Effects of Iodine Deficiency in Pregnancy and Iodine Supplementation on Neurointellectual Development of Offspring

doi:10.12114/j.issn.1007-9572.2019.00.231

Abstract

Abstract: Iodine is a necessary trace element for the synthesis of thyroid hormone，which is crucial for human brain development and physical growth.Due to increased physiological demand for iodine during pregnancy，iodine deficiency is a common problem of malnutrition during pregnancy，which has attracted much attention.During pregnancy，especially in the first trimester，even mild and moderate iodine deficiency may cause irreversible damage to neurointellectual development and cognitive function of the offspring.However，the necessity and timing of iodine supplementation are still controversial.On the basis of literature review，we summarized recent advances in the impact of iodine deficiency during pregnancy，especially mild and moderate iodine deficiency during pregnancy on neurodevelopment in children，and in iodine supplementation，and concluded that iodine supplementation therapy should be used mainly for preventing iodine deficiency rather than curing，and maintaining optimal iodine nutrition status in pregnancy is crucial to the prevention of brain development injury of offspring.

Key words: Iodine, Pregnant women, Nervous system, Intelligence, Iodine deficiency, Thyroid hormones, Fetus

摘要： 碘是合成甲状腺激素必需的微量元素，而甲状腺激素对人体的脑发育及生长发育至关重要。由于妊娠期机体对碘的需求量明显增加，妊娠期碘缺乏已成为妊娠期营养不良的常见问题，目前备受关注。妊娠期尤其是妊娠早期，即使是轻、中度碘缺乏也可能导致后代的神经智力发育及认知功能产生不可逆性损伤，然而补充碘剂的必要性及时机还存在争议。本文回顾了相关文献，对妊娠期碘缺乏，尤其是妊娠期轻、中度碘缺乏对儿童神经智力发育的影响及补碘干预的相关研究进展进行总结，指出补碘治疗应以预防为主，妊娠期维持最佳碘营养状态对于后代神经智力发育至关重要。

关键词: 碘, 孕妇, 神经系统, 智力, 碘缺乏, 甲状腺激素类, 胎儿

ZHANG Le,BAI Yu,ZHAI Xiaodan. Effects of Iodine Deficiency in Pregnancy and Iodine Supplementation on Neurointellectual Development of Offspring　[J]. Chinese General Practice, 2019, 22(24): 2962-2966. DOI: 10.12114/j.issn.1007-9572.2019.00.231.
张乐,白宇,翟晓丹. 妊娠期碘缺乏及补碘干预对后代神经智力发育的影响[J]. 中国全科医学, 2019, 22(24): 2962-2966. DOI: 10.12114/j.issn.1007-9572.2019.00.231.

References

［1］ZIMMERMANN M B，BOELAERT K.Iodine deficiency and thyroid disorders［J］．Lancet Diabetes Endocrinol，2015，3（4）：286-295．DOI：10.1016/s2213-8587（14）70225-6.
［2］REDMAN K，RUFFMAN T，FITZGERALD P，et al．Iodine deficiency and the brain：effects and mechanisms［J］．Crit Rev Food Sci Nutr，2016，56（16）：2695-2713．DOI：10.1080/10408398.2014.922042.
［3］LAURBERG P.Thyroid function：thyroid hormones，iodine and the brain-an important concern［J］．Nat Rev Endocrinol，2009，5（9）：475-476．DOI：10.1038/nrendo.2009.155.
［4］ZIMMERMANN M B.The role of iodine in human growth and development［J］．Semin Cell Dev Biol，2011，22（6）：645-652．DOI：10.1016/j.semcdb.2011.07.009.
［5］LAZARUS J H.Role of the iodine global network in elimination of iodine deficiency［J］．Recent Pat Endocr Metab Immune Drug Discov，2017，10（2）：119-122．DOI：10.2174/1872214811666170330152202.
［6］STAGNARO-GREEN A，PEARCE E N.Iodine and pregnancy：a call to action［J］．Lancet，2013，382（9889）：292-293．DOI：10.1016/S0140-6736（13）60717-5.
［7］ZIMMERMANN M B，JOOSTE P L，PANDAV C S.Iodine-deficiency disorders［J］．Lancet，2008，372（9645）：1251-1262．DOI：10.1016/S0140-6736（08）61005-3.
［8］ANDERSEN S L，LAURBERG P.Iodine supplementation in pregnancy and the dilemma of ambiguous recommendations［J］．Eur Thyroid J，2016，5（1）：35-43．DOI：10.1159/000444254.
［9］Scientific opinion on dietary reference values for iodine［J］．EFSA Journal，2014，12（5）：3660．DOI：10.2903/j.efsa.2014.3660.
［10］ALEXANDER E K，PEARCE E N，BRENT G A，et al．2017 guidelines of the American thyroid association for the diagnosis and management of thyroid disease during pregnancy and the postpartum［J］．Thyroid，2017，27（3）：315-389．DOI：10.1089/thy.2016.0457.
［11］ZIMMERMANN M B，AEBERLI I，TORRESANI T，et al．Increasing the iodine concentration in the Swiss iodized salt program markedly improved iodine status in pregnant women and children：a 5-y prospective national study［J］．Am J Clin Nutr，2005，82（2）：388-392．DOI：10.1093/ajcn.82.2.388.
［12］MORAIS N A O E S，ASSIS A S A，CORCINO C M，et al．Recent recommendations from ATA guidelines to define the upper reference range for serum TSH in the first trimester match reference ranges for pregnant women in Rio de Janeiro［J］．Arch Endocrinol Metab，2018，62（4）：386-391．DOI：10.20945/2359-3997000000064.
［13］NG S M，TURNER M A，AVULA S.Ultrasound measurements of thyroid gland volume at 36 weeks' corrected gestational age in extremely preterm infants born before 28 weeks' gestation［J］．Eur Thyroid J，2018，7（1）：21-26．DOI：10.1159/000481857.
［14］MA Z F，SKEAFF S A.Thyroglobulin as a biomarker of iodine deficiency：a review［J］．Thyroid，2014，24（8）：1195-1209．DOI：10.1089/thy.2014.0052.
［15］CHONG W，SHI X G，SHAN Z Y，et al．Tg in adults as a sensitive biomarker of iodine status：a 5-year follow up population study in different levels of iodine intake regions［J］．PLoS One，2015，10（8）：e0135553．DOI：10.1371/journal.pone.0135553.
［16］BATH S C，POP V J，FURMIDGE-OWEN V L，et al．Thyroglobulin as a functional biomarker of iodine status in a cohort study of pregnant women in the united kingdom［J］．Thyroid，2017，27（3）：426-433．DOI：10.1089/thy.2016.0322.
［17］ANDERSSON M，KARUMBUNATHAN V，ZIMMERMANN M B.Global iodine status in 2011 and trends over the past decade［J］．J Nutr，2012，142（4）：744-750．DOI：10.3945/jn.111.149393.
［18］BURNS K，YAP C，MINA A，et al．Iodine deficiency in women of childbearing age：not bread alone?［J］．Asia Pac J Clin Nutr，2018，27（4）：853-859．DOI：10.6133/apjcn.102017.02.
［19］CALDWELL K L，MAKHMUDOV A，ELY E，et al．Iodine status of the US population，National Health and Nutrition Examination Survey，2005—2006 and 2007—2008［J］．Thyroid，2011，21（4）：419-427．DOI：10.1089/thy.2010.0077.
［20］KOYUNCU K，TURGAY B，S?YLEMEZ F.Iodine deficiency in pregnant women at first trimester in Ankara［J］．J Turk Ger Gynecol Assoc，2019，20（1）：37-40．DOI：10.4274/jtgga.galenos.2018.2017.0150.
［21］TORRES M T，FRANCéS L，VILA L，et al．Iodine nutritional status of women in their first trimester of pregnancy in Catalonia［J］．BMC Pregnancy Childbirth，2017，17（1）：249．DOI：10.1186/s12884-017-1423-4.
［22］TAM W H，CHAN R S，CHAN M H，et al．Moderate iodine deficiency among pregnant women in Hong Kong：revisit the problem after two decades［J］．Hong Kong Med J，2017，23（6）：586-593．DOI：10.12809/hkmj176841.
［23］FISHER J，TRAN T，BIGGS B，et al．Iodine status in late pregnancy and psychosocial determinants of iodized salt use in rural northern Viet Nam［J］．Bull World Health Organ，2011，89（11）：813-820．DOI：10.2471/BLT.11.089763.
［24］WANG Z Y，LIU P，SU X H，et al．A comparison of iodine status in children and pregnant women after a policy change in the iodized salt standard in Shanghai，China［J］．Biol Trace Elem Res，2018，185（2）：275-281．DOI：10.1007/s12011-018-1257-6.
［25］HENJUM S，AAKRE I，LILLEENGEN A M，et al．Suboptimal iodine status among pregnant women in the Oslo area，Norway［J］．Nutrients，2018，10（3）.pii：E280．DOI：10.3390/nu10030280.
［26］MIOTO V C B，MONTEIRO A C C N G，DE CAMARGO R Y A，et al．High prevalence of iodine deficiency in pregnant women living in adequate iodine area［J］．Endocr Connect，2018，7（5）：762-767．DOI：10.1530/EC-18-0131.
［27］史晓光，滕晓春，单忠艳，等．妊娠早期碘营养状况与甲状腺功能关系的流行病学调查［J］．中国实用内科杂志，2009，29（6）：520-522.
SHI X G，TENG X C，SHAN Z Y，et al．An epidemiological study of the relationship between iodine intake levels and thyroid function during early pregnancy［J］．Chinese Journal of Practical Internal Medicine，2009，29（6）：520-522.
［28］WANG Z F，XING M L，ZHU W M，et al．Iodine deficiency in Zhejiang pregnant women in the context of universal salt iodization programme［J］．Sci Rep，2018，8（1）：8835．DOI：10.1038/s41598-018-26942-z.
［29］KRASNODEBSKA-KILJANSKA M，KONDRACKA A，BARTOSZEWICZ Z，et al．Iodine supply and thyroid function in the group of healthy pregnant women living in Warsaw［J］．Pol Merkur Lekarski，2013，34（202）：200-204.
［30］STOUTJESDIJK E，SCHAAFSMA A，DIJCK-BROUWER D A J，et al．Iodine status during pregnancy and lactation：a pilot study in the Netherlands［J］．Neth J Med，2018，76（5）：210-217.
［31］HETZEL B S.Iodine deficiency disorders（IDD）and their eradication［J］．Lancet，1983，2（8359）：1126-1129.
［32］DELANGE F.The disorders induced by iodine deficiency［J］．Thyroid，1994，4（1）：107-128．DOI：10.1089/thy.1994.4.107.
［33］ABEL M H，CASPERSEN I H，MELTZER H M，et al．Suboptimal maternal iodine intake is associated with impaired child neurodevelopment at 3 years of age in the Norwegian mother and child cohort study［J］．J Nutr，2017，147（7）：1314-1324．DOI：10.3945/jn.117.250456.
［34］MARKHUS M W，DAHL L，MOE V，et al．Maternal iodine status is associated with offspring language skills in infancy and toddlerhood［J］．Nutrients，2018，10（9）：E1270．DOI：10.3390/nu10091270.
［35］HYNES K L，OTAHAL P，HAY I，et al．Mild iodine deficiency during pregnancy is associated with reduced educational outcomes in the offspring：9-year follow-up of the gestational iodine cohort［J］．J Clin Endocrinol Metab，2013，98（5）：1954-1962．DOI：10.1210/jc.2012-4249.
［36］VAN MIL N H，TIEMEIER H，BONGERS-SCHOKKING J J，et al．Low urinary iodine excretion during early pregnancy is associated with alterations in executive functioning in children［J］．J Nutr，2012，142（12）：2167-2174．DOI：10.3945/jn.112.161950.
［37］BATH S C，STEER C D，GOLDING J，et al．Effect of inadequate iodine status in UK pregnant women on cognitive outcomes in their children：results from the Avon Longitudinal Study of Parents and Children（ALSPAC）［J］．Lancet，2013，382（9889）：331-337．DOI：10.1016/S0140-6736（13）60436-5.
［38］HYNES K L，OTAHAL P，BURGESS J R，et al．Reduced educational outcomes persist into adolescence following mild iodine deficiency in utero，despite adequacy in childhood：15-year follow-up of the gestational iodine cohort investigating auditory processing speed and working memory［J］．Nutrients，2017，9（12）：E1354．DOI：10.3390/nu9121354.
［39］MURCIA M，ESPADA M，JULVEZ J，et al．Iodine intake from supplements and diet during pregnancy and child cognitive and motor development：the INMA Mother and Child Cohort Study［J］．J Epidemiol Community Health，2018，72（3）：216-222．DOI：10.1136/jech-2017-209830.
［40］BOUGMA K，ABOUD F E，HARDING K B，et al．Iodine and mental development of children 5 years old and under：a systematic review and meta-analysis［J］．Nutrients，2013，5（4）：1384-1416．DOI：10.3390/nu5041384.
［41］ROBINSON S M，CROZIER S R，MILES E A，et al．Preconception maternal iodine status is positively associated with IQ but not with measures of executive function in childhood［J］．J Nutr，2018，148（6）：959-966．DOI：10.1093/jn/nxy054.
［42］MOLETI M，TRIMARCHI F，TORTORELLA G，et al．Effects of maternal iodine nutrition and thyroid status on cognitive development in offspring：a pilot study［J］．Thyroid，2016，26（2）：296-305．DOI：10.1089/thy.2015.0336.
［43］DE ESCOBAR G M，OBREGóN M J，DEL REY F E.Iodine deficiency and brain development in the first half of pregnancy［J］．Public Health Nutr，2007，10（12A）：1554-1570．DOI：10.1017/S1368980007360928.
［44］PEARCE E N，LAZARUS J H，MORENO-REYES R，et al．Consequences of iodine deficiency and excess in pregnant women：an overview of current knowns and unknowns［J］．Am J Clin Nutr，2016，104（Suppl 3）：918S-923S．DOI：10.3945/ajcn.115.110429.
［45］TROFIMIUK-MUDLNER M，HUBALEWSKA-DYDEJCZYK A.Iodine deficiency and iodine prophylaxis in pregnancy［J］．Recent Pat Endocr Metab Immune Drug Discov，2017，10（2）：85-95．DOI：10.2174/1872214811666170309151538.
［46］GORDON R C，ROSE M C，SKEAFF S A，et al．Iodine supplementation improves cognition in mildly iodine-deficient children［J］．Am J Clin Nutr，2009，90（5）：1264-1271．DOI：10.3945/ajcn.2009.28145.
［47］STAGNARO-GREEN A，SULLIVAN S，PEARCE E N.Iodine supplementation during pregnancy and lactation［J］．JAMA，2012，308（23）：2463-2464．DOI：10.1001/jama.2012.45423.
［48］CAO X Y，JIANG X M，DOU Z H，et al．Timing of vulnerability of the brain to iodine deficiency in endemic cretinism［J］．N Engl J Med，1994，331（26）：1739-1744．DOI：10.1056/NEJM199412293312603.
［49］BERBEL P，MESTRE J L，SANTAMARíA A，et al．Delayed neurobehavioral development in children born to pregnant women with mild hypothyroxinemia during the first month of gestation：the importance of early iodine supplementation［J］．Thyroid，2009，19（5）：511-519．DOI：10.1089/thy.2008.0341.
［50］MOLETI M，LO PRESTI V P，CAMPOLO M C，et al．Iodine prophylaxis using iodized salt and risk of maternal thyroid failure in conditions of mild iodine deficiency［J］．J Clin Endocrinol Metab，2008，93（7）：2616-2621．DOI：10.1210/jc.2008-0352.
［51］MOLETI M，DI BELLA B，GIORGIANNI G，et al．Maternal thyroid function in different conditions of iodine nutrition in pregnant women exposed to mild-moderate iodine deficiency：an observational study［J］．Clin Endocrinol（Oxf），2011，74（6）：762-768．DOI：10.1111/j.1365-2265.2011.04007.x.
［52］ABEL M H，YSTROM E，CASPERSEN I H，et al．Maternal iodine intake and offspring attention-Deficit/Hyperactivity disorder：results from a large prospective cohort study［J］．Nutrients，2017，9（11）：E1239．DOI：10.3390/nu9111239.
［53］ABEL M H，KOREVAAR T I M，ERLUND I，et al．Iodine intake is associated with thyroid function in mild to moderately iodine deficient pregnant women［J］．Thyroid，2018，28（10）：1359-1371．DOI：10.1089/thy.2018.0305.
［54］MURCIA M，REBAGLIATO M，I?IGUEZ C，et al．Effect of iodine supplementation during pregnancy on infant neurodevelopment at 1 year of age［J］．Am J Epidemiol，2011，173（7）：804-812．DOI：10.1093/aje/kwq424.
［55］SHI X G，HAN C，LI C Y，et al．Optimal and safe upper limits of iodine intake for early pregnancy in iodine-sufficient regions：a cross-sectional study of 7190 pregnant women in China［J］．J Clin Endocrinol Metab，2015，100（4）：1630-1638．DOI：10.1210/jc.2014-3704.

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