Maternal hypothyroidism and subsequent metabolic outcomes in children: a systematic review and meta-analysis.
Hypothyroidism
Metabolic outcomes
Offspring
Pregnancy
Systematic review
Journal
BMC pediatrics
ISSN: 1471-2431
Titre abrégé: BMC Pediatr
Pays: England
ID NLM: 100967804
Informations de publication
Date de publication:
01 Aug 2024
01 Aug 2024
Historique:
received:
28
12
2023
accepted:
23
07
2024
medline:
2
8
2024
pubmed:
2
8
2024
entrez:
1
8
2024
Statut:
epublish
Résumé
As the fetus relies on maternal thyroid hormones in early pregnancy, maternal hypothyroidism plays an important role in fetal development. However, the association between maternal hypothyroidism and metabolic disease in offspring is unclear. To examine the association between maternal hypothyroidism in pregnancy and metabolic outcomes (obesity, hypertension, type 2 diabetes mellitus, and dyslipidemia) in children < 18 years. We systematically searched 5 databases from inception to May 2023. Eligible studies included cohort, case-control, and randomized controlled trials involving children born to mothers with or without hypothyroidism in pregnancy. Data were pooled across studies using random-effects models for outcomes reported in at least three studies. Quality assessment was performed using the ROBINS-E tool for observational studies and the Cochrane Risk of Bias tool for trials. The search identified 3221 articles, of which 7 studies were included (1 trial, 6 observational). All studies were conducted outside of North America and ranged in size from 250 to > 1 million children. The follow-up time ranged from 6 to 20 years. Included studies support an increased risk of hypertension and glucose dysregulation in offspring exposed to maternal hypothyroidism (hypertension: OR 1.08, 95% CI 0.75, 1.57 and HR 1.81, 95% CI 1.21, 2.69; diabetes: RR 2.7, 95% CI 0.7, 10). In the pooled analysis, maternal hypothyroidism was not associated with obesity in offspring (OR 1.04, 95% CI 0.64, 1.70). This study found inconsistent evidence on the association between maternal hypothyroidism in pregnancy and metabolic outcomes in offspring, though associations with hypertension and glucose dysregulation are possible.
Identifiants
pubmed: 39090558
doi: 10.1186/s12887-024-04963-0
pii: 10.1186/s12887-024-04963-0
doi:
Types de publication
Journal Article
Systematic Review
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
490Informations de copyright
© 2024. The Author(s).
Références
Cignini P, Cafà EV, Giorlandino C, Capriglione S, Spata A, Dugo N. Thyroid physiology and common diseases in pregnancy: review of literature. J Prenat Med. 2012;6(4):64–71.
pubmed: 23272277
pmcid: 3530964
Sahay RK, Nagesh VS. Hypothyroidism in pregnancy. Indian J Endocrinol Metab. 2012;16(3):364–70. https://doi.org/10.4103/2230-8210.95667 .
doi: 10.4103/2230-8210.95667
pubmed: 22629500
pmcid: 3354841
Dulek H, Vural F, Aka N, Zengin S. The prevalence of thyroid dysfunction and its relationship with perinatal outcomes in pregnant women in the third trimester. North Clin Istanb. 2019;6(3):267–72. https://doi.org/10.14744/nci.2018.51422 .
doi: 10.14744/nci.2018.51422
pubmed: 31650114
pmcid: 6790929
Smallridge RC, Ladenson PW. Hypothyroidism in pregnancy: consequences to neonatal health. J Clin Endocrinol Metab. 2001;86(6):2349–53. https://doi.org/10.1210/jcem.86.6.7577 .
doi: 10.1210/jcem.86.6.7577
pubmed: 11397821
Glinoer D, Soto MF, Bourdoux P, et al. Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions. J Clin Endocrinol Metab. 1991;73(2):421–7. https://doi.org/10.1210/jcem-73-2-421 .
doi: 10.1210/jcem-73-2-421
pubmed: 1906897
Léger J, dos Santos S, Larroque B, Ecosse E. Pregnancy outcomes and relationship to treatment adequacy in women treated early for congenital hypothyroidism: a longitudinal population-based study. J Clin Endocrinol Metab. 2015;100(3):860–9. https://doi.org/10.1210/jc.2014-3049 .
doi: 10.1210/jc.2014-3049
pubmed: 25423569
Kannan L, Shaw PA, Morley MP, et al. Thyroid dysfunction in Heart failure and Cardiovascular outcomes. Circ Heart Fail. 2018;11(12):e005266. https://doi.org/10.1161/CIRCHEARTFAILURE.118.005266 .
doi: 10.1161/CIRCHEARTFAILURE.118.005266
pubmed: 30562095
pmcid: 6352308
Miao M, Liu H, Yuan W et al. Association of Maternal Hypothyroidism With Cardiovascular Diseases in the Offspring. Front Endocrinol. 2021;12. Accessed May 8, 2023. https://www.frontiersin.org/articles/ https://doi.org/10.3389/fendo.2021.739629
Fowden AL, Giussani DA, Forhead AJ. Intrauterine programming of physiological systems: causes and consequences. Physiology. 2006;21(1):29–37. https://doi.org/10.1152/physiol.00050.2005 .
doi: 10.1152/physiol.00050.2005
pubmed: 16443820
Nattero-Chávez L, Luque-Ramírez M, Escobar-Morreale HF. Systemic endocrinopathies (thyroid conditions and diabetes): impact on postnatal life of the offspring. Fertil Steril. 2019;111(6):1076–91. https://doi.org/10.1016/j.fertnstert.2019.04.039 .
doi: 10.1016/j.fertnstert.2019.04.039
pubmed: 31155115
Yamakawa H, Kato TS, Noh JY, et al. Thyroid hormone plays an important role in Cardiac function: from bench to Bedside. Front Physiol. 2021;12:606931. https://doi.org/10.3389/fphys.2021.606931 .
doi: 10.3389/fphys.2021.606931
pubmed: 34733168
pmcid: 8558494
Rosenbaum M, Hirsch J, Murphy E, Leibel RL. Effects of changes in body weight on carbohydrate metabolism, catecholamine excretion, and thyroid function. Am J Clin Nutr. 2000;71(6):1421–32. https://doi.org/10.1093/ajcn/71.6.1421 .
doi: 10.1093/ajcn/71.6.1421
pubmed: 10837281
Lucaccioni L, Ficara M, Cenciarelli V, Berardi A, Predieri B, Iughetti L. Long term outcomes of infants born by mothers with thyroid dysfunction during pregnancy. Acta Bio-Medica Atenei Parm. 2020;92(1):e2021010. https://doi.org/10.23750/abm.v92i1.9696 .
doi: 10.23750/abm.v92i1.9696
van Tuyl M, Blommaart PE, de Boer PAJ, et al. Prenatal exposure to thyroid hormone is necessary for normal postnatal development of murine heart and lungs. Dev Biol. 2004;272(1):104–17. https://doi.org/10.1016/j.ydbio.2004.03.042 .
doi: 10.1016/j.ydbio.2004.03.042
pubmed: 15242794
Lino CA, da Silva IB, Shibata CER, Monteiro P, de Barreto-Chaves S. Maternal hyperthyroidism increases the susceptibility of rat adult offspring to cardiovascular disorders. Mol Cell Endocrinol. 2015;416:1–8. https://doi.org/10.1016/j.mce.2015.08.015 .
doi: 10.1016/j.mce.2015.08.015
pubmed: 26277399
Santos SO, Loureiro SMA, Alves IGN, et al. Experimental gestational hypothyroidism evokes hypertension in adult offspring rats. Auton Neurosci. 2012;170(1):36–41. https://doi.org/10.1016/j.autneu.2012.07.004 .
doi: 10.1016/j.autneu.2012.07.004
pubmed: 22878215
Kemkem Y, Nasteska D, de Bray A, et al. Maternal hypothyroidism in mice influences glucose metabolism in adult offspring. Diabetologia. 2020;63(9):1822–35. https://doi.org/10.1007/s00125-020-05172-x .
doi: 10.1007/s00125-020-05172-x
pubmed: 32472193
pmcid: 7406527
Jølving LR, Nielsen J, Kesmodel US, Nielsen RG, Nørgård BM, Beck-Nielsen SS. Chronic diseases in the children of women with maternal thyroid dysfunction: a nationwide cohort study. Clin Epidemiol. 2018;10:1381–90. https://doi.org/10.2147/CLEP.S167128 .
doi: 10.2147/CLEP.S167128
pubmed: 30310330
pmcid: 6167124
Eom YS, Wilson JR, Bernet VJ. Links between thyroid disorders and glucose homeostasis. Diabetes Metab J. 2022;46(2):239–56. https://doi.org/10.4093/dmj.2022.0013 .
doi: 10.4093/dmj.2022.0013
pubmed: 35385635
pmcid: 8987680
Andersen SL, Andersen S, Liew Z, et al. Maternal thyroid disease and adiposity in mother and child. Clin Endocrinol (Oxf). 2021;94(3):484–93. https://doi.org/10.1111/cen.14314 .
doi: 10.1111/cen.14314
pubmed: 32794201
Rytter D, Andersen SL, Bech BH, et al. Maternal thyroid function in pregnancy may program offspring blood pressure, but not adiposity at 20 y of age. Pediatr Res. 2016;80(1):7–13. https://doi.org/10.1038/pr.2016.56 .
doi: 10.1038/pr.2016.56
pubmed: 26991263
Risk of bias tools - ROBINS-E tool. Accessed November 7. 2023. https://www.riskofbias.info/welcome/robins-e-tool
RoB 2: A revised Cochrane risk-of-bias tool for randomized trials | Cochrane Bias. Accessed November 7. 2023. https://methods.cochrane.org/bias/resources/rob-2-revised-cochrane-risk-bias-tool-randomized-trials
Campbell M, McKenzie JE, Sowden A, et al. Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. BMJ. 2020;368:l6890. https://doi.org/10.1136/bmj.l6890 .
doi: 10.1136/bmj.l6890
pubmed: 31948937
pmcid: 7190266
10.4.3.1 Recommendations on testing for funnel plot asymmetry. Accessed November 7. 2023. https://handbook-5-1.cochrane.org/chapter_10/10_4_3_1_recommendations_on_testing_for_funnel_plot_asymmetry.htm
Eshkoli T, Wainstock T, Sheiner E, Beharier O, Fraenkel M, Walfisch A. Maternal hypothyroidism during pregnancy and the risk of Pediatric Endocrine Morbidity in the offspring. Am J Perinatol. 2019;36(09):975–80. https://doi.org/10.1055/s-0038-1675834 .
doi: 10.1055/s-0038-1675834
pubmed: 30477033
Heikkinen AL, Päkkilä F, Hartikainen AL, Vääräsmäki M, Männistö T, Suvanto E. Maternal thyroid antibodies associates with cardiometabolic risk factors in children at the age of 16. J Clin Endocrinol Metab. 2017;102(11):4184–90. https://doi.org/10.1210/jc.2017-01137 .
doi: 10.1210/jc.2017-01137
pubmed: 28945847
Muller I, Taylor PN, Daniel RM, et al. CATS II long-term Anthropometric and Metabolic effects of maternal sub-optimal thyroid function in offspring and mothers. J Clin Endocrinol Metab. 2020;105(7):dgaa129. https://doi.org/10.1210/clinem/dgaa129 .
doi: 10.1210/clinem/dgaa129
pubmed: 32396189
Godoy GAF, Korevaar TIM, Peeters RP, et al. Maternal thyroid hormones during pregnancy, childhood adiposity and cardiovascular risk factors: the Generation R Study. Clin Endocrinol (Oxf). 2014;81(1):117–25. https://doi.org/10.1111/cen.12399 .
doi: 10.1111/cen.12399
pubmed: 24386874
Silbert R, Salcido-Montenegro A, Rodriguez-Gutierrez R, Katabi A, McCoy RG. Hypoglycemia among patients with type 2 diabetes: epidemiology, risk factors, and Prevention Strategies. Curr Diab Rep. 2018;18(8):53. https://doi.org/10.1007/s11892-018-1018-0 .
doi: 10.1007/s11892-018-1018-0
pubmed: 29931579
pmcid: 6117835
Alex Stagnaro-Green. Guidelines of the American thyroid Association for the diagnosis and management of thyroid disease during pregnancy and Postpartum. https://doi.org/10.1089/thy.2011.0087
Lazarus J, Brown RS, Daumerie C, Hubalewska-Dydejczyk A, Negro R, Vaidya B. 2014 European thyroid Association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J. 2014;3(2):76–94. https://doi.org/10.1159/000362597 .
doi: 10.1159/000362597
pubmed: 25114871
pmcid: 4109520
Javed Z, Sathyapalan T. Levothyroxine treatment of mild subclinical hypothyroidism: a review of potential risks and benefits. Ther Adv Endocrinol Metab. 2016;7(1):12–23. https://doi.org/10.1177/2042018815616543 .
doi: 10.1177/2042018815616543
pubmed: 26885359
pmcid: 4740939
Fatourechi V. Subclinical hypothyroidism: an update for Primary Care Physicians. Mayo Clin Proc. 2009;84(1):65–71.
doi: 10.4065/84.1.65
pubmed: 19121255
pmcid: 2664572
Hales C, Taylor PN, Channon S, et al. Controlled antenatal thyroid screening II: effect of treating maternal suboptimal thyroid function on child cognition. J Clin Endocrinol Metab. 2018;103(4):1583–91. https://doi.org/10.1210/jc.2017-02378 .
doi: 10.1210/jc.2017-02378
pubmed: 29346569
Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy. J Clin Endocrinol Metab. 2010;95(9):E44–48. https://doi.org/10.1210/jc.2010-0340 .
doi: 10.1210/jc.2010-0340
pubmed: 20534758
Sheehan MT. Biochemical testing of the thyroid: TSH is the best and, oftentimes, only test needed – a review for primary care. Clin Med Res. 2016;14(2):83–92. https://doi.org/10.3121/cmr.2016.1309 .
doi: 10.3121/cmr.2016.1309
pubmed: 27231117
pmcid: 5321289
Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87(2):489–99. https://doi.org/10.1210/jcem.87.2.8182 .
doi: 10.1210/jcem.87.2.8182
pubmed: 11836274
Vol 10 Issue 5 p.8. American Thyroid Association. Accessed May 10. 2023. https://www.thyroid.org/patient-thyroid-information/ct-for-patients/may-2017/vol-10-issue-5-p-8/
Alexander EK, Pearce EN, Brent GA, et al. 2017 guidelines of the American thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the Postpartum. Thyroid. 2017;27(3):315–89. https://doi.org/10.1089/thy.2016.0457 .
doi: 10.1089/thy.2016.0457
pubmed: 28056690
Gottwald-Hostalek U, Schulte B. Low awareness and under-diagnosis of hypothyroidism. Curr Med Res Opin. 2022;38(1):59–64. https://doi.org/10.1080/03007995.2021.1997258 .
doi: 10.1080/03007995.2021.1997258
pubmed: 34698615
Mendes D, Alves C, Silverio N, Batel Marques F. Prevalence of undiagnosed hypothyroidism in Europe: a systematic review and Meta-analysis. Eur Thyroid J. 2019;8(3):130–43. https://doi.org/10.1159/000499751 .
doi: 10.1159/000499751
pubmed: 31259155
pmcid: 6587201
Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160(4):526–34. https://doi.org/10.1001/archinte.160.4.526 .
doi: 10.1001/archinte.160.4.526
pubmed: 10695693
Garmendia Madariaga A, Santos Palacios S, Guillén-Grima F, Galofré JC. The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab. 2014;99(3):923–31. https://doi.org/10.1210/jc.2013-2409 .
doi: 10.1210/jc.2013-2409
pubmed: 24423323