Old Question Revisited: Are High-Protein Diets Safe in Pregnancy?

BACKGROUND: A previous randomized dietary intervention in pregnant women from the 1970s, the Harlem Trial, reported retarded fetal growth and excesses of very early preterm births and neonatal deaths among those receiving high-protein supplementation. Due to ethical challenges, these findings have not been addressed in intervention settings. Exploring these findings in an observational setting requires large statistical power due to the low prevalence of these outcomes. The aim of this study was to investigate if the findings on high protein intake could be replicated in an observational setting by combining data from two large birth cohorts. METHODS: Individual participant data on singleton pregnancies from the Danish National Birth Cohort (DNBC) (n = 60,141) and the Norwegian Mother, Father and Child Cohort Study (MoBa) (n = 66,302) were merged after a thorough harmonization process. Diet was recorded in mid-pregnancy and information on birth outcomes was extracted from national birth registries. RESULTS: The prevalence of preterm delivery, low birth weight and fetal and neonatal deaths was 4.77%, 2.93%, 0.28% and 0.17%, respectively. Mean protein intake (standard deviation) was 89 g/day (23). Overall high protein intake (>100 g/day) was neither associated with low birth weight nor fetal or neonatal death. Mean birth weight was essentially unchanged at high protein intakes. A modest increased risk of preterm delivery [odds ratio (OR): 1.10 (95% confidence interval (CI): 1.01, 1.19)] was observed for high (>100 g/day) compared to moderate protein intake (80-90 g/day). This estimate was driven by late preterm deliveries (weeks 34 to <37) and greater risk was not observed at more extreme intakes. Very low (<60 g/day) compared to moderate protein intake was associated with higher risk of having low-birth weight infants [OR: 1.59 (95%CI: 1.25, 2.03)]. CONCLUSIONS: High protein intake was weakly associated with preterm delivery. Contrary to the results from the Harlem Trial, no indications of deleterious effects on fetal growth or perinatal mortality were observed.

Maternal dietary selenium intake is associated with increased gestational length and decreased risk of preterm delivery.

The first positive genome-wide association study on gestational length and preterm delivery showed the involvement of an Se metabolism gene. In the present study, we examine the association between maternal intake of Se and Se status with gestational length and preterm delivery in 72 025 women with singleton live births from the population-based, prospective Norwegian Mother, Father and Child Cohort Study (MoBa). A self-reported, semi-quantitative FFQ answered in pregnancy week 22 was used to estimate Se intake during the first half of pregnancy. Associations were analysed with adjusted linear and Cox regressions. Se status was assessed in whole blood collected in gestational week 17 (n 2637). Median dietary Se intake was 53 (interquartile range (IQR) 44-62) µg/d, supplements provided additionally 50 (IQR 30-75) µg/d for supplement users (n 23 409). Maternal dietary Se intake was significantly associated with prolonged gestational length (ß per sd = 0·25, 95 % CI, 0·07, 0·43) and decreased risk of preterm delivery (n 3618, hazard ratio per sd = 0·92, 95 % CI, 0·87, 0·98). Neither Se intake from supplements nor maternal blood Se status was associated with gestational length or preterm delivery. Hence, the present study showed that maternal dietary Se intake but not intake of Se-containing supplements, during the first half of pregnancy was significantly associated with decreased risk of preterm delivery. Further investigations, preferably in the form of a large randomised controlled trial, are needed to elucidate the impact of Se on pregnancy duration.

Prenatal iron exposure and childhood type 1 diabetes.

Iron overload due to environmental or genetic causes have been associated diabetes. We hypothesized that prenatal iron exposure is associated with higher risk of childhood type 1 diabetes. In the Norwegian Mother and Child cohort study (n = 94,209 pregnancies, n = 373 developed type 1 diabetes) the incidence of type 1 diabetes was higher in children exposed to maternal iron supplementation than unexposed (36.8/100,000/year compared to 28.6/100,000/year, adjusted hazard ratio 1.33, 95%CI: 1.06-1.67). Cord plasma biomarkers of high iron status were non-significantly associated with higher risk of type 1 diabetes (ferritin OR = 1.05 [95%CI: 0.99-1.13] per 50 mg/L increase; soluble transferrin receptor: OR = 0.91 [95%CI: 0.81-1.01] per 0.5 mg/L increase). Maternal but not fetal HFE genotypes causing high/intermediate iron stores were associated with offspring diabetes (odds ratio: 1.45, 95%CI: 1.04, 2.02). Maternal anaemia or non-iron dietary supplements did not significantly predict type 1 diabetes. Perinatal iron exposures were not associated with cord blood DNA genome-wide methylation, but fetal HFE genotype was associated with differential fetal methylation near HFE. Maternal cytokines in mid-pregnancy of the pro-inflammatory M1 pathway differed by maternal iron supplements and HFE genotype. Our results suggest that exposure to iron during pregnancy may be a risk factor for type 1 diabetes in the offspring.

Suboptimal Maternal Iodine Intake Is Associated with Impaired Child Neurodevelopment at 3 Years of Age in the Norwegian Mother and Child Cohort Study.

Background: Severe iodine deficiency in pregnancy has major effects on child neurodevelopment, but less is known about the potential consequences of mild-to-moderate deficiency and iodine supplement use.Objective: We explored the associations between maternal iodine intake and child neurodevelopment at 3 y of age and the potential impact of maternal intake of iodine from supplements on the same outcomes.Methods: This population-based prospective observational study included 48,297 mother-child pairs recruited during pregnancy from 2002 to 2008. Maternal iodine intake was calculated based on a validated food-frequency questionnaire answered during midpregnancy that covered mean intake since the beginning of pregnancy. Associations between iodine intake and maternal-reported child language and motor development and behavior problems were explored by multivariable regression analyses.Results: In 33,047 mother-child pairs, excluding iodine supplement users, maternal iodine intake was associated with child language delay (P = 0.024), externalizing and internalizing behavior problems (both P < 0.001), and fine motor skills (P = 0.002) but not gross motor skills or the risk of not walking unaided at 17 mo of age. In 74% of the participants who had an iodine intake <160 µg/d (Estimated Average Requirement), suboptimal iodine intake was estimated to account for ∼5% (95% CI: -5%, 14%) of the cases of language delay, 16% (95% CI: 0%, 21%) of the cases of externalizing behavior problems >1.5 SD, and 16% (95% CI: 10%, 21%) of the cases of internalizing behavior problems >1.5 SD. In 48,297 mother-child pairs, including iodine supplement users, we found no protective effects of supplemental iodine during pregnancy on neurodevelopment.Conclusions: Maternal iodine intake below the Estimated Average Requirement during pregnancy was associated with symptoms of child language delay, behavior problems, and reduced fine motor skills at 3 y of age. The results showed no evidence of a protective effect of iodine supplementation during pregnancy.

Maternal Folate Intake during Pregnancy and Childhood Asthma in a Population-based Cohort.

RATIONALE: A potential adverse effect of high folate intake during pregnancy on children's asthma development remains controversial. OBJECTIVES: To prospectively investigate folate intake from both food and supplements during pregnancy and asthma at age 7 years when the diagnosis is more reliable than at preschool age. METHODS: This study included eligible children born 2002-2006 from the Norwegian Mother and Child Cohort Study, a population-based pregnancy cohort, linked to the Norwegian Prescription Database. Current asthma at age 7 was defined by asthma medications dispensed at least twice in the year (1,901 cases; n = 39,846) or by maternal questionnaire report (1,624 cases; n = 28,872). Maternal folate intake was assessed with a food frequency questionnaire validated against plasma folate. We used log-binomial and multinomial regression to calculate adjusted relative risks with 95% confidence intervals. MEASUREMENTS AND MAIN RESULTS: Risk of asthma was increased in the highest versus lowest quintile of total folate intake with an adjusted relative risk of 1.23 (95% confidence interval, 1.06-1.44) that was similar for maternally reported asthma. Mothers in the highest quintile had a relatively high intake of food folate (median, 308; interquartile range, 241-366 µg/d) and nearly all took at least 400 µg/d of supplemental folic acid (median, 500; interquartile range, 400-600 µg/d). CONCLUSIONS: In this large prospective population-based cohort with essentially complete follow-up, pregnant women taking supplemental folic acid at or above the recommended dose, combined with a diet rich in folate, reach a total folate intake level associated with a slightly increased risk of asthma in children.

Prenatal methylmercury exposure and language delay at three years of age in the Norwegian Mother and Child Cohort Study.

Prenatal methylmercury (MeHg) exposure and its possible neurodevelopmental effects in susceptible children are of concern. Studies of MeHg exposure and negative health outcomes have shown conflicting results and it has been suggested that co-exposure to other contaminants and/or nutrients in fish may confound the effect of MeHg. Our objective was to examine the association between prenatal exposure to MeHg and language and communication development at three years, adjusting for intake of fish, n-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) and co-exposure to dioxins and dioxin like polychlorinated biphenyls (dl-PCBs). We used data from the Norwegian Mother and Child Cohort Study (MoBa) collected between 2002 and 2008. The study sample consisted of 46,750 mother-child pairs. MeHg exposure was calculated from reported fish intake during pregnancy by a FFQ in mid-pregnancy. Children's language and communication skills were measured by maternal report on the Dale and Bishop grammar rating and the Ages and Stages communication scale (ASQ). We estimated odds ratios (OR) and 95% confidence intervals (CI) using logistic regressions. Median MeHg exposure was 1.3µg/day, corresponding to 0.14µg/kgbw/week. An exposure level above the 90th percentile (>2.6µg/day, >0.29µg/kgbw/week) was defined as the high MeHg exposure. Results indicated an association between high MeHg exposure and unintelligible speech with an adjusted OR 2.22 (1.31, 3.72). High MeHg exposure was also associated with weaker communication skills adjusted OR 1.33 (1.03, 1.70). Additional adjustment for fish intake strengthened the associations, while adjusting for PCBs and n-3 LCPUFA from diet or from supplements had minor impact. In conclusion, significant associations were found between prenatal MeHg exposure above the 90th percentile and delayed language and communication skills in a generally low exposed population.

Effect of genetic polymorphisms involved in folate metabolism on the concentration of serum folate and plasma total homocysteine (p-tHcy) in healthy subjects after short-term folic acid supplementation: a randomized, double blind, crossover study.

Data on the effect of combined genetic polymorphisms, involved in folate metabolism, on the concentration of serum folate after folic acid supplementation are scarce. Therefore, we investigated the impact of seven gene polymorphisms on the concentration of serum folate and p-tHcy in healthy subjects after short-term folic acid supplementation. In a randomized, double blind, crossover study, apparently healthy subjects were given either 0.8 mg folic acid per day (n = 46) or placebo (n = 45) for 14 days. The washout period was 14 days. Fasting blood samples were collected on day 1, 15, 30 and 45. Data on subjects on folic acid supplementation (n = 91) and on placebo (n = 45) were used for the statistical analysis. The concentration of serum folate increased higher in subjects with higher age (53.5 ± 7.0 years) than in subjects with lower age (24.3 ± 3.2 years) after folic acid supplementation (p = 0.006). The baseline concentration of serum folate in subjects with polymorphism combination, reduced folate carrier protein, RFC1-80 GA and methylenetetrahydrofolate reductase, MTHFR677 CT+TT, was lower than RFC1-80 AA and MTHFR677 CT+TT (p = 0.002). After folic acid supplementation, a higher increase in the concentration of serum folate was detected in subjects with polymorphism combination RFC1-80 GA and MTHFR677 CC than RFC1-80 GG and MTHFR CT+TT combination (p < 0.0001). The baseline concentration of plasma total homocysteine (p-tHcy) was altered by combined polymorphisms in genes associated with folate metabolism. After folic acid supplementation, in subjects with combined polymorphisms in methylenetetrahydrofolate dehydrogenase, MTHFD1-1958 and MTHFR-677 genes, the concentration of p-tHcy was changed (p = 0.002). The combination of RFC1-80 and MTHFR-677 polymorphisms had a profound affect on the concentration of serum folate in healthy subjects before and after folic acid supplementation.

Effects of polymorphisms in endothelial nitric oxide synthase and folate metabolizing genes on the concentration of serum nitrate, folate, and plasma total homocysteine after folic acid supplementation: a double-blind crossover study.

OBJECTIVES: A number of studies have explored the effects of dietary nitrate on human health. Nitrate in the blood can be recycled to nitric oxide, which is an essential mediator involved in many important biochemical mechanisms. Nitric oxide is also formed in the body from l-arginine by nitric oxide synthase. The aim of this study was to investigate whether genetic polymorphisms in endothelial nitric oxide synthase (eNOS) and genes involved in folate metabolism affect the concentration of serum nitrate, serum folate, and plasma total homocysteine in healthy individuals after folic acid supplementation. METHODS: In a randomized double-blind, crossover study, participants were given either folic acid 800 µg/d (n = 52) or placebo (n = 51) for 2 wk. Wash-out period was 2 wk. Fasting blood samples were collected, DNA was extracted by salting-out method and the polymorphisms in eNOS synthase and folate genes were genotyped by polymerase chain reaction methods. Measurement of serum nitrate and plasma total homocysteine (p-tHcy) concentration was done by high-performance liquid chromatography. RESULTS: The concentration of serum nitrate did not change in individuals after folic acid supplements (trial 1); however, the concentration of serum nitrate increased in the same individuals after placebo (P = 0.01) (trial 2). The individuals with three polymorphisms in eNOS gene had increased concentration of serum folate and decreased concentration of p-tHcy after folic acid supplementation. Among the seven polymorphisms tested in folate metabolizing genes, serum nitrate concentration was significantly decreased only in DHFR del 19 gene variant. A significant difference in the concentration of serum nitrate was detected among individuals with MTHFR C > T677 polymorphisms. CONCLUSIONS: Polymorphisms in eNOS and folate genes affect the concentration of serum folate and p-tHcy but do not have any effect on the concentration of NO3 in healthy individuals after folic acid supplementation.

Folic acid supplementation, dietary folate intake during pregnancy and risk for spontaneous preterm delivery: a prospective observational cohort study.

BACKGROUND: Health authorities in numerous countries recommend periconceptional folic acid supplementation to prevent neural tube defects. The objective of this study was to examine the association of dietary folate intake and folic acid supplementation during different periods of pregnancy with the risk of spontaneous preterm delivery (PTD). METHODS: The Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 66,014 women with singleton pregnancies resulting in live births in 2002-2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until pregnancy week 24. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4-5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22+0 and 36+6 (n = 1,755). RESULTS: The median total folate intake was 313 µg/d (interquartile range IQR 167-558) in the overall population and 530 µg/d (IQR 355-636) in the supplement users. Eighty-five percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while only 44% initiated folic acid supplementation before pregnancy. Cox regression analysis showed that the amount of dietary folate intake (hazard ratio HR 1.00; confidence interval 95% CI 0.61-1.65) and supplemental folate intake (HR 1.00; CI 1.00-1.00) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for spontaneous PTD (HR 1.18; CI 1.05-1.32) compared to no folic acid supplementation preconception. There was no significant association with PTD when supplementation was initiated within 8 weeks preconception (HR 0.99; CI 0.87-1.13). All analyses were adjusted for maternal characteristics and socioeconomic, health and dietary variables. CONCLUSIONS: Our findings do not support a protective effect of dietary folate intake or folic acid supplementation on spontaneous PTD. Preconceptional folic acid supplementation starting more than 8 weeks before conception was associated with an increased risk of spontaneous PTD. These results require further investigation before discussing an expansion of folic acid supplementation guidelines.

Folic acid supplementation and interpregnancy interval.

BACKGROUND: Maternal folic acid supplementation between subsequent pregnancies may be important to reduce the risk of low folate status associated with short interpregnancy intervals. We examined how the prevalence of preconception folic acid use for a given pregnancy in Norwegian women varied according to the time interval from the previous pregnancy. METHODS: Analysis was based on 48 855 pairs of pregnancies with the second pregnancy included in the Norwegian Mother and Child Cohort Study (birth years 1999-2009). Interpregnancy interval was defined as the time from birth of a child to the conception of the subsequent sibling. Preconception folic acid use was defined as any use of folic acid-containing supplements within the last 4 weeks before the second pregnancy. RESULTS: The prevalence of preconception folic acid use was 31%. Among women with a term birth (≥37 weeks) in the previous pregnancy (92%), those with interpregnancy intervals ≤12 and ≥49 months were associated with up to 35% lower prevalence of preconception folic acid use for the second pregnancy, relative to the reference group (13-24 months). The low use in short intervals was mainly attributable to lower proportion of planned pregnancies and fewer women with higher education. Among women with a preterm birth (<37 weeks) in the previous pregnancy (8%), preconception folic acid use significantly decreased with increasing pregnancy spacing. CONCLUSIONS: Our finding of a lower preconception folic acid use in women with both short and long interpregnancy intervals might help identifying those with higher risk of folate deficiency and preventing unwanted pregnancy outcomes.

Probiotic milk consumption in pregnancy and infancy and subsequent childhood allergic diseases.

BACKGROUND: Whether probiotics, which can influence the microbiome, prevent infant eczema or allergic disease remains an open question. Most studies have focused on high-risk infants. OBJECTIVES: We sought to assess whether consumption of probiotic milk products protects against atopic eczema, rhinoconjunctivitis, and asthma in early childhood in a large population-based pregnancy cohort (the Norwegian Mother and Child Cohort study). METHODS: We examined associations between consumption of probiotic milk products in pregnancy and infancy with questionnaire-reported atopic eczema, rhinoconjunctivitis, and asthma in 40,614 children. Relative risks (RRs) were calculated by using general linear models adjusted for potential confounders. RESULTS: Consumption of probiotic milk in pregnancy was associated with a slightly reduced relative risk (RR) of atopic eczema at 6 months (adjusted RR, 0.94; 95% CI, 0.89-0.99) and of rhinoconjunctivitis between 18 and 36 months (adjusted RR, 0.87; 95% CI, 0.78-0.98) compared with no consumption during pregnancy. Maternal history of allergic disease did not notably influence the associations. When both the mother (during pregnancy) and infant (after 6 months of age) had consumed probiotic milk, the adjusted RR of rhinoconjunctivitis was 0.80 (95% CI, 0.68-0.93) relative to no consumption by either. Probiotic milk consumption was not associated with asthma at 36 months. CONCLUSIONS: In this population-based cohort consumption of probiotic milk products was related to a reduced incidence of atopic eczema and rhinoconjunctivitis, but no association was seen for incidence of asthma by 36 months of age.

Association between maternal iron supplementation during pregnancy and risk of celiac disease in children.

BACKGROUND & AIMS: The aim of our study was to determine whether the use of iron supplements during pregnancy affects the risk for celiac disease in children. METHODS: We assessed data from the prospective Norwegian Mother and Child cohort study, in which individuals with celiac disease were identified by answers on questionnaires and linkage to the Norwegian Patient Register. Complete data were available for 78,846 children (mean age 5.9 years, range 2-12 years); 314 children were identified with celiac disease. Questionnaires were given to pregnant women to collect information on use of iron-containing supplements, diet, anemia, and levels of hemoglobin. RESULTS: Celiac disease was diagnosed in 4.65 of 1000 children whose mothers took iron supplements while they were pregnant, compared with 3.15 of 1000 children whose mothers did not. After adjusting for children's age, sex, and age of gluten introduction, and the presence of celiac disease in mothers, iron supplementation during pregnancy remained significantly associated with celiac disease in children (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.05-1.68; P = .019). However, celiac disease was not associated with the mothers' intake of iron from foods (adjusted OR, 1.00; 95% CI, 0.97-1.03). Anemia before or during the early stages of pregnancy was not significantly associated with the risk of celiac disease in children (adjusted OR, 1.24; 95% CI, 0.84-2.00; P = .24). The use of iron supplements during pregnancy remained significantly associated with celiac disease in children after adjusting for children who were given iron supplements before 18 months of age, which itself was associated with celiac disease. CONCLUSIONS: In a prospective Norwegian Mother and Child cohort study, we found an increased risk of celiac disease in children whose mothers used iron supplements during pregnancy; this association does not appear to arise from maternal anemia.

Folic acid supplementation, dietary folate intake during pregnancy and risk for spontaneous preterm delivery: a prospective observational cohort study.

BACKGROUND: Health authorities in numerous countries recommend periconceptional folic acid to pregnant women to prevent neural tube defects. The objective of this study was to examine the association of folic acid supplementation during different periods of pregnancy and of dietary folate intake with the risk of spontaneous preterm delivery (PTD). METHODS: The Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 65,668 women with singleton pregnancies resulting in live births in 1999-2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until week 24 during pregnancy. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4-5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22+0 and 36+6 (n = 1,628). RESULTS: The median total folate intake was 266 µg/d (interquartile range IQR 154-543) in the overall population and 540 µg/d (IQR 369-651) in the supplement users. Eighty-three percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while 42% initiated folic acid supplementation before their pregnancy. Cox regression analysis showed that the amount of folate intake from the diet (hazard ratio HR 1.16; confidence interval CI 0.65-2.08) and from the folic acid supplements (HR 1.04; CI 0.95-1.13) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for PTD (HR 1.19; CI 1.05-1.34) compared to no folic acid supplementation pre-conception. There was no significant association with PTD when supplementation was initiated within 8 weeks pre-conception (HR 1.01; CI 0.88-1.16). All analyses were adjusted for maternal characteristics and socioeconomic, health and dietary variables. CONCLUSIONS: Our findings do not support a protective effect of dietary folate intake or folic acid supplementation on spontaneous PTD. Pre-conceptional folic acid supplementation starting more than 8 weeks before conception was associated with an increased risk of PTD. These results require further investigation before discussing an expansion of folic acid supplementation guidelines.

Risk of suboptimal iodine intake in pregnant Norwegian women.

Pregnant women and infants are exceptionally vulnerable to iodine deficiency. The aims of the present study were to estimate iodine intake, to investigate sources of iodine, to identify predictors of low or suboptimal iodine intake (defined as intakes below 100 µg/day and 150 µg/day) in a large population of pregnant Norwegian women and to evaluate iodine status in a sub-population. Iodine intake was calculated based on a validated Food Frequency Questionnaire in the Norwegian Mother and Child Cohort. The median iodine intake was 141 µg/day from food and 166 µg/day from food and supplements. Use of iodine-containing supplements was reported by 31.6%. The main source of iodine from food was dairy products, contributing 67% and 43% in non-supplement and iodine-supplement users, respectively. Of 61,904 women, 16.1% had iodine intake below 100 µg/day, 42.0% had iodine intake below 150 µg/day and only 21.7% reached the WHO/UNICEF/ICCIDD recommendation of 250 µg/day. Dietary behaviors associated with increased risk of low and suboptimal iodine intake were: no use of iodine-containing supplements and low intake of milk/yogurt, seafood and eggs. The median urinary iodine concentration measured in 119 participants (69 µg/L) confirmed insufficient iodine intake. Public health strategies are needed to improve and secure the iodine status of pregnant women in Norway.

Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children.

IMPORTANCE: Prenatal folic acid supplements reduce the risk of neural tube defects in children, but it has not been determined whether they protect against other neurodevelopmental disorders. OBJECTIVE: To examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder-not otherwise specified [PDD-NOS]) in children. DESIGN, SETTING, AND PATIENTS: The study sample of 85,176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Relative risks of ASDs were estimated by odds ratios (ORs) with 95% CIs in a logistic regression analysis. Analyses were adjusted for maternal education level, year of birth, and parity. MAIN OUTCOME MEASURE: Specialist-confirmed diagnosis of ASDs. RESULTS: At the end of follow-up, 270 children in the study sample had been diagnosed with ASDs: 114 with autistic disorder, 56 with Asperger syndrome, and 100 with PDD-NOS. In children whose mothers took folic acid, 0.10% (64/61,042) had autistic disorder, compared with 0.21% (50/24,134) in those unexposed to folic acid. The adjusted OR for autistic disorder in children of folic acid users was 0.61 (95% CI, 0.41-0.90). No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use. CONCLUSIONS AND RELEVANCE: Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation.

Fish liver and seagull eggs, vitamin D-rich foods with a shadow: results from the Norwegian Fish and Game Study.

SCOPE: Fish liver, fish liver oil, oily fish and seagull eggs have been major sources of vitamin D for the coastal population of Norway. They also provide dioxin and polychlorinated dioxin-like compounds (dl-compounds), which may interfere with vitamin D homeostasis. We investigated whether serum 25-hydroxyvitamin D (25(OH)D) might be compromised by concomitant intake of dl-compounds. METHODS AND RESULTS: We studied 182 adults participating in the Norwegian Fish and Game Study. Participants who consumed fish liver and/or seagull eggs had higher dl-compound intake and blood concentrations than non-consumers (p < 0.001). Vitamin D intake was higher (p < 0.001), whereas serum 25(OH)D was lower (p = 0.029) in consumers than in non-consumers. Among non-consumers, vitamin D intake was associated with serum 25(OH)D (ß=1.06; 95% CI: 0.48, 1.63). This association was weaker among consumers (ß = 0.52; 95% CI: -0.05, 1.08), but strengthened when adjusted for retinol intake (ß = 0.66; 95% CI: 0.12, 1.21). The association between vitamin D intake and serum 25(OH)D did not seem to be compromised by intake of dl-compounds. CONCLUSION: To secure adequate vitamin D status while keeping the intake of dioxins and dl-polychlorinated biphenyls low, a healthy diet should include both supplemental vitamin D and oily fish. Despite high nutrient content, dietary fish liver and seagull eggs should be restricted, due to dl-compounds and possible vitamin A-D antagonism.

Treatment of fibromyalgia at the Maharishi Ayurveda Health Centre in Norway II--a 24-month follow-up pilot study.

Treatments offered at the Maharishi Ayurveda Health Centre in Norway are based on Maharishi Vedic Medicine (MVM). MVM is a consciousness-based revival by Maharishi Mahesh Yogi, the founder of the Transcendental Meditation (TM) program of the ancient Ayurvedic medicine tradition in India. To extend from 6 to 24 months, a pilot study of the effects of the treatment program at the Health Centre on fibromyalgia. Retesting 2 years after a clinical trial. In this intention to treat study, 31 women with a diagnosis of fibromyalgia received an individually tailored program of (1) physiological purification therapy (Maharishi Panchakarma) and (2) Ayurvedic recommendations regarding daily routine and diet including a novel approach to food intolerance. Five subjects chose to learn TM for stress reduction, pain management and personal development. All were recommended Ayurvedic herbal products for follow-up treatment. A modified Fibromyalgia Impact Questionnaire (FIQ) that included seven dimensions. Scores at 24 months follow-up were compared with pre-treatment scores. At 24-months follow-up, there were significant reductions (26% to 44%) in six of the seven fibromyalgia dimensions: impairment of working ability, pain, tiredness, morning tiredness, stiffness and anxiety. The 7th, depression, decreased 32% (borderline significant). At 24 months, the four subjects who continued practising TM, had almost no symptoms and significantly lower FIQ change scores (-92% to 97%) than the non-meditators on all outcomes. This pilot study suggests that the treatments and health promotion programs offered at the Maharishi Ayurveda Health Centre in Norway lead to long-term reductions in symptoms of fibromyalgia, which is considered a treatment-resistant condition, and further studies are warranted.

Dietary supplement use immediately before and during pregnancy in Norwegian women with eating disorders.

OBJECTIVE: Many pregnant women use dietary supplements. Little is known about dietary supplement use during pregnancy in women with eating disorders. METHOD: We examined dietary supplement use in 37,307 pregnant women, from the Norwegian Mother and Child Cohort Study. RESULTS: Dietary supplement use during pregnancy was as follows: 91.2% of women with anorexia nervosa, 92.2% of women with bulimia nervosa, 93.2% of women with eating disorder not otherwise specified-purging subtype (EDNOS-P), 90.6% of women with binge eating disorder, and 93.5% of the women without eating disorders. Between group differences were not statistically significant. After adjusting for covariates, women with EDNOS-P were more likely to take iron containing supplements (p ≤ .04). DISCUSSION: Overall dietary supplement use in this sample is similar in women with and without eating disorders.

Infant birth size is not associated with maternal intake and status of folate during the second trimester in Norwegian pregnant women.

Maternal folate status and smoking are potentially strong risk factors for infant birth size. We assessed the association of several folate indicators and smoking with birth outcomes in a subsample of participants in the Norwegian Mother and Child Cohort Study, consisting of 2934 singleton pregnancies in 2002-2003. Blood plasma folate and cotinine concentrations and self-reported intake of food folate and supplemental folic acid were measured during the second trimester (median 18 wk). Birth outcomes included gestational age, infant birth weight, head circumference, crown-heel length, and small for gestational age (SGA). Mean total dietary folate intake from foods (mean 268.0 microg/d) and supplements (mean 187.7 microg/d) was 455.7 microg/d. Smokers (plasma cotinine > or = 85 nmol/L) had substantially lower supplemental folic acid intake than nonsmokers, but they did not differ regarding folate intake from food only. Nevertheless, smoking was correlated with plasma folate both before and after adjusting for total dietary folate intake (both P < 0.001). We found no significant associations of food folate intake, supplemental folic acid use, total dietary folate intake, or plasma folate with the various birth outcomes after adjustment for potential confounders. Consistent with previous studies, infant birth size was strongly predicted by maternal smoking (adjusted odds ratio for SGA: 2.3; 95% CI: 1.6, 3.3). This study of well-nourished Norwegian pregnant women suggests that dietary folate and plasma folate during the second trimester are not risk factors for infant birth size.

Exploration of biomarkers for total fish intake in pregnant Norwegian women.

OBJECTIVE: Few biomarkers for dietary intake of various food groups have been established. The aim of the present study was to explore whether selenium (Se), iodine, mercury (Hg) or arsenic may serve as a biomarker for total fish and seafood intake in addition to the traditionally used n-3 fatty acids EPA and DHA. DESIGN: Intake of fish and seafood estimated by an FFQ was compared with intake assessed by a 4 d weighed food diary and with biomarkers in blood and urine. SETTING: Validation study in the Norwegian Mother and Child Cohort Study (MoBa). SUBJECTS: One hundred and nineteen women. RESULTS: Total fish/seafood intake (median 39 g/d) calculated with the MoBa FFQ was comparable to intake calculated by the food diary (median 30 g/d, rS = 0.37, P < 0.001). Erythrocyte DHA and blood Hg, Se and arsenic concentrations were positively correlated with intake of fish and seafood, but the association for DHA was weakened by the widespread use of supplements. The main finding was the consistent positive association between the intake of fish/seafood and blood arsenic concentration. In multivariate analyses, blood arsenic was associated with blood Hg and fish and seafood intake. In these models, arsenic turned out to be the best indicator of intake of fish and seafood, both totally and in subgroups of fish/seafood intake. CONCLUSIONS: While DHA reflected the intake of fatty fish and n-3 PUFA supplements, blood arsenic concentration also reflected the intake of lean fish and seafood. Blood arsenic appears to be a useful biomarker for total fish and seafood intake.