Association of birth mode of delivery with infant faecal microbiota, potential pathobionts, and short chain fatty acids: a longitudinal study over the first year of life.

OBJECTIVE: Caesarean section (CS) interrupts mother-to-newborn microbial transfer at birth. Beyond the neonatal period, the impact of CS on offspring gut microbiota and their short-chain fatty acids (SCFAs) remains unclear. Here, we examine birth delivery mode (CS versus vaginal delivery) with the infant gut microbiota and faecal SCFAs measured 3 and 12 months after birth. DESIGN: Longitudinal study. SETTING: North Carolina. POPULATION: In 2013-15, we enrolled pregnant women and followed up their offspring for 12 months. We asked a subset of participants, enrolled over a 3-month period, to provide faecal samples at the 3- and 12-month follow-up visits. METHODS AND MAIN OUTCOMES: We sequenced the 16S rRNA V4 region with Illumina MiSeq and quantified SCFA concentrations using gas chromatography. We examined delivery mode with differential abundance of microbiota amplicon sequence variants (ASVs) using beta-binomial regression and faecal SCFAs using linear regression. We adjusted models for confounders. RESULTS: Of the 70 infants in our sample, 25 (36%) were delivered by CS. Compared with vaginal delivery, CS was associated with differential abundance of 14 infant bacterial ASVs at 3 months and 13 ASVs at 12 months (all FDR P < 0.05). Of note, CS infants had a higher abundance of the potential pathobionts Clostridium neonatale (P = 0.04) and Clostridium perfringens (P = 0.04) and a lower abundance of potentially beneficial Bifidobacterium and Bacteroides spp. (both P < 0.05) at 3 months. Other ASVs were differentially abundant at 12 months. Infants delivered by CS also had higher faecal butyrate concentration at 3 months (P < 0.005) but not at 12 months. CONCLUSIONS: Caesarean section was associated with increased butyrate excretion, decreased Bifidobacterium and Bacteroides spp., and more colonisation of the infant gut by pathobionts at 3 months of age. CS was also associated with altered gut microbiota composition, but not faecal SCFAs, at 12 months. TWEETABLE ABSTRACT: Caesarean section delivery was associated with increased butyrate excretion, decreased Bifidobacterium, and increased colonisation of the infant gut by pathobionts at 3 months of age.

Does vaginal delivery mitigate or strengthen the intergenerational association of overweight and obesity? Findings from the Boston Birth Cohort.

BACKGROUND/OBJECTIVES: The intergenerational association of obesity may be driven by mother-to-newborn transmission of microbiota at birth. Yet cesarean delivery circumvents newborn acquisition of vaginal microbiota, and has been associated with greater childhood adiposity. Here we examined the independent and joint associations of maternal pre-pregnancy body mass index (BMI; kg m-2) and delivery mode with childhood overweight or obesity. SUBJECTS/METHODS: We prospectively followed 1441 racially and ethnically diverse mother-child dyads in the Boston Birth Cohort until age 5 years (range: 2.0-8.0 years). We used logistic regression to examine the independent and joint associations of delivery mode (cesarean and vaginal delivery) and pre-pregnancy BMI with childhood overweight or obesity (age-sex-specific BMI ⩾85th percentile). RESULTS: Of 1441 mothers, 961 delivered vaginally and 480 by cesarean. Compared with vaginally delivered children, cesarean delivered children had 1.4 (95% confidence interval (CI) 1.1-1.8) times greater odds of becoming overweight or obese in childhood, after adjustment for maternal age at delivery, race/ethnicity, education, air pollution exposure, pre-pregnancy BMI, pregnancy weight gain and birth weight. Compared with children born vaginally to normal weight mothers, after multivariable adjustment, odds of childhood overweight or obesity were highest in children born by cesarean delivery to obese mothers (odds ratio (OR): 2.8; 95% CI: 1.9-4.1), followed by children born by cesarean delivery to overweight mothers (OR: 2.2; 95% CI: 1.5-3.2), then children born vaginally to obese mothers (OR: 1.8; 95% CI: 1.3-2.6) and finally children born vaginally to overweight mothers (OR: 1.7; 95% CI: 1.2-2.3). CONCLUSIONS: In our racially and ethnically diverse cohort, cesarean delivery and pre-pregnancy overweight and obesity were associated with childhood overweight or obesity. Needed now are prospective studies that integrate measures of the maternal and infant microbiome, and other potentially explanatory covariates, to elucidate the mechanisms driving this association and to explore whether exposure to vaginal microbiota in cesarean delivered newborns may be an innovative strategy to combat the intergenerational cycle of obesity.

Sex-specific associations of birth weight with measures of adiposity in mid-to-late adulthood: the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND/OBJECTIVES: To investigate sex-specific associations of birth weight with body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) in mid-to-late adulthood. SUBJECTS/METHODS: ELSA-Brasil is a multicenter cohort study of adults aged 35-74 years affiliated with universities or research institutions of six capital cities in Brazil. After exclusions, we investigated 11 636 participants. Socio-demographic factors and birth weight were obtained by interview. All anthropometry was directly measured at baseline. We categorized birth weight as low (⩽2.5 kg); normal (2.5-4 kg) and high (⩾4 kg). We performed analysis of covariance (ANCOVA) for continuous outcomes and ordinal logistic regression for categorical adiposity outcomes. We examined interaction on the multiplicative scale by sex and by race. RESULTS: High birth weight uniformly predicted greater overall and central obesity in men and women. However, low (vs normal) birth weight, in ANCOVA models adjusted for participant age, family income, race, education, maternal education, and maternal and paternal history of diabetes, was associated with lower BMI, WC and WHR means for men, but not for women (Pinteraction=0.01, <0.0001 and <0.0001, respectively). In similarly adjusted ordinal logistic regression models, odds of obesity (odds ratio (OR)=0.65, 0.46-0.90) and of being in the high (vs low) tertile of WC (OR=0.66, 0.50-0.87) and of WHR (OR=0.79, 0.60-1.03) were lower for low (vs normal) birth weight men, but trended higher (BMI: OR=1.18, 0.92-1.51; WC: OR=1.21, 0.97-1.53; WHR: OR=1.44, 1.15-1.82) for low (vs normal) birth weight women. CONCLUSIONS: In this Brazilian sample of middle-aged and elderly adults who have lived through a rapid nutritional transition, low birth weight was associated with adult adiposity in a sex-specific manner. In men, low birth weight was associated with lower overall and central adult adiposity, while in women low birth weight was generally associated with greater central adiposity.

Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity.

BACKGROUND/OBJECTIVES: Cesarean section (CS) and antibiotic use during pregnancy may alter normal maternal-offspring microbiota exchange, thereby contributing to aberrant microbial colonization of the infant gut and increased susceptibility to obesity later in life. We hypothesized that (i) maternal use of antibiotics in the second or third trimester of pregnancy and (ii) CS are independently associated with higher risk of childhood obesity in the offspring. SUBJECTS/METHODS: Of the 727 mothers enrolled in the Northern Manhattan Mothers and Children Study, we analyzed the 436 mother-child dyads followed until 7 years of age with complete data. We ascertained prenatal antibiotic use by a questionnaire administered late in the third trimester, and delivery mode by medical record. We derived age- and sex-specific body mass index (BMI) z-scores using the CDC SAS Macro, and defined obesity as BMI z⩾95th percentile. We used binary regression with robust variance and linear regression models adjusted for maternal age, ethnicity, pre-gravid BMI, maternal receipt of public assistance, birth weight, sex, breastfeeding in the first year and gestational antibiotics or delivery mode. RESULTS: Compared with children not exposed to antibiotics during the second or third trimester, those exposed had 84% (33-154%) higher risk of obesity, after multivariable adjustment. Second or third trimester antibiotic exposure was also positively associated with BMI z-scores, waist circumference and % body fat (all P<0.05). Independent of prenatal antibiotic usage, CS was associated with 46% (8-98%) higher offspring risk of childhood obesity. Associations were similar for elective and non-elective CS. CONCLUSIONS: In our cohort, CS and exposure to antibiotics in the second or third trimester were associated with higher offspring risk of childhood obesity. Future studies that address the limitations of our study are warranted to determine if prenatal antibiotic use is associated with offspring obesity. Research is also needed to determine if alterations in neonatal gut microbiota underlie the observed associations.

Higher parity is associated with an increased risk of type-II diabetes in Chinese women: the Singapore Chinese Health Study.

OBJECTIVE: The association between parity and type-II diabetes has been studied primarily in Western populations, and the findings have been inconsistent. Here, we examine whether parity was positively associated with incident type-II diabetes in Singaporean Chinese women. DESIGN: Prospective cohort study. SETTING: Singapore. POPULATION: A total of 25,021 Singaporean Chinese women aged 45-74 years from the Singapore Chinese Health Study who were free of cancer, heart disease, stroke, and diabetes at baseline (1993-1998). METHODS: Women were followed through 2004 for incident diabetes. Hazard ratios for type-II diabetes were computed across parity (of live births) categories and adjusted for baseline age, interview year, dialect, education, smoking, dietary pattern, physical activity, age at menarche, oral contraceptive use, menopausal status, hormone therapy use, and body mass index (BMI). MAIN OUTCOME MEASURE: Self-reported diabetes, as diagnosed by a doctor. RESULTS: Over an average of 5.7 person-years of follow-up, 1294 women were diagnosed with diabetes. Before and after multivariable adjustment there was a positive graded association between parity and type-II diabetes risk (P < 0.001). In the fully adjusted model, which included adult BMI, the risk of type-II diabetes increased by 31% (from -2 to 76%), 62% (from 22 to 116%), and 74% (from 29 to 133%) for women with one or two, three or four, and five or more live births, respectively, compared with women with no live births. Moreover, in a supplementary multivariate analysis in non-diabetic women we found a positive monotonic association between parity and glycated haemoglobin (HbA1c) (P = 0.01). CONCLUSIONS: Increased parity may be a risk factor for type-II diabetes in Chinese women. More research is needed on lifestyle and physiologic factors that may explain this association.

Association of prenatal antibiotics with foetal size and cord blood leptin and adiponectin.

BACKGROUND: Early postnatal antibiotic use has been shown to promote excess weight gain, but it is unclear whether intrauterine exposure to antibiotics is associated with foetal growth and adiposity. The objective of this study was to examine associations of antibiotic prescription in each trimester of pregnancy with foetal size and adipokine levels at birth. METHODS: In 2128 pregnant women from the pre-birth Project Viva cohort, from electronic medical records, we estimated antibiotic prescribing by timing during pregnancy. Outcomes were sex-specific birth weight-for-gestational-age z-score (BW/GA-z) and levels of umbilical cord leptin and adiponectin. We used linear regression models adjusted for maternal age, pre-pregnancy body mass index, parity, race/ethnicity, education, smoking during pregnancy, household income and child sex and additionally adjusted cord blood leptin and adiponectin models for gestation length. RESULTS: Of the 2128 women in our sample, 643 (30.2%) were prescribed with oral antibiotics during pregnancy. Mean (standard deviation) BW/GA-z was 0.17 (0.97), cord blood leptin was 9.0 ng mL-1 (6.6) and cord blood adiponectin was 28.8 ng mL-1 (6.8). Overall, antibiotic prescription in pregnancy was associated with lower BW/GA-z [multivariable adjusted ß -0.11; 95% confidence interval {CI} -0.20, -0.01]. In trimester-specific analyses, only second trimester antibiotic prescription was associated with lower BW/GA-z (ß -0.23; 95% CI -0.37, -0.08). Overall, antibiotic prescription in pregnancy was not associated with cord blood leptin or adiponectin levels. However, in trimester-specific analyses, third trimester antibiotic prescription was associated with higher cord blood leptin (ß 2.28 ng mL-1 ; 95% CI 0.38, 4.17). CONCLUSIONS: Antibiotics in mid-pregnancy were associated with lower birth weight for gestational age, whereas third trimester antibiotics were associated with higher cord blood leptin.