| Background:Cardiovascular diseases(CVDs),account for 30%of total deaths worldwide and are the leading cause of global noncommunicable disease premature mortality.Although the majority of CVDs develop clinical symptoms only in adulthood,it is necessary to identify target groups that should receive greater preventive attention at an early age through known cardiovascular risk factors.The recognized risk factors include elevated body mass index,blood pressure,fasting blood glucose,and abnormal cholesterol profiles.Large for gestational age(LGA)that affected 2.3%to 22.1%Asian newborns was generally defined as birthweight above 90th percentile for gestational age.LGA is associated with adverse intrauterine exposures,such as gestational diabetes mellitus,maternal obesity,and excessive weight gain during pregnancy.These adverse intrauterine environmental exposures may have a profound impact on long-term health.Numerous studies have reported that LGA children(LGAs)have an elevated risk of obesity,hypertension,and metabolic disorders.However,conflicting findings show that a high birthweight is not associated with future cardiovascular and metabolic health problems.Objective:To explore whether LGA can increase risk of obesity,glucose and lipid metabolism disorders,and hypertension in the future.To explore whether the effects of LGA on cardiovascular metabolism will disappear with age.Methods:The PubMed,Web of science,and the Cochrane,were searched to identify studies reporting on LGA and interested outcomes included overweight/obesity,body mass index,hypertension,blood pressure,type 1 diabetes,glucose metabolism,dyslipidemia,lipid profiles.Two individuals extracted the data independently.Random effect model was adopted in analysis.A subgroup analysis was performed based on the child’s BMI status,age,and maternal GDM.Newcastlee Ottawa Scale and funnel graph was used to assess the quality and publication bias respectively.Results:Overall 42 studies and 841325 individuals were included.Compared with infants born appropriate for gestational age(AGA),infants born LGA shown a higher risk of overweight/obesity(OR=1.66 95%CI:1.47-1.87),type 1 diabetes(OR=1.28 95%CI:1.151.43),hypertension(OR=1.28 95%CI:1.00-1.64),and metabolic syndrome(OR 1.63 95%CI 1.06-2.51).There was no significant difference in hypertriglyceridemia and hypercholesterolemia.Stratified analyses shown that infants born LGA had higher risk of overweight/obesity from toddler’s age to puberty(toddler’s age,OR 2.12 95%CI 1.22-3.70;preschool,OR 1.81 95%CI 1.55-2.12;school age,OR 1.53 95%CI 1.09-2.14;puberty,OR 1.4095%CI 1.11-1.77)than infants born AGA.Conclusions:The LGAs suffered from risks of obesity and metabolic disturbances in the future life.The elevated risks of obesity appeared as early as in infancy in the LG A children,and remained consistently high to their puberty.Further research should focus on elucidating the potential mechanism and finding intervening factors.Background:Worldwide,over 8 million children had been conceived after assisted reproductive technology(ART).Assisted reproductive technology,infertility causes,pregnancy complications,such as frozen embryo transfer,parental obesity,and gestational diabetes all will increase the incidence rate of LGA.To the best of our knowledge,no study has investigated the effect of LGA on cardiovascular health in the children conceived from ART.Our previous meta-analyses have several limitations.First,although there was a correlation between BMI status and glucose metabolism or BP,the mediating effect of BMI could not be explored based on the current data.Second,although significant efforts were made to adjust the influence of family history,only the disease history of the mother was obtained.Besides,the influence of the disease history of father and other family members cannot be completely ignored.Third,there was heterogeneity and publication bias in our meta-analysis.The results of those subgroups analyses should be explained with more caution.Fourth,the division of developmental stages was based on the average age,which potentially resulted in wrong categories.Objective:To explored whether LGA conceived from ART is associated with long-term cardiovascular metabolic risks.And explore whether the cardiovascular metabolic risk of LGA children will disappear with age.To further explore whether BMI plays a mediating role between LGA and other cardiovascular metabolic risks.Methods:This was a bidirectional cohort study that recruited children whose parents had received ART treatment in the Center for Reproductive Medicine,Shandong Provincial Hospital,affiliated to Shandong University.The information of parents and newborns(birth weight,gestational age,etc.)were collected.The children’s height,weight,systolic and diastolic blood pressure were measured,and their metabolic glucose metabolism and lipid metabolism were detected.Linear mixed model was used to compared the main outcomes.Subgroup analysis on children’s age was performed.The mediation model was used to evaluate the intermediary effect of BMI.Results:3626(29.5%)children born LGA and 8478(70.5%)children born appropriate for gestational age(AGA)were included in the study.The offspring ranged from 0.4 to 9.9 years.After adjusting for all covariates,term LGAs conceived through ART had body mass index(BMI)and BMI z-scores that were 0.47 kg/m2 and 0.33 units greater than those of AGAs,respectively.The effect of LGA on BMI was identified as early as infancy and remained consistently significant throughout to pre-puberty.The LGAs conceived through ART were shown to have higher BP,FBG,FIN,and HOMA-IR values even after controlling for all covariates.Moreover,the higher FIN and HOMA-IR values in the LGAs could be explained completely by increased BMI,whereas for BP and FBG,the indirect effect of BMI only accounted for one-sixth to two-thirds of the effect.Conclusions:Compared to AGA,term LGA children conceived from ART were associated with an increased cardiovascular-metabolic risks,which appeared as early as infancy and with no recovery by pre-puberty. |
