| Objective Energy consumption quadruples in pregnancy to support fetal growth,and triglyceride(TG)metabolism plays an important role in supporting these increased energy requirements.Excess TG exposure during early or late pregnancy increases risks of adverse perinatal outcomes.However,it remains unclear whether persistently high maternal TG(mTG)during gestation will further increase the risks of adverse pregnancy outcomes.Furthermore,what is the relationship between pre-pregnancy obesity and maternal lipids during pregnancy?In order to answer the above questions,we designed this population-based retrospective cohort study to explore the associations between pre-pregnancy BMI,maternal triglyceride and adverse pregnancy outcomes.The main objectives were as followings1.To explore whether persistently high triglyceride levels from early to late pregnancy further increase the risks of adverse pregnancy outcomes2.To explore high mTG in which trimester could be the crucial risk factor that associated with adverse pregnancy outcomes3.To explore the associations between pre-pregnancy BMI and maternal triglyceride levels during early and late pregnancy;4.To explore the undelined possible pathogenesis mechanisms of fat metabolites,inflammatory factors,and possible hormone levels that may played roles in adverse pregnancy outcomes.Methods This population based retrospective cohort study was conducted in an university-based maternity center.All women who had a singleton birth and who had undergone routine serum lipid screenings in both early and late pregnancy during May,2018 and July,2019 were included in this study.Serum mTG levels were defined as "high"(>90th percentile)or "low"(≤ 90th percentile)during the first(9-13 weeks)trimester.In late pregnancy,due to the progressive increase in mTG levels during gestation(28-42 weeks),we defined mTG values above the 90th percentile of this study population every 2 gestational weeks as "high";otherwise,they were defined as "low"(just a definition,not an indication of low standard).The high-to-high group included women with high mTG levels(>90th percentile)during both early and late pregnancy.The low-to-low group included women with low mTG levels(≤90th percentile)during both early and late pregnancy.Risks of preterm delivery,preeclampsia,gestational diabetes mellitus(GDM),placental abruption,intrahepatic cholestasis of pregnancy(ICP),and having a large for gestational age(LGA)/a small for gestational(SGA)newborn were estimated.To evaluate the associations between different mTG groups and pregnancy outcomes,multiple logistic regressions were performed.Multivariable logistic models were used to estimate the probability of adverse outcomes as a function of mTG level and the associations between changes in mTG from early to late pregnancy and the risks of specific pregnancy outcomes.To investigate the combined effects of high mTG levels in both early and late pregnancy,all women were divided into the following 4 groups based on mTG concentration changes from early to late pregnancy:the low-to-low,high-to-low,low-to-high,and high-to-high groups.With the low-to-low group as a reference,risk values for the other 3 groups were evaluated by means of statistical methods.We further compared women in 2 subgroups,including a persistently high mTG group(i.e.,high levels in both the 1st and 3rd trimesters)and a nonpersistently high m TG group(i.e.,high levels in only the 1st or 3rd trimester).With the nonpersistently high mTG group as a reference,risk values for the persistently high mTG group were evaluated by means of statistical methods.Furthermore,with the high-to-low group as the reference,risks values for the persistently high mTG group were evaluated by means of statistical methodsThe AOR(95%CI)was adjusted for maternal age,prepregnancy BMI,years of education,parity,birthplace,and timing of the blood draw in early pregnancy.Further adjusted factor was maternal weight gain during gestation.Further sensitivity analysis was performed after excluding advanced age(≥40 years)and multiple-parity(≥3 times)Levels of inflammatory factors,fatty acids and hormones of maternal blood and cord blood among high mTG group and control were measured to explore the possible pathogenesis mechanisms of adverse pregnancy outcomesResults After exclusions,the final study population comprised 12,715 women with both early and late pregnancy lipid screenings.Elevated mTG levels during early pregnancy were associated with increased risks of preterm delivery(AOR,1.52;95%CI,1.21 to 1.90),preeclampsia(1.75;1.29 to 2.36),gestational diabetes mellitus(1.95;1.69 to 2.25),and LGA(1.28;1.12 to 1.46).The high-to-high group was associated with increased risks of preeclampsia(AOR,2.53;95%CI,1.66 to 3.84),GDM(AOR,1.97;95%CI,1.57 to 2.47),and LGA(AOR,1.68;95%CI,1.37,2.07)when the low-to-low group was used as the reference,and the effect values were higher than those for women with high mTG levels only in early pregnancy[preeclampsia(AOR,1.46;95%CI,0.99 to 2.16)and GDM(AOR,1.94;95%CI,1.64 to 2.31)]and those for women with high mTG levels only in late pregnancy[preeclampsia(AOR,1.56;95%CI,1.06 to 2.30)and GDM(AOR,1.01;95%CI,0.82 to 1.25)].Compared with those with nonpersistently high mTG levels(i.e.,high levels during the 1St or 3rd trimester),women with persistently high mTG levels during both early and late pregnancy had increased risks of preeclampsia(AOR 1.72;95%CI,1.08 to 2.75)and GDM(AOR,1.33;95%CI,1.03 to 1.71)after adjustments for weight gain.Compared with high mTG levels in early pregnancy alone,persistently high mTG levels from early to late pregnancy only slightly increased the risks of LGA(AOR,1.34;95%CI,1.01 to 1.77).The NW(normal weight)group was defined as reference.The OWO group showed an increased risk for high mTG levels during early pregnancy(AOR,2.64;95%CI,2.26 to 3.08),but not in late pregnancy(1.12;0.93 to 1.35).The LW(low weight)group showed decreased risks for high mTG levels during both early(0.32;0.24 to 0.42)and late pregnancy(0.67;0.55 to 0.83).Compared with the non-preterm group,we conducted NEFA(P<0.0001),TNFα(P=0.1619),IL-1β(P=0.3104),IL-2(P=0.6069),IL-4(P=0.2514)),IL-6(P=0.0377),IL-8(P=0.4918),and IL-10(P=0.1913).Among them,significant statistical difference(P<0.05)was found in NEFA and IL-6.Conclusions1.Persistently high mTG levels from early to late pregnancy increased the risks of preeclampsia,GDM,and LGA,compared with always low mTG levels.2.Compared with high mTG in the first or third trimester alone,persistently high maternal triglyceride levels throughout pregnancy increase the risks of preeclampsia and GDM.3.Persistently high mTG levels only slightly increased risks of LGA when compared with high mTG levels during the first trimester alone.4.Elevated mTG levels during early pregnancy not in late pregnancy could be the crucial risk factor associated with adverse pregnancy outcomes.5.These findings suggest the importance of lipid screenings and preventions during early pregnancy,and lowering pre-pregnancy obesity,which may help to reduce adverse pregnancy outcomes. |
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