Dietary folate intake and fecundability in two preconception cohorts.

STUDY QUESTION: To what extent is dietary folate intake and total folate intake (dietary and supplemental intakes) associated with fecundability, the per cycle probability of conception? SUMMARY ANSWER: Preconception dietary folate intake was positively associated with fecundability in a monotonic pattern. WHAT IS KNOWN ALREADY: Supplemental folic acid has been associated with improved fertility, but little is known about the relation between dietary folate and fecundability. STUDY DESIGN, SIZE, DURATION: A prospective cohort study including 9559 women trying to conceive without fertility treatment and enrolled in the period 2013-2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: We used data from two internet-based prospective cohort studies of pregnancy planners from Denmark, where folic acid fortification is not performed (SnartForældre.dk (SF); n = 3755) and North America, where the food supply is fortified with folic acid (Pregnancy Study Online (PRESTO); n = 5804). Women contributed menstrual cycles at risk until they reported conception or experienced a censoring event. We used proportional probabilities regression models to compute fecundability ratios (FRs) and 95% CI, adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with a dietary folate intake ≥400 µg/day, the adjusted FRs for women in SF were 0.92 (95% CI: 0.85-0.99) for intake 250-399 µg/day, and 0.80 (95% CI: 0.68-0.94) for intake of <250 µg/day. The corresponding FRs in PRESTO were 0.95 (95% CI: 0.89-1.01) and 0.81 (95% CI: 0.65-1.00). Compared with the highest level of total folate intake (diet folate ≥400 µg/day plus folic acid supplementation), in both cohorts fecundability was lowest among women with the lowest dietary intake <250 µg/day dietary folate and no supplementation (FR: 0.76, 95% CI: 0.59-0.98 [SF] and 0.49, 95% CI: 0.31-0.77 [PRESTO]). Further, total intake dietary folate <250 µg/day plus supplementation was associated with reduced fecundability for SF participants (FR; 0.79, 95% CI: 0.65-0.98) and for PRESTO participants (FR; 0.92, 95% CI: 0.72-1.16). LIMITATIONS, REASONS FOR CAUTION: It is unknown whether dietary folate and folic acid intake affect fecundability on its own or if there is an interaction with other micronutrients provided in healthy diet. Thus, the observed associations may not reflect dietary folate intake alone, but overall healthy diet. WIDER IMPLICATIONS OF THE FINDINGS: Recommendations for preconception dietary folate intake and folic acid supplementation are of importance not only to prevent neural tube defects but also to enhance fecundability. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the National Institute of Child Health and Human Development (R01-HD086742). The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Iron Consumption Is Not Consistently Associated with Fecundability among North American and Danish Pregnancy Planners.

BACKGROUND: Infertility is an important public health problem with few known modifiable risk factors. Dietary factors including folic acid have been associated with improved fertility, but the association between iron and fertility is understudied. One study among US nurses found a 40% lower risk of ovulatory infertility with higher intake of nonheme iron and iron supplements. OBJECTIVES: The aim of this study was to determine the extent to which iron intake from diet and supplements reported on structured questionnaires is associated with fecundability. METHODS: We conducted parallel analyses that used data from 2 prospective cohort studies of pregnancy planners from Denmark (Snart Foraeldre; n = 1693) and North America (PRESTO; n = 2969) during 2013-2018. Follow-up comprised menstrual cycles at risk until pregnancy or censoring for fertility treatment, stopped trying to conceive, withdrawal, loss to follow-up, or 12 cycles of attempt. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs, adjusting for confounders. RESULTS: We found little association between dietary heme iron intake and fecundability in either cohort. The FR for nonheme iron intake (≥11 mg/d compared with <9 mg/day) was 1.11 for Snart Foraeldre participants (95% CI: 0.92, 1.34) and 1.01 for PRESTO participants (95% CI: 0.89, 1.14). The FR for iron-containing supplements was 1.01 in Snart Foraeldre (95% CI: 0.90, 1.13) and 1.19 in PRESTO (95% CI: 1.03, 1.38). In PRESTO, but not Snart Foraeldre, stronger positive associations were found for nonheme iron intake and iron supplement use among women with heavy menses or short menstrual cycles. CONCLUSIONS: Overall, dietary intake of iron was not consistently associated with fecundability, although there was some evidence for a positive association among women with risk factors for iron deficiency. We also found a small positive association between supplemental iron intake and fecundability among North American, but not Danish, pregnancy planners.

Alcohol consumption and fecundability: prospective Danish cohort study.

OBJECTIVE:  To investigate to what extent alcohol consumption affects female fecundability. DESIGN:  Prospective cohort study. SETTING:  Denmark, 1 June 2007 to 5 January 2016. PARTICIPANTS:  6120 female Danish residents, aged 21-45 years, in a stable relationship with a male partner, who were trying to conceive and not receiving fertility treatment. MAIN OUTCOME MEASURES:  Alcohol consumption was self reported as beer (330 mL bottles), red or white wine (120 mL glasses), dessert wine (50 mL glasses), and spirits (20 mL) and categorized in standard servings per week (none, 1-3, 4-7, 8-13, and ≥14). Participants contributed menstrual cycles at risk until the report of pregnancy, start of fertility treatment, loss to follow-up, or end of observation (maximum 12 menstrual cycles). A proportional probability regression model was used to estimate fecundability ratios (cycle specific probability of conception among exposed women divided by that among unexposed women). RESULTS:  4210 (69%) participants achieved a pregnancy during follow-up. Median alcohol intake was 2.0 (interquartile range 0-3.5) servings per week. Compared with no alcohol consumption, the adjusted fecundability ratios for alcohol consumption of 1-3, 4-7, 8-13, and 14 or more servings per week were 0.97 (95% confidence interval 0.91 to 1.03), 1.01 (0.93 to 1.10), 1.01 (0.87 to 1.16) and 0.82 (0.60 to 1.12), respectively. Compared with no alcohol intake, the adjusted fecundability ratios for women who consumed only wine (≥3 servings), beer (≥3 servings), or spirits (≥2 servings) were 1.05 (0.91 to1.21), 0.92 (0.65 to 1.29), and 0.85 (0.61 to 1.17), respectively. The data did not distinguish between regular and binge drinking, which may be important if large amounts of alcohol are consumed during the fertile window. CONCLUSION:  Consumption of less than 14 servings of alcohol per week seemed to have no discernible effect on fertility. No appreciable difference in fecundability was observed by level of consumption of beer and wine.

Folic acid supplement use and menstrual cycle characteristics: a cross-sectional study of Danish pregnancy planners.

PURPOSE: To examine the association between folic acid (FA) supplementation obtained through either single FA tablets or multivitamins (MVs) and menstrual cycle characteristics among 5386 women aged 18-40 years, enrolled in an Internet-based study of Danish women attempting pregnancy during 2007-2011. METHODS: In a cross-sectional study, we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of FA supplementation with menstrual cycle regularity; short (<27 days), long (30-33 days), and very long (≥34 days) cycle lengths; and duration and intensity of menstrual bleeding. RESULTS: Compared with nonuse, FA supplementation was associated with reduced odds of short cycle length (OR = 0.80, 95% CI: 0.68-0.94) and a trend toward increased odds of very long cycle length (OR = 1.21, 95% CI: 0.87-1.68) compared with cycle length of 27-29 days. The inverse association with short cycle length was stronger among 18- to 30-year-old women (OR = 0.68, 95% CI: 0.53-0.87), nulliparous women (OR = 0.66, 95% CI: 0.52-0.84), and women who used both FA and MVs (OR = 0.75, 95% CI: 0.60-0.95). We found no clear association between FA supplementation and cycle regularity and duration and intensity of menstrual bleeding. CONCLUSIONS: FA supplementation was inversely associated with short menstrual cycle length. This association was strongest among women aged 18-30 years, nulliparous women, and women who used both FA and MVs.

Predictors of preconceptional folic acid or multivitamin supplement use: a cross-sectional study of Danish pregnancy planners.

PURPOSE: Compliance with the Danish preconceptional folic acid (FA) recommendation - a daily supplement of 400 µg - is reported to be poor. Uncertainty remains, however, about the prevalence of compliers and health-related predictors of compliance in the preconceptional period. METHODS: We used self-reported baseline data from 5383 women, aged 18-40 years, enrolled in an Internet-based prospective cohort study of Danish pregnancy planners during 2007-2011. We estimated the prevalence proportions of FA or multivitamin (MV) use in relation to selected sociodemographic, lifestyle, reproductive, and medical characteristics. Multivariate binomial regression was used to obtain prevalence proportion differences with 95% confidence intervals for each level of study predictors, adjusted for all other predictors. RESULTS: Overall, 7.7% of women used FA supplements, 20.4% used MV supplements, 34.0% used both, 1.5% used other single vitamins or minerals, and 36.4% did not use any dietary supplements. The prevalence of FA or MV supplement use was higher among older women, women with higher education and income, and women with healthy lifestyle factors such as being a nonsmoker, nondrinker, physically active, maintaining a normal body mass index and having regular pap smears. Greater intercourse frequency and a history of spontaneous abortion were also positively associated with FA or MV supplement use. We found no clear association between use of FA or MV supplements and a diagnosis of hypertension, diabetes, thyroid disease, pelvic inflammatory disease, or chlamydia. CONCLUSION: A large proportion of pregnancy planners do not use FA or MV supplements. Pregnancy planners with generally risky lifestyle behaviors are less likely to comply with the FA recommendation.

The effect of salatrim, a low-calorie modified triacylglycerol, on appetite and energy intake.

BACKGROUND: Salatrim is modified triacylglycerol that is rich in short-chain fatty acids and stearic acid. It is used as a lower-calorie fat replacer. In addition, it has been hypothesized that salatrim's reduced absorption in the small intestine may lead to greater amounts of fat in the gastrointestinal tract, which may decrease appetite and energy intake through the release of appetite-regulating gastrointestinal hormones. OBJECTIVE: We aimed to compare the effects of salatrim and traditional fat on appetite, ad libitum energy intake, and gastrointestinal hormones. DESIGN: Twenty-two healthy, young, normal-weight men participated in a randomized, double-blind, crossover study. Test meals were a traditional fat meal and a salatrim meal with a mixture of traditional fat and salatrim. Visual analogue scales were used to record appetite and well-being every 30 min, and blood was sampled frequently. An ad libitum lunch was served 4.5 h after the test meal. RESULTS: The salatrim meal increased fullness (P = 0.04) and decreased hunger (P = 0.06) significantly more than did the traditional fat meal. The traditional fat meal increased well-being (P = 0.02). There was no significant difference in ad libitum energy intake or overall energy intake between the 2 test days. No significant differences in blood glucose, insulin, triacylglycerol, ghrelin, cholecystokinin, glucagon-like peptide-1, or peptide YY concentrations were found. A significantly (P = 0.01) smaller increase in free fatty acids was observed after the salatrim meal than after the traditional fat meal. CONCLUSIONS: Salatrim had a modestly more suppressive effect on appetite than did a traditional fat. Gastrointestinal hormones did not seem to be involved.