Vitamin B12 and Folate Status in Pregnant Females and Their Infants in Norway: Secondary Analysis from the Mommy's Food Study.

BACKGROUND: Vitamin B12 and folate are essential micronutrients important for normal infant growth and development. OBJECTIVES: The aims were to describe vitamin B12 and folate status in pregnant females and their infants according to commonly used status cutoffs and examine the associations between maternal status, maternal supplement use, and breastfeeding and infant status. METHODS: Pregnant females were recruited at 18 wk gestation in Bergen, Norway. Maternal vitamin B12 and folate status were measured at gestational weeks 18 (n = 136) and 36 (n = 116), and infant status was measured at ages 3 (n = 73) and 6 (n = 74) mo. RESULTS: At gestational weeks 18 and 36, respectively, 4.4% and 2.6% of the mothers had plasma cobalamin concentrations <148 pmol/L, 0.7% and 6.9% had methylmalonic acid (MMA) concentrations >0.26 µmol/L, and 3.7% and 30% had folate concentrations <10 nmol/L. None of the females had total homocysteine (t-Hcy) concentrations >13 µmol/L or 3 combined indicator of vitamin B12 (cB12) < -0.5. At 3 and 6 mo, respectively, 4.1% and 5.4% of the infants had cobalamin concentrations <148 pmol/L, 63% and 74% had t-Hcy concentrations >6.5 µmol/L, 59% and 66% had MMA concentrations >0.26 µmol/L, and 47% and 60% had cB12 > -0.5. None of the infants had folate concentrations <10 nmol/L. Several of the vitamin B12 biomarkers in infants were associated with maternal vitamin B12 status during pregnancy. Breastfed infants had lower vitamin B12 status (as indicated by plasma cobalamin, t-Hcy, and cB12) than nonbreastfed infants at both 3 and 6 mo. Use of supplements during pregnancy was associated with better vitamin B12 status among infants at 3 and 6 mo, as indicated by infants' cobalamin and t-Hcy concentrations. CONCLUSIONS: Subclinical vitamin B12 deficiency among infants was common and associated with maternal vitamin B12 status during pregnancy and breastfeeding. Among the mothers, an increase in biochemical folate deficiency was discovered toward the end of gestation. Further studies are needed to investigate clinical consequences. This trial was registered at clinicaltrials.gov as NCT02610959.

Maternal Cod Intake during Pregnancy and Infant Development in the First Year of Life: Secondary Analyses from a Randomized Controlled Trial.

BACKGROUND: Maternal seafood intake during pregnancy is associated with child neurodevelopment. No randomized controlled trials (RCTs) have examined the effect of maternal lean fish consumption during pregnancy on child neurodevelopment. OBJECTIVES: The objective of the study was to examine the effect of increased maternal cod intake during pregnancy on infant general and socio-emotional development in the first year of life, and whether any effects observed were mediated by maternal iodine status. METHODS: In an RCT, 133 pregnant women (≤19 weeks of gestation) were randomly assigned to receive 200 g cod fillet twice weekly (intervention) or to continue with their habitual diet (control) for 16 wk. The mothers completed the developmental screening questionnaires Ages and Stages Questionnaire, 2nd edition (ASQ-2) and Ages and Stages Questionnaire: Social-Emotional (ASQ:SE) when the infants were 3, 6, and 11 mo old. We compared scores between groups using linear mixed-effects models and examined whether iodine status postintervention mediated the effect on child development. RESULTS: We found no difference between infants in the intervention and control groups on total ASQ-2 scores (P = 0.633), but a difference on the ASQ:SE scores in favor of the intervention group (20.9 and 20.5 in the intervention group and 26.1 and 26.8 in the control group for 3 and 6 mo, respectively; P = 0.020). There was no difference in change of the scores between the groups over time (P = 0.946). The effect of group on the total ASQ:SE scores was not mediated via maternal urinary iodine concentration postintervention (ß = -1.03, SE = 0.68, P = 0.126). CONCLUSIONS: Our results provide no evidence for an effect of increased cod intake during pregnancy on general child development in the first year of life, but there was a positive effect on socio-emotional problems. More studies are needed to define the role of fish consumption during pregnancy and the effects on child neurodevelopment.This trial was registered at clinicaltrials.gov as NCT02610959.

Biomarkers and Fatty Fish Intake: A Randomized Controlled Trial in Norwegian Preschool Children.

BACKGROUND: Biomarkers such as omega-3 (n-3) PUFAs, urinary iodine concentration (UIC), 1-methylhistidine (1-MH), and trimethylamine N-oxide (TMAO) have been associated with fish intake in observational studies, but data from children in randomized controlled trials are limited. OBJECTIVES: The objective of this exploratory analysis was to investigate the effects of fatty fish intake compared with meat intake on various biomarkers in preschool children. METHODS: We randomly allocated (1:1) 232 children, aged 4 to 6 y, from 13 kindergartens. The children received lunch meals of either fatty fish (herring/mackerel) or meat (chicken/lamb/beef) 3 times a week for 16 wk. We analyzed 86 biomarkers in plasma (n = 207), serum (n = 195), RBCs (n = 211), urine (n = 200), and hair samples (n = 210). We measured the effects of the intervention on the normalized biomarker concentrations in linear mixed-effect regression models taking the clustering within the kindergartens into account. The results are presented as standardized effect sizes. RESULTS: We found significant effects of the intervention on the following biomarkers: RBC EPA (20:5n-3), 0.61 (95% CI: 0.36, 0.86); DHA (22:6n-3), 0.43 (95% CI: 0.21, 0.66); total n-3 PUFAs, 0.41 (95% CI: 0.20, 0.64); n-3/n-6 ratio, 0.48 (95% CI: 0.24, 0.71); adrenic acid (22:4n-6, -0.65 (95% CI: -0.91, -0.40), arachidonic acid (20:4n-6), -0.54 (95% CI: -0.79, -0.28); total n-6 PUFAs, -0.31 (95% CI: -0.56, -0.06); UIC, 0.32 (95% CI: 0.052, 0.59); hair mercury, 0.83 (95% CI: 0.05, 1.05); and plasma 1-MH, -0.35 (95% CI: -0.61, -0.094). CONCLUSIONS: Of the 86 biomarkers, the strongest effect of fatty fish intake was on n-3 PUFAs, UIC, hair mercury, and plasma 1-MH. We observed no or limited effects on biomarkers related to micronutrient status, inflammation, or essential amino acid, choline oxidation, and tryptophan pathways.The trial was registered at clinicaltrials.gov (NCT02331667).

Iodine Nutrition and Iodine Supplement Initiation in Association with Thyroid Function in Mildly-to-Moderately Iodine-Deficient Pregnant and Postpartum Women.

BACKGROUND: Whereas the adverse effects of severe iodine deficiency during pregnancy are well documented, the effects of mild-to-moderate deficiency are not well established. OBJECTIVES: We aimed to explore whether iodine nutrition and timing of iodine supplement initiation are associated with thyroid function in pregnant and postpartum women. METHODS: In this cohort study, 137 pregnant women were enrolled and followed up at gestational weeks (GWs) 18 and 36, and 3 and 6 mo postpartum. Thyroid function tests [thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4)], urinary iodine and creatinine concentration (UIC:Cr), and iodine intake (including iodine supplement use) were measured at each time point. The associations between thyroid hormone concentrations and UIC:Cr, iodine intakes, and iodine supplement use were estimated using multiple generalized estimating equation models. RESULTS: The median UIC at GW18 was 94 µg/L, indicating mild-to-moderate iodine deficiency. UIC:Cr (ß; 95% CI) per 100 µg/g was negatively associated with fT3 (-0.191; -0.331, -0.051) and fT4 (-0.756; -1.372, -0.141) concentrations. Iodine intake (ß; 95% CI) per 100 µg/d was positively associated with TSH (0.099; 0.022, 0.177), and negatively associated with fT3 (-0.084; -0.0141, -0.027) and fT4 (-0.390; -0.599, -0.182) concentrations. Compared with no use of supplement, those initiating an iodine-containing supplement prepregnancy and continuing through pregnancy had lower TSH (estimated means) (1.35 compared with 1.68 mIU/L, P = 0.021), and higher fT3 (4.48 compared with 4.28 pmol/L, P = 0.035) and fT4 (15.2 compared with 14.4 pmol/L, P = 0.024) concentrations. CONCLUSIONS: Lower iodine availability during pregnancy and postpartum was associated with lower TSH, and higher fT3 and fT4 concentrations. The use of an iodine-containing supplement that was initiated prepregnancy and continuing through pregnancy was associated with lower TSH, and higher fT3 and fT4 concentrations, which may suggest improved thyroid function. These findings support the notion that optimization of iodine intake should start before pregnancy.This trial was registered at clinicaltrials.gov as NCT02610959.

Dietary Intake and Biomarkers of Folate and Cobalamin Status in Norwegian Preschool Children: The FINS-KIDS Study.

BACKGROUND: Folate and cobalamin (vitamin B-12) are essential for growth and development. However, few population-based studies have investigated B-vitamin status in children. OBJECTIVES: This study aimed to assess biomarkers of folate and vitamin B-12 status and to explore their dietary determinants in healthy Norwegian children. METHODS: Using baseline data obtained from a randomized controlled trial on the effect of fish intake on neurodevelopment in children aged 4-6 y, we measured the plasma concentrations of folate, cobalamin, total plasma homocysteine (tHcy), and methylmalonic acid (MMA). Food-frequency questionnaires (FFQs) were used to assess dietary intake. We used unadjusted and multiple linear regression models to explore the determinants of biomarker concentrations. RESULTS: The median (IQR) of plasma folate (n = 197) and plasma cobalamin (n = 195) concentrations were 15.2 (12.2-21.1) nmol/L and 785 (632-905) pmol/L, respectively. Plasma folate concentrations of <10 nmol/L were observed in 13% of the children. No child had a cobalamin concentration <148 pmol/L. Two children were identified with elevated plasma MMA concentrations (>0.26 µmol/L) and 8 children had elevated tHcy concentrations (>6.5 µmol/L). Plasma folate concentration was inversely correlated with tHcy (ρ = -0.24, P < 0.001); we found no correlation between tHcy and cobalamin (ρ = -0.075, P = 0.30). Children who consumed vitamin supplements had 51% higher plasma folate concentrations (P < 0.0001) than those who did not. Consumption of red meat for dinner more than twice a week was associated with 23% lower plasma folate (P < 0.01). No other significant associations between dietary intake and the biomarkers were observed. CONCLUSIONS: The Norwegian preschool children from this cohort had adequate vitamin B-12 status. Poor folate status was common and associated with elevated tHcy. The implications of poor folate status during childhood should be a prioritized research question. This trial was registered at ClinicalTrials.gov as NCT02331667.

The effects of fatty fish intake on adolescents' nutritional status and associations with attention performance: results from the FINS-TEENS randomized controlled trial.

BACKGROUND: Adolescence involves changes in dietary habits that may induce imbalances in the intake of different nutrients. Fish is an important dietary source of omega-3 (n-3) long-chain polyunsaturated fatty acids (LCPUFAs), vitamin D, several minerals and high-quality protein. By using secondary outcomes and exploratory analyses, the aims of this paper were to evaluate if nutritional biomarkers (red blood cell fatty acids, serum (s)-25(OH)D, s-ferritin and urinary iodine concentration (UIC)) were altered during a dietary intervention, and if they mediated previously reported changes in attention performance. In addition, to examine the status of the biomarkers and explore associations between dietary pattern, biomarkers and attention performance cross-sectionally at baseline. METHODS: The Fish Intervention Studies-TEENS (FINS-TEENS) was a three-armed intervention trial, including adolescents from eight secondary schools (n = 415; age: 14-15y) in Bergen, Norway. Participants were individually randomized to receive either fish meals, meat meals or n-3 LCPUFA supplements, three times a week for a total of 12 weeks. Blood and urine samples were collected pre and post intervention and attention performance was assessed with the d2 test of attention. Analyses of covariance (ANCOVA) assessed differences between groups in changes of biomarkers and linear mixed models were applied in analyses of attention performance and biomarkers. The trial is registered in ClinicalTrials.gov (NCT02350322). RESULTS: At baseline, the mean omega-3 index was 5.8 ± 1.3% and deficient status were identified for s-25(OH)D (54%), s-ferritin (10%) and UIC (40%). The intervention resulted in an increase in DHA and the omega-3 index which was larger in the supplement group compared to the fish and meat group (P < 0.01), and in the fish group compared to the meat group (P < 0.01). No differences between the groups were observed for changes in 25(OH)D, s-ferritin or UIC. None of the biomarkers mediated performance in the d2 test. The intake of fatty fish and a healthy dietary pattern was associated with scores in processing speed at baseline. CONCLUSIONS: These results show that Norwegian adolescents have insufficient status of important nutrients, which may be improved with fatty fish consumption or n-3 LCPUFA supplements. However, nutritional status was not associated with scores in the d2 test of attention.

Establishment of a seafood index to assess the seafood consumption in pregnant women.

BACKGROUND: Seafood (fish and shellfish) is an excellent source of several essential nutrients for pregnant and lactating women. A short food frequency questionnaire (FFQ) that can be used to quantitatively estimate seafood consumption would be a valuable tool to assess seafood consumption in this group. Currently there is no such validated FFQ in Norway. OBJECTIVE: The objective of this study was to establish and validate a seafood index from a seafood FFQ against blood biomarkers (the omega-3 index, the omega-3 HUFA score, and serum 25OH vitamin D). DESIGN: We assessed maternal seafood consumption during the 28th gestation week in healthy Norwegian women (n=54) with a seafood FFQ. A seafood index was developed to convert ordinal frequency data from the FFQ into numerical scale data. The following blood biomarkers were used as a validation method: omega-3 index, omega-3 HUFA score, and the serum 25OH vitamin D. RESULTS: The reported frequency of seafood as dinner and as spread was strongly correlated with the estimated frequencies of seafood as dinner and as spread. This indicated that the seafood index is a valuable tool to aggregate reported frequencies from the seafood FFQ. The seafood index composed of the frequency of seafood consumption and intake of omega-3 supplements, termed the total seafood index, correlated positively with the omega-3 index, omega-3 HUFA score, and 25OH vitamin D. CONCLUSION: We established and validated a seafood index from a seafood FFQ. The developed seafood index can be used when studying health effects of seafood consumption in large populations. This seafood FFQ captures seafood consumption and omega-3 supplement intake considerably well in a group of pregnant women.