| ObjectiveIn recent years, with the increasing of the level of people’s material life, the incidence of macrosomia presents a rising trend, which not only increases dystocia for pregnant women in childbirth, the postpartum hemorrhage and the risk of infection, but also increases the risk of fetal intracranial hemorrhage, clavicular fracture, brachial plexus injury during the surgery of assisted delivery. Furthermore, macrosomia has a higher risk of obesity during the development and diabetes in adulthood. Insulin-like growth factor is closely linked to fetal growth and development and plays an important role in blood glucose uptake and utilization during foetal period. Glycosylated hemoglobin is an important indicator to detect the level of blood sugar in long-term, and insulin plays an important role in both blood glucose regulation and protein synthesis. For discussing the etiology of macrosomia, it is important to explore the combined effects of these three factors to reduce and control the incidence of macrosomia.Methods1. Study object and grouping:A1:2case-control study has been conducted in the department of obstetrics and gynecology of a general hospital from April to November2012. Single live newborn infants whose birth weight≥4000g and mother was non-GDM pregnant women were selected in the case group; while single live newborn infants whose birth weight<4000g and mother was non-GDM pregnant women were selected in the control group. All the participants were chose according to the matching order:the same scene, the same period in childbirth and the section order was first case then control. Exclusive criteria:pregnant women with gestational diabetes mellitus (GDM).2. Data collection:Established respectively Questionnaire of pregnant women before delivery and Registration form of pregnant women delivery to investigate the relevant factors of these pregnant women and newborn infants. After obtaining the informed consent, collected all the cord blood, venous blood of the mothers, and placental tissue specimens information, then selected the case-group and control-group specimens coincidence with this study to do lab testing. Among these,2-3ml fasting venous blood specimens of pregnant women before delivery were collected by using EDTA-K2and additive-free tubes,2-3ml cord blood were collected by using additive-free tubes at the childbirth, and separated serum samples were stocked at-80℃.2samples of50g tissue from the non-calcification area of the center of the maternal side of the placenta had been collected, one piece of placental tissue was fixed in10%formalin for histological examination, the other one was cleaned and stocked at-80℃.3. Detection methods:Enzyme-linked immunosorbent assay (ELISA) was used to determinate the IGF-1and IGF-2levels in maternal and umbilical cord blood samples; electrochemiluminescence method was used to determinate the level of insulin in maternal and umbilical cord blood samples; high-pressure liquid chromatography (HPLC) was used to measure the glycosylated hemoglobin (GHb) level in maternal blood samples; enzyme method was used to detect the triglyceride (TG) and total cholesterol (TCH) levels in maternal and umbilical cord blood samples; Western-blot was used to detect the expression levels of IGF-1and IGF-2in placental tissues; immunohistochemical staining was used to detect the platelet-endothelial cell adhesion molecule CD31expression level in placental tissues.4. Statistical methods:The verification of investigated data based on the medical history, data verification based on the detection of the original data record, all the information were recorded and kept in Excel2003. SPSS17.0statistical analysis software was used to compare the data between the case and control groups. All measurement data were presented by x±s for average level and dispersion tendency; chose homogeneity test of variance firstly for analysis and comparion between the case group and control group data. Independent sample t-test was used for the measurement data with equal variance, and approximate t-test was used for the data without equal variance. X2test was used for counting data between groups. Ranked data use nonparametric test. Multivariate data analysis use conditional Logistic regression analysis method to screening the influential factors and the risk of macrosomia, which was expressed by odds ratio and its95%confidence interval. The multiplicative interaction model was chose to do interaction analysis, while the covariate effects were corrected. a=0.05, two tailed test.Results1. According to the selection criteria of objects,33cases were selected in case group, while66cases in control group. We found that the percentage of boy in the newborn was higher in the case group than that in the control group (P <0.05).There were no statistical difference (P>0.05) in the following eleven factors of the pregnant women in both groups:nation, family income, education level, supplementation during pre-pregnancy and pregnancy, parity, history of abortion, history of smoking and passive smoking, history of alcohol consumption, hypertension during pregnancy, combined infection during pregnancy and family history of diabetes. While eight factors of the pregnant women in the case group were higher than the control group (P<0.05). they were early gestational age, current gestational age, height, pre-pregnancy weight, pre-pregnancy BMI, gestational weeks, weight gain during pregnancy and the volume of pregnancy amniotic fluid. Conditional Logistic regression for multivariate analysis found that pre-pregnancy BMI (OR=2.819,95%CI=1.527-5.205), pregnancy weight gain (OR=1.846,95%CI=1.217-2.799). gestational weeks (OR=9.826,95%CI=1.125-85.790), and fetal gender (OR=0.013,95%CI=0.001-0.300), these four factors were correlated with macrosomia incidence. 2. The result of venous blood indicators in pregnant women:In the case group of pregnant women, IGF-1:(242.14±28.77)ng/L, IGF-2:(5.19±0.64)ng/L, INS (13.46±5.76)μU/ml, TG:(3.76±1.63)mmol/L and TCH:(5.87±1.24)mmol/L; while in the control group, IGF-1:(245.97±34.71)ng/L, IGF-2:(5.12±0.53)ng/L, INS:(12.59±9.09)μU/ml, TG:(3.38±0.92)mmol/L, TCH:(6.23±1.20)mmol/L. There was no significant difference (P>0.05). The GHb level of pregnant women in the case group (5.6±0.43%) was higher than that in control group (4.9±0.35%), P<0.05.3. The result of umbilical cord blood indicators:IGF-1:(71.21±6.27)ng/L, IGF-2:(8.44±1.16)ng/L, INS:(7.61±1.53)μU/ml of cord blood in the case group were higher than those in the control group (IGF-1:(50.07±10.34)ng/L, IGF-2:(6.51±0.80)ng/L, INS:(4.69±2.58)μU/ml),P<0.05; while TG:(0.199±0.09)mmol/L and TCH:(1.78±0.50)mmol/L in the case group had no significant difference (P>0.05) with the control group(TG:(0.197±0.08) mmol/L,TCH:(1.69±0.32) mmol/L).4. The result of placental tissue indicators:Western blot determined the IGF-1and IGF-2levels in placental tissue and its IOD value, the results showed that IGF-1and IGF-2IOD values in placental tissue in the case group were (1434.67±171.13) and (626.07±130.66), respectively, higher than those in control group ((672.88±236.93) and (307.69±81.46)), P<0.05. The average weight of placental tissue in the case group were (768.00±92.47)g. which was higher than the control group (578.50±89.05)g, P<0.05. The maturity grade of placenta in the case group was grade Ⅲ, which was higher than the control group, P<0.05. The level of expression of CD31in placental tissue indicated that the vascular density in placental tissue in the case group is higher than that in the control group (P<0.05).5. The multiplicity analysis of IGF, INS, and GHb with the risk of macrosomia: The Collinearity test was used between pregnant women’s venous blood IGF, INF, GHb and umbilical cord blood IGF, INS respectively. There were no collinearity results by using tolerance and variance inflation factor. Conditional logistic regression model was comprehensive analysised among pregnant women’s venous blood IGF, INF, GHb, pre-pregnancy BMI, weight gain during pregnancy, gestational weeks and the newborn gender. The pregnant women’s GHb(OR=5.775,95%CI=1.199-27.807), pre-pregnancy BMI(OR=2.690,95%CI=1.539-4.702), weight gain during pregnancy(OR=1.777,95%CI=1.248-2.532) and gestational weeks(OR=l3.573,95%CI=2.064-89.268) were the risk factors of macrosomia incidence, while newborn female gender was the protective factor for macrosomia incidence. There was no statistical significance of pregnant women’s IGF-1、 IGF-2、INS for macrosomia. Likewise, conditional logistic regression model was also comprehensive analysised among umbilical cord blood IGF, INF, pre-pregnancy BMI, weight gain during pregnancy, gestational weeks and the newborn gender. The umbilical cord blood IGF-1(OR=1.103,95%CI=1.012～1.203), pre-pregnancy BMI (OR=1.814,95%CI=1.183-2.783), weight gain during pregnancy (OR=1.509,95%CI=1.158～1.966) were the risk factors of macrosomia incidence, while newborn female gender (OR=0.111,95%CI=0.015-0.814) was the protective factor for macrosomia incidence. And there was no statistical significance of cord blood IGF-2、INS and gestational weeks for macrosomia.6. Combined analysis between these indexes. The multiplicative interaction was used between pregnant women’s venous blood GHb and pre-pregnancy BMI, weight gain during pregnancy, gestational weeks and the newborn gender respectively. The GHb was positive multiplicative interaction to pre-pregnancy BMI, weight gain during pregnancy, gestational weeks while it was negative multiplicative interaction to newborn gender. Likewise, the IGF-1of cord blood was positive multiplicative interaction to pre-pregnancy BMI, weight gain during pregnancy while it was negative multiplicative interaction to newborn gender, and there was no multiplicative interaction to gestational weeks.Conclusions1. Mother venous blood GHb and cord blood IGF-1increase the risk of macrosomia, but INS, IGF-2in both cord blood and mother venous blood are not correlated with macrosomia. Mother venous blood GHb can be used to monitor the risk of macrosomia.2. The high secretion level of placenta IGF will increase the risk of macrosomia through increased blood vessel density and placental tissue weight.3. Reasonable adjustments to pre-pregnancy BMI, paying close attention to the gestational weeks and weight gain during pregnancy, adjusting the diet during pregnancy to control the level of carbohydrate intake in females, these factors are important to reduce the risk of macrosomia. |
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