Adherence to different forms of plant-based diets and pregnancy outcomes in the Danish National Birth Cohort: A prospective observational study.

INTRODUCTION: The number of people adhering to plant-based diets has been increasing dramatically in recent years, fueled by both environmental and animal welfare concerns. Beneficial or possible adverse consequences of such diets, particularly the most restrictive forms during pregnancy, have been minimally explored. The aim of this prospective observational study was to examine associations between different forms of plant-based diets during pregnancy with birth outcomes and pregnancy complications. MATERIAL AND METHODS: The Danish National Birth Cohort included 100 413 pregnancies to 91 381 women in 1996-2002. The population consisted of 66 738 pregnancies, about which sufficient dietary data were available and included in the study. Dietary and supplemental intake was assessed by Food Frequency Questionnaire in gestational week 25 and women were characterized as fish/poultry-vegetarians, lacto/ovo-vegetarians, vegans or omnivorous, based on their self-report in gestational week 30. Main outcome measures were pregnancy and birth complications, birthweight and small for gestational age. RESULTS: A total of 98.7% (n = 65 872) of participants were defined as omnivorous, whereas 1.0% (n = 666), 0.3% (n = 183) and 0.03% (n = 18) identified themselves as fish/poultry vegetarians, lacto/ovo-vegetarians or vegans, respectively. Protein intake was lower among lacto/ovo-vegetarians (13.3%) and vegans (10.4%) than among omnivorous participants (15.4%). Intake of micronutrients was also considerably lower among vegans, but when dietary supplements were taken into consideration, no major differences were observed. Compared with omnivorous mothers, vegans had a higher prevalence of preeclampsia and their offspring had on average -240 g (95% confidence interval -450 to -30) lower birthweight. CONCLUSIONS: The women reporting that they adhered to vegan diets during pregnancy had offspring with lower mean birthweight and higher risk of preeclampsia compared with omnivorous mothers. Low protein intake might be one plausible explanation for the observed association with birthweight.

Omega-3 fatty acid supply in pregnancy for risk reduction of preterm and early preterm birth.

This clinical practice guideline on the supply of the omega-3 docosahexaenoic acid and eicosapentaenoic acid in pregnant women for risk reduction of preterm birth and early preterm birth was developed with support from several medical-scientific organizations, and is based on a review of the available strong evidence from randomized clinical trials and a formal consensus process. We concluded the following. Women of childbearing age should obtain a supply of at least 250 mg/d of docosahexaenoic+eicosapentaenoic acid from diet or supplements, and in pregnancy an additional intake of ≥100 to 200 mg/d of docosahexaenoic acid. Pregnant women with a low docosahexaenoic acid intake and/or low docosahexaenoic acid blood levels have an increased risk of preterm birth and early preterm birth. Thus, they should receive a supply of approximately 600 to 1000 mg/d of docosahexaenoic+eicosapentaenoic acid, or docosahexaenoic acid alone, given that this dosage showed significant reduction of preterm birth and early preterm birth in randomized controlled trials. This additional supply should preferably begin in the second trimester of pregnancy (not later than approximately 20 weeks' gestation) and continue until approximately 37 weeks' gestation or until childbirth if before 37 weeks' gestation. Identification of women with inadequate omega-3 supply is achievable by a set of standardized questions on intake. Docosahexaenoic acid measurement from blood is another option to identify women with low status, but further standardization of laboratory methods and appropriate cutoff values is needed. Information on how to achieve an appropriate intake of docosahexaenoic acid or docosahexaenoic+eicosapentaenoic acid for women of childbearing age and pregnant women should be provided to women and their partners.

Maternal intake of folate and folic acid during pregnancy and pubertal timing in girls and boys: A population-based cohort study.

BACKGROUND: Folate is essential for normal foetal development as it plays an important role for gene expression during different periods of foetal development. Thus, prenatal exposure to folate may have a programming effect on pubertal timing. OBJECTIVES: To study the association between maternal intake of folate during pregnancy and pubertal timing in girls and boys. METHODS: We studied 6585 girls and 6326 boys from a Danish population-based Puberty Cohort, 2000-2021. Information on maternal intake of folate from diet and folic acid from supplements was obtained from a food-frequency questionnaire in mid-pregnancy, and total folate was calculated as dietary folate equivalents. Information on age at menarche in girls, age at first ejaculation and voice break in boys, and Tanner stages, acne and axillary hair in both girls and boys was obtained every 6 months throughout puberty. We estimated mean monthly differences according to exposure groups for each pubertal milestone in addition to a combined estimate for the average age at attaining all pubertal milestones using multivariable interval-censored regression models. Total folate was analysed in quintiles, continuous and as restricted cubic splines. RESULTS: Maternal intake of total folate in mid-pregnancy was not associated with pubertal timing in girls (combined estimate for overall pubertal timing per standard deviation (SD 325 µg/day) decrease in maternal intake of total folate: -0.14 months (95% confidence interval [CI] -0.51, 0.22)). Boys had slightly later overall pubertal timing per standard deviation (SD 325 µg/day) decrease in maternal intake of total folate (combined estimate: 0.40 months, 95% CI 0.01, 0.72). Spline plots supported these findings. CONCLUSIONS: Prenatal exposure to low maternal intake of total folate in mid-pregnancy was not associated with pubertal timing in girls but associated with slightly later pubertal timing in boys. This minor delay is likely not of clinical importance.

Maternal intake of folate and folic acid during pregnancy and markers of male fecundity: A population-based cohort study.

BACKGROUND: Poor male fecundity is of concern, and a prenatal origin has been proposed. Folate, a methyl donor involved in DNA methylation, is essential for normal fetal development by regulating gene expression during different periods of fetal development. Thus, prenatal exposure to low maternal folate intake might have a programing function of the developing reproductive organs. OBJECTIVES: To examine the association between maternal intake of folate from diet and folic acid from supplements during pregnancy and markers of fecundity in young men. MATERIALS AND METHODS: We conducted a follow-up study using a Danish mother-son cohort of 787 young men born 1998-2000. Percentage differences in semen characteristics, testes volume, and reproductive hormone levels were analyzed according to total folate calculated as dietary folate equivalents from diet and supplements in midpregnancy, using multivariable negative binomial regression models. Total folate was analyzed in quintiles, continuous per standard deviation decrease (SD: 318 µg/day) and as restricted cubic splines. RESULTS: Low maternal intake of total folate was associated with lower total sperm count (-5% (95% confidence intervals [CI]: -11%; 2%)), a lower proportion of non-progressive and immotile spermatozoa (-5% [95% CI: -8%; -3%]), and lower testes volume (-4% [95% CI: -6%; -2%]) per SD decrease in total folate intake. Spline plots supported these findings. DISCUSSION: The finding of a lower proportion of non-progressive and immotile spermatozoa, and hence a higher proportion of motile spermatozoa, in men of mothers with a lower intake of total folate in midpregnancy was surprising and may be a chance finding. CONCLUSION: Lower maternal intake of total folate in midpregnancy was associated with lower sperm count and lower testes volume, however, also with a lower proportion of non-progressive and immotile spermatozoa in adult men. Whether this actually affects the ability to obtain a pregnancy warrants further investigation.

Effects of probiotics (Vivomixx®) in obese pregnant women and their newborn: study protocol for a randomized controlled trial.

BACKGROUND: Maternal obesity is associated with increased risks of adverse pregnancy-related complications and outcomes for both mothers and infants. Overweight and obese women have an increased risk of pregnancy-induced hypertension, preeclampsia and gestational diabetes mellitus (GDM). Infant Body Mass index (BMI) and the risk of obesity in adulthood are related to maternal gestational weight gain (GWG). Preventive lifestyle and dietary interventions are time-consuming and do not always reduce GWG or the risk of maternal pregnancy complications. Recent research has indicated that the gut microbiota may play a significant role in the development of obesity. Some studies have indicated that the daily consumption of probiotics may reduce the risk of preeclampsia, maintain serum insulin levels and reduce the frequency of GDM in pregnant women. The aims of this study are to investigate whether daily probiotic supplements in obese women during pregnancy can limit gestational weight gain, improve glucose homeostasis and thereby improve maternal, fetal and infant health outcomes. METHODS: A pilot study including 50 obese pregnant nulliparous women with a prepregnancy BMI of between 30 and 35 kg/m2 will be randomized to receive daily probiotics (four capsules of Vivomixx®; total of 450 billion CFU/day, including eight probiotic bacterial strains) or placebo from gestational age 14-20 weeks until delivery. The infants will be followed until 9 months of age. The women will be monitored by weight, blood, fecal, vaginal and urine samples, diet questionnaires and hospital record review. Primary outcomes are: maternal weight gain, glycated hemoglobin (HbA1c) level and changes in glucose concentration measured during an oral glucose tolerance test. Secondary outcomes are: microbiota and inflammatory markers in mother and child, pregnancy complications, pregnancy outcomes, physical activity and the body composition of the neonate. DISCUSSION: We expect to find alterations in the metabolic profiles, microbiota and possibly pregnancy outcomes. From a clinical point of view the effects of Vivomixx® could control weight gain and reduce complications during pregnancy by inducing changes in the gut microbiota. Furthermore, this intervention during pregnancy could influence the infant's microbiota, which could have important implications for infant development and health. TRIAL REGISTRATION: ClincalTrials.gov Identifier: NCT02508844 , registered on 11 May 2015.

Development and validation of a vitamin D status prediction model in Danish pregnant women: a study of the Danish National Birth Cohort.

Vitamin D has been hypothesized to reduce risk of pregnancy complications such as preeclampsia, gestational diabetes mellitus, and preterm delivery. However, many of these outcomes are rare and require a large sample size to study, representing a challenge for cohorts with a limited number of preserved samples. The aims of this study were to (1) identify predictors of serum 25-hydroxy-vitamin D (25(OH)D) among pregnant women in a subsample (N = 1494) of the Danish National Birth Cohort (DNBC) and (2) develop and validate a score predicting 25(OH)D-status in order to explore associations between vitamin D and maternal and offspring health outcomes in the DNBC. In our study sample, 42.3% of the population had deficient levels of vitamin D (<50 nmol/L 25(OH)D) and average levels of 25(OH)D-status were 56.7(s.d. 24.6) nmol/L. A prediction model consisting of intake of vitamin D from diet and supplements, outdoor physical activity, tanning bed use, smoking, and month of blood draw explained 40.1% of the variance in 25(OH)D and mean measured 25(OH)D-level increased linearly by decile of predicted 25(OH)D-score. In total 32.2% of the women were placed in the same quintile by both measured and predicted 25(OH)D-values and 69.9% were placed in the same or adjacent quintile by both methods. Cohen's weighted kappa coefficient (Κ = 0.3) reflected fair agreement between measured 25(OH)D-levels and predicted 25(OH)D-score. These results are comparable to other settings in which vitamin D scores have shown similar associations with disease outcomes as measured 25(OH)D-levels. Our findings suggest that predicted 25(OH)D-scores may be a useful alternative to measured 25(OH)D for examining associations between vitamin D and disease outcomes in the DNBC cohort, but cannot substitute for measured 25(OH)D-levels for estimates of prevalence.

Intake of marine n-3 fatty acids during pregnancy and risk for epilepsy in the offspring: a population-based cohort study.

AIM OF THE STUDY: To estimate if maternal intake of n-3 long-chain polyunsaturated fatty acids (LCPUFA) during pregnancy is related to the risk of epilepsy in the offspring. METHODS: We identified 65,754 live-born singletons from the Danish National Birth Cohort (DNBC, 1996-2002) and followed them for up to 11 years of age. Information on maternal diet in the 4 weeks around the 25th gestational week was obtained from a self-administered food frequency questionnaire and maternal intake of n-3 LCPUFA was estimated from the reported amount and type of fish in diet. Information on epilepsy was obtained from the Danish National Hospital Register. Cox regression models were used to estimate the incidence rate ratios (IRR) of epilepsy. RESULTS: Children born to mothers in the lowest (IRR=1.28, 95% CI: 0.98, 1.67) and highest (IRR=1.33, 95% CI: 1.02, 1.74) quintile of n-3 LCPUFA intake had an increased risk of epilepsy after adjustment for potential confounders compared to children born to mothers with an average intake. The associations may be related to the age of onset of epilepsy. CONCLUSIONS: Maternal deficiency of n-3 LCPUFA and a high intake of n-3 LCPUFA perhaps related to a high consumption of contaminated fish may be associated with an increased risk of epilepsy in early childhood.

Oral clefts and life style factors--a case-cohort study based on prospective Danish data.

This study examines the association between oral clefts and first trimester maternal lifestyle factors based on prospective data from the Danish National Birth Cohort. The cohort includes approximately 100,000 pregnancies. In total 192 mothers gave birth to child with an oral cleft during 1997-2003. Information on risk factors such as smoking, alcohol consumption, tea, coffee, cola, and food supplements was obtained during pregnancy for these and 828 randomly selected controls. We found that first trimester maternal smoking was associated with an increased risk of oral clefts (odds ratio (OR): 1.50; 95% confidence interval (CIs): 1.05, 2.14). Although not statistically significant, we also saw associations with first trimester consumption of alcohol (OR: 1.11; CIs: 0.79, 1.55), tea (OR: 1.31; CIs: 0.93, 1.86), and drinking more than 1 l of cola per week (OR: 1.40; CIs: 0.92, 2.12). Furthermore supplementation with > or =400 mcg folic acid daily during the entire first trimester (OR: 0.75; CIs: 0.46, 1.22) suggested an inverse associated with oral clefts, similar to our results on coffee drinking. No effects were found for smaller doses of folic acid, vitamin A, B6 or B12 in this study. The present study found an association between oral clefts and smoking and, although not conclusive, supports an association of oral cleft with alcohol.

Low consumption of seafood in early pregnancy as a risk factor for preterm delivery: prospective cohort study.

OBJECTIVE: To determine the relation between intake of seafood in pregnancy and risk of preterm delivery and low birth weight. DESIGN: Prospective cohort study. SETTING: Aarhus, Denmark. PARTICIPANTS: 8729 pregnant women. MAIN OUTCOME MEASURES: Preterm delivery and low birth weight. RESULTS: The occurrence of preterm delivery differed significantly across four groups of seafood intake, falling progressively from 7.1% in the group never consuming fish to 1.9% in the group consuming fish as a hot meal and an open sandwich with fish at least once a week. Adjusted odds for preterm delivery were increased by a factor of 3.6 (95% confidence interval 1.2 to 11.2) in the zero consumption group compared with the highest consumption group. Analyses based on quantified intakes indicated that the working range of the dose-response relation is mainly from zero intake up to a daily intake of 15 g fish or 0.15 g n-3 fatty acids. Estimates of risk for low birth weight were similar to those for preterm delivery. CONCLUSIONS: Low consumption of fish was a strong risk factor for preterm delivery and low birth weight. In women with zero or low intake of fish, small amounts of n-3 fatty acids--provided as fish or fish oil--may confer protection against preterm delivery and low birth weight.