Effects of Two Weekly Servings of Cod for 16 Weeks in Pregnancy on Maternal Iodine Status and Infant Neurodevelopment: Mommy's Food, a Randomized-Controlled Trial.

Background: Mild-to-moderate iodine deficiency is still present in many countries, particularly in pregnant women. Observational studies suggest that mild-to-moderate iodine deficiency during pregnancy may be associated with impaired thyroid function and child neurodevelopment. Randomized-controlled food trials to increase iodine status are scarce. We assessed the impact of an increased intake of cod during pregnancy on maternal iodine status and infant neurodevelopment. Methods: In this randomized-controlled trial, pregnant women in Bergen, Norway, recruited through Haukeland University Hospital, were randomly assigned (1:1) to an intervention of 200 g of cod twice a week for 16 weeks (gestational week 20-36) or to continue with their standard diet (control group). Randomization was done by lottery. Primary outcome was urinary iodine concentration (UIC) (spot samples from six consecutive days) measured postintervention. Secondary outcome was infant neurodevelopment assessed by the cognitive, language, and motor scales of the Bayley Scales of Infant and Toddler Developmental third edition (Bayley-III) at 11 months of age. In addition, maternal thyroid function was measured (thyrotropin [TSH], free triiodothyronine [fT3], free thyroxine [fT4]) at baseline and postintervention. Results: Between January 2016 until February 2017, 137 women were recruited. Postintervention UIC was higher in the intervention group (n = 61) [median (interquartile range, IQR) 98 (64-145) µg/L], compared with control (n = 61) [median (IQR) 73 (52-120) µg/L] (p = 0.028), also after adjusting for baseline UIC (p = 0.048). Infants of mothers in the intervention group had a lower cognitive composite score on the Bayley-III compared with the control group (p = 0.045). There were no group differences in the Bayley III language- or motor composite scores. Maternal thyroid hormones (TSH, fT3, fT4) did not differ between the groups postintervention. Conclusions: Increased cod intake during pregnancy improved the iodine status in women with mild-to-moderate iodine deficiency, however, did not affect thyroid function. The negative effect on cognition should be followed up to assess whether this is a stable effect over time. More studies are warranted to enable good health advice on iodine nutrition in pregnancy. ClinicalTrials.gov NCT02610959. Registered November 20, 2015.

Iodine and Mercury Content in Raw, Boiled, Pan-Fried, and Oven-Baked Atlantic Cod (Gadus morhua).

There is a lack of scientific evidence regarding the stability of iodine and mercury during cooking and processing of seafood. In this study, the iodine and mercury content were determined after thawing frozen fillets of Atlantic cod (Cadus morhua), and further in raw compared to boiled, pan-fried, and oven baked fillets. Iodine was determined by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) and mercury by atomic absorption spectrophotometry with Direct Mercury Analyzer (DMA-80). Thawing of the cod resulted on average in a 12% loss of iodine to the thawing water. Boiling significantly decreased the total content of iodine per slice of cod fillet corresponding to the concentration of iodine found in the boiling water. Pan-frying and oven-baking did not cause any significant changes of the total iodine content per slice of cod fillet, although iodine content per 100 g increased due to weight reduction of the cod slices from evaporation of water during preparation. For mercury, we found minimal changes of the different cooking methods. In summary, the findings in our study show that boiling had the greatest effect on the iodine content in the cod fillets. Type of cooking method should be specified in food composition databases as this in turn may influence estimation of iodine intake.

Fatty Acid Reference Intervals in Red Blood Cells among Pregnant Women in Norway-Cross Sectional Data from the 'Little in Norway' Cohort.

There is a growing interest in determining fatty acid reference intervals from pregnancy cohort, especially considering the lack of reference values for pregnant women in the literature and the generalized misconception of equating reference intervals for nonpregnant women as equivalent to pregnant women. Seafood and supplements are important dietary sources for the omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA), such as eicosapentaenoic acid (EPA, 20:5ω-3), docosapentaenoic acid (DPA, 22:55ω-3), and docosahexaenoic acid (DHA, 22:6ω-3). Sufficient intake of EPA and DHA is vital during pregnancy for the development of the fetus, as well as for maintaining adequate levels for the mother. This study describes the fatty acid status and suggests reference values and cut-offs for fatty acids in red blood cells (RBC) from pregnant women (n = 247). An electronic food frequency questionnaire (e-FFQ) mapped the dietary habits of the participants, and gas chromatography was used to determine the fatty acid levels in RBC. The association between e-FFQ variables and fatty acid concentrations was established using a principal component analysis (PCA). Twenty-nine-point-one percent (29.1%) of the participants reported eating seafood as dinner according to the Norwegian recommendations, and they added in their diet as well a high percentage (76.9%) intake of ω-3 supplements. The concentration levels of fatty acids in RBC were in agreement with those reported in similar populations from different countries. The reference interval 2.5/97.5 percentiles for EPA, DPA, DHA were 0.23/2.12, 0.56/2.80, 3.76/10.12 in relative concentration units (%), and 5.99/51.25, 11.08/61.97, 64.25/218.08 in absolute concentration units (µg/g), respectively. The number of participants and their selection from all over Norway vouch for the representativeness of the study and the validity of the proposed reference values, and therefore, the study may be a useful tool when studying associations between fatty acid status and health outcome in future studies. To the best of our knowledge, this is the first PCA study reporting a direct association between ω-3 LCPUFA and intake of seafood and ω-3 supplements in a pregnancy cohort.

Effects of seafood consumption on mercury exposure in Norwegian pregnant women: A randomized controlled trial.

BACKGROUND: Seafood provides nutrients that are important for optimal development of the unborn child. However, seafood is also a source of contaminants including mercury (Hg) and methylmercury (MeHg) that may have adverse effects on neurodevelopment of the fetus. Humans are predominantly exposed to MeHg through seafood consumption, however, levels of MeHg vary considerably between species. OBJECTIVES: Investigate, in a randomized controlled trial (RCT) during pregnancy, if an increased intake of Atlantic cod (Gadus morhua), a fish species with relatively low levels of MeHg contamination, influences total hair Hg (THHg) concentrations in humans. METHODS: Pregnant women (n = 137) were enrolled in the RCT "Mommy's Food" (2016-2017), which was designed to increase iodine status. Participants were randomly assigned to intervention (400 g of cod fillets per week) or control (continued habitual diet) groups for 16 weeks (gestational week 20-36). THHg concentrations were measured at baseline and post-intervention using thermal decomposition, amalgamation, and atomic absorption spectrophotometry (US EPA method 7473). The trial is registered in ClinicalTrials.gov, NCT02610959. RESULTS: Post-intervention, the intervention group had median (inter-quartile range) THHg concentrations of 554 (392-805) µg/kg, and the control group 485 (341-740) µg/kg (p = 0.186). When adjusting for baseline THHg concentrations, there was a significant difference between the groups in those participants with baseline THHg concentrations below 534 µg/kg. Post-intervention, 8% of the study population exceeded the US EPA reference dose in hair (1,000 µg/kg) (intervention group: n = 6, control group: n = 4). CONCLUSION: THHg concentrations were generally low in both study groups of pregnant women, despite the relatively high seafood intake. While the intervention with 400 g of cod per week slightly increased THHg concentrations, it did not lead to an increase in number of subjects exceeding the US EPA reference dose; a dose level at which no adverse effects are expected to occur over a period of lifetime exposure.

Validation and reproducibility of a new iodine specific food frequency questionnaire for assessing iodine intake in Norwegian pregnant women.

BACKGROUND: Iodized salt is not mandatory in Norway, and the permitted level of iodine in table salt is low (5 µg/g). Thus, milk and dairy products, fish and eggs are the main dietary sources of iodine in Norway. Mild-to-moderate iodine deficiency in pregnant women has been described in several European countries, including Norway. There are few validated tools available to assess iodine intake in an efficient manner. The aim of the current study was to assess the validity and reproducibility of a new iodine-specific food frequency questionnaire (I-FFQ) in Norwegian pregnant women. METHODS: An I-FFQ consisting of a total of 60 food items and the use of supplements was developed to assess iodine intake and was administrated to 137 pregnant women at gestational week 18-19. Reference methods were a structured 6-days iodine specific food diary, urinary iodine concentration (UIC) (pooled sample of spot UIC from six consecutive days), and thyroid function tests. Correlation analyses, Cohen's weighted kappa, Bland-Altman plots, and linear regression analyses were used to assess validity. Reproducibility of the I-FFQ was assessed in a subgroup (n = 47) at gestational week 35-36. RESULTS: There was a strong correlation between estimated iodine intake from the I-FFQ and food diary (r = 0.62, P < 0.001) and an acceptable correlation between the I-FFQ and UIC (r = 0.21, P = 0.018). There was no significant association between the I-FFQ and thyroid function tests. The I-FFQ estimated higher iodine intake compared to the food diary with a mean absolute difference 33 µg/day. The limits of agreement from the Bland-Altman plots were large, however few participants fell outside the limits of agreement (5.2-6.5%). There was no difference between the estimated iodine intake from the I-FFQ assessed at gestational week 18-19, and gestational week 35-36 (P = 0.866), and there was a strong correlation between the two time points (r = 0.63, P < 0.001). CONCLUSION: In summary, this study suggests that the I-FFQ can be used as a valid tool to estimate and rank iodine intake among Norwegian pregnant women. We further suggest that this I-FFQ may also be valid in other populations with similarly dietary patterns and where salt is not iodized. TRIAL REGISTRATION: The study is registered in ClinicalTrials.gov (NCT02610959).

Iodine status in Norwegian preschool children and associations with dietary iodine sources: the FINS-KIDS study.

PURPOSE: Iodine is an essential trace element necessary for thyroid hormone synthesis. Iodine deficiency is a continuing public health problem despite international efforts to eliminate it. Studies on iodine status in preschoolers are scarce. Thus, the aims of the current study were to determine the iodine status and to investigate possible associations between urinary iodine concentration (UIC) and estimated 24 h iodine extraction (UIE) and iodine-rich foods. METHODS: Data are cross-sectional baseline data, obtained from the two-armed randomized controlled dietary trial "Fish Intervention Studies-KIDS" (FINS-KIDS) conducted in Bergen, Norway. UIC was determined by inductively coupled plasma-mass spectrometry in spot urine samples. Inadequate UIC was defined as median < 100 µg/L, and low estimated 24 h UIE as < 65 µg/day. Habitual dietary intake was assessed by a short food frequency questionnaire. Logistic regression models were used to investigate possible associations between UIC and estimated 24 h UIE and iodine-rich dietary sources including seafood, dairy products and eggs. Iodine/creatinine ratio (I/Cr) was also estimated. RESULTS: Urinary spot samples were obtained from 220 children. The median (interquartile range) UIC and estimated 24 h UIE was 132 (96) µg/L, and 65 (55) µg/day, respectively. The majority of children had an estimated I/Cr ratio within 100-199 µg/g. Intake of sweet milk < 2 times/day versus ≥ 2 times/day was associated with UIC < 100 µg/L (OR 2.17, 95% CI 1.07-4.38, p = 0.031). Intake of dairy products (OR 3.59, 95% CI 1.13-11.43, p = 0.031) and sweet milk (OR 2.77, 95% CI 1.37-5.61, p = 0.005) < 2 times/day versus ≥ 2 times day was associated with estimated 24 h UIE < 65 µg/day. CONCLUSIONS: The preschoolers had adequate iodine status. Low intake of sweet milk and dairy products were associated with low iodine status.

Iodine content of six fish species, Norwegian dairy products and hen's egg.

Iodine is a trace element required for the production of thyroid hormones, essential for metabolism, growth and brain development, particularly in the first trimester of pregnancy. Milk and lean fish are the main dietary sources of iodine in the Norwegian diet. Thus, the aim of the present study was to provide updated analysed values of iodine concentration in six fish species, 27 selected Norwegian iodine-rich dairy foods and Norwegian hen's eggs. The iodine concentrations in the wild fish species varied between 18 µg/100 g (Atlantic halibut) and 1,210 µg/100 g (pollack). The iodine concentration of cow milk varied between 12 and 19 µg/100 g and the iodine concentration of the eggs varied between 23 and 43 µg/100 g. The results in this study deviate somewhat from the current iodine concentrations in the Norwegian Food Composition Table. This deviation may have a large impact on the assessment of the iodine intake. Hence, updated knowledge about the variation in iodine level of fish, milk, dairy products and hen's egg are of great importance when estimating the iodine intake in the population. These data will contribute substantially to future estimations of dietary iodine intake and will be made available for the public Norwegian Food Composition Table.

Effects of cod intake in pregnancy on iodine nutrition and infant development: study protocol for Mommy's Food - a randomized controlled trial.

BACKGROUND: Iodine is a key component of thyroid hormones that are critical for normal development of the brain and nervous system in utero. Recent results indicate that two thirds of pregnant women in Europe have sub-optimal iodine nutrition. In Norway, milk and seafood are the most important dietary iodine sources and contributes to about 80% of the intake. METHOD: Two-armed randomized trial where 137 pregnant women were randomized to either receiving cod twice weekly, or continue with habitual diet for 16 weeks (pregnancy week 20-36). Socioeconomic- and demographic factors, dietary information and biological (urine, blood, and hair) samples are collected pre- and post-intervention, and at six weeks, three-, six-, and eleven months postpartum. Biological samples (urine, blood, and hair) of the infant are collected at six weeks, three-, six-, and eleven months postnatal. Child development is assessed by The Bayley Scale of Infant and Toddler Development, 3rd edition, at eleven months, and by parent report on the Ages and Stages Questionnaire, 3rd edition, and Ages and Stages Questionnaire: Social Emotional at three-, six-, and eleven months. DISCUSSION: The Mommy's Food study will provide knowledge on changes in iodine nutrition when consuming iodine rich fish during pregnancy and contribute to the understanding of the impact of iodine status in pregnancy on infant neurodevelopment. TRIAL REGISTRATION: This study is registered in ClinicalTrials.gov (NCT02610959). Registered November 17, 2015.