant umbilical cord blood vitamin A concentrations were significantly and positively correlated with birth weight [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. However, this study did not measure serum vitamin A concentrations in pregnant mothers. Additionally, a cluster-randomised placebo-controlled trial conducted in rural northwestern Bangladesh found that prenatal vitamin A or β-carotene supplementation did not result in a decrease in the incidence of LBW [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e]. The heterogeneous nature of results from previous studies may be attributable to variations in study design and populations. Furthermore, a retrospective cohort study by Catov et al. suggested that regular periconceptional multivitamin use was associated with a reduced risk of non-overweight women having SGA newborns [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e], but did not analyse the effects of serum concentrations of vitamin A on SGA. The findings of the present study indicate that high serum concentrations of vitamin A (0.69\u0026ndash;0.82 \u0026micro;mol/L) were associated with a decreased incidence of SGA (OR: 0.32, 95% CI: 0.12\u0026ndash;0.82).\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, we lacked detailed information on dietary patterns and physical activity during pregnancy, although we controlled for some covariates, the effects of unmeasured or unknown residual confounders might not have been eliminated. Second, this study was conducted in a hospital in Shenzhen. Thus, although pregnant women from all areas of China may give birth at this hospital, it remains to be verified that our findings are generalisable to the whole population of China. Third, we measured only serum vitamin A concentrations, measurement of markers of oxidative stress and other antioxidant concentrations may enhance our understanding of the balance of factors affecting oxidative stress status and adverse pregnancy outcomes in women with GDM.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eThis prospective cohort study conducted in China showed that increased maternal serum vitamin A concentrations during early pregnancy were significantly associated with a reduced risk of GDM, LBW, and SGA. However, high serum concentrations of vitamin A were significantly associated with a high risk of emergency caesarean section. Therefore, it appears that monitoring of vitamin A concentrations should be a key part of the clinical care of pregnant women to optimise their pregnancy outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGDM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGestational diabetes mellitus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eT2DM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eType 2 diabetes mellitus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eROS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eReactive oxygen species\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSOD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSuperoxide dismutase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRBP4\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRetinol binding protein 4\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSGA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSmall for gestational age infants\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLGA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLarge for gestational age infants\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLBW\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLow\u0026ndash;birth\u0026ndash;weight infants\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRCS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRestricted cubic spline\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSBP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esystolic blood pressure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDBP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ediastolic blood pressure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOGTT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eoral glucose tolerance test\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePROM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epremature rupture of membranes\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePTB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epreterm birth.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the mothers and children who participated in this study and all the clinical staff at\u0026nbsp;Shenzhen Nanshan People\u0026rsquo;s Hospital\u0026nbsp;for their support and contribution.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGuifang Deng, Qinqin Ren and Yijin Wang conceived and designed the study. Yang Wang and Yao Liu assisted with study design. Hui Yuan, Yuanhuan Wei, Ruifang Sun and Ping Tian collected the data. Qinqin Ren contributed to statistical analysis and wrote the manuscript. Hongguang Yang and Yao Liu provided statistical advice and assisted with data analysis. Guifang Deng and Jianjun Yang reviewed and edited the manuscript. \u0026nbsp;All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by grants from the National Natural Science Foundation of China [grant number 82103821], the Major Technological Project of Shenzhen Nanshan District Health System [grant number NSZD2023024], and the Key Project of Shenzhen Nanshan District of Science and Technology [grant number NS2024005].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo protect the privacy of pregnant women, the datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants written informed consent forms at the beginning of the study. The protocol for this study was approved by the Ethics Committee of the\u0026nbsp;Shenzhen Nanshan People\u0026rsquo;s Hospital\u0026nbsp;(No. 2019072644) and all methods were performed in accordance with the relevant guidelines and regulations (Declaration of Helsinki).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e[1]\u0026nbsp;Department of Public Health, School of Public Health, Ningxia Medical University, Yinchuan, People\u0026rsquo;s Republic of China\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003e Department of Clinical Nutrition, Shenzhen Nanshan People\u0026rsquo;s Hospital, No. 89 Taoyuan Road, Shenzhen, Guangdong 518052, P.R. China.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e3\u003c/sup\u003e Department of Children Healthcare, Shenzhen Nanshan People\u0026rsquo;s Hospital, No. 89 Taoyuan Road, Shenzhen, Guangdong 518052, P.R. China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLiu C, Luo D, Wang Q, Ma Y, Ping L, Wu T, et al. Serum homocysteine and folate concentrations in early pregnancy and subsequent events of adverse pregnancy outcome: the Sichuan Homocysteine study. BMC Pregnancy Childbirth. 2020;20(1):176.\u003c/li\u003e\n\u003cli\u003eAssociation AD. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37 Suppl 1:S81-90.\u003c/li\u003e\n\u003cli\u003eWang H, Li N, Chivese T, Werfalli M, Sun H, Yuen L, et al. IDF Diabetes Atlas: Estimation of Global and Regional Gestational Diabetes Mellitus Prevalence for 2021 by International Association of Diabetes in Pregnancy Study Group\u0026apos;s Criteria. 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The relationship of fat soluble antioxidants with gestational diabetes in Iran: a case-control study. J Matern Fetal Neonatal Med. 2014;27(16):1676-9.\u003c/li\u003e\n\u003cli\u003eSuhail M, Patil S, Khan S, Siddiqui S. Antioxidant Vitamins and Lipoperoxidation in Non-pregnant, Pregnant, and Gestational Diabetic Women: Erythrocytes Osmotic Fragility Profiles. J Clin Med Res. 2010;2(6):266-73.\u003c/li\u003e\n\u003cli\u003eGrissa O, At\u0026egrave;gbo JM, Yessoufou A, Tabka Z, Miled A, Jerbi M, et al. Antioxidant status and circulating lipids are altered in human gestational diabetes and macrosomia. Transl Res. 2007;150(3):164-71.\u003c/li\u003e\n\u003cli\u003eYang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature. 2005;436(7049):356-62.\u003c/li\u003e\n\u003cli\u003eNoy N. Vitamin A in regulation of insulin responsiveness: mini review. 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The association between umbilical cord blood fat-soluble vitamin concentrations and infant birth weight. Front Endocrinol (Lausanne). 2023;14:1048615.\u003c/li\u003e\n\u003cli\u003eChristian P, Klemm R, Shamim AA, Ali H, Rashid M, Shaikh S, et al. Effects of vitamin A and \u0026beta;-carotene supplementation on birth size and length of gestation in rural Bangladesh: a cluster-randomized trial. Am J Clin Nutr. 2013;97(1):188-94.\u003c/li\u003e\n\u003cli\u003eCatov JM, Bodnar LM, Olsen J, Olsen S, Nohr EA. Periconceptional multivitamin use and risk of preterm or small-for-gestational-age births in the Danish National Birth Cohort. Am J Clin Nutr. 2011;94(3):906-12.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"vitamin A, adverse pregnancy outcomes, gestational diabetes mellitus, emergency caesarean section, low-birth-weight infant, small-for-gestational-age infant","lastPublishedDoi":"10.21203/rs.3.rs-4935218/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4935218/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eTo examine the association of serum vitamin A concentrations in early pregnancy with the risk of adverse pregnancy outcomes in Chinese women.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis prospective cohort study was conducted in the Department of Gynecology and Obstetrics at Shenzhen Nanshan People\u0026rsquo;s Hospital from 2019 to 2020. Serum vitamin A concentrations were measured during the first trimester (the first 6\u0026ndash;13 weeks) of pregnancy, and pregnancy outcomes were recorded in the hospital information system. Serum vitamin A concentrations were categorised into the following quintiles: \u0026le; 0.57 \u0026micro;mol/L, 0.57\u0026ndash;0.63 \u0026micro;mol/L, 0.63\u0026ndash;0.69 \u0026micro;mol/L, 0.69\u0026ndash;0.82 \u0026micro;mol/L, and \u0026gt;\u0026thinsp;0.82 \u0026micro;mol/L. The participants with serum vitamin A concentrations in the lowest quintile were used as the reference group. Statistical analysis was performed using multivariate logistic regression.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOne thousand and seventy-seven singleton mothers were recruited as participants. After multivariable adjustment, it was found that serum vitamin A concentrations\u0026thinsp;\u0026gt;\u0026thinsp;0.82 \u0026micro;mol/L and within a safe range were associated with a decreased risk of gestational diabetes mellitus (GDM) (odds ratio [OR]: 0.50; 95% confidence interval [CI]: 0.31\u0026ndash;0.81). In addition, compared with participants with serum vitamin A concentrations in the lowest quintile, those of participants with serum vitamin A concentrations in the highest quintile had a decreased risk of low birth weight (LBW) (OR: 0.26; 95% CI: 0.07\u0026ndash;0.96). Moreover, after adjustment and compared with participants with serum vitamin A concentrations in the lowest quintile, those with serum vitamin A concentrations in the fourth quintile had a decreased risk of small for gestational age (OR: 0.32; 95% CI: 0.12\u0026ndash;0.82). Furthermore, compared with participants with vitamin A concentrations\u0026thinsp;\u0026le;\u0026thinsp;0.57 \u0026micro;mol/L, participants with vitamin A concentrations\u0026thinsp;\u0026gt;\u0026thinsp;0.82 \u0026micro;mol/L had an increased risk of emergency caesarean section (OR: 2.31; 95% CI: 1.26\u0026ndash;4.26).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eDuring the first trimester, maternal serum vitamin A concentrations\u0026thinsp;\u0026gt;\u0026thinsp;0.82 \u0026micro;mol/L and within a safe range were found to be associated with a reduced risk of GDM and LBW. However, an increase in serum vitamin A concentrations was found to be associated with an increase in the risk of emergency caesarean section.\u003c/p\u003e","manuscriptTitle":"Association of Maternal Serum Vitamin A Levels in the First Trimester with the Risk of Adverse Pregnancy Outcomes: A Prospective Cohort Study of Chinese Women","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-15 04:51:48","doi":"10.21203/rs.3.rs-4935218/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3edc1811-fcb7-482f-b626-41fb8d05d40e","owner":[],"postedDate":"October 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-08T12:39:09+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-15 04:51:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4935218","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4935218","identity":"rs-4935218","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}