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

Maria Wik Markhus, Mari Hysing, Lisa Kolden Midtbø, Ive Nerhus, Synnøve Næss, Inger Aakre, Ingrid Kvestad, Lisbeth Dahl, Marian Kjellevold, Maria Wik Markhus, Mari Hysing, Lisa Kolden Midtbø, Ive Nerhus, Synnøve Næss, Inger Aakre, Ingrid Kvestad, Lisbeth Dahl, Marian Kjellevold

Abstract

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.

Keywords: RCT; infants; iodine; neurodevelopment; pregnancy; thyroid hormones.

Conflict of interest statement

The authors declare they have no actual or potential competing financial interest of receiving the grant to perform this study, or no other actual or potential competing financial interests exist.

Figures

FIG. 1.
FIG. 1.
Trial profile depicting the flow of participants through the intervention trial. Bayley III, Bayley Scales of Infant and Toddler Developmental third edition; UIC, urinary iodine concentration.

References

    1. Andersson M, Karumbunathan V, Zimmermann MB. 2012. Global iodine status in 2011 and trends over the past decade. J Nutr 142:744–750
    1. WHO, UNICEF, ICCIDD. 2007. Assessment of Iodine Deficiency Disorders and Monitoring Their Elimination. World Health Organisation, Geneva, Switzerland
    1. Zimmermann MB, Gizak M, Abbott K, Andersson M, Lazarus JH. 2015. Iodine deficiency in pregnant women in Europe. Lancet Diabetes Endocrinol 3:672–674
    1. Zimmermann MB 2008. Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on the offspring: a review. Am J Clin Nutr 89:668S–672S
    1. Nordic Council of Ministers 2014. Nordic Nutrition Recommendations 2012: Integrating Nutrition and Physical Activity. Nordic Council of Ministers, Copenhagen, Denmark
    1. Abel MH, Korevaar TI, Erlund I, Villanger GD, Caspersen IH, Arohonka P, Alexander J, Meltzer HM, Brantsæter AL. 2018. Iodine intake is associated with thyroid function in mild to moderately iodine deficient pregnant women. Thyroid 28:1359–1371
    1. Markhus M, Dahl L, Moe V, Abel M, Brantsæter A, Øyen J, Meltzer H, Stormark K, Graff I, Smith L. 2018. Maternal iodine status is associated with offspring language skills in infancy and toddlerhood. Nutrients 10:1270
    1. Brantsæter AL, Abel M, Haugen M, Meltzer HM. 2013. Risk of suboptimal iodine intake in pregnant Norwegian women. Nutrients 5:424–440
    1. Dahl L, Markhus MW, Sanchez P, Moe V, Smith L, Meltzer HM, Kjellevold M. 2018. Iodine deficiency in a study population of Norwegian pregnant women—results from the little in Norway Study (LiN). Nutrients 10:513
    1. Henjum S, Aakre I, Lilleengen A, Garnweidner-Holme L, Borthne S, Pajalic Z, Blix E, Gjengedal E, Brantsæter AL. 2018. Suboptimal iodine status among pregnant women in the Oslo area, Norway. Nutrients 10:280
    1. Berg V, Nøst TH, Skeie G, Thomassen Y, Berlinger B, Veyhe AS, Jorde R, Odland JØ, Hansen S. 2017. Thyroid homeostasis in mother–child pairs in relation to maternal iodine status: the MISA study. Eur J Clin Nutr 71:1002.
    1. The Norwegian Directorate of Health 2019. Utviklingen i norsk kosthold 2018 [Trends in the Norwegian diet]. The Norwegian Directorate of Health, Oslo
    1. Carlsen M, Andersen L, Dahl L, Norberg N, Hjartåker A. 2018. New iodine food composition database and updated calculations of iodine intake among Norwegians. Nutrients 10:930
    1. Pharoah P, Buttfield I, Hetzel B. 1971. Neurological damage to the fetus resulting from severe iodine deficiency during pregnancy. Lancet 297:308–310
    1. WHO and United Nations Children's Fund 2007 Reaching optimal iodine nutrition in pregnant and lactating women and young children. World Health Organization, Geneva, Switzerland
    1. Zhou SJ, Anderson AJ, Gibson RA, Makrides M. 2013. Effect of iodine supplementation in pregnancy on child development and other clinical outcomes: a systematic review of randomized controlled trials. Am J Clin Nutr 98:1241–1254
    1. Pearce EN, Lazarus JH, Moreno-Reyes R, Zimmermann MB. 2016. Consequences of iodine deficiency and excess in pregnant women: an overview of current knowns and unknowns. Am J Clin Nutr 104(Suppl 3):918S–923S
    1. Markhus MW, Kvestad I, Midtbø LK, Nerhus I, Ødegaard ER, Graff IE, Lie Ø, Dahl L, Hysing M, Kjellevold M. 2018. Effects of cod intake in pregnancy on iodine nutrition and infant development: study protocol for Mommy's Food—a randomized controlled trial. BMC Nutr 4:7.
    1. Araujo P, Nguyen T-T, Frøyland L, Wang J, Kang JX. 2008. Evaluation of a rapid method for the quantitative analysis of fatty acids in various matrices. J Chromatogr A 1212:106–113
    1. Bayley N 2006. Bayley Scales of Infant and Toddler Development. PsychCorp, Pearson
    1. Bayley N 2009 Bayley Scales of Infant and Toddler Development (Bayley-III) Norsk Manual Supplement, 3rd ed., Pearson, San Antonio, TX
    1. Næss S, Aakre I, Kjellevold M, Dahl L, Nerhus I, Midtbø LK, Markhus MW. 2019. Validation and reproducibility of a new iodine specific food frequency questionnaire for assessing iodine intake in Norwegian pregnant women. Nutr J 18:62.
    1. Nerhus I, Markhus MW, Nilsen BM, Øyen J, Maage A, Ødegård ER, Midtbø LK, Frantzen S, Kögel T, Graff IE 2018 Iodine content of six fish species, Norwegian dairy products and hen's egg. Food Nutr Res 62 DOI: 10.29219/fnr.v62.1291
    1. Moe V, Fredriksen E, Kjellevold M, Dahl L, Markhus MW, Stormark KM, von Soest T, Olafsen KS, Vannebo UT, Smith L. 2019. Little in Norway: a prospective longitudinal community-based cohort from pregnancy to child age 18 months. BMJ Open 9:e031050
    1. Faul F, Erdfelder E, Lang A-G, Buchner A. 2007. G* Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39:175–191
    1. Nich C, Carroll KM. 2002. ‘Intention-to-treat'meets ‘missing data’: implications of alternate strategies for analyzing clinical trials data. Drug Alcohol Depend 68:121–130
    1. Uccello E, Kauffmann D, Calo M, Streissel M. 2017. Nutrition-Sensitive Agriculture and Food Systems in Practice. FAO, Rome, Italy
    1. Harding KB, Peña-Rosas JP, Webster AC, Yap CM, Payne BA, Ota E, De-Regil LM. 2017. Iodine supplementation for women during the preconception, pregnancy and postpartum period. Cochrane Database Syst Rev 3:CD011761.
    1. Brucker-Davis F, Ganier-Chauliac F, Gal J, Panaïa-Ferrari P, Pacini P, Fénichel P, Hiéronimus S. 2015. Neurotoxicant exposure during pregnancy is a confounder for assessment of iodine supplementation on neurodevelopment outcome. Neurotoxicol Teratol 51:45–51
    1. Zhou SJ, Skeaff SA, Ryan P, Doyle LW, Anderson PJ, Kornman L, Mcphee AJ, Yelland LN, Makrides M. 2015. The effect of iodine supplementation in pregnancy on early childhood neurodevelopment and clinical outcomes: results of an aborted randomised placebo-controlled trial. Trials 16:563.
    1. Gowachirapant S, Jaiswal N, Melse-Boonstra A, Galetti V, Stinca S, Mackenzie I, Thomas S, Thomas T, Winichagoon P, Srinivasan K, Zimmermann MB. 2017. Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 5:853–863
    1. Murcia M, Rebagliato M, Iniguez C, Lopez-Espinosa M-J, Estarlich M, Plaza B, Barona-Vilar C, Espada M, Vioque J, Ballester F. 2011. Effect of iodine supplementation during pregnancy on infant neurodevelopment at 1 year of age. Am J Epidemiol 173:804–812
    1. Rebagliato M, Murcia M, Álvarez-Pedrerol M, Espada M, Fernández-Somoano A, Lertxundi N, Navarrete-Muñoz E-M, Forns J, Aranbarri A, Llop S, Julvez J, Tardón A, Ballester F. 2013. Iodine supplementation during pregnancy and infant neuropsychological development: INMA Mother and Child Cohort Study. Am J Epidemiol 177:944–953
    1. Abel MH, Caspersen IH, Meltzer HM, Haugen M, Brandlistuen RE, Aase H, Alexander J, Torheim LE, Brantsaeter AL. 2017. Suboptimal maternal iodine intake is associated with impaired child neurodevelopment at 3 years of age in the Norwegian Mother and Child Cohort Study. J Nutr 147:1314–1324
    1. Abel MH, Brandlistuen RE, Caspersen IH, Aase H, Torheim LE, Meltzer HM, Brantsaeter AL. 2018. Language delay and poorer school performance in children of mothers with inadequate iodine intake in pregnancy: results from follow-up at 8 years in the Norwegian Mother and Child Cohort Study. Eur J Nutr 58:3047–3058
    1. Dineva M, Fishpool H, Rayman MP, Mendis J, Bath SC. 2020. Systematic review and meta-analysis of the effects of iodine supplementation on thyroid function and child neurodevelopment in mildly-to-moderately iodine-deficient pregnant women. Am J Clin Nutr 112:389–412
    1. Eastman CJ, Zimmermann MB 2018 The iodine deficiency disorders Endotext [Internet]. , Inc., South Dartmouth, MA
    1. Pearce EN, Andersson M, Zimmermann MB. 2013. Global iodine nutrition: where do we stand in 2013? Thyroid 23:523–528
    1. Markou K, Georgopoulos N, Kyriazopoulou V, Vagenakis A. 2001. Iodine-induced hypothyroidism. Thyroid 11:501–510
    1. Laurberg P, Jørgensen T, Perrild H, Ovesen L, Knudsen N, Pedersen IBl, Rasmussen LB, Carlé A, Vejbjerg P. 2006. The Danish investigation on iodine intake and thyroid disease, DanThyr: status and perspectives. Eur J Endocrinol 155:219–228
    1. Bernal J, Nunez JJ. 1995. Thyroid hormones and brain development. Eur J Endocrinol 133:390–398
    1. Zimmermann MB 2008. Iodine requirements and the risks and benefits of correcting iodine deficiency in populations. J Trace Elem Med Biol 22:81–92
    1. Delange F 1994. The disorders induced by iodine deficiency. Thyroid 4:107–128
    1. Waise A, Price HC. 2009. The upper limit of the reference range for thyroid-stimulating hormone should not be confused with a cut-off to define subclinical hypothyroidism. Ann Clin Biochem 46:93–98
    1. Zoeller R, Rovet J. 2004. Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings. J Neuroendocrinol 16:809–818
    1. Øyen J, Kvestad I, Midtbø LK, Graff IE, Hysing M, Stormark KM, Markhus MW, Baste V, Frøyland L, Koletzko B. 2018. Fatty fish intake and cognitive function: FINS-KIDS, a randomized controlled trial in preschool children. BMC Med 16:41.
    1. Handeland K, Skotheim S, Baste V, Graff IE, Frøyland L, Lie Ø, Kjellevold M, Markhus MW, Stormark KM, Øyen J. 2018. The effects of fatty fish intake on adolescents' nutritional status and associations with attention performance: results from the FINS-TEENS randomized controlled trial. Nutr J 17:30.
    1. Jacobs DR, Tapsell LC. 2007. Food, not nutrients, is the fundamental unit in nutrition. Nutr Rev 65:439–450
    1. Lauritzen L, Brambilla P, Mazzocchi A, Harsløf L, Ciappolino V, Agostoni C. 2016. DHA effects in brain development and function. Nutrients 8:6
    1. Innis SM 2007. Dietary (n-3) fatty acids and brain development. J Nutr 137:855–859
    1. Næss S, Kjellevold M, Dahl L, Nerhus I, Midtbø LK, Bank MS, Rasinger JD, Markhus MW. 2020. Effects of seafood consumption on mercury exposure in Norwegian pregnant women: a randomized controlled trial. Environ Int 141:105759.
    1. Rothman KJ 2014. Six persistent research misconceptions. J Gen Intern Med 29:1060–1064
    1. König F, Andersson M, Hotz K, Aeberli I, Zimmermann MB. 2011. Ten repeat collections for urinary iodine from spot samples or 24-hour samples are needed to reliably estimate individual iodine status in women. J Nutr 141:2049–2054

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