Breastfeeding After Maternal Iodine Contrast: Neonatal Hypothyroidism Revealing an Underlying Congenital Disorder

Breastfeeding After Maternal Iodine Contrast: Neonatal Hypothyroidism Revealing an Underlying Congenital Disorder | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Breastfeeding After Maternal Iodine Contrast: Neonatal Hypothyroidism Revealing an Underlying Congenital Disorder Elena Sasso, Roxana L Aguirre Castaneda, Rena Linderer, Miguel Barajas, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7546763/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Feb, 2026 Read the published version in International Breastfeeding Journal → Version 1 posted 10 You are reading this latest preprint version Abstract Background: Iodine plays a critical role in producing thyroid hormones essential for brain development. Both iodine deficiency and excess can disrupt thyroid function, particularly in neonates. Iodine-induced hypothyroidism is rare but has been reported, particularly in premature infants exposed to excess iodine. Currently, Iohexol, a nonionic radiocontrast agent, has limited data but is considered compatible with breastfeeding. This is a case of a small for gestational age infant that was found to have hypothyroidism after ingesting breastmilk from a mom who was given IV Iohexol. Case Presentation: A small for gestation neonate was delivered at 36 weeks and 3 days of gestation and admitted to the neonatal intensive care unit for respiratory distress and prematurity. Newborn Screens done at admission and repeated after 48 hours of life were negative for thyroid abnormalities. At 5 days of life, the mother underwent a contrast-enhanced imaging study using iohexol, after which the infant received breast milk from days 5-11. On day 11, the neonate had an elevated thyroid-stimulating hormone (TSH) and low free thyroxine (T4) levels, consistent with hypothyroidism. Urine iodine level in the infant was checked and found to be elevated, which prompted the medical team’s concern for the exposure to iodine in breastmilk. However, the thyroid levels in the infant remained abnormal, which was unexpected from a transient process such as exposure to iodine. Genetic testing revealed missense variants in the Iodide Deiodinase Deficiency ( IYD) gene, which are associated with thyroid dyshormonogenesis, as well as a likely pathogenic intragenic deletion in the gene RPS6KA3 , which is consistent with Coffin–Lowry syndrome. Conclusions: This case highlights the complex interplay between genetic factors and environmental influences in the development of neonatal hypothyroidism. While iodine contrast exposure through breast milk is generally considered safe, this case underscores the potential risks in preterm infants. Initially, iodine exposure through breastmilk was considered a contributor to thyroid dysfunction, but with further time and evaluation, congenital thyroid dysgenesis with underlying genetic findings complicated the diagnosis. Caution should be taken for iodine-exposed breastmilk, but because iodine is only one potential cause of neonatal hypothyroidism, persistent thyroid abnormalities warrant a complete congenital hypothyroidism work-up to assess for alternative or coexisting etiologies. Background Iodine is essential for thyroid hormone synthesis; deficiency and excess can disrupt thyroid function. In children under three years of age, such disruptions may adversely affect brain development during this critical period of neurodevelopment. 1 The thyroid gland has autoregulatory mechanisms to manage iodine excess, including the acute Wolff-Chaikoff effect, which temporarily suppresses thyroid hormone synthesis in response to high iodine levels. 1 With prolonged exposure, the thyroid gland downregulates iodine uptake and gradually resumes normal hormone production. However, this adaptive response may be delayed or underdeveloped in fetuses and neonates, increasing the risk of hypothyroidism. Iodine-induced hypothyroidism has been most commonly reported in premature infants, particularly in those exposed to excessive iodine through skin antiseptics, prompting many neonatal units to discontinue the routine use of these products. 2 Themelin et al., reported a case in which a preterm infant developed transient hypothyroidism after receiving breast milk from a mother who had undergone a computed tomography (CT) scan with iodinated contrast despite a 24-hour pause in breastfeeding. 3 This report underscores the importance of monitoring thyroid function in at-risk neonates exposed to iodine through breast milk after maternal use of such contrast agents. During the postpartum period, imaging studies with intravenous contrast can be essential diagnostic tools for maternal diagnosis. The manufacturer’s guidelines for iohexol, a common contrast agent used in imaging studies, advise withholding breastfeeding for 10 hours after administration to minimize exposure of the neonate. 4 Guidelines from Hale's Medications & Mothers' Milk and recommendations from other professional organizations state that uninterrupted breastfeeding after iohexol contrast is safe for neonates with no known reported adverse effects. 5 , 6 , 7 These recommendations are built upon “Excretion of iohexol and metrizoate in human breast milk,” which evaluated four lactating women who received iohexol. Blood and breast milk samples were analyzed to assess the extent of contrast agent excretion into breast milk and the estimated exposure to nursing infants. The study found that the neonates received an average weight-adjusted dose of only 0.5% of the maternal dose . 8 Given iohexol’s low oral bioavailability, the study concluded that breastfeeding may be safely continued after maternal administration of iohexol unless the neonate has a known hypersensitivity to the agent. Iodotyrosine deiodinase ( IYD ) encodes the enzyme responsible for recovering iodine from byproducts of thyroid hormone synthesis to be recycled for future thyroid hormone production. This iodine salvage process maintains sufficient thyroid hormone production. When there are biallelic IYD pathogenic variants, this process is disrupted, causing an iodine deficiency that can lead to hypothyroidism and goiter. Affected individuals can experience developmental delays and typically require lifelong thyroid hormone replacement therapy. IYD pathogenic variants cause elevated levels of iodine in the urine because these mutations decrease the amount of iodine reused. 9 Many IYD pathogenic variants have been identified, leading to the onset of hypothyroidism in both childhood and adulthood. 9 It has been hypothesized that these mutations often cause a gradual onset of hypothyroidism, because in countries with newborn screening programs for congenital hypothyroidism, patients have been diagnosed only after developing irreversible cognitive impairments later in childhood, not in the neonatal period. 10 Coffin–Lowry syndrome, an X-linked dominant genetic disorder often occurring sporadically, is characterized by intellectual disability, seizures, cardiac abnormalities, skeletal deformities, and distinctive facial features. Although there is no established association between Coffin–Lowry syndrome and hypothyroidism in the literature, one case study documents a 14-year-old boy with an instance of comorbidity between the two disorders. The patient had a history of hypothyroidism since infancy and was treated with levothyroxine until the age of thirteen. 11 We present a case of a neonate with previously normal thyroid function who developed hypothyroidism, initially suspected to be iodine-induced after exposure to breast milk from a mother who received intravenous iohexol. Still, subsequent evaluation revealed congenital thyroid dysgenesis with underlying genetic findings that complicated the diagnosis. Case presentation The patient was a late preterm neonate born at 36 weeks and 3 days of gestation, with a birth weight of 1,900 grams (1st percentile on Fenton growth chart), consistent with small for gestational age. Gestational age was established by an 11-week prenatal ultrasound and confirmed postnatally by a Ballard score corresponding to 36 weeks. There was no reported maternal or family history of thyroid disorders. The pregnancy was complicated by chronic hypertension with superimposed preeclampsia. There was concern for possible nonprimary herpes simplex virus lesions during the peripartum period. Prenatal ultrasound revealed fetal growth restriction, with an abdominal circumference below the 1st percentile. Delivery was complicated by a double nuchal cord and maternal magnesium exposure. APGAR score was eight at 1 minute and nine at 5 minutes. The cord gas was pH 7.24, PCO2 55 mmHg, and PO2 20 mmHg for the umbilical artery and pH 7.30, PCO2 47 mmHg, and PO2 20 mmHg for the umbilical vein. The patient was admitted to the NICU for prematurity, magnesium exposure, and fetal growth restriction. Physical exam identified dysmorphic facial features, including down-slanting palpebral fissures, an upturned nose, a left single transverse palmar crease, long, slender fingers, and feet. The clinical course was complicated by respiratory distress syndrome, requiring transfer to the NICU for support with continuous positive airway pressure (CPAP). The patient was successfully weaned to room air within 24 hours of life. The Illinois newborn screening performed on day of life (DOL) 3 was notable only for sickle cell trait, with results for congenital hypothyroidism reported as negative. The patient received ampicillin and gentamicin for 36 hours as part of empiric treatment for potential sepsis. In addition, the patient received acyclovir until a negative herpes simplex virus culture became available at DOL 6. Starting on DOL 2, while the baby was still receiving positive pressure respiratory support, breast milk was administered as trophic feeds at a volume of 5 mL every three hours via nasogastric tube. On infant DOL 5, the mother developed a fever. As part of the evaluation for maternal fever, the mother underwent contrast-enhanced CT with administration of 100 mL of intravenous iohexol (300 mg iodine/mL). The use of breast milk continued without interruption after the mother received intravenous iohexol. The volume of breast milk ingested by the infant increased daily from 10 mL on DOL 3 to 210 mL by DOL 7. On DOL 9, the neonate was found to have direct hyperbilirubinemia. Due to persistence of elevated levels, the patient received 20 mg of ursodiol every 8 hours between DOLs 12 and 18. The trend of hyperbilirubinemia is shown below (Table 1 ). Thyroid function was assessed as part of the evaluation for persistent jaundice on DOL 11. Thyroid hormones were consistent with hypothyroidism (see Table 2 ). The patient was started on levothyroxine (Synthroid®) at 25 mcg daily. Due to a history of prematurity, previous normal thyroid levels from the state Newborn Screen and maternal exposure to iodine contrast, urine iodine level was measured and found to be very elevated at > 2,040.8µg per gram of creatinine (normal is 35–540µg per gram of creatinine), suggesting that hypothyroidism could be secondary to iodine exposure. A thyroid ultrasound was performed, which demonstrated a hypoplastic gland. Thyroid hormone levels normalized while on Levothyroxine (Table 2 ). Table 1 Hyperbilirubinemia trends before and after treatment with ursodiol on DOLs 12–18 Day of Life 4 5 6 10 11 15 16 18 19 22 25 29 43 Total Bilirubin (mg/dL) 9.7 10.0 10.7 9.9 7.8 6.9 4.6 3.5 2.9 2.7 3.2 3.6 1.9 Direct Bilirubin (mg/dL) 1.4 1.0 1.6 2.1 2.6 3.3 2.9 2.3 1.7 1.7 2.2 2.5 1.2 Table 2 Thyroid function test trends before, during, and after initiation of levothyroxine (Synthroid®) at DOL 12 Day of Life 3 11 17 24 32 46 TSH (mcIU/mL) 33.4 75.16 30.18 18.84 13.67 4.84 Free T4 (ng/dL) 9.9 0.5 0.9 1.4 1.1 1.6 Given the concern for dysmorphic features, direct hyperbilirubinemia, and hypothyroidism, Genetics was consulted. The patient underwent a comprehensive genetic evaluation and broad genetic testing, including chromosomal microarray, karyotype, and whole-genome sequencing. The chromosomal microarray and karyotype results were normal, effectively ruling out significant chromosomal abnormalities. Whole-genome sequencing through the Rady Institute for Genomic Medicine identified three variants of uncertain significance (VUSs). The first VUS was a heterozygous variant in the IYD gene (c.89A > C; p.Lys30Thr), associated with thyroid dyshormonogenesis 4 (TDH4), a disorder linked to hypothyroidism, goiter, and impaired cognitive function. The second VUS was a heterozygous change in the IYD gene (c.748C > T; p.Pro250Ser). The third VUS was a maternally inherited Xp22.12 intragenic deletion of exons 15–17 of the RPS6KA3 gene, which is associated with Coffin-Lowry syndrome and intellectual disability. Subsequent testing at Invitae classified this variant as likely pathogenic. Discussion Iodine is crucial for thyroid function and neurocognitive development. In the underdeveloped thyroid glands of neonates and fetuses, the Wolff‒Chaikoff effect cannot be as effective, increasing vulnerability to iodine-induced hypothyroidism. Current guidelines endorse the safe continuation of breastfeeding during maternal use of iohexol. This case report describes an infant with hypothyroidism after exposure to iohexol through breastmilk and underscores the importance of a comprehensive workup when hypothyroidism occurs in the context of iodine exposure, particularly in the presence of elevated urine iodine levels. In this case, the negative newborn screening initially supported iodine exposure as the likely cause of hypothyroidism; however, further work-up demonstrated a hypoplastic thyroid on ultrasound, consistent with thyroid dysgenesis seen in congenital hypothyroidism. This diagnosis was subsequently confirmed through clinical follow-up. This case is particularly noteworthy due to the initial misleading picture of iodine-induced hypothyroidism, ultimately leading to the identification of an underlying congenital etiology. In neonatal care, it is essential to consider not only prematurity but also the infant's weight. This infant was born at 36 weeks of gestation, with a weight of 1800grams, which is the lower end of the expected weight spectrum for that gestational age, and is more comparable to an average 32-week-old infant. As this infant was small for gestational age with fetal growth restriction, these factors could have increased the susceptibility to the effects of excessive iodine. Preeclampsia was present in this mother and carries a high risk of placental insufficiency, which may induce intrauterine hypothyroidism. 12 It has also been reported that perinatal asphyxia results in lower TSH, T4, T3, and FT4 cord blood levels in newborns. This infant did have a nuchal cord; however, both the cord gas and APGARS were within normal limits. 13 Owing to the normal Illinois neonatal thyroid screen on DOL 3, timeline alignment with the consumption of breastmilk after contrast use by the mother, and elevated urine iodine level, it seemed unlikely that this infant had hypothyroidism in the first days of life, either because of pregnancy or delivery complications. In relation to a child’s IYD VUS, current evidence suggests that these defects are usually diagnosed with overt hypothyroidism later in childhood or adulthood, not at the neonatal stage. 4 Typically, infants with IYD defects have normal thyroid function at birth, leading to these cases not being detected at the time of the neonatal screening programs for congenital hypothyroidism. 10 This aligns with our patient's normal newborn screen at DOL 3. Additionally, in reports of IYD-related disorder , hypothyroidism is described as a goiter, which was notably absent in all documented exams, and the thyroid was found to be hypoplastic on ultrasound on DOL 12. 9 Due to inconsistencies in the severity and onset of hypothyroidism with IYD-related disorder , it has been hypothesized that different environmental or nutritional factors, such as iodine deficiency or excess iodine, could influence the presentation of these variants. 10 It is possible that the combination of this patient’s IYD mutation and the exposure to iodine in breastmilk that they ingested could have contributed to the timeline of this infant’s presentation of neonatal hypothyroidism. Additionally, the patient had Coffin–Lowry syndrome, and one documented case was comorbid with hypothyroidism, suggesting that this could be another genetic interaction predisposing this patient to developing hypothyroidism. A notable limitation of this case report is the absence of quantitative data regarding iohexol levels in both the breast milk and the maternal and infant’s serum. Despite these limitations, this report provides valuable insights into the potential effects of iohexol exposure through breast milk on neonates. While professional recommendations generally support the safety of maternal iohexol use during breastfeeding, existing data are insufficient to fully understand the circumstances that cause hypothyroidism in infants with genetic susceptibility. Conclusion Human milk is widely recognized as the ideal nutritional source for all infants, particularly for preterm and critically ill infants, who require optimal nourishment to support growth and development. This case report adds to the limited information that is known about the risk of hypothyroidism caused by maternal iohexol use in hospitalized breastfed preterm or low birth weight infants. The initial attribution of hypothyroidism to iodine exposure was considered; however, the sustained dysfunction was inconsistent with typical iodine-induced effects. While precaution regarding iodine-contaminated breastmilk is still appropriate, persistent thyroid dysfunction should prompt differential diagnostic evaluation. This case highlights the complexity of thyroid regulation, which is influenced not only by environmental factors such as iodine exposure but also by genetic mutations that can impair thyroid function. This case adds to the literature concerning patients with IYD variants and their development of hypothyroidism. Genetic syndromes, such as Coffin–Lowry syndrome, are not commonly associated with hypothyroidism. This is the second reported case of co-morbid Coffin–Lowry syndrome and hypothyroidism, indicating a potential correlation between those conditions. These genetic factors, combined with environmental influences such as iodine excess or deficiency, emphasize the multifaceted nature of thyroid dysfunction. In vulnerable populations, particularly neonates and children with rare genetic conditions, the presence of these mutations can contribute to the delayed or atypical onset of hypothyroidism, making early diagnosis and management crucial. Clinicians should be aware of these complexities when evaluating infants for thyroid dysfunction, especially when considering the potential effects of maternal contrast media use, and pursue a full evaluation. This case serves as a reminder of the need for ongoing research to understand better the intricate relationships among genetics, environmental factors, and thyroid health in neonates and young children. Further studies will provide essential insights for guiding clinical practice and ensuring the best possible outcomes for mothers and infants. Abbreviations IYD Iodide Dehaloperoxidase Deficiency TSH Thyroid-Stimulating Hormone T4 Thyroxine T3 Triiodothyronine Hormone RPS6KA3 Ribosomal Protein S6 Kinase A3 CT Computed Tomography DOL Day of Life NICU Neonatal Intensive Care Unit CPAP Continuous Positive Airway Pressure IV Intravenous VUS Variant of Uncertain Significance PCR Polymerase Chain Reaction FT4 Free Thyroxine APGAR Appearance, Pulse, Grimace, Activity, Respiration PCO2 Partial Pressure of Carbon Dioxide PO2 Partial Pressure of Oxygen CRP C-reactive Protein PICC Peripherally Inserted Central Catheter Declarations This case report was conducted in accordance with relevant ethical standards. No identifiable information was used, and the mother provided written informed consent to publish this case report. Data sharing does not apply to this article as no datasets were generated or analyzed during the current study. The authors declare that they have no competing interests. There was no funding for this report. ES interpreted the patient data and was a major contributor in writing the manuscript. All authors read and approved the final manuscript. Acknowledgements: https://www.biomedcentral.com/getpublished/editorial-policies#authorship Author Contribution ES interpreted the patient data and was a major contributor in writing the manuscript. All authors read, made contributions, revised and approved the final manuscript. References Klosinska M, Kaczynska A, Ben-Skowronek I. Congenital hypothyroidism in preterm newborns - The challenges of diagnostics and treatment: A review. Front Endocrinol (Lausanne). 2022;13:860862. 10.3389/fendo.2022.860862 . Aitken J, Williams FL. A systematic review of thyroid dysfunction in preterm neonates exposed to topical iodine. Arch Dis Child Fetal Neonatal Ed. 2014;99(1):F21–8. 10.1136/archdischild-2013-303799 . Themelin C, Pierron C, Calafat JF, de Beaufort C. Transient neonatal hypothyroidism secondary to postnatal maternal exposure to contrast medium. BMJ Case Rep. 2019;12(10):e230854. 10.1136/bcr-2019-23085 . Iohexol. In. Drugs and Lactation Database (LactMed®). Bethesda, MD: National Institute of Child Health and Human Development; 2022. Nov 30. Chen MM, Coakley FV, Kaimal A, Laros RK Jr. Guidelines for computed tomography and magnetic resonance imaging use during pregnancy and lactation. Obstet Gynecol. 2008;112(2 Pt 1):333–40. 10.1097/AOG.0b013e318180a505 . Committee Opinion No. 723: Guidelines for Diagnostic Imaging During Pregnancy and Lactation. Obstet Gynecol. 2017;130(4):e210-e216. 10.1097/AOG.0000000000002355 . Erratum in: Obstet Gynecol. 2018;132(3):786. doi:10.1097/AOG.0000000000002858. Webb JA, Thomsen HS, Morcos SK, Members of Contrast Media Safety Committee of European Society of Urogenital Radiology (ESUR). The use of iodinated and gadolinium contrast media during pregnancy and lactation. Eur Radiol. 2005;15(6):1234–40. 10.1007/s00330-004-2583-y . Nielsen ST, Matheson I, Rasmussen JN, Skinnemoen K, Andrew E, Hafsahl G. Excretion of iohexol and metrizoate in human breast milk. Acta Radiol. 1987;28(5):523–6. Moreno JC, Klootwijk W, van Toor H, et al. Mutations in the iodotyrosine deiodinase gene and hypothyroidism. N Engl J Med. 2008;358(17):1811–8. 10.1056/NEJMoa0706819 . Iglesias A, García-Nimo L, Cocho de Juan JA, Moreno JC. Towards the pre-clinical diagnosis of hypothyroidism caused by iodotyrosine deiodinase (DEHAL1) defects. Best Pract Res Clin Endocrinol Metab. 2014;28(2):151–9. 10.1016/j.beem.2013.10.009 . Singh PM, Baidya DK, Govindarajan S, Trikha A. Ocular surgery in a child with Coffin-Lowry syndrome: anesthetic concerns. J Anaesthesiol Clin Pharmacol. 2013;29(1):114–6. 10.4103/0970-9185.105818 . Levine RJ, Vatten LJ, Horowitz GL, et al. Pre-eclampsia, soluble fms-like tyrosine kinase 1, and the risk of reduced thyroid function: nested case-control and population-based study. BMJ. 2009;339:b4336. 10.1136/bmj.b4336 . Kobayashi A, Usuda T, Wada M, Kaneko T, Kojima K, Saitoh A. Thyroid function in asphyxiated newborns who received hypothermia therapy. Pediatr Int. 2018;60(5):433–7. 10.1111/ped.13534 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 14 Feb, 2026 Read the published version in International Breastfeeding Journal → Version 1 posted Editorial decision: Revision requested 22 Oct, 2025 Reviews received at journal 03 Oct, 2025 Reviewers agreed at journal 23 Sep, 2025 Reviews received at journal 22 Sep, 2025 Reviewers agreed at journal 22 Sep, 2025 Reviewers agreed at journal 20 Sep, 2025 Reviewers invited by journal 09 Sep, 2025 Editor assigned by journal 06 Sep, 2025 Submission checks completed at journal 06 Sep, 2025 First submitted to journal 05 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7546763","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":512924315,"identity":"59ee5216-d12d-4e49-8b74-8e66750af7f8","order_by":0,"name":"Elena Sasso","email":"","orcid":"","institution":"University of Illinois at Chicago","correspondingAuthor":false,"prefix":"","firstName":"Elena","middleName":"","lastName":"Sasso","suffix":""},{"id":512924316,"identity":"3490a1a8-26b4-4f7d-bb67-c29242a069bd","order_by":1,"name":"Roxana L Aguirre Castaneda","email":"","orcid":"","institution":"University of Illinois Hospital \u0026 Health Sciences System","correspondingAuthor":false,"prefix":"","firstName":"Roxana","middleName":"L","lastName":"Aguirre Castaneda","suffix":""},{"id":512924317,"identity":"0ce08de6-f4c6-4f5e-9b0a-eaabe8714a74","order_by":2,"name":"Rena Linderer","email":"","orcid":"","institution":"University of Illinois Hospital \u0026 Health Sciences System","correspondingAuthor":false,"prefix":"","firstName":"Rena","middleName":"","lastName":"Linderer","suffix":""},{"id":512924318,"identity":"ea5c6899-d6c9-43a4-998c-423b3a0ea1c2","order_by":3,"name":"Miguel Barajas","email":"","orcid":"","institution":"University of Illinois Hospital \u0026 Health Sciences System","correspondingAuthor":false,"prefix":"","firstName":"Miguel","middleName":"","lastName":"Barajas","suffix":""},{"id":512924319,"identity":"95868178-a6ae-4140-9c3c-7eb53f61bade","order_by":4,"name":"Shannon Murphy","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAr0lEQVRIiWNgGAWjYDACCSjNz8DYAKSYSdAi2UCyFoMDYIoILfKzm589LqjYlrj5RnLjB4YK68QGQloM7hwzN55x5nbithuJzRIMZ9KJ0CKRYCbN2wbW0sbA2HaYsBb5GenfwFo2zwBp+UeEFoYbORBbNkiAtDQQocXgRk6ZNM+Z20D/PGyWSDiWbkyMw7ZJ81Tclu1vT3/44UONtSxhh6GABNKUj4JRMApGwSjABQA+K0A53TUkXAAAAABJRU5ErkJggg==","orcid":"","institution":"University of Illinois Hospital \u0026 Health Sciences System","correspondingAuthor":true,"prefix":"","firstName":"Shannon","middleName":"","lastName":"Murphy","suffix":""}],"badges":[],"createdAt":"2025-09-05 19:23:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7546763/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7546763/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13006-026-00822-z","type":"published","date":"2026-02-14T15:57:16+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":107480917,"identity":"18984a5f-c3e3-454b-8771-e19dc1349dce","added_by":"auto","created_at":"2026-04-22 02:14:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":219344,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7546763/v1/d58d0140-6a5b-4015-a949-261bf744a070.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Breastfeeding After Maternal Iodine Contrast: Neonatal Hypothyroidism Revealing an Underlying Congenital Disorder","fulltext":[{"header":"Background","content":"\u003cp\u003eIodine is essential for thyroid hormone synthesis; deficiency and excess can disrupt thyroid function. In children under three years of age, such disruptions may adversely affect brain development during this critical period of neurodevelopment.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e The thyroid gland has autoregulatory mechanisms to manage iodine excess, including the acute Wolff-Chaikoff effect, which temporarily suppresses thyroid hormone synthesis in response to high iodine levels.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e With prolonged exposure, the thyroid gland downregulates iodine uptake and gradually resumes normal hormone production. However, this adaptive response may be delayed or underdeveloped in fetuses and neonates, increasing the risk of hypothyroidism. Iodine-induced hypothyroidism has been most commonly reported in premature infants, particularly in those exposed to excessive iodine through skin antiseptics, prompting many neonatal units to discontinue the routine use of these products.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Themelin et al., reported a case in which a preterm infant developed transient hypothyroidism after receiving breast milk from a mother who had undergone a computed tomography (CT) scan with iodinated contrast despite a 24-hour pause in breastfeeding.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e This report underscores the importance of monitoring thyroid function in at-risk neonates exposed to iodine through breast milk after maternal use of such contrast agents.\u003c/p\u003e\u003cp\u003eDuring the postpartum period, imaging studies with intravenous contrast can be essential diagnostic tools for maternal diagnosis. The manufacturer\u0026rsquo;s guidelines for iohexol, a common contrast agent used in imaging studies, advise withholding breastfeeding for 10 hours after administration to minimize exposure of the neonate.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Guidelines from Hale's Medications \u0026amp; Mothers' Milk and recommendations from other professional organizations state that uninterrupted breastfeeding after iohexol contrast is safe for neonates with no known reported adverse effects.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e These recommendations are built upon \u0026ldquo;Excretion of iohexol and metrizoate in human breast milk,\u0026rdquo; which evaluated four lactating women who received iohexol. Blood and breast milk samples were analyzed to assess the extent of contrast agent excretion into breast milk and the estimated exposure to nursing infants. The study found that the neonates received an average weight-adjusted dose of only 0.5% of the maternal dose .\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Given iohexol\u0026rsquo;s low oral bioavailability, the study concluded that breastfeeding may be safely continued after maternal administration of iohexol unless the neonate has a known hypersensitivity to the agent. Iodotyrosine deiodinase (\u003cem\u003eIYD\u003c/em\u003e) encodes the enzyme responsible for recovering iodine from byproducts of thyroid hormone synthesis to be recycled for future thyroid hormone production. This iodine salvage process maintains sufficient thyroid hormone production. When there are biallelic \u003cem\u003eIYD\u003c/em\u003e pathogenic variants, this process is disrupted, causing an iodine deficiency that can lead to hypothyroidism and goiter. Affected individuals can experience developmental delays and typically require lifelong thyroid hormone replacement therapy. \u003cem\u003eIYD\u003c/em\u003e pathogenic variants cause elevated levels of iodine in the urine because these mutations decrease the amount of iodine reused. \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Many IYD pathogenic variants have been identified, leading to the onset of hypothyroidism in both childhood and adulthood.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e It has been hypothesized that these mutations often cause a gradual onset of hypothyroidism, because in countries with newborn screening programs for congenital hypothyroidism, patients have been diagnosed only after developing irreversible cognitive impairments later in childhood, not in the neonatal period.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eCoffin\u0026ndash;Lowry syndrome, an X-linked dominant genetic disorder often occurring sporadically, is characterized by intellectual disability, seizures, cardiac abnormalities, skeletal deformities, and distinctive facial features. Although there is no established association between Coffin\u0026ndash;Lowry syndrome and hypothyroidism in the literature, one case study documents a 14-year-old boy with an instance of comorbidity between the two disorders. The patient had a history of hypothyroidism since infancy and was treated with levothyroxine until the age of thirteen.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e We present a case of a neonate with previously normal thyroid function who developed hypothyroidism, initially suspected to be iodine-induced after exposure to breast milk from a mother who received intravenous iohexol. Still, subsequent evaluation revealed congenital thyroid dysgenesis with underlying genetic findings that complicated the diagnosis.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eThe patient was a late preterm neonate born at 36 weeks and 3 days of gestation, with a birth weight of 1,900 grams (1st percentile on Fenton growth chart), consistent with small for gestational age. Gestational age was established by an 11-week prenatal ultrasound and confirmed postnatally by a Ballard score corresponding to 36 weeks. There was no reported maternal or family history of thyroid disorders. The pregnancy was complicated by chronic hypertension with superimposed preeclampsia. There was concern for possible nonprimary herpes simplex virus lesions during the peripartum period. Prenatal ultrasound revealed fetal growth restriction, with an abdominal circumference below the 1st percentile. Delivery was complicated by a double nuchal cord and maternal magnesium exposure. APGAR score was eight at 1 minute and nine at 5 minutes. The cord gas was pH 7.24, PCO2 55 mmHg, and PO2 20 mmHg for the umbilical artery and pH 7.30, PCO2 47 mmHg, and PO2 20 mmHg for the umbilical vein. The patient was admitted to the NICU for prematurity, magnesium exposure, and fetal growth restriction. Physical exam identified dysmorphic facial features, including down-slanting palpebral fissures, an upturned nose, a left single transverse palmar crease, long, slender fingers, and feet. The clinical course was complicated by respiratory distress syndrome, requiring transfer to the NICU for support with continuous positive airway pressure (CPAP). The patient was successfully weaned to room air within 24 hours of life.\u003c/p\u003e\u003cp\u003eThe Illinois newborn screening performed on day of life (DOL) 3 was notable only for sickle cell trait, with results for congenital hypothyroidism reported as negative. The patient received ampicillin and gentamicin for 36 hours as part of empiric treatment for potential sepsis. In addition, the patient received acyclovir until a negative herpes simplex virus culture became available at DOL 6. Starting on DOL 2, while the baby was still receiving positive pressure respiratory support, breast milk was administered as trophic feeds at a volume of 5 mL every three hours via nasogastric tube.\u003c/p\u003e\u003cp\u003eOn infant DOL 5, the mother developed a fever. As part of the evaluation for maternal fever, the mother underwent contrast-enhanced CT with administration of 100 mL of intravenous iohexol (300 mg iodine/mL). The use of breast milk continued without interruption after the mother received intravenous iohexol. The volume of breast milk ingested by the infant increased daily from 10 mL on DOL 3 to 210 mL by DOL 7.\u003c/p\u003e\u003cp\u003eOn DOL 9, the neonate was found to have direct hyperbilirubinemia. Due to persistence of elevated levels, the patient received 20 mg of ursodiol every 8 hours between DOLs 12 and 18. The trend of hyperbilirubinemia is shown below (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThyroid function was assessed as part of the evaluation for persistent jaundice on DOL 11. Thyroid hormones were consistent with hypothyroidism (see Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The patient was started on levothyroxine (Synthroid\u0026reg;) at 25 mcg daily. Due to a history of prematurity, previous normal thyroid levels from the state Newborn Screen and maternal exposure to iodine contrast, urine iodine level was measured and found to be very elevated at \u0026gt;\u0026thinsp;2,040.8\u0026micro;g per gram of creatinine (normal is 35\u0026ndash;540\u0026micro;g per gram of creatinine), suggesting that hypothyroidism could be secondary to iodine exposure. A thyroid ultrasound was performed, which demonstrated a hypoplastic gland. Thyroid hormone levels normalized while on Levothyroxine (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eHyperbilirubinemia trends before and after treatment with ursodiol on DOLs 12\u0026ndash;18\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"14\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay of Life\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c14\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal Bilirubin\u003c/p\u003e\u003cp\u003e(mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e9.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e7.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e6.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e4.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e3.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e2.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e2.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e\u003cp\u003e3.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e\u003cp\u003e3.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e\u003cp\u003e1.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDirect Bilirubin\u003c/p\u003e\u003cp\u003e(mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e2.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e2.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e\u003cp\u003e2.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e\u003cp\u003e2.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e\u003cp\u003e1.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eThyroid function test trends before, during, and after initiation of levothyroxine (Synthroid\u0026reg;) at DOL 12\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay of Life\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e32\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e46\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTSH\u003c/p\u003e\u003cp\u003e(mcIU/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e33.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e75.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e30.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e18.84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e13.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e4.84\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFree T4\u003c/p\u003e\u003cp\u003e(ng/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eGiven the concern for dysmorphic features, direct hyperbilirubinemia, and hypothyroidism, Genetics was consulted. The patient underwent a comprehensive genetic evaluation and broad genetic testing, including chromosomal microarray, karyotype, and whole-genome sequencing. The chromosomal microarray and karyotype results were normal, effectively ruling out significant chromosomal abnormalities. Whole-genome sequencing through the Rady Institute for Genomic Medicine identified three variants of uncertain significance (VUSs). The first VUS was a heterozygous variant in the \u003cem\u003eIYD\u003c/em\u003e gene (c.89A\u0026thinsp;\u0026gt;\u0026thinsp;C; p.Lys30Thr), associated with thyroid dyshormonogenesis 4 (TDH4), a disorder linked to hypothyroidism, goiter, and impaired cognitive function. The second VUS was a heterozygous change in the \u003cem\u003eIYD\u003c/em\u003e gene (c.748C\u0026thinsp;\u0026gt;\u0026thinsp;T; p.Pro250Ser). The third VUS was a maternally inherited Xp22.12 intragenic deletion of exons 15\u0026ndash;17 of the \u003cem\u003eRPS6KA3\u003c/em\u003e gene, which is associated with Coffin-Lowry syndrome and intellectual disability. Subsequent testing at Invitae classified this variant as likely pathogenic.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIodine is crucial for thyroid function and neurocognitive development. In the underdeveloped thyroid glands of neonates and fetuses, the Wolff‒Chaikoff effect cannot be as effective, increasing vulnerability to iodine-induced hypothyroidism. Current guidelines endorse the safe continuation of breastfeeding during maternal use of iohexol. This case report describes an infant with hypothyroidism after exposure to iohexol through breastmilk and underscores the importance of a comprehensive workup when hypothyroidism occurs in the context of iodine exposure, particularly in the presence of elevated urine iodine levels. In this case, the negative newborn screening initially supported iodine exposure as the likely cause of hypothyroidism; however, further work-up demonstrated a hypoplastic thyroid on ultrasound, consistent with thyroid dysgenesis seen in congenital hypothyroidism. This diagnosis was subsequently confirmed through clinical follow-up. This case is particularly noteworthy due to the initial misleading picture of iodine-induced hypothyroidism, ultimately leading to the identification of an underlying congenital etiology.\u003c/p\u003e\u003cp\u003eIn neonatal care, it is essential to consider not only prematurity but also the infant's weight. This infant was born at 36 weeks of gestation, with a weight of 1800grams, which is the lower end of the expected weight spectrum for that gestational age, and is more comparable to an average 32-week-old infant. As this infant was small for gestational age with fetal growth restriction, these factors could have increased the susceptibility to the effects of excessive iodine. Preeclampsia was present in this mother and carries a high risk of placental insufficiency, which may induce intrauterine hypothyroidism.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e It has also been reported that perinatal asphyxia results in lower TSH, T4, T3, and FT4 cord blood levels in newborns. This infant did have a nuchal cord; however, both the cord gas and APGARS were within normal limits.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Owing to the normal Illinois neonatal thyroid screen on DOL 3, timeline alignment with the consumption of breastmilk after contrast use by the mother, and elevated urine iodine level, it seemed unlikely that this infant had hypothyroidism in the first days of life, either because of pregnancy or delivery complications.\u003c/p\u003e\u003cp\u003eIn relation to a child\u0026rsquo;s \u003cem\u003eIYD\u003c/em\u003e VUS, current evidence suggests that these defects are usually diagnosed with overt hypothyroidism later in childhood or adulthood, not at the neonatal stage.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Typically, infants with IYD defects have normal thyroid function at birth, leading to these cases not being detected at the time of the neonatal screening programs for congenital hypothyroidism. \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e This aligns with our patient's normal newborn screen at DOL 3. Additionally, in reports of \u003cem\u003eIYD-related disorder\u003c/em\u003e, hypothyroidism is described as a goiter, which was notably absent in all documented exams, and the thyroid was found to be hypoplastic on ultrasound on DOL 12.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Due to inconsistencies in the severity and onset of hypothyroidism with \u003cem\u003eIYD-related disorder\u003c/em\u003e, it has been hypothesized that different environmental or nutritional factors, such as iodine deficiency or excess iodine, could influence the presentation of these variants.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e It is possible that the combination of this patient\u0026rsquo;s \u003cem\u003eIYD\u003c/em\u003e mutation and the exposure to iodine in breastmilk that they ingested could have contributed to the timeline of this infant\u0026rsquo;s presentation of neonatal hypothyroidism. Additionally, the patient had Coffin\u0026ndash;Lowry syndrome, and one documented case was comorbid with hypothyroidism, suggesting that this could be another genetic interaction predisposing this patient to developing hypothyroidism.\u003c/p\u003e\u003cp\u003eA notable limitation of this case report is the absence of quantitative data regarding iohexol levels in both the breast milk and the maternal and infant\u0026rsquo;s serum. Despite these limitations, this report provides valuable insights into the potential effects of iohexol exposure through breast milk on neonates. While professional recommendations generally support the safety of maternal iohexol use during breastfeeding, existing data are insufficient to fully understand the circumstances that cause hypothyroidism in infants with genetic susceptibility.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eHuman milk is widely recognized as the ideal nutritional source for all infants, particularly for preterm and critically ill infants, who require optimal nourishment to support growth and development. This case report adds to the limited information that is known about the risk of hypothyroidism caused by maternal iohexol use in hospitalized breastfed preterm or low birth weight infants. The initial attribution of hypothyroidism to iodine exposure was considered; however, the sustained dysfunction was inconsistent with typical iodine-induced effects. While precaution regarding iodine-contaminated breastmilk is still appropriate, persistent thyroid dysfunction should prompt differential diagnostic evaluation. This case highlights the complexity of thyroid regulation, which is influenced not only by environmental factors such as iodine exposure but also by genetic mutations that can impair thyroid function.\u003c/p\u003e\u003cp\u003eThis case adds to the literature concerning patients with \u003cem\u003eIYD\u003c/em\u003e variants and their development of hypothyroidism. Genetic syndromes, such as Coffin\u0026ndash;Lowry syndrome, are not commonly associated with hypothyroidism. This is the second reported case of co-morbid Coffin\u0026ndash;Lowry syndrome and hypothyroidism, indicating a potential correlation between those conditions. These genetic factors, combined with environmental influences such as iodine excess or deficiency, emphasize the multifaceted nature of thyroid dysfunction.\u003c/p\u003e\u003cp\u003eIn vulnerable populations, particularly neonates and children with rare genetic conditions, the presence of these mutations can contribute to the delayed or atypical onset of hypothyroidism, making early diagnosis and management crucial. Clinicians should be aware of these complexities when evaluating infants for thyroid dysfunction, especially when considering the potential effects of maternal contrast media use, and pursue a full evaluation. This case serves as a reminder of the need for ongoing research to understand better the intricate relationships among genetics, environmental factors, and thyroid health in neonates and young children. Further studies will provide essential insights for guiding clinical practice and ensuring the best possible outcomes for mothers and infants.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIYD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eIodide Dehaloperoxidase Deficiency\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTSH\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eThyroid-Stimulating Hormone\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eT4\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eThyroxine\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eT3\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTriiodothyronine Hormone\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eRPS6KA3\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eRibosomal Protein S6 Kinase A3\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eComputed Tomography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eDOL\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eDay of Life\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNICU\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNeonatal Intensive Care Unit\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCPAP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eContinuous Positive Airway Pressure\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIV\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eIntravenous\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eVUS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eVariant of Uncertain Significance\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePCR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePolymerase Chain Reaction\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eFT4\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eFree Thyroxine\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAPGAR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAppearance, Pulse, Grimace, Activity, Respiration\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePCO2\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePartial Pressure of Carbon Dioxide\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePO2\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePartial Pressure of Oxygen\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCRP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eC-reactive Protein\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePICC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePeripherally Inserted Central Catheter\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eThis case report was conducted in accordance with relevant ethical standards. No identifiable information was used, and the mother provided written informed consent to publish this case report.\u003c/p\u003e\n\u003cp\u003eData sharing does not apply to this article as no datasets were generated or analyzed during the current study.\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eThere was no funding for this report.\u003c/p\u003e\n\u003cp\u003eES interpreted the patient data and was a major contributor in writing the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgements: https://www.biomedcentral.com/getpublished/editorial-policies#authorship\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eES interpreted the patient data and was a major contributor in writing the manuscript. All authors read, made contributions, revised and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKlosinska M, Kaczynska A, Ben-Skowronek I. Congenital hypothyroidism in preterm newborns - The challenges of diagnostics and treatment: A review. Front Endocrinol (Lausanne). 2022;13:860862. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fendo.2022.860862\u003c/span\u003e\u003cspan address=\"10.3389/fendo.2022.860862\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAitken J, Williams FL. A systematic review of thyroid dysfunction in preterm neonates exposed to topical iodine. Arch Dis Child Fetal Neonatal Ed. 2014;99(1):F21\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/archdischild-2013-303799\u003c/span\u003e\u003cspan address=\"10.1136/archdischild-2013-303799\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eThemelin C, Pierron C, Calafat JF, de Beaufort C. Transient neonatal hypothyroidism secondary to postnatal maternal exposure to contrast medium. BMJ Case Rep. 2019;12(10):e230854. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bcr-2019-23085\u003c/span\u003e\u003cspan address=\"10.1136/bcr-2019-23085\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIohexol. In. Drugs and Lactation Database (LactMed\u0026reg;). Bethesda, MD: National Institute of Child Health and Human Development; 2022. Nov 30.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen MM, Coakley FV, Kaimal A, Laros RK Jr. Guidelines for computed tomography and magnetic resonance imaging use during pregnancy and lactation. Obstet Gynecol. 2008;112(2 Pt 1):333\u0026ndash;40. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/AOG.0b013e318180a505\u003c/span\u003e\u003cspan address=\"10.1097/AOG.0b013e318180a505\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCommittee Opinion No. 723: Guidelines for Diagnostic Imaging During Pregnancy and Lactation. Obstet Gynecol. 2017;130(4):e210-e216. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/AOG.0000000000002355\u003c/span\u003e\u003cspan address=\"10.1097/AOG.0000000000002355\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Erratum in: Obstet Gynecol. 2018;132(3):786. doi:10.1097/AOG.0000000000002858.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWebb JA, Thomsen HS, Morcos SK, Members of Contrast Media Safety Committee of European Society of Urogenital Radiology (ESUR). The use of iodinated and gadolinium contrast media during pregnancy and lactation. Eur Radiol. 2005;15(6):1234\u0026ndash;40. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00330-004-2583-y\u003c/span\u003e\u003cspan address=\"10.1007/s00330-004-2583-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNielsen ST, Matheson I, Rasmussen JN, Skinnemoen K, Andrew E, Hafsahl G. Excretion of iohexol and metrizoate in human breast milk. Acta Radiol. 1987;28(5):523\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMoreno JC, Klootwijk W, van Toor H, et al. Mutations in the iodotyrosine deiodinase gene and hypothyroidism. N Engl J Med. 2008;358(17):1811\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa0706819\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa0706819\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIglesias A, Garc\u0026iacute;a-Nimo L, Cocho de Juan JA, Moreno JC. Towards the pre-clinical diagnosis of hypothyroidism caused by iodotyrosine deiodinase (DEHAL1) defects. Best Pract Res Clin Endocrinol Metab. 2014;28(2):151\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.beem.2013.10.009\u003c/span\u003e\u003cspan address=\"10.1016/j.beem.2013.10.009\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSingh PM, Baidya DK, Govindarajan S, Trikha A. Ocular surgery in a child with Coffin-Lowry syndrome: anesthetic concerns. J Anaesthesiol Clin Pharmacol. 2013;29(1):114\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/0970-9185.105818\u003c/span\u003e\u003cspan address=\"10.4103/0970-9185.105818\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLevine RJ, Vatten LJ, Horowitz GL, et al. Pre-eclampsia, soluble fms-like tyrosine kinase 1, and the risk of reduced thyroid function: nested case-control and population-based study. BMJ. 2009;339:b4336. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmj.b4336\u003c/span\u003e\u003cspan address=\"10.1136/bmj.b4336\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKobayashi A, Usuda T, Wada M, Kaneko T, Kojima K, Saitoh A. Thyroid function in asphyxiated newborns who received hypothermia therapy. Pediatr Int. 2018;60(5):433\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/ped.13534\u003c/span\u003e\u003cspan address=\"10.1111/ped.13534\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-breastfeeding-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ibfj","sideBox":"Learn more about [International Breastfeeding Journal](http://internationalbreastfeedingjournal.biomedcentral.com/)","snPcode":"13006","submissionUrl":"https://submission.nature.com/new-submission/13006/3","title":"International Breastfeeding Journal","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7546763/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7546763/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground:\u003c/p\u003e\n\u003cp\u003eIodine plays a critical role in producing thyroid hormones essential for brain development. Both iodine deficiency and excess can disrupt thyroid function, particularly in neonates. Iodine-induced hypothyroidism is rare but has been reported, particularly in premature infants exposed to excess iodine. Currently, Iohexol, a nonionic radiocontrast agent, has limited data but is considered compatible with breastfeeding. This is a case of a small for gestational age infant that was found to have hypothyroidism after ingesting breastmilk from a mom who was given IV Iohexol.\u003c/p\u003e\n\u003cp\u003eCase Presentation:\u003c/p\u003e\n\u003cp\u003eA small for gestation neonate was delivered at 36 weeks and 3 days of gestation and admitted to the neonatal intensive care unit for respiratory distress and prematurity. Newborn Screens done at admission and repeated after 48 hours of life were negative for thyroid abnormalities. At 5 days of life, the mother underwent a contrast-enhanced imaging study using iohexol, after which the infant received breast milk from days 5-11. On day 11, the neonate had an elevated thyroid-stimulating hormone (TSH) and low free thyroxine (T4) levels, consistent with hypothyroidism. Urine iodine level in the infant was checked and found to be elevated, which prompted the medical team’s concern for the exposure to iodine in breastmilk. However, the thyroid levels in the infant remained abnormal, which was unexpected from a transient process such as exposure to iodine. Genetic testing revealed missense variants in the Iodide Deiodinase Deficiency (\u003cem\u003eIYD) \u003c/em\u003egene, which are associated with thyroid dyshormonogenesis, as well as a likely pathogenic intragenic deletion in the gene \u003cem\u003eRPS6KA3\u003c/em\u003e, which is consistent with Coffin–Lowry syndrome.\u003c/p\u003e\n\u003cp\u003eConclusions:\u003c/p\u003e\n\u003cp\u003eThis case highlights the complex interplay between genetic factors and environmental influences in the development of neonatal hypothyroidism. While iodine contrast exposure through breast milk is generally considered safe, this case underscores the potential risks in preterm infants. Initially, iodine exposure through breastmilk was considered a contributor to thyroid dysfunction, but with further time and evaluation, congenital thyroid dysgenesis with underlying genetic findings complicated the diagnosis. Caution should be taken for iodine-exposed breastmilk, but because iodine is only one potential cause of neonatal hypothyroidism, persistent thyroid abnormalities warrant a \u003cstrong\u003ecomplete congenital hypothyroidism work-up \u003c/strong\u003eto assess for alternative or coexisting etiologies.\u003c/p\u003e","manuscriptTitle":"Breastfeeding After Maternal Iodine Contrast: Neonatal Hypothyroidism Revealing an Underlying Congenital Disorder","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-17 19:12:12","doi":"10.21203/rs.3.rs-7546763/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-22T20:14:48+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-03T15:11:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"220157858071877148626841768612046002271","date":"2025-09-23T15:15:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-22T16:50:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"79654226593453823453557161748538301003","date":"2025-09-22T15:08:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"166997739667306028421313556337626828560","date":"2025-09-20T09:23:09+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-09T18:48:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-06T17:20:26+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-06T17:19:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Breastfeeding Journal","date":"2025-09-05T19:14:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-breastfeeding-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ibfj","sideBox":"Learn more about [International Breastfeeding Journal](http://internationalbreastfeedingjournal.biomedcentral.com/)","snPcode":"13006","submissionUrl":"https://submission.nature.com/new-submission/13006/3","title":"International Breastfeeding Journal","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a581dda6-6ba4-4943-920f-cde9b80d8578","owner":[],"postedDate":"September 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-15T16:05:27+00:00","versionOfRecord":{"articleIdentity":"rs-7546763","link":"https://doi.org/10.1186/s13006-026-00822-z","journal":{"identity":"international-breastfeeding-journal","isVorOnly":false,"title":"International Breastfeeding Journal"},"publishedOn":"2026-02-14 15:57:16","publishedOnDateReadable":"February 14th, 2026"},"versionCreatedAt":"2025-09-17 19:12:12","video":"","vorDoi":"10.1186/s13006-026-00822-z","vorDoiUrl":"https://doi.org/10.1186/s13006-026-00822-z","workflowStages":[]},"version":"v1","identity":"rs-7546763","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7546763","identity":"rs-7546763","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}