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Long-term Influence Of Gestational Diabetes Mellitus On The Offspring

Posted on:2014-03-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y L ZhaoFull Text:PDF
GTID:1264330401466487Subject:Surgery
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Part I Influence of blood glucose concentrations of mothers during pregnancy and relevant factors on neonatal body composition Background and Objective:Gestational diabetes mellitus (GDM) increased risk of macrosomia and large for gestational age (LGA), at the same time, the offspring of mothers with GDM had an increased risk of obesity, abnormal glucose metabolism and cardiovascular disease during childhood, adolescence and adulthood. Fetal overgrowth was associated with abnomal intrauterine environment of increased maternal glucose. Neonates of mothers with GDM had increased body fat. On the other hand, even the mother who received effective treatment and achieved normal blood glucose concentration, there is still high risk of LGA in their offspring. The objective of this study was to investigate the influence of blood glucose concentrations of mothers during pregnancy and other relevant factors on body composition of large-for-gestational-age (LGA) and appropriate-for-gestational-age (AGA) neonates.Methods:A study was conducted on206infants (123male cases and83female cases) of women with gestational diabetes mellitus (GDM group) and412infants (225male cases and187female cases) of women with normal glucose tolerance (control group). Anthropometric measurements including birth weight, length, circumferences of the head, chest and upper arm, triceps, biceps, subscapular, abdominal and flank superficial skin fold and body composition including fat mass, percent body fat and fat free mass were obtained within24to48hours of birth. Multiple stepwise regressions was used to determine factors correlating with fat mass, percent of body fat and fat free mass mass.Results:(1)There was no significant difference in gestational age, birth weight, length, body mass index, circumferences of the head, chest and upper arm, biceps and abdominal and superficial skin fold between LGA/GDM group and LGA/NGT group, but LGA infants of women with GDM was characterized by higher skin folds of triceps and subscapular and flank compared with LGA infants of women with normal glucose tolerance levels (8.1±0.9mm vs.6.4±0.6mm,p=0.000;7.8±0.6mm vs.6.2±0.4mm,p=0.019). LGA infants of women with GDM had greater fat mass (666.9±18.8g vs.522.3±23.3g,p=0.007) and percent of body fat (17.29±0.89%vs.13.33±0.65%,p=0.003) than that of LGA infants of women with normal glucose tolerance levels, but decreased fat free mass compared with control group (3177.2±280vs.3407.3±96,p=0.006).(2) There was no significant difference in gestational age, birth weight, length, body mass index, circumferences of the head, chest and upper arm, biceps and abdominal superficial skin fold between AGA/GDM group and AGA/NGT group, but AGA/GDM group was characterized by higher skin folds of triceps and subscapular and flank compared with AGA/NGT [5.2±0.4) vs.(4.4±0.3) mm, P=0.000,(5.2±0.3) vs.(4.0±0.2) mm, P=0.000,(5.4±0.5) vs.(4.5±0.4) mm, P=0.000]; GDM group had greater fat mass (505±34vs.421±28,p=0.000);(15.4±0.5%vs.12.9±1.9%,p=0.000), but decreased fat free mass compared with control group (2766±155vs.2842±142,p=0.000).(3) Stepwise regression showed that maternal fasting glucose level of the oral glucose tolerance test and pregravid BMI correlated with fat mass and percent of body fat, maternal fasting glucose level of the oral glucose tolerance test correlated with fat mass in GDM group (r2=0.265, p=0.001). On the other hand, maternal weight gain (r2=0.097,p=0.021)and maternal height (r2=0.065,p=0.000)correlated with fat free mass in GDM group. maternal weight gain correlated with fat mass,(r2=0.090, p=0.015), maternal pregravid weight (r2=0.140,p=0.002) and prepartal weight(r2=0110, p=0.043) were related to percent of body fat, maternal height had correlation with fat free mass in control group.Conclusions:(1) The Larger-for-gestational-age and appropriate-for-gestational-age infants of women with GDM had increased fat mass and percent of body fat, but decreased fat free mass.(2) Maternal fasting glucose level of the oral glucose tolerance test, pregravid body mass index, weight gain correlated with neonatal body composition. Part Ⅱ growth patterns in appropriate for gestational age infants of gestational diabetic mothers during the first year. Background and Objective:A lot of adult diseases originated from the fetal period. It has been reached a consensus that abnormal intrauterine environment of gestational diabetes mellitus (GDM) increased the risk of obesity, abnormal glucose metabolism and cardiovascular disease in the offspring. The early growth pattern in offspring of GDM mother after birth needs to be further studied. The initial growth of infants after birth (the first year after birth) is very rapid, especially in the first3months. However we still know little about the regulation mechanism of this growth phase so far. It has been estimated that the growth pattern of this phase may be the continuation of the fetal growth pattern. Authough neonates of women with GDM are average weight for gestational age, they have incrased body fat compared with neonates of women with normal glucose tolerance. This indicated that the growth of AGA was affected by hyperglycemia environment in intrauterine. It is unclear whether the growth pattern in infants of mother with GDM is a continuation of the fetal growth pattern. Is early growth pattern in infants of mother with GDM different from that of mother with normal glucose tolerance? Whether the special growth pattern in offspring of mother with GDM is the outcome of the influence of intrauterine hyperglycemia environment on offspring? To answer these questions, we performed a prospective cohort study to follow-up AGA infants of mother with GDM to explore the growth pattern in infant of mother with GDM.Methods:The objects of this study were offspring of women who delivered in our hospital from2011January to2011December. GDM were screened by75g oral glucose tolerance test firstly. The case group (GDM group) included70AGA infants (36male cases and34female cases) of mother withGDM. The control group included154AGA infants (66male cases and88female cases) of women with normal glucose tolerance. The data of demographic characteristics of mothers of two groups were collected. Body weight and body length of infants in two groups were measured at3,6and12months age respectively. Body mass index (BMI), weight gain and height gain during infancy (0-3months,3-6months and6-12months) of infants in two groups were also calculated. Then the data of infants in two groups were compared.Results:(1) Male AGA infants in GDM group had greater body weight and BMI than that of control group (3437.5±218.59vs.248.78±243.83, P=0.023;13.48±0.66vs.12.90±0.78, P=0.022). There was no significantly difference in birth weight and body mass index between female AGA infants in two groups.(2) Body weight、body length and BMI of male AGA infants in GDM group were less than that of control group at3months and6months age, but more than that of control group at12months age, there were no significant differences between two group(P>0.05). Body weight、body length and BMI of female AGA infants in GDM group were similar to that of control group at3months、6months and12months age, but there were no significant differences between two group(P>0.05).(3) The weight and height gain during infancy (0-3months,3-6months) of male AGA infants in GDM group were lower than that of control group, but the difference was statistically significant only at3-6months (1.1±0.44vs.1.42±0.35,P=0.04;4.93±2.33vs.6.33±1.21,P=0.026)。 According to the data of general growth patterns of Chinese infants at0-18years, the weight and height gain during infancy (0-3months,3-6months) of male AGA infants in GDM group were lower than that of the third percentile. The weight and height gain during infancy (6-12months) of male AGA infants of gestational diabetic mothers were higher than that of control group, but the difference was not statistically significant (2.07±0.50vs.1.77±0.53, P=0.361;8.35±1.28vs.7.79±1.43,P=0.464). There were no significant differences in weight and height gain during infancy (0-3months,3-6months and6-12months age) of female AGA infants between two groups (P>0.05).Conclusions:The infants of gestational diabetic mothers had a different growth pattern from that of the infants of mothers with normal glucose tolerance during the first year after birth. The growth level of infants of gestational diabetic mothers is lower than that of offspring of mother with normal blood glucose, especially during0-6months after birth. Male infants of gestational diabetic mothers grew slowly during their infancy of0-6months and then their growth becomes increasingly fast, which suggested that the influence of intrauterine hyperglycemia environment of GDM mothers on fetal growth might continue after birth. Part III Effects of maternal gestational diabetes mellitus on offspring overweight and obesity in childhood. Background and Objectives:The prevalence of obesity around the world continues to rise in recent years, and the age of onset become younger. The prevalence of obesity and diabetes of children has taken on a sustainable growth. The present study showed that adverse intrauterine environment increased the susceptibility to chronic disease (obesity, hypertension diabetes and cardiovascular disease) of offspring in their adulthood. It is commonly stated that exposure to an intrauterine hyperglycemia environment of gestational diabetes mellitus (GDM) increased the risk of offspring obesity and diabetes in later life. However, little is known about the magnitude of risk for offspring obesity that attributable to maternal diabetes in utero in Chinese Mainland. While treatment of GDM is effective in reducing the occurrence of the adverse pregnancy outcomes such as macrosomia, shoulder dystocia, it remains to be established whether the long-term effects of exposure to diabetes mellitus during intrauterine development can be prevented. Is it the same that he long-term outcome of large-for-gestational-age(LGA), appropriate-for-gestational-age (AGA) and small-for-gestational-age(SGA) offspring of mothers diagnosed with GDM? Based on the above research background, the purpose of the study is twofold. The first is to evaluate the growth pattern of offspring of Chinese Mainland women with GDM. The second purpose is to investigate the long-term effects of maternal perinatal factors including GDM, obesity and weight gain during pregnancy on childhood overweight and obesity from1.1to10years of age.Methods:A study was conducted on1068children of mothers with gestational diabetes mellitus (GDM group) and1756children of mothers with normal glucose tolerance (control group) who were born between from January1,2003to December31,2011in the first affiliated hospital of Kunming medical university. The height and weight of children were obtained from parental reports through telephone interview. Multiple Logistic regressions were used to determine perinatal risk factors correlating with overweight and obesity of offspring in childhood.Results:(1) There were1068children in GDM group (554male cases and514female cases), and there were148SGA cases,771AGA cases and149LGA cases in this group. There were1765children in control group (915male cases and850female cases), and there were180SGA cases,1401AGA cases and180LGA cases in this group. The maximum age is10years old, the minimum age of1.1years old, the mean age is4.1years old.(2) Before5years old, the mean weight of male SGA and AGA offspring in GDM group was lower than that of control group, but the mean weight of male LGA offspring in GDM group was similar to that of control group. After5years old, male LGA offspring in GDM group weight more than all other study groups. The mean weight of male SGA and AGA offspring in GDM group caught up to that of control group. The mean weight of female LGA, SGA and AGA offspring in GDM group was similar to that of control group during1-2years old. The mean weight of female SGA and AGA offspring in GDM group was lower than that of control group during2-5years old, but the mean weight of female LGA offspring in GDM group was similar to that of control group. After5years old, there was no significant difference in weight between female children in GDM group and control group.(3) Before5years old, the mean height of the SGA, AGA and LGA offspring in GDM group was lower than that of control group. After5years old, offspring in GDM group had similar height as control group. The mean height of SGA offspring caught up to that of AGA children in two groups.(4) Before5years old, the mean BMI of the SGA, AGA and LGA offspring in GDM group was similar to that of control group. After5years old, the mean BMI of the LGA offspring in GDM group was higher than that of control group.(5) There were178overweight children (16.6%) and97obesity children (9.1%) in GDM group, and222overweight children (12.6%) and212obesity children (12.0%) in control group. Before5years old, there was no significant difference in the prevalence of overweight between GDM and control groups. The prevalence of obesity of children in GDM group was lower than that of control group. After5years old, AGA and LGA offspring in GDM group had an increased prevalence of overweight and obesity compared with control group.(6) In GDM group, compared with the offspring of mothers with normal weight prepregnancy, offspring of mothers with prepregnancy overweight had a higher risk of overweight [OR:1.036(95%CI:1.007~1.067)], but after adjusting for0-3month feeding mode, this correlation disappeared [OR:1.034(95%CI:0.9981.071)].Compared with the offspring of mothers with appropriate weight gain during pregnancy, the risk of overweight of offspring of mothers with overmuch weight gain during pregnancy did not increase significantly [OR:1.003(95%CI:0.323~3.12)]. Compared with AGA offspring, SGA offspring had a lower risk of overweight [OR:0.362(95%CI:0.171~0.768)], but this correlation disappeared after controlling for confounder. LGA offspring had a higher risk of overweight [OR:2.267(95%CI:1.533~3.351)]. Male offspring had a higher risk of overweight[OR:2.042(95%CI:1.316~3.169)], but this correlation disappeared after controlling for confounder. Compared with offspring with0-3month artificial feeding, the risk of overweight of offspring with0-3month breastfeeding reduced significantly [OR:0.426(95%CI:0.197~0.939)].(7) In control group, compared with the offspring of mothers with normal prepregnancy weight, offspring of the mothers with prepregnancy overweigh had a higher risk of overweight [OR:1.073(95%CI:1.070~1.118)], and after the introduction of0-3month feeding regression type, this correlation still existed[OR:1.057(95%CI:1.011~1.015)]. Compared with offspring of mothers with appropriate weight gain during pregnancy, the risk of overweight of offspring of mothers with overmuch weight gain during pregnancy did not increase significantly [OR:1.001(95%CI:0.977~1.026)].Compared with AGA offspring, SGA offspring had a lower risk of overweight [OR:0.513(95%CI:0.319~0.823)], however LGA offspring had no higher risk [OR:1.387(95%CI:0.992~1.940)]. Compared with female offspring, male offspring had a higher risk of overweight [OR:0.703(95%CI: 0.564~0.877)], but this correlation disappeared after controlling for confounder. Compared with offspring with0-3month artificial feeding,the risk of overweight of offspring with0-3month breasfeeding did not decreased significantly [OR:0.861(95%CI:0.545~1.358)].Conclusions:(1) Before5years old, there was no significant difference in weight, height and BMI between LGA offspring in GDM and control groups. SGA and AGA offspring of mothers with GDM were lower in weight, height and BMI compared with SGA and AGA control subjects. After5years old, LGA offspring of mothers with GDM were heavier than all other study groups. The height of SGA offspring in two groups catch up to that of AGA offspring. There was no significant difference in weight, height and BMI between AGA offspring in GDM and control groups.(2) Before5years old, the prevalence of overweight and obesity was reduced in offspring of mothers with GDM compared with control group. After5years old, offspring of mothers with GDM had a higher prevalence of overweight and obesity than that of control group.(3) The risk of overweight was highest in LGA offspring with concomitant exposure to GDM and maternal prepregnancy overweight. However, adjusting for the0to3feeding mode after birth attenuated the association. Part IV The effect of breastfeeding on childhood overweight among offspring exposed to maternal gestational diabetes mellitus Background and Objective:The offspring of gestational diabetes mellitus (GDM) was the high risk population of obesity, overweight and diabetes. The objective of this study was to evaluate whether that breastfeeding reduced the risk of childhood overweight in the offspring of mother with gestational diabetes mellitus.Methods: A prospective observational study was performed in1189offspring of GDM mothers whom were treated and had delivery in our hospital from January2003to December2009. The influence of the breastfeeding of0to3months after birth and the duration of breastfeeding on the risk of overweight was analyzed by Logistic regression.Results:After adjusting for prepregnancy BMI, maternal weight gain during pregnancy, maternal glucose concentration, birth weight, sex, age and paternal weight, compared with the artificial feeding group, those who were breasted exclusive breastfeeding during the first3months of life had lower risks of overweight [OR:0.479(95%CI:0.256-0.897)]; Those who were breasted for1to3months,4to6months and6months longer had lower risks of overweight [OR:0.456(95%CI:0.233~0.827)];[OR:0.29(95%CI:0.103~0.817)];[OR:0.534(95%CI:0.280~0.970)] than that of never-breastfed group; Those who were breasted for4to6months had lower risks of overweight than those who were breasted for1to3months [OR:0.372(95%CI:0.129~0.874)]; However, compared with those who were breasted for less6months, those who were breasted for6months or longer had no lower risks of overweight [OR:0.769(95%CI:0.470-1.258)].Conclusions:The breastfeeding during the first3months of life, especially exclusive breastfeeding may reduce the risk of childhood overweight. With the increasing of the duration of breastfeeding, the risk of childhood overweight may decrease. But after postnatal six months, prolonged duration of breastfeeding may not reduce the occurrence of overweight.
Keywords/Search Tags:Gestational diabetes mellitus, large-for-gestational-age infants, fat mass, fat free massgestational diabetic, appropriate-for-gestational-age, infants period, growth patternGestational diabetes mellitus, children, overweight
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