Prevalence and determinants of Transient Congenital Hypothyroidism in children with Eutopic Gland in France: a retrospective cohort study

Context The increase in the incidence of congenital hypothyroidism (CH) reported worldwide may in part be explained by an increase in the transient form of CH. Objectives We aimed to estimate the proportion of transient CH (TCH) in France, and to identify associated neonatal and young child characteristics. Patients and Methods We used probabilistic record linkage to link children with eutopic gland born between 2006 and 2012 recorded in the national French CH registry and the French national health data system (SNDS). Of the 703 children recorded, 484 (68.8%) were linked. We retrospectively examined reimbursement for oral levothyroxine (LT4) between 01/01/2006 and 31/12/2017. Children who had discontinued treatment for six months or more before 31/12/2017 were classified as having TCH. We used a Cox model to examine the factors associated with TCH. Results Among the main study sample (n=471), 53.5% were female, 14.2% were preterm, and 13.8% had low birth weight. One-quarter (n=111, 24.3%) had mild CH (thyroid-stimulating hormone (TSH)<50mU/L (serum) at diagnosis and a median LT4 dose at treatment initiation of 30 μg/day. One third (n=155, 32.9%) had TCH. Premature birth (adjusted Hazard Ratio=2.1 [1.0-4.2]), a TSH<50 mU/L at CH screening (7.4 [3.2-17.1]), LT4 dose received at 12 months of age (0.98 [0.97-0.99, p=0.003]), congenital cardiac malformations (6.6 [1.5-29.0]), and year of birth (1.2 [1.1-1.4]) were all associated with TCH. Conclusions One third of the children had TCH and it was associated with several characteristics at birth and post-partum. These data are useful for CH medical management and epidemiological surveillance.

Thyroid Gene Mutations in Pregnant and Breastfeeding Women Diagnosed With Transient Congenital Hypothyroidism: Implications for the Offspring’s Health

Fetus and infants require appropriate thyroid hormone levels and iodine during pregnancy and lactation. Nature endorses the mother to supply thyroid hormones to the fetus and iodine to the lactating infant. Genetic variations on thyroid proteins that cause dyshormonogenic congenital hypothyroidism could in pregnant and breastfeeding women impair the delivery of thyroid hormones and iodine to the offspring. The review discusses maternal genetic variations in thyroid proteins that, in the context of pregnancy and/or breastfeeding, could trigger thyroid hormone deficiency or iodide transport defect that will affect the proper development of the offspring.

Unusual cause of congenital hypothyroidism in a term infant

Both insufficient and excessive maternal iodine consumption can result in congenital hypothyroidism. In East Asian cultures, seaweed is traditionally consumed in high quantities by peripartum women as it is thought to improve lactation. We present a case of transient congenital hypothyroidism due to maternal seaweed consumption at a daily basis during pregnancy and lactation in a Dutch family without Asian background. This case highlights that even in families of non-Asian background, high maternal intake of iodine-rich seaweed occurs and can result in transient or permanent hyperthyrotropinemia in the neonate with risk of impaired neurodevelopmental outcome if untreated.

Association of Maternal Iodine Intake with Congenital Hypothyroidism

The iodine intake in a pregnant woman has been closely correlated with development of transient congenital hypothyroidism which leads to decline in neurocognitive abilities of the child later in life as the effects are very subtle at birth. Both low and excess ingestion of iodine has been found to contribute to this cause, although iodine deficiency is more commonly observed in women of underdeveloped nations. It poses risks not only to the foetus but also to the mother leading to obstetric complications such as still birth and spontaneous abortions. It can be prevented using WHO recommended daily iodine supplementation in deficient regions or decreasing the excess load in groups exposed to high iodine. Programmes designed to screen the new-born at birth can also help in improving the quality of life of the child. The deficient iodine condition is managed by administration of levothyroxine in dosage range of 10-15 mcg/kg/day. Generally, the prognosis of infants starting treatment early in life have a better neurocognitive outcome as compared to the treated infants late age at a later age. Avoidance of agents causing iodine exposure has resulted in decrease in the abnormal thyroid function levels.

EPIDEMIOLOGIC CHARACTERISTICS AND RISK FACTORS FOR CONGENITAL HYPOTHYROIDISM FROM 2009 TO 2018 IN XIAMEN, CHINA

Objective: Early diagnosis and treatment of children with congenital hypothyroidism (CH) through newborn screening can effectively prevent delayed development. This study was designed to investigate the pathogenesis and factors that influence CH in urban areas of China between 2009 and 2018. Methods: A retrospective analysis of newborn screening data and diagnosis and treatment information for CH diagnosed in the information database of the neonatal disease screening center in one of China's five special economic zones from 2009 to 2018. Results: Of the 947,258 newborns screened between 2009 and 2018, 829 (406 girls) were diagnosed with CH at birth (1 diagnosis/1,136 births). Among the 608 cases of CH diagnosed at birth and re-evaluated at the age of 3 years, 487 were permanent congenital hypothyroidism (PCH, 1/1,429), and 121 were transient congenital hypothyroidism (TCH, 1/5,882). A total of 83.2% of infants with PCH (405/487) underwent thyroid imaging in the neonatal period, of which thyroid dysgenesis accounted for 28.64% (116/405) and functional defects accounted for 71.36% (289/405). The incidence of CH changed significantly in infants with initial serum thyroid-stimulating hormone concentrations of 41 to 100 mIU/L and ≥100 mIU/L, whereas the incidence of mild CH showed a slight increase. The incidence of CH was significantly higher in postterm infants (1/63) and low-birth-weight infants (1/370). Conclusion: In the past decade, the incidence of CH has increased, mainly due to the increase in the incidence of PCH and TCH. The incidence of mild CH has increased slightly. Postterm birth and low birth weight are important factors affecting the incidence of CH. Abbreviations: CH = congenital hypothyroidism; FT4 = free thyroxine; L-T4 = levothyroxine sodium; PCH = permanent congenital hypothyroidism; TCH = transient congenital hypothyroidism; TSH = thyroid-stimulating hormone; TT4 = total thyroxine