Patterns Of Gestational Weight Gain In Association With Birth Outcomes And Infant Growth And The Mediating Effect Of Serum Lipids

Gestational weight gain(GWG)includes the weight gain in mammary glands,blood volume,maternal adipose tissue,uterus,placenta,amniotic fluid,and fetus,etc.during pregnancy,which is an important indicator of nutrition during pregnancy.Total GWG is defined as the difference between prenatal weight and pre-pregnancy weight,and adequate total GWG is associated with optimal pregnancy outcomes.The GWG patterns reflect the changing characteristics of GWG rate at different trimesters of pregnancy,and are associated with birth outcomes and infant growth.In addition,birth outcomes are also influenced by genetic factors,and exploring the association between GWG patterns and birth outcomes under different genetic predispositions will help to develop individualized weight management plans for pregnant women.Overweight and obesity are closely related to elevated lipids,and physiologic lipid elevation during pregnancy is beneficial to meet the nutritional needs of the fetus.The associations of GWG patterns with serum lipids remain unclear.Exploring the association between GWG patterns and serum lipids during pregnancy,and investigating the mediating effect of serum lipids in the association between GWG patterns and birth outcomes and infant growth,will help to elucidate the mechanism of GWG patterns influencing the physical development of offspring.Objectives(1)To evaluate the associations of total GWG and GWG patterns with birth outcomes and infant growth;(2)To explore the modification of genetic predisposition on the associations of total GWG and GWG patterns with birth outcomes;(3)To investigate the associations of total GWG and GWG patterns with serum lipids,and to investigate their mediating effects in the association with birth outcomes and infant growth.MethodsPregnant women were from the Tongji Maternal and Child Health Cohort(TMCHC)and the Chinese Maternal Nutrition and Health Science Survey.(1)At enrollment,pregnant women’s basic characteristics were obtained by questionnaire,their current weight and height were measured,and body mass index(BMI)was calculated.Maternal weight was measured at each antenatal visit.Total GWG was calculated and GWG patterns was identified by using the latent growth mixture model(LGMM).(2)Blood samples were collected,white blood cells were isolated,genomic deoxyribonucleic acid(DNA)was extracted,and genotyping was performed using a genome-wide ASA beadchip.Unweighted-genetic score(uGS)was constructed according to the results of a Europe population.(3)The triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were tested.(4)Information on infant sex,birth weight and length was recoded,and small-forgestational-age(SGA)and large-for-gestational-age(LGA)were defined.(5)At 3,6,12,and 24 months postpartum,information on infant weight and length was obtained.Infant weight was transformed into z-score(weight-for-age z-score,WAZ),and infant rapid weight gain was defined as the change in WAZ more than 0.67.(6)Robust Poisson regression analysis,multinomial Logistic regression analysis,and mediation effect analysis were applied,by using STATA or R software.Results1.Among the 4477 pregnant women,3.2%,33.9%,and 62.9%had inadequate,adequate,and excessive total GWG,respectively,according to the Chinese standard WS/T801-2022.Three GWG patterns were identified by LGMM,as GWG pattern 1(rapid GWG earlier in pregnancy,16.3%),GWG pattern 2(uniform GWG through pregnancy,59.6%),and GWG pattern 3(rapid GWG later in pregnancy,24.1%).Compared with adequate total GWG,the RR(95%CI)of SGA among women with inadequate total GWG was 1.89(1.36,2.65),and the RR(95%CI)of LGA among women with excessive total GWG was 1.77(1.46,2.14).Compared with GWG pattern 2,the RR(95%CI)of LGA among women with GWG pattern 1 was 1.32(1.09,1.60),and the RR(95%CI)of SGA among women with GWG pattern 3 was 1.40(1.13,1.75).Among women with adequate total GWG,the RR(95%CI)of LGA in GWG pattern 1 was 1.73(1.16,2.60),and the RR(95%CI)of SGAin GWG pattern 3 was 1.44(1.03,2.00).Based on the results,the reference curve of GWG for pregnant women was proposed,a validation study was conducted among pregnant women with adequate total GWG from the Chinese Maternal Nutrition and Health Science Survey,and similar results were found.Compared with GWG pattern 2,the RR(95%CI)of LGA among women with GWG pattern 1 was 1.35(0.92,1.97),and the RR(95%CI)of SGA among women with GWG pattern 3 was 1.57(1.01,2.42).2.Compared with GWG pattern 2,the RR(95%CI)of infant rapid weight gain between 12-24 months among women with GWG pattern 3 was 1.68(1.18,2.39).Among women with adequate total GWG,the RR(95%CI)of infant rapid weight gain between 12-24 months in GWG pattern 3 was 1.99(1.06,3.73).3.89 single nucleotide polymorphisms(SNP)were selected,and the mean of the uGS was 81.9 ± 5.3.The distribution of uGS was approximately normally,and pregnant women were divided according to the median of uGS.Among pregnant women with high uGS group,the RR(95%CI)of LGA in GWG pattern 1 was 1.65(1.15,2.38);among women with low uGS group,the RR(95%CI)of LGA in GWG pattern 1 was 1.06(0.72,1.58).No interactions between uGS and the GWG patterns were observed.4.With the P25-P75 of each lipid item as the normal ranges,at least one item below the normal range and none above the normal range was defined as low lipid levels,and at least one item above the normal range and none below the normal range was high lipid levels.28.6%(562)and 29.9%(575)of pregnant women were in the low and high lipid levels,respectively.Compared with GWG pattern 2,the OR(95%CI)was 1.19(0.78,1.81)for low lipid levels and 1.29(0.86,1.93)for high lipid levels among women with GWG pattern 1,and 1.67(1.14,2.46)and 0.96(0.65,1.44)among women with GWG pattern 3,respectively.Moreover,among women with adequate total GWG,the OR(95%CI)of low lipid levels was 2.77(1.15,6.66)in GWG pattern 3.In addition,low lipid levels mediated the association between GWG pattern 3 and the risk of SGA(0.103,95%CI 0.008,0.240),by 30.9%.ConclusionsAmong women with adequate total GWG,the GWG pattern characterized by rapid GWG earlier in pregnancy was associated with an increased risk of LGA;the GWG pattern characterized by rapid GWG later in pregnancy was associated with higher risks of SGA and infant rapid weight gain between 12-24 months.The association of GWG pattern characterized by rapid GWG earlier in pregnancy with the risk of LGA was more pronounced in women with high uGS.Prenatal low lipid levels mediated the association of GWG pattern characterized by rapid GWG later in pregnancy with the risk of SGA.Having adequate total GWG and uniform GWG through pregnancy is beneficial to birth outcomes and infant physical development.Pregnant women should maintain a uniform GWG pattern and have adequate total GWG.