Does a mother’s diet influence her infant’s gut microbiome?

July 10, 2018

A study by investigators from New England suggests that a mother’s diet during pregnancy and lactation may have an impact on the microbiome in her infant’s gut. PLUS: Are prenatal vitamin D levels tied to adverse pregnancy outcomes? ALSO: Results of a survey-based study of attending surgeons shows that they play a major role in whether women with breast cancer receive genetic testing.

A study by investigators from New England suggests that a mother’s diet during pregnancy and lactation may have an impact on the microbiome in her infant’s gut. The association, the authors said, may vary depending on whether the infant is delivered vaginally or by cesarean.

The findings, published in Microbiome, are from analysis of infant stool samples and data on maternal diet during pregnancy collected via questionnaire. The mother-infant dyads who participated were enrolled in the New Hampshire Birth Cohort Study.  The authors examined the association between maternal diet during pregnancy and the infant gut microbiome 6 weeks post-delivery. 

Stool samples were collected from 145 infants at age 6 weeks and a validated food frequency questionnaire was administered to their mothers at 24 to 28 weeks’ gestation.  The women were aged 22 to 44 and most were first-time mothers who had at least a college degree. Approximately two-thirds of the infants (66.9%) were born vaginally and 70.3% were exclusively breastfed at age 6 weeks. 

The most abundant microbial species found in the stool samples was Enterobacteriaceae(20%) followed by Bifidobacterium(18.4%), Bacteroides(10.4%), and Streptococcus(8.10%) overall and in the vaginally delivered infants. In the infants delivered by cesarean, the findings were somewhat different: high abundance of Bifidobacterium, high Clostridium, low Streptococcusand Ruminococcusgenera, and high abundance of Enterobacteriaceae.Maternal dairy intake was associated with increased odds of high Clostridium in infants born by cesarean. 

After adjustment for infant feeding method, maternal body mass index, parity, and batch, maternal fruit consumption was associated with infant stool microbiome composition (P= 0.028). That effect persisted in babies born vaginally when the analysis was restricted to infants who were exclusively breastfed (P= 0.022). The results were unchanged by exclusion of infants who may have received antibiotics or whose births were premature.

The researchers noted that maternal fish consumption has been associated with child development outcomes including decreased risk of asthma and improved cognition. Their study found a positive relationship between maternal fish and seafood consumption and Streptococcusin the infant gut. Also seen was a decrease in presence of Clostridium neonatalein the stool samples of infants born by cesarean to mothers with increased fish and seafood in their diets, which the authors said was beneficial to the microbiome.

The beneficial microbe Bifidobacteriumwas found to be decreased in the stool samples of infants born vaginally to mothers with increased fruit consumption. However, it was increased in infants born by cesarean to mothers with higher intake of red and processed meat. 

Commenting on the strengths and weaknesses of the research, the authors said the generalizability of the results may be limited in that the sample was drawn from Northern New England, which has a relatively homogenous population. They said the effects observed may be due in part to maternal diet during lactation and it is not possible to determine whether the associations between diet and the infant microbiome occur only in breastfed babies, also in those mostly fed formula, or in those fed a combination of formula and breast milk.

The authors said that future studies of the relationship between maternal diet, components of breast milk and their effects on the fetal microbiome are warranted. “Determining the impact of changes in the gut microbiome of infants due to maternal diet on infant health and development,” the researchers concluded, “is an opportunity to refine dietary recommendations for pregnant and lactating women to support infant health.”


Are prenatal vitamin D levels tied to adverse pregnancy outcomes?

Women with low levels of 25-hydroxyvitamin D (vitamin D) are not at increased risk of gestational hypertension or preeclampsia, according to the results of a study published in The British Medical Journal. The findings are from an analysis by European researchers.

Using a technique called Mendelian randomization, the authors examined whether genetic variants associated with variable vitamin D production and metabolism also influenced the risk of pregnancy-induced hypertension and preeclampsia among 7,389 women (751 had gestational hypertension and 135 preeclampsia). Data were extracted from two large European studies (Avon Longitudinal Study of Parents and Children and Generation R Study). They also performed another (two sample) Mendelian randomization analysis of 3,388 preeclampsia cases and 6,059 controls. 

Analyzing genetic information as proxies for the exposure of interest in this way avoids some of the problems that afflict traditional observational studies, making the results less prone to confounding. An association observed using Mendelian randomization would therefore strengthen inference of a causal relationship. In this study, the genes assessed in relation to vitamin D synthesis were CYP2R1 DHCR7/NADSYN1 and in relation to metabolism were CYP24A1 and GC.

A marginally significant relative risk (RR) for preeclampsia of 1.03 (95% confidence interval [CI] 1.00 to 1.07) per 10% decrease in vitamin D level was observed. A RR of 2.04 (1.02 to 4.07) was noted for vitamin D levels < 25 nmol/L compared with levels ≥75 nmol/L. No association was found for gestational hypertension. No strong evidence of a linear effect of vitamin D on risk of either gestational hypertension or preeclampsia was found in the one-sample Mendelian randomization: odds ratio (OR) 0.90 (95% CI 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. In the two-sample Mendelian randomization, the OR for preeclampsia was also not significant at 0.98 (0.89 to 1.07) per 10% decrease in vitamin D level, 0.96 (0.80 to 1.15) per unit increased in the log(odds) of vitamin D level < 75 nmol/L and OR of 0.93 (0.78 to 1.19) per unit increased in the log(odds) of vitamin D levels < 50 nmol/L.  No consistent evidence was seen of any associations between four single-nucleotide polymorphisms (SNPs) with gestational hypertension or preeclampsia in the two cohorts. Evaluation of those four genetic variants showed weak evidence of an association between one of the SNPs and preeclampsia.

The authors said that vitamin D levels in the one-sample Mendelian randomization in both cohorts were positively associated with age (difference 1 to 2 years) and education (7% to 9% difference in proportion with high education). An inverse association was seen with smoking (13% to 20% difference in proportion of women who smoked during pregnancy) and body mass index (BMI) (6% to 38% difference in proportion with normal BMI. 

The authors concluded that a lower vitamin D level was weakly associated with lower risk of gestational risk of hypertension and higher risk of preeclampsia in the one-sample mendelian analysis. “Further evidence from larger studies is needed to provide conclusive evidence,” they said. No evidence was found of an association between vitamin D level and preeclampsia in the two-sample mendelian randomization analysis. The strengths of the study, the authors noted, were use of genetic variants to reduce confounding and the inclusion of multiple cohorts. 

The findings, the authors said, support the current World Health Organization position on vitamin D which is that evidence is insufficient on which to base a recommendation for vitamin D supplementation by women during pregnancy. The National Academy of Medicine (formerly the Institute of Medicine) recommends a dietary allowance of 600 IU daily of vitamin D during pregnancy and lactation.Breast Ca surgeon attitudes influence genetic testing

Results of a survey-based study of attending surgeons shows that they play a major role in whether women with breast cancer receive genetic testing. Published in JAMA Surgery, the findings indicate that many women who would benefit from the tests are not getting them, despite recommendations in guidelines. 

The data are from the iCanCare study of women aged 20 to 79 (mean 61.4 years) who were diagnosed with ductal carcinoma in situ or invasive breast cancer and whose cases were reported to the Georgia or Los Angeles (California) Surveillance, Epidemiology and End Results registry. The researchers sent surveys to 5080 women with stages 0 to II breast cancer who were treated between July 1, 2013 and August 31, 2015, 98.0% and who identified their attending surgeon. Just over 77% of those surgeons responded to a seven-question survey. 

The surveys were sent approximately 2 months after surgery. Four of the questions for the surgeons referred to a scenario in which a patient is deemed by the responding surgeon to be a candidate for genetic testing; in two, the scenario was one in which the surgeon deemed the patient not to be a candidate for testing; and in the last scenario, the surgeon’s confidence in discussing genetic testing was assessed. The researchers then developed a Tendency to Test Scale to assess the responses and determine the likelihood that a surgeon would order genetic testing and counseling in the different scenarios. 

Approximately one-third (34.5%) of the women included in the study had an elevated risk of being mutation carriers but overall, 27.0% of the patients had genetic testing. Of those tested, 13.8% were at average pretest risk and 52.1% were at higher pretest risk. 

Surgeons scored higher on the scale and were more likely to do genetic testing if they said they often or always delayed surgery to get genetic testing for their patients (35.2%) or were quite or extremely comfortable discussing testing with their patients (50.2%). The odds of testing increased by 1.88 (95% CI, 1.49-2.38) for each 1-SD increase in the scale score. If a patient with the highest pretest risk saw a surgeon in the 5thpercentile of test ordering, she had about a 26.3% (95% CI, 21.9%-31.2%) probability of undergoing testing. However, if she saw a surgeon who ordered genetic tests more often than 95% of the other surgeons included in the study, she had a 72.3% (95% CI, 66.7%-77.2%) of having a genetic test done. For average-risk women, the probabilities of testing were 4.1% (95% CI, 2.9%-5.6%) and 23.8% (95% CI, 20.0%-27.9%), respectively, for the 5thand 95thpercentiles. 

The researchers found that about 17.3% of the variation in genetic testing rates could be accounted for based on the surgeons’ practice patterns. In regard to the highest-volume surgeons, patients seen by medium- and lower-volume surgeons were less likely to be tested. 

The authors mentioned a few strengths and limitations to their study. Among the noted strengths were the large population-based sample of patients, genetic test information gathered directly from the testing laboratories, a valid measure of clinical indication for testing, and high response rates. Among the noted limitations were possible missed details of pretest risk of mutation carriage based on family history, inability to directly measure whether surgeons appropriately recommended testing or counseling to a given patient, and the fact that data were collected solely from two states and may not be applicable to the general US population. The authors believe the results from this study illustrate the need to build consensus about approaches to genetic testing and counseling as well as risk evaluation for breast cancer patients.