剖宫产分娩对男女童青春期发育影响的队列研究
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摘要
目的探讨在控制青春期发育遗传背景后,剖宫产分娩方式对男女童青春期发育的前瞻性影响,为选择有利于青春期发育正常进程的分娩方式提供参考依据。方法采用整群抽样方法于2016年在安徽省蚌埠市2所小学招募一至三年级学生997名,建立儿童青春期发育队列。采用父母问卷调查收集儿童分娩方式、出生体重、胎龄、早期喂养方式、家庭经济状况和父母文化程度等信息,每年评估儿童身高、体重和青春期发育(女童乳房发育Tanner分期和男童睾丸容积)。基于青春期相关17个单核苷酸多态性(SNP)位点计算青春期发育多基因遗传风险评分(PRS)。采用Kaplan-Meier生存分析探讨剖宫产分娩与男女童青春期发育的关联。结果调查对象基线年龄为(8.01±0.84)岁,体质量指数(BMI)为(17.96±2.96)kg/m~2。男女童剖宫产比例分别为43.30%和32.47%。基线和随访结束,剖宫产女童乳房发育启动检出率(39.89%,95.21%)高于自然分娩组女童(4.39%,68.48%)(χ~2值分别为118.65, 51.42,P值均<0.01)。控制PRS、年龄、BMI、早期喂养方式等因素发现,剖宫产与女童乳房发育启动年龄提前有关(风险比HR=1.98,95%CI=1.67～2.34,P<0.01)。结论剖宫产分娩可能增加女童乳房发育提前风险。需要更多研究证实自然分娩或为儿童青春期发育提前的预防途径之一。
Objective To examine the prospective effect of cesarean section on pubertal development after controlling the polygenic susceptibility for early puberty in boys and girls,and to provide a reference for choosing a delivervary way beneficial to pubertal development. Methods Cluster sampling method was used to select 997 students of grade 1 to 3 from 2 priwary schools in Bengbu of Anhui in 2016 to establish the puberty development cohort. Delivery mode,birth weight,gestational age,early teeding way,family income and parental educational background were derived from parental questionnaire. Breast Tanner stage and testicular volume of 997 children were annually assessed. The polygenic risk score(PRS) was computed based on 17 SNPs derived from published genome-wide association studies for early pubertal timing. Kaplan-Meier analyses was used to examine associations between cesarean section with pubertal development in boys and girls. Results The average age of 997 children was 8.01±0.84 years old, and average BMI was(17.96±2.96) kg/m~2. The prevalence of cesarean section for boys and girls was 43.30% and 32.47%, respectively. At baseline, the detection of thelarche in girls delivered by cesarean section(39.89%) was higher than that of girls delivered naturally(4.39%)(χ~2=118.65, P<0.01). Similar result was observed during the last follow-up, the detection of thelarche in girls born by cesarean section(95.21%) was higher than girls born vaginally(68.48%), respectively(χ~2=51.42, P<0.01). After adjusting for confounding factors(age, BMI, birthweight, infancy feeding, gestational age, household monthly income and parental education), girls delivered by cesarean section had maturation at significantly younger than girls who delivered naturally(Hazard Ratio, HR=1.98,95%CI=1.67-2.34,P<0.01). Conclusion Caesarean section might increase the risk of earlier age at pubertal onset in a sex-specific manner. Whether natural delivery could be one of the protective measures to prevent early pubertal timing in children warrants further investigation.
Objective To examine the prospective effect of cesarean section on pubertal development after controlling the polygenic susceptibility for early puberty in boys and girls,and to provide a reference for choosing a delivervary way beneficial to pubertal development. Methods Cluster sampling method was used to select 997 students of grade 1 to 3 from 2 priwary schools in Bengbu of Anhui in 2016 to establish the puberty development cohort. Delivery mode,birth weight,gestational age,early teeding way,family income and parental educational background were derived from parental questionnaire. Breast Tanner stage and testicular volume of 997 children were annually assessed. The polygenic risk score(PRS) was computed based on 17 SNPs derived from published genome-wide association studies for early pubertal timing. Kaplan-Meier analyses was used to examine associations between cesarean section with pubertal development in boys and girls. Results The average age of 997 children was 8.01±0.84 years old, and average BMI was(17.96±2.96) kg/m~2. The prevalence of cesarean section for boys and girls was 43.30% and 32.47%, respectively. At baseline, the detection of thelarche in girls delivered by cesarean section(39.89%) was higher than that of girls delivered naturally(4.39%)(χ~2=118.65, P<0.01). Similar result was observed during the last follow-up, the detection of thelarche in girls born by cesarean section(95.21%) was higher than girls born vaginally(68.48%), respectively(χ~2=51.42, P<0.01). After adjusting for confounding factors(age, BMI, birthweight, infancy feeding, gestational age, household monthly income and parental education), girls delivered by cesarean section had maturation at significantly younger than girls who delivered naturally(Hazard Ratio, HR=1.98,95%CI=1.67-2.34,P<0.01). Conclusion Caesarean section might increase the risk of earlier age at pubertal onset in a sex-specific manner. Whether natural delivery could be one of the protective measures to prevent early pubertal timing in children warrants further investigation.
引文
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[17] 李翠蓉,胡建群,杨进.不同测量方法对睾丸体积测量的准确性研究[J].实用临床医药杂志,2009,13(15):42-45.
[18] MA H M,CHEN S K,CHEN R M,et al.Pubertal development timing in urban Chinese boys[J].Int J Androl,2011,34(5 Pt 2):e435-445.
[19] BELDA-FERRE P,ALCARAZ L D,CABRERA-RUBIO R,et al.The oral metagenome in health and disease[J].ISME J,2012,6(1):46-56.
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[22] SUN Y,TAO F B,SU P Y,et al.National estimates of the pubertal milestones among urban and rural Chinese girls[J].J Adolesc Health,2012,51(3):279-284.DOI:10.1016/j.jadohealth.2011.12.019.
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[24] GRONLUND M M,LEHTONEN O P,EEROLA E,et al.Fecal microflora in healthy infants born by different methods of delivery:permanent changes in intestinal flora after cesarean delivery[J].J Pediatr Gastroenterol Nutr,1999,28(1):19-25.
[25] LEUNG C Y,LEUNG G M,SCHOOLING C M.Mode of delivery and child and adolescent psychological well-being:evidence from Hong Kong’s "Children of 1997" birth cohort[J].Sci Rep,2017,7(1):15673.
[26] TURNBAUGH P J,LEY R E,MAHOWALD M A,et al.An obesity-associated gut microbiome with increased capacity for energy harvest[J].Nature,2006,444(7122):1027-1131.
[27] AJSLEV T A,ANDERSEN C S,GAMBORG M,et al.Childhood overweight after establishment of the gut microbiota:the role of delivery mode,pre-pregnancy weight and early administration of antibiotics[J].Int J Obes (Lond),2011,35(4):522-529.
[28] KENNEDY H P,KIDANTO H,TAYLOR P,et al.Temmerman M.Short-term and long-term effects of caesarean section on the health of women and children[J].Lancet,2018,392(10155):1349-1357.
[29] SCHULLER C,K?NEL N,MüLLER O,et al.Stress and pain response of neonates after spontaneous birth and vacuum-assisted and cesarean delivery[J].Am J Obstet Gynecol,2012,207(5):416.e1-6.
[30] LI H T,ZHOU Y B,LIU J M.The impact of cesarean section on offspring overweight and obesity:a systematic review and meta-analysis[J].Int J Obes (Lond),2013,37(7):893-899.
[31] MANTZOROS C S,RIFAS-SHIMAN S L,WILLIAMS C J,et al.Cord blood leptin and adiponectin as predictors of adiposity in children at 3 years of age:a prospective cohort study[J].Pediatrics,2009,123(2):682-689.
[2] GAMBLE J.Puberty:early starters[J].Nature,2017,550(7674):S10-S11.
[3] PARENT A S,TEILMANN G,JUUL A,et al.The timing of normal puberty and the age limits of sexual precocity:variations around the world,secular trends,and changes after migration[J].Endocr Rev,2003,24(5):668-693.
[4] BIRO F M,GREENSPAN L C,GALVEZ M P,et al.Onset of breast development in a longitudinal cohort[J].Pediatrics,2013,132(6):1019-1027.
[5] PERRY J R,MURRAY A,DAY F R,et al.Molecular insights into the aetiology of female reproductive ageing[J].Nat Rev Endocrinol,2015,11:725-734.
[6] BETRáN A P,YE J,MOLLER A B,et al.The increasing trend in caesarean section rates:global,regional and national estimates:1990-2014[J].PLoS One,2016,11(2):e0148343.
[7] SAEED K B,GREENE R A,CORCORAN P,et al.Incidence of surgical site infection following caesarean section:a systematic review and meta-analysis protocol[J].BMJ Open,2017,7(1):e013037.
[8] BAGER P,WOHLFAHRT J,WESTERGAARD T.Caesarean delivery and risk of atopy and allergic disease:meta-analyses[J].Clin Exp Allergy,2008,38(4):634-642.
[9] THAVAGNANAM S,FLEMING J,BROMLEY A,et al.A meta-analysis of the association between Caesarean section and childhood asthma[J].Clin Exp Allergy,2008,38(4):629-633.
[10] CARDWELL C R,STENE L C,JONER G,et al.Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus:a meta-analysis of observational studies[J].Diabetologia,2008,51(5):726-735.
[11] CAI M,LOY S L,TAN K H,et al.Association of elective and emergency cesarean delivery with early childhood overweight at 12 months of age[J].JAMA Netw Open,2018,1(7):e185025.
[12] CHEN G,CHIANG W L,SHU B C,et al.Associations of caesarean delivery and the occurrence of neurodevelopmental disorders,asthma or obesity in childhood based on Taiwan birth cohort study[J].BMJ Open,2017,7(9):e017086.
[13] RUTAYISIRE E,WU X,HUANG K,et al.Cesarean section may increase the risk of both overweight and obesity in preschool children[J].BMC Pregnancy Childbirth,2016,16(1):338.
[14] YUAN C,GASKINS A J,BLAINE A I,et al.Association between cesarean birth and risk of obesity in offspring in childhood,adolescence,and early adulthood[J].JAMA Pediatr,2016,170(11):e162385.
[15] WANG Y.Is obesity associated with early sexual maturation?A comparison of the association in American boys versus girls[J].Pediatrics,2002,110(5):903-910.
[16] 李辉,季成叶,宗心南,等.中国0～18岁儿童青少年身高、体重的标准化生长曲线[J].中华儿科杂志,2009,47(7):487-492.
[17] 李翠蓉,胡建群,杨进.不同测量方法对睾丸体积测量的准确性研究[J].实用临床医药杂志,2009,13(15):42-45.
[18] MA H M,CHEN S K,CHEN R M,et al.Pubertal development timing in urban Chinese boys[J].Int J Androl,2011,34(5 Pt 2):e435-445.
[19] BELDA-FERRE P,ALCARAZ L D,CABRERA-RUBIO R,et al.The oral metagenome in health and disease[J].ISME J,2012,6(1):46-56.
[20] ELKS C E,PERRY J R,SULEM P,et al.Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies[J].Nat Genet,2010,42(12):1077-1085.
[21] DAY F R,BULIK-SULLIVAN B,HINDS D A,et al.Shared genetic aetiology of puberty timing between sexes and with health-related outcomes[J].Nat Commun,2015,6:8842.DOI:10.1038/ncomms9842.
[22] SUN Y,TAO F B,SU P Y,et al.National estimates of the pubertal milestones among urban and rural Chinese girls[J].J Adolesc Health,2012,51(3):279-284.DOI:10.1016/j.jadohealth.2011.12.019.
[23] SUN Y,TAO F B,SU P Y.China puberty research collaboration.national estimates of pubertal milestones among urban and rural Chinese boys[J].Ann Hum Biol,2012,39(6):461-467.DOI:10.3109/03014460.2012.712156.
[24] GRONLUND M M,LEHTONEN O P,EEROLA E,et al.Fecal microflora in healthy infants born by different methods of delivery:permanent changes in intestinal flora after cesarean delivery[J].J Pediatr Gastroenterol Nutr,1999,28(1):19-25.
[25] LEUNG C Y,LEUNG G M,SCHOOLING C M.Mode of delivery and child and adolescent psychological well-being:evidence from Hong Kong’s "Children of 1997" birth cohort[J].Sci Rep,2017,7(1):15673.
[26] TURNBAUGH P J,LEY R E,MAHOWALD M A,et al.An obesity-associated gut microbiome with increased capacity for energy harvest[J].Nature,2006,444(7122):1027-1131.
[27] AJSLEV T A,ANDERSEN C S,GAMBORG M,et al.Childhood overweight after establishment of the gut microbiota:the role of delivery mode,pre-pregnancy weight and early administration of antibiotics[J].Int J Obes (Lond),2011,35(4):522-529.
[28] KENNEDY H P,KIDANTO H,TAYLOR P,et al.Temmerman M.Short-term and long-term effects of caesarean section on the health of women and children[J].Lancet,2018,392(10155):1349-1357.
[29] SCHULLER C,K?NEL N,MüLLER O,et al.Stress and pain response of neonates after spontaneous birth and vacuum-assisted and cesarean delivery[J].Am J Obstet Gynecol,2012,207(5):416.e1-6.
[30] LI H T,ZHOU Y B,LIU J M.The impact of cesarean section on offspring overweight and obesity:a systematic review and meta-analysis[J].Int J Obes (Lond),2013,37(7):893-899.
[31] MANTZOROS C S,RIFAS-SHIMAN S L,WILLIAMS C J,et al.Cord blood leptin and adiponectin as predictors of adiposity in children at 3 years of age:a prospective cohort study[J].Pediatrics,2009,123(2):682-689.