| Backgrounds and ObjectivesPreterm birth (PTB) is the leading cause of death in newborns, and the second leading cause of death in children under five years old. Globally, the prevalence of preterm birth ranged from5%to18%, and increased gradually. Risk factors for preterm birth and the specific biological mechanisms are not entirely sure. Many factors were associated with preterm birth, including maternal age, race, occupation, education level, marital status, pre-pregnancy BMI, gestational weight gain, physical activity, bad life behavior, nutritional status, multiple births, gestational complications, psychological stress and history of preterm labor.Pregnancy is a critical period for women, pregnant women were inclined to intake more food in order to ensure nutritional requirements. But pre-pregnancy obese and excessive gestational weight gain (GWG) were associated with a variety of adverse pregnancy outcomes, for example, gestational diabetes, preeclampsia, eclampsia and preterm birth. Vitamin D (VitD) may induce preterm birth through regulating immune function. In addition, both pre-pregnancy obesity and VitD deficiency would affect the level of inflammatory factor. The elevated levels of pro-inflammatory factor may increase prostaglandin and contractions related proteins which could trigger preterm labor. Till now, results about the effect of pre-pregnancy obese, GWG and VitD were inconsistent from various studies. Some studies found pre-pregnancy obese, excessive GWG and VitD deficiency would increase the risk of preterm birth, but others did not. Therefore, this research was conducted in Zhoushan Maternal and Child Health Hospital. We explored the associations of pre-pregnancy body mass index (BMI) and GWG with the risk of preterm birth in a prospective cohort study, and explored the associations of vitamin D, interleukin (IL)-1β and IL-10levels with the risk of preterm birth using a nested case-control study design, aiming to provide scientific basis for the prevention and control of preterm birth.Materials and MethodsWe took Zhoushan Maternal and Child Health Hospital as the research field. In the prospective cohort study, participants’social-demographic characteristics, life behavior, height and weight were obtained through epidemiological investigation questionnaires, by face-to-face interview, and blood samples were collected at three timepoints with informed consent. From August2011to April2014, a total of1580and1091valid questionnaires were collected in the first and second trimester, respectively. The Log-binomial regression models were used to assess the associations of pre-pregnancy BMI and GWG with the risk of preterm birth.Based on the prospective cohort study, a1:2matched nested case-control study was designed.62cases of preterm birth (gestational age less than37weeks) and124controls of term birth (gestational age between37-42weeks) matched by age, parity and blood sampling season were selected in the first trimester. A high performance liquid chromatography tandem mass spectrometry was used to detect plasma25(OH)D, 25(OH)D3and25(OH)D2levels. We screened40inflammatory factors using Human Inflammation Array-3to select those (IL-1β and IL-10), which there was significantly different between PTB and controls, then measured their concentrations using Elisa method. Conditional Logistic regression model was used to evaluate the association of25(OH)D,25(OH)D3,25(OH)D2, IL-1β, IL-10and the ratio of IL-10and IL-1β with preterm birth risk.ResultsThe average age of pregnant women in the preterm birth group was a little higher than that in term birth group among1580participants included in the prospective cohort study (28.5vs.27.7years, p=0.047). The distributions of demographic characteristics and life behavior between two groups were balanced between term and preterm women. Compared with pregnant women who had normal weight, the odds ratio of preterm birth was2.55(95%CI:1.39-4.68) for pre-pregnancy overweight and obese women, and0.73(95%CI:0.37-1.44) for pre-pregnancy underweight women. For spontaneous deliveries, pre-pregnancy greater than24kg/m2was not associated with the risk of preterm birth (RR=1.52,95%CI:0.38-6.14), but significantly increased among gravida with caesarean section (RR=2.53,95%CI:1.19-5.38). The risk of preterm birth significantly increased in primipara or single foetus women whose pre-pregnancy BMI greater than24kg/m2. The ORs were2.58and3.08respectively. The joint association of passive smoking and pre-pregnancy BMI remarkly increased the risk of preterm birth (RR=4.38,95%CI:1.97-9.72). However, there was no significant relationship of GWG in the first trimester or in the second trimester with the risk of preterm birth. Pregnant women whose GWG in the first six months over15kg increased the risk of preterm birth (RR=1.99,95%CI:1.01-3.92), and pregnant women whose GWG in the first six months less than10kg did not increase the risk of preterm birth (RR=1.01,95%CI:0.59-1.73), compared with women whose GWG among10-15kg. For spontaneous deliveries, the odds ratio of preterm birth for women who gained excessive weight was3.56(95%CI:1.42-8.90). For caesarean section, excessive GWG was not significantly associated with the risk of PTB (RR=1.53, 95%CI:0.56-4.21). Results from the joint association showed that the risk of preterm birth for women whose age over30years and excessive GWG increased significantly (RR=4.78,95%CI:1.89-12.10), so did for women who exposed to passive smoking and excessive GWG (RR=2.88,95%CI:1.22-6.81).The average concentration of25(OH)D was17.2ng/ml among186pregnant women in the nested case-control study.67.2%of pregnant women were VitD deficiency,24.2%were VitD insufficiency, and only8.6%were VitD adequate.25(OH)D and25(OH)D3levels had obvious seasonal difference, which was lowest in winter. As compared with25(OH)D level greater than20ng/ml pregnant women, the odds ratio for preterm birth was not significantly increased among pregnant women with a25(OH)D concentration less than20ng/ml (OR=1.19,95%CI:0.45-3.15). There was not the joint effect between age, passive smoking and vitamin D on the risk of preterm birth. Sensitive analyses also showed that there was no significant association of VitD and PTB among primipara, single foteus women or the different delivery methods. There was no significant association of VitD3and VitD2with the risk of PTB. Compared with mothers whose IL-1β levels at0.13-0.40pg/ml, there was a decreased risk of preterm birth for mothers whose IL-1β levels above0.40pg/ml (OR=0.34,95%CI:0.13-0.87), but not for mothers whose IL-1β levels below0.13pg/ml (OR=0.34,95%CI:0.12-1.00). Additionally, we did not find any remarkable association between IL-10level and the ratio of IL-10and IL-1β with the risk of preterm birth.ConclusionsPre-pregnancy overweight or obesity significantly increased the risk of PTB, compared with pre-pregnancy normal weight women. And the risk of preterm delivery significantly increased among women who gained excessive weight during the first6months. The joint association of age and pre-pregnancy BMI, GWG with the risk of preterm birth was significant, so was passive smoking. The level of VitD changed with various seasons, which was lowest in winter. No statistical associations of VitD, VitD3and VitD2with PTB were found. High IL-1β level reduced the risk of PTB, compared with pregnant women whose IL-1β level were intermediate. However, there was no significant association of IL-10and the ratio of IL-10and IL-1βwith the risk of preterm birth. |
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