| ObjectiveBased on a large sample of Maternal and Infant Health cohort study in Hefei（MIH-Hefei）,this study explored the associations among the diagnosis time of gestational diabetes mellitus（GDM）with fetal intrauterine growth,neonatal birth morphology and changes in the growth trajectory of infant BMI.Besides,further clarified the role of excessive weight gain in early pregnancy and maternal inflammation in these associations.MethodsFrom March 2015 to December 2020,a total of 8,991 pregnant women were recruited from three hospitals in Hefei for regular prenatal check-ups.They were followed up from the middle trimester to 48 months after the birth of their offspring.Pregnant women’s general characteristics（sociodemographic characteristics,perinatal health status and behavioral lifestyle during pregnancy）and fetal two-time ultrasound data（biparietal diameter,abdominal circumference,femur length and gestational weeks）were collected during pregnancy.Birth outcome information（gender,birth weight,delivery mode and date of gestational weeks）was obtained from follow-up until birth,and related information such as height,weight,gender and physical examination date of offspring was obtained from follow-up until 48 months after birth.All subjects were tested for OGTT at 24-28 weeks of gestation,and the test results and gestational weeks were recorded.Fasting venous blood of pregnant women during the second trimester of pregnancy was collected,and 3085 samples were randomly selected for hs CRP level detection.According to the previous literature,GDM diagnosis time could used as an alternative indicator of hyperglycemia exposure.The subjects were divided into three groups:non-GDM,GDM diagnosis<26 weeks and GDM diagnosis≥26 weeks.The main observation indexes included GDM diagnosis time,pre-pregnancy weight gain and hs CRP level.The main outcome indicators include fetal ultrasound measurement indicators（biparietal diameter,abdominal circumference and femoral length）,neonatal birth morphology indicators（body length,body weight and head circumference）and related indicators of infant BMI（peak value,peak age and prepeak average velocity）.Physical parameters of both fetuses and newborns are adjusted by gestational age and sex to obtain standardized Z scores and percentiles,and overgrowth is defined as over P90.Multivariate linear regression model was used to analyze the association of GDM diagnosis time,pre-pregnancy weight gain and hs CRP with neonatal birth morphology and BMI.Multivariate Logistic regression model was used to analyze the association of GDM diagnosis time,excessive pre-pregnancy weight gain and high hs CRP with neonatal physical overgrowth.The linear mixed model was used to analyze the correlation between GDM diagnosis time,pre-pregnancy weekly weight gain,hs CRP and Z score of fetal ultrasound data.Generalized estimation equation was used to analyze the relationship between GDM diagnosis time,excessive pre-pregnancy weight gain and high hs CRP and intrauterine growth.All models have adjusted the corresponding mixed factors.ResultsIn this study,7609 pregnant women with complete information were finally included,with an average age of（29.10±4.32）years old.The average BMI before pregnancy was（21.57±2.94）kg/m2,and the incidence of GDM was 19.69%.Among them,951 people were diagnosed as GDM before 26 weeks of pregnancy,and the incidence was 12.5%.After 26 weeks of pregnancy,547 people were diagnosed as GDM,and the incidence was 7.2%.The average birth weight of newborns was（3408.67±455.34）g,and the average gestational week of delivery was（33.37±1.33）weeks.The average peak BMI of infants was（18.46±1.53）kg/m~2,the average age of reaching the peak BMI was（7.03±1.03）months,and the average speed before the peak BMI was（0.73±0.34）kg/m~2/month.The infants with GDM diagnosis<26 weeks had higher BMI peak,smaller age at BMI peak,and higher pre-peak average velocity of BMI,and the difference was statistically significant.Pregnant women diagnosed with GDM before 26 weeks of gestation have an increased risk of overgrowth of their offspring.After adjusting the corresponding confounding factors,it was found that compared with non-GDM,the Z score of fetal abdominal circumference（β=0.25,95%CI:0.18,0.33）,neonatal length（β=0.09,95%CI:0.01,0.18）and body weight（β=0.10,95%CI:0.01,0.18）of pregnant women diagnosed with GDM before 26 weeks of pregnancy increased,and the peak BMI（β=0.16,95%CI:0.03,0.28）and pre-peak average speed（β=0.16,95%CI:0.01,0.07）of infants increased.It was associated with lower peak age of BMI（β=-0.16,95%CI:-0.31,-0.01）.Pregnant women diagnosed with GDM before 26 weeks of gestation had increased risks of fetal abdominal circumference（OR=1.19,95%CI:1.04,1.36）,neonatal head circumference（OR=1.32,95%CI:1.01,1.73）overgrowth and LGA（OR=1.51,95%CI:1.19,1.91）.The level of hs CRP（0.53±0.43 vs 0.44±0.38）in pregnant women diagnosed with GDM<26 weeks was significantly higher than that in pregnant women diagnosed with GDM≥26 weeks.With the increase of hs CRP level,neonatal head circumference（β=0.18,95%CI:0.08,0.27）and birth weight（β=0.23,95%CI:0.10,0.36）.According to the stratification of hs CRP level,when hs CRP>P75,compared with non-GDM,the fetal double parietal diameter（OR=2.41,95%CI:1.33,4.34）and abdominal circumference（OR=1.58,95%CI:1.13,2.20）and femur length（OR=1.79,95%CI:1.30,2.48）,neonatal head circumference（OR=3.82,95%CI:2.20,6.66）and LGA（OR=3.32,95%CI:2.08,5.67）were also significantly increased.Early pregnancy weekly weight gain（0.33±0.18 vs 0.30±0.14）with GDM diagnosis<26 weeks was higher than that with GDM diagnosis≥26 weeks.Compared with normal weight gain,fetal biparietal diameter（OR=1.30,95%CI:1.03,1.65）,abdominal circumference（OR=1.35,95%CI:1.20,1.52）and femur length（OR=1.24,95%CI:1.10,1.40）increased the risk of overgrowth,neonatal length（OR=1.50,95%CI:1.30,1.75）,head circumference（OR=1.51,95%CI:1.26,1.81）and LGA（OR=2.16,95%CI:1.85,2.51）.When grouping early pregnancy excessive weight gain and diagnosis time of GDM,non-GDM was used as the control group,and the biparietal diameter（OR=2.02,95%CI:1.13,3.63）and abdominal circumference（OR=1.48,95%CI:1.06,2.09）and femur length（OR=1.32,95%CI:1.02,1.70）significantly increased the risk of overgrowth,and neonatal body length（OR=1.49,95%CI:1.07,2.09）and head circumference（OR=1.63,95%CI:1.09,2.44）increased the risk of overgrowth and LGA（OR=2.92,95%CI:2.13,4.01）;Infant peak BMI（β=0.77,95%CI:0.53,1.02）and mean prepeak velocity（β=0.11,95%CI:0.05,0.16）increased,while peak BMI age（β=-0.31,95%CI:-0.60,-0.02）decreased.ConclusionsThe diagnosis of GDM before 26 weeks of gestation was associated with fetal and neonatal overgrowth,increased peak and prepeak mean velocity of BMI in infants,and earlier peak age.Since a part of GDM diagnosed after 26 weeks of gestation must have occurred before 26 weeks of gestation,but GDM diagnosed before 26 weeks of gestation still has a significant impact on the growth and development of offspring,indicating that the current analysis has underestimated the harm of early onset of GDM.The combined effect of GDM diagnosis before 26 weeks of pregnancy and excessive weight gain in prepregnancy has a greater effect on the overgrowth of the offspring at all stages.Excessive weight gain in prepregnancy may not only be an identifiable risk factor for early GDM,but also have a superimposed effect with early GDM on the growth and development of the offspring.Hs CRP is a possible mechanism for the occurrence of the above association,and the increase of maternal inflammation may mediate the association between early onset of GDM and excessive weight gain in prepregnancy and overgrowth of offspring.Current studies may underestimate the risk of early onset of GDM,because some of GDM diagnosed after 26 weeks of gestation may have occurred before 26 weeks of gestation,but this study still found that GDM diagnosed before 26 weeks of gestation has a significant impact on the growth and development of offspring. |
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