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• W129622995 abstract "original articleRisk factors for congenital hypothyroidism in Egypt: results of a population case-control study (2003–2010) Ahmed Mahmoud Abdelmoktader Ahmed Mahmoud Abdelmoktader Search for more papers by this author Published Online:6 Jun 2013https://doi.org/10.5144/0256-4947.2013.273SectionsPDF ToolsAdd to favoritesDownload citationTrack citations ShareShare onFacebookTwitterLinked InRedditEmail AboutAbstractBACKGROUND AND OBJECTIVES: Although the prevention of the neuropsychological consequences of congenital hypothyroidism (CH) through the use of replacement therapy represents an important public health success, knowledge about the modifiable risk factors could reduce the number of infants affected by this disease. This study was carried out to identify risk factors for CH at Fayoum Governorate, Egypt.DESIGN AND SETTINGS: This was a population-based case-control study, which started in 2003 and was carried out for 8 years through Fayoum center of the Egyptian Ministry of Health and Population screening program for CH.METHODS: This study was a population-based case-control study carried out by using national project for CH. One control was enrolled for each new CH infant; 320 cases and 320 controls were enrolled in 8 years. Maternal and neonatal influences were investigated.RESULTS: A statistically significant association of CH was observed with birth defects, female gender, gestational age >40 weeks, and gestational diabetes. An increased risk for CH was detected in twins by a multivariate analysis.CONCLUSION: Our results suggest a multifactorial origin of CH in which genetic (high frequency of additional malformations) and environmental factors (especially maternal diabetes) play a role in the development of the disease.IntroductionCongenital hypothyroidism (CH) is defined as thyroid hormone deficiency at birth. CH is most commonly caused by a problem with thyroid gland development (dysgenesis) or a disorder of thyroid hormone biosynthesis (dyshormonogenesis); these disorders result in primary hypothyroidism.1CH is one of the most common preventable causes of mental retardation. The worldwide incidence is approximately 1:2,000 to 1:4,000 newborns.2Kurinczuk3 reported that the approximate incidence rate is 1 in 3,400 births; girls had more than twice the risk than boys. The authors also observed a U-shaped curve in incidence rates with birth weight and with gestational age (37 or 41 weeks of gestation). Approximately 10% of affected newborns had another birth defect, which is approximately twice the frequency of birth defects among the general population. Emanuel et al reported an increased risk of subclinical hypothyroidism during pregnancy in a group of women with gestational diabetes.4Screening programs for CH, which have been extensively implemented in developed countries, provide the opportunity to investigate the etiology and the pathogenesis of CH.5In Egypt, the overall incidence of CH was 1:2,020 live births in 2005.6 The Egyptian Ministry of Health and Population started to implement the screening program for CH in 2000 in 5 governorates, and by the end of 2003, all 27 Governorates were covered.7As the occurrence of genetic mutations has been observed only in a small proportion of the patients, the etiology of CH due to thyroid dysgenesis is still largely unknown. Hence, it is clear that the investigation of modifiable risk factors for CH is important because of the potential to prevent CH.8The results of a population-based case-control study are presented in this paper. Maternal and neonatal exposure was investigated with the aim of identifying the most important risk factors for CH at Fayoum Governorate, Egypt.METHODSThe study enrolment started in 2003 and was carried out for 8 years. Only recently, the diagnosed cases of CH screened by the selected center were included in the study. The screening test for CH was performed on dried blood spots. Thyroid-stimulating hormone (TSH) and thyroxine (T4) were measured. The positive results of the first screening test were then confirmed by serum TSH, T4, and free T4. Infants with normalized TSH between screening and recall were not included in the sample. One control was enrolled for each new CH case. This control was the first infant recorded in the same Health office where the new CH case was recorded. Cases and controls included in the study were residents of the same region. Parents were interviewed and gave their informed consent for participation in the study. The reproductive and medical history of mothers was recorded, including gestational diabetes to assess the effect of these factors during pregnancy. Neonatal features of cases and controls were collected directly from medical records. The study protocol was approved by the institutional ethics committee (Fayoum Faculty of Medicine ethics committee).Statistical analysisAnalyses by two-by-two contingency tables were performed to estimate the association between CH and possible risk factors. Continuous variables were categorized according to biological considerations or conventional cut-off points. Matched crude ORs were estimated by the Mantel–Haenszel method. The Mantel–Haenszel summary χ2 test was used to test the significance of the matched ORs. A conditional logistic regression was performed to evaluate the adjusted effect of the considered variables on the risk of being a CH case.RESULTSDuring the 8 years of the study, 320 cases and 320 controls were enrolled and were considered for statistical analysis. Results are summarized in Tables 1, 2, and 3.Table 1 The selected demographic characteristics, consanguinity, and pregnancy history of CH cases compared to their matched controls.CharacteristicCases (n=320)Controls (n=320)Pn%n%Sociodemographic factorsMother’s age ≤25 years4213.1214445 25–39 years25078.1216350.93.09a ≥40 years288.75134.06Consanguinity Pregnancy103.12206.25.99 First pregnancy18256.8711836.87.78 Previous abortion7122.185115.93.61Gestational diabetes16541.24<.01CH: Congenital hypothyroidism.aOverall χ2 test.Table 2 The neonatal characteristics of CH cases compared to their matched controls.Neonatal characteristicsCases (n=320)Controls (n=320)Pn%n%Female gender20162.815448.12<.01Gestational age (weeks)≤37237.18154.6837–4018457.5025479.37≥4111335.315115.93<.01aBirth weight (grams)≤2500216.56175.312500–350019661.2519661.123500–45009830.6210432.50≥450051.5630.93.20aTwins16520.62<.01Additional birth defects4514.0672.18<.01aOverall χ2 testTable 3 The OR for CH estimated by the conditional logistic regression.Risk factorsCases (n=320)ORControls (n=320)95% CIsFemale genderMother’s age (years)2.01.2–3.3 ≤251.70.96–3.4 ≥401.60.6–4.6Gestational age (weeks) ≤371.40.5–3.9 ≥403.01.8–5.1Twins pregnancy12.22.4–62.3Additional birth defects7.52.9–19.0CH: Congenital hypothyroidism.The mother’s age at delivery was slightly higher in the CH cases than in the controls (28 [8.8%] vs. 13 [4%]; age at delivery ≥40 years). No differences in risk factors related to pregnancy (parity, previous spontaneous abortion) were observed between the 2 groups. With regard to neonatal risk factors, the frequency of females was significantly higher in the CH infants than in the controls “P=.01.” Also, an advanced gestational age was significantly associated with CH. In fact, 113 (35.3%) of CH infants were born after 40 weeks of gestation as compared to 51 (15.9%) of the controls “P=.01.” Overall, no statistically significant difference was found in the birth weight between the cases and controls. With regard to the other neonatal features, a higher frequency of twinning was observed among cases compared to controls (5.1% vs. 0.7%, P<.01).In the multivariate analysis, 4 neonatal features were significantly associated with the birth of a CH infant: female gender (OR=2.0, 95% CI: 1.2–3.3), twinning (OR=12.2, 95% CI: 2.4–62.3), additional birth defects (OR=7.5, 95% CI: 2.9–19.0), and gestational age >40 weeks (OR=3.0, 95% CI: 1.8–5.1).DISCUSSIONOur study confirmed the already known higher prevalence of CH among females than males.9–12 In fact, in this case-control study, a 2-fold higher risk of permanent CH was estimated in females than in males. However, it is still unclear why females were more susceptible to developing CH.In our study, a significant association was observed between prolonged gestational age (≥41 weeks) and CH. Some authors had suggested that infants with CH had a tendency to a prolonged gestation.13,14With regard to the other neonatal risk factors, our results showed that twins had a high risk for CH. However, further investigations were needed to understand the causal association between twinning and CH.As expected,15–17 a high frequency of malformations had been observed among cases with CH 45 (14.3%) while a frequency similar to that expected in the general population was found in the control group 7 (2.1%). Although the association of congenital birth defects and CH had already been well documented, the inclusion of that variable in the multivariate model allowed an adjusted estimate of the relative risk for other factors, such as twins pregnancy,18,19 related to both CH and malformations.Our results reported an increased risk of CH with gestational diabetes. These results were also consistent with those obtained by other authors in an experimental model;20 it was reported in this report that maternal diabetes in pregnancy negatively affects the fetal thyroid hormone status in pregnant rats with streptozotocin-induced diabetes mellitus. The causal relationship between diabetes in pregnancy and CH is not clear. However, it is well known that maternal diabetes affects embryonic development, leading to increased morbidity in the offspring.14In addition to the inherent limitations of this type of study, we used a sample of convenience from Fayoum Governorate, a technique that may have limited the generalizability of our findings. To help overcome this limitation, we selected our participants via a population-based case-control study to reduce the selection bias from the sample. Fortunately, the demographics of our sample were similar to the overall population of Egyptian mothers.7In conclusion, our results suggest that genetic (high frequency of malformations) and environmental factors (especially maternal diabetes) play a role in the development of CH at Fayoum Governorate, EgyptARTICLE REFERENCES:1. Gaudino R, Garel C, Czernichow P, Leger J. Proportion of various types of thyroid disorders among newborns with congenital hypothyroidism and normally located gland: a regional cohort study . Clin Endocrinol (Oxf). 2005; 62(4):444-8. Google Scholar2. Rastogi MV, LaFranchi SH. Congenital hypothyroidism . Orphanet J Rare Dis. 2010; 5:17. Google Scholar3. Kurinczuk JJ, Bower C, Lewis B, Byrne G. Congenital hypothyroidism in Western Australia 1981–1998 . J Paediatr Child Health. 2002; 38(2):187-91. Google Scholar4. Medda E, Olivieri A, Stazi MA, Grandolfo ME, Fazzini C, Baserga M. Risk factors for congenital hypothyroidism: results of a population case-control study (1997–2003) . Eur J Endocrinol. 2005; 153:765-73. Google Scholar5. Grüters A, Biebermann H, Krude H. Neonatal thyroid disorders . Horm Res. 2003; 59:24-9. Google Scholar6. El-Zanaty F, Way A. Egypt demographic and health statisticsEgyptian National Population Council, Cairo, Egypt, 2006. Google Scholar7. Ministry of Health, Cairo, Egypt. Demographic and Health Surveys. 2009. Google Scholar8. Park SM, Clifton-Bligh RJ, Betts P, Chatterjee VK. Congenital hypothyroidism and apparent athyreosis with compound heterozygosity or compensated hypothyroidism with probable hemizygosity for inactivating mutations of the TSH receptor . Clin Endocrinol (Oxf). 2004; 60:220-7. Google Scholar9. Sobel EH, Saenger P. Hypothyroidism in the newborn . Pediatr Rev. 1989; 11:15-20. Google Scholar10. Waller DK, Anderson JL, Lorey F, Cunningham GC. Risk factors for congenital hypothyroidism: an investigation of infant’s birth weight, ethnicity, and gender in California, 1990–1998 . Teratology. 2000; 62:36-41. Google Scholar11. Law WY, Bradley DM, Lazarus JH, John R, Gregory JW. Congenital hypothyroidism in Wales (1982–1993): demographic features, clinical presentation and effects on early neurodevelopment . Clin Endocrinoln (Oxf). 1998; 48:201-7. Google Scholar12. Sun G, Xu Zm, Liang JF, Lin L, Tang DX. Twelve-year prevalence of common neonatal congenital malformations in Zhejiang Province, China . World J Pediatr. 2011; 7:331-6. Google Scholar13. Parazzini F, Cortinovis I, Bortolus R, Fedele L, Decarli A. Weight at birth by gestational age in Italy . Hum Reprod. 1995; 10:1862-3. Google Scholar14. Nold JL, Georgieff MK. Infants of diabetic mothers . Pediatr Clin North Am. 2004; 51:619-37. Google Scholar15. Sorcini M, Fazzini C, Olivieri A, Grandolfo ME, Medda E, Stazi MA, et al. Neonatal screening in congenital hypothyroidism in Italy. The National Registry . Ann Ist Super Sanita. 1994; 30:275-87Italian. Google Scholar16. Mastroiacovo P, Castilla EE, Arpino C, Botting B, Cocchi G, Goujard J, et al. Congenital malformations in twins: an international study . Am J Med Genet. 1999; 83:117-24. Google Scholar17. Doyle PE, Beral V, Botting B, Wale CJ. Congenital malformations in twins in England and Wales . J Epidemiol Community Health. 1991; 45:43-8. Google Scholar18. Weisz B, Pajkrt E, Jauniaux E. Early detection of fetal structural abnormalities . Reprod Biomed Online. 2005; 10:541-53. Google Scholar19. Dussault JH, Letarte J, Guyda H, Laberge C. Lack of influence of thyroid antibodies on thyroid function in the newborn infant and on a mass screening program for congenital hypothyroidism . J Pediatr. 1980; 96:385-9. Google Scholar20. Olivieri A, Medda E, Fazzini C, Cotichini R, De Angelis S, Sorcini M. High risk of congenital hypothyroidism (CH) in twin pregnancies. Data from the Italian register for CH (1987–2000) . Abstracts of the27th Annual Meeting of the European Thyroid AssociationWarsaw, Poland25–29 August 2001Journal of Endocrinological Investigation. 2001; 24(Suppl. to no. 6):9. Google Scholar Previous article Next article FiguresReferencesRelatedDetailsCited byRezaeian S (2019) Difference in the incidence of congenital hypothyroidism among world countries, Annals of Saudi Medicine , 33:6, (633-634), Online publication date: 1-Nov-2013. Volume 33, Issue 3May-June 2013 Metrics History Published online6 June 2013 AcknowledgmentsThe author thanks Dr. Fakhery Farag and Dr. Ahmed Yaseen, pediatricians of Fayoum Insurance Hospital, for data supplementation. The author also thanks Dr. Yaseen’s wife for linguistic revision.InformationCopyright © 2013, Annals of Saudi MedicineThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.PDF download" @default.
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