Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada.
JAMA Pediatr. 2018 Apr 1;172(4):368-377. doi: 10.1001/jamapediatrics.2017.5535.
Maternal overweight, which often results in cesarean delivery, is a strong risk factor for child overweight. Little is known about the joint contribution of birth mode and microbiota in the infant gut to the association between maternal prepregnancy overweight and child overweight.
To investigate the association of birth mode with microbiota in the infant gut, and whether this mediates the association between maternal and child overweight.
DESIGN, SETTING, AND PARTICIPANTS: An observational study was conducted of 935 full-term infants born between January 1, 2009, and December 31, 2012, in the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Maternal prepregnancy body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared using height and weight data taken from medical records or maternal report. Infant gut microbiota were profiled with 16S ribosomal RNA sequencing in fecal samples collected at a mean (SD) age of 3.7 (1.0) months. At ages 1 and 3 years, BMI z scores adjusted for age and sex were generated according to World Health Organization criteria. Statistical analysis was conducted from January 29 to June 15, 2017.
Mothers of normal weight (BMI, 18.5-24.9) and overweight or obese (BMI, ≥25.0) mothers.
Risk of overweight and obesity (>97th percentile BMI z scores) among children at ages 1 and 3 years.
Of the 935 mother-infant pairs in the study (mean [SD] age, 32.5 [4.5] years) 382 (40.9%) were overweight, 69 of 926 infants (7.5%) were overweight at age 1 year, and 90 of 866 infants (10.4%) were overweight at age 3 years. Compared with being born vaginally to a mother of normal weight, infants born vaginally to overweight or obese mothers were 3 times more likely to become overweight at age 1 year (adjusted odds ratio [OR], 3.33; 95% CI, 1.49-7.41), while cesarean-delivered infants of overweight mothers had a 5-fold risk of overweight at age 1 year (adjusted OR, 5.02; 95% CI, 2.04-12.38). Similar risks were also observed at age 3 years. Multiple mediator path modeling revealed that birth mode and infant gut microbiota (Firmicutes species richness, especially of the Lachnospiraceae family) sequentially mediated the association between maternal prepregnancy overweight and childhood overweight at ages 1 and 3 years. Bacterial genera belonging to the Lachnospiraceae family were more abundant in infants of overweight mothers; however, the participating genera of Lachnospiraceae differed between infants delivered vaginally and those delivered via cesarean birth.
This study found evidence of a novel sequential mediator pathway involving birth mode and Firmicutes species richness (especially higher abundance of Lachnospiraceae) for the intergenerational transmission of overweight.
母亲超重通常会导致剖腹产，这是儿童超重的一个强烈危险因素。关于出生方式和婴儿肠道微生物群在母子超重关联中的共同作用，知之甚少。
研究出生方式与婴儿肠道微生物群的关系，以及这种关系是否可以介导母亲和儿童超重之间的关联。
设计、地点和参与者：对 2009 年 1 月 1 日至 2012 年 12 月 31 日期间在加拿大健康婴儿纵向发展（CHILD）出生队列中出生的 935 名足月婴儿进行了一项观察性研究。母亲怀孕前的体重指数（BMI）是通过记录或母亲报告的身高和体重数据，用体重（kg）除以身高（m）的平方计算得出的。在平均（SD）年龄为 3.7（1.0）个月时，使用 16S 核糖体 RNA 测序对粪便样本进行了肠道微生物组分析。根据世界卫生组织的标准，在 1 岁和 3 岁时生成了调整年龄和性别后的 BMI z 评分。统计分析于 2017 年 1 月 29 日至 6 月 15 日进行。
正常体重（BMI，18.5-24.9）和超重或肥胖（BMI，≥25.0）母亲的婴儿。
1 岁和 3 岁儿童超重和肥胖（BMI z 评分>97th 百分位）的风险。
在这项研究的 935 对母婴（平均[SD]年龄，32.5[4.5]岁）中，382 名（40.9%）母亲超重，926 名婴儿中有 69 名（7.5%）在 1 岁时超重，866 名婴儿中有 90 名（10.4%）在 3 岁时超重。与正常体重的母亲阴道分娩相比，超重或肥胖母亲阴道分娩的婴儿在 1 岁时超重的风险增加了 3 倍（调整后的优势比[OR]，3.33；95%CI，1.49-7.41），而超重母亲剖宫产分娩的婴儿在 1 岁时超重的风险增加了 5 倍（调整后的 OR，5.02；95%CI，2.04-12.38）。在 3 岁时也观察到了类似的风险。多重中介路径模型显示，出生方式和婴儿肠道微生物群（厚壁菌门物种丰富度，特别是lachnospiraceae 科）依次介导了母亲怀孕前超重与儿童超重之间的关联，在 1 岁和 3 岁。属于lachnospiraceae 科的细菌属在超重母亲的婴儿中更为丰富；然而，阴道分娩和剖宫产分娩婴儿的lachnospiraceae 参与菌属不同。
这项研究发现了一种新的、与母体超重有关的、涉及出生方式和厚壁菌门物种丰富度（尤其是lachnospiraceae 科丰度较高）的、具有代际传递作用的超重的中介途径的证据。
