Associations Of Preconception Fasting Plasma Glucose And Hemoglobin Concentration With Adverse Pregnancy Outcomes Among Reproductive-aged Women

BackgroundAdverse pregnancy outcomes(APO)are defined as any pathological pregnancy or intrapartum complications except for normal livebirths,which seriously affect the health of the population and restrict social and economic development.It is very important to explore the risk factors,do early screening and identify high-risk populations in the fields of perinatal medicine and public health.With the aging of the population,urbanization,and related dramatic changes toward sedentary lifestyle during the past few decades,the prevalence of overnutrition has been growing rapidly.Meanwhile,there still exist malnutrition problems in some poor rural areas.Diabetes mellitus(DM)and anemia have become the major burden affecting reproductive-aged women.Many studies have explored the associations between gestational diabetes mellitus and adverse pregnancy outcomes.However,studies seldom focus precisely on the adverse effects of maternal fasting plasma glucose(FPG)level prior to pregnancy on pregnancy outcomes,especially for early embryonic development,from a large sample.In addition,previous studies have reported conflicting results about the association between maternal anemia during pregnancy and pregnancy outcomes.Evidence on the association between maternal hemoglobin(Hb)level before pregnancy and adverse pregnancy outcomes is still limited.This thesis will focus on two nutrition-related blood indicators,preconception FPG level and Hb level,among reproductive-aged women,and aims to explore the association of preconception hyperglycemia,as well as anemia and high Hb level with adverse pregnancy outcomes,and to explore the combine their effects on outcomes.MethodsWe conducted a population-based retrospective cohort study among women aged 20～49 years,who participated in National Free Pre-Pregnancy Checkups Project from 2907 counties in 31 provinces between 2010 and 2016 and completed pregnancy outcomes follow-up before December 31,2016.The outcomes in the current study included:(1)each adverse pregnancy outcomes:,spontaneous abortion(SA),preterm birth(PTB),macrosomia,small for gestational age infant(SGA),birth defect,and perinatal infant death;(2)APO,defined as any of the above adverse pregnancy outcomes;(3)MAPO(Multiple adverse pregnancy outcomes),defined as two or more kinds of adverse pregnancy outcomes.A total of 6,447,339 women were included to evaluate the associations between preconception FPG level and the outcomes.Women were classified into three groups(normal FPG group:FPG<5.6 mmol/L and no self-reported history of DM;impaired fasting glucose[IFG]:FPG 5.6～6.9 mmol/L and no self-reported history of DM;and DM:FPG≥ 7.0 mmol/L or self-reported history of DM).Women with self-reported history of DM were defined as awareness group,the other women in DM group were defined as non-awareness group.Among women with self-reported history of DM,women whose FPG level<7.0 mmol/L were considered as controlled group,others were non-controlled group.Logistic regression model was used to calculate odds ratio(OR)and 95%confidence interval(CI)after adjusting for confounding variables.Women without self-reported history of DM were grouped according to FPG in 1 mmol/L categories from<5.0 to>10.0 mmol/L,the multivariable-adjusted ORs(95%CIs)were estimated by logistic regression models and then we tested the significance of the linear trend of ORs in the regression model.Meanwhile,restricted cubic splines(RCS)function was also used to explore the exposure-response relationships.A total of 4,510,670 women were included to evaluate the associations between preconception Hb level and the outcomes.Hb concentrations of women who lived in areas over 1000 meters were adjusted by subtracting the adjustment values at the relevant altitude range from the measured Hb concentrations,which was suggested by the World Health Organization.Women were successively classified into 3 groups(anemia:<110 g/L;normal Hb concentration:110～149 g/L;and high Hb concentration:≥ 150 g/L),as well as 7 groups(severe anemia:<70 g/L;moderate anemia:70～99 g/L;mild anemia:100～109 g/L;normal Hb concentration:110～149 g/L;mild high Hb concentration:150～159 g/L;moderate high Hb concentration:160～169 g/L;and severe high Hb concentration:≥170 g/L),based on the criteria for diagnosing anemia and the severity of the disease.Logistic model was used to estimate OR and 95%CI.RCS models were applied to evaluate the dose-response relationships.A total of 4,456,699 women were included to evaluate the combined associations of preconception FPG and Hb level with the outcomes.Women were classified into eight groups(2*4)according to hyperglycemia or not and different levels of Hb(severe anemia,mild to moderate anemia,normal Hb ad high Hb).Logistic regression model was used to calculate OR and 95%CI,with normal FPG and normal Hb group as the reference group.Results1.The prevalence of IFG and DM was 13.15%(847,737)and 1.18%(76,297),respectively.Only 917(1.20%)women awareness of their DM status,of whom 62.16%(570)had FPG level controlled.A total of 15.60%(1,005,568)women had adverse pregnancy outcomes.The cumulative incidence for each of the adverse pregnancy outcomes were as follows:SA(2.87%),PTB(7.79%),macrosomia(5.16%),SGA(0.32%),birth defect(0.05%),perinatal infant death(0.34%)and MAPO(0.67%).Compared with women with normal FPG,women with IFG and DM had significantly higher risks of SA(OR,1.07,95%CI:1.06-1.09;OR,1.11,95%CI:1.06-1.15),PTB(OR,1.01,95%CI:1.00-1.02;OR,1.15,95%CI:1.12-1.18),macrosomia(OR,1.07,95%CI:1.06-1.08;OR,1.17,95%CI:1.13-1.21),SGA(OR,1.06,95%CI:1.02-1.11;OR,1.15,95%CI:1.02-1.30)and perinatal infant death(OR,1.08,95%CI:1.04-1.12;OR,1.59,95%CI:1.44-1.76).Women with DM also had significantly higher risk of birth defect(OR 1.54;95%CI,1.20-1.99).Compared with women with normal FPG,the multivariable ORs of APO were 1.07(95%CI:1.06-1.07)for women with IFG and 1.21(95%CI:1.19-1.23)for women with DM.The corresponding ORs of MAPO were 1.08(95%CI:1.04-1.11)and 1.42(95%CI:1.31-1.54),respectively.The risk of APO increased 54%(OR,1.54,95%CI:1.33-1.78)among women in awareness group when compared with women in non-awareness group.The rates of PTB,macrosomia,perinatal infant death,APO,and MAPO were significantly lower for women with controlled DM when compared with women who were not controlled,the corresponding ORs were 0.36(95%CI:0.24-0.54),0.52(95%CI:0.32-0.84),0.04(95%CI:0.01-0.24),0.48(95%CI:0.36-0.65)and 0.07(95%CI:0.02-0.27),respectively.Among women without self-reported history of DM,there was a positive linear association between FPG levels and SA,PTB,macrosomia,and perinatal infant death,APO,and MAPO(P for linear trend<0.05).When FPG concentration was used as a continuous variable,RCS showed similar results,except for PTB,and U-shaped relationship between preconception FPG and PTB was identified(P for nonlinear<0.05).2.Overall,7.78%(351,011)women were anemic and 4.54%(204,986)had high Hb concentration.Compared with women in the normal group,women with severe anemia had higher risk of SA,PTB and APO,the ORs were 1.67(95%CI:1.41-1.99),1.19(95%CI:1.04-1.36)and 1.24(95%CI:1.12-1.36),respectively;women with anemia had lower risk of macrosomia(OR,0.93,95%CI:0.92-0.95),higher risk of SGA(OR,I.08,95%CI:1.01-1.15),and perinatal infant death(OR,1.06,95%CI:1.00-1.12).Women with high Hb concentration had higher risk of SA,PTB,macrosomia,perinatal infant death,APO,and MAPO,the corresponding ORs were 1.16(95%CI:1.13-1.19),1.12(95%CI:1.10-1.14),1.12(95%CI:1.10-1.14),1.23(95%CI:1.14-1.32),1.12(95%CI:1.11-1.14)and 1.27(95%CI:1.20-1.34);severe high Hb level was associated with increased risk of birth defect(OR,1.81,95%CI:1.12-2.92).Approximate U-shaped curves for the risk of SA,PTB,perinatal infant death,and APO with preconception Hb concentrations were observed.3.Compared with the reference group,the risk of SA and PTB increased 104%(OR,2.04,95%CI:1.38-3.01)and 38%(OR,1.38,95%CI:1.02-1.99)for women with hyperglycemia and severe anemia,respectively,the risk of macrosomia increased 25%(OR,1.25,95%CI:1.19-1.31)for women with hyperglycemia and high Hb level.ConclusionsOur study found that both preconception IFG and DM were associated with increased risk of adverse pregnancy outcomes,including SA,PTB,macrosomia,SGA,and perinatal infant death,DM was associated with increased risk of birth defect.Diabetes women with controlled FPG level before pregnancy had lower risk of adverse pregnancy outcomes.And we found that severe anemia and high Hb level before pregnancy were associated with increased risk of adverse pregnancy outcomes.Preconception Hb concentrations were associated with risk of SA,PTB,perinatal infant death,and APO in approximate U-shaped manners.FPG and Hb levels had a joint effect on adverse pregnancy outcomes.It is very necessary to strengthen the hyperglycemia screening and Hb concentration screening for reproductive-aged women who are planning to conceive.It is one of the most important aspects of preconception care that early monitoring the risk for adverse pregnancy outcomes and providing appropriate medical intervention,to improve maternal and child health.