A Novel Conception Towards Effect of Preconception Hypothyroidism and First Diagnosed Hypothyroidism During Pregnancy on Offspring's Neurocognitive Function: Evidence from a Prospective, Cohort Study in China

Abstract

Background: Hypothyroidism during pregnancy is associated with offspring’s neurodevelopment. Current prenatal screening is not effective, and hypothyroidism screening before conception is expected to be beneficial for improving offspring’s neurocognitive development. This study was to evaluate offspring’s neurocognitive development and pregnancy outcomes among women with hypothyroidism before conception and firstly diagnosed in early pregnancy. Method: In this prospective cohort study, women with hypothyroidism before 14 gestational week were recruited in Obstetrics and Gynecology Hospital of Fudan University. They were assigned into preconception controlled hypothyroidism, preconception uncontrolled hypothyroidism and hypothyroidism firstly diagnosed in early pregnancy based on their history of hypothyroidism before pregnancy and thyroid stimulating hormone (TSH) at first antenatal visit. Their general characteristics and pregnancy outcome were recorded. Gesell development diagnosis scale (GDDS) was applied for the evaluation of offspring’s neurocognitive function at six-month and one-year old. Results: During January 2012-December 2013, 295 women were firstly diagnosed during pregnancy (TSH≥3.61mIU/L), and 78 women with hypothyroidism controlled (TSH<2.5mIU/L) and 107 with uncontrolled thyroid function (TSH≥2.5mIU/L). Full-scale quotation of Gesell scale in clinical hypothyroidism group was of no statistical difference compared to that of subclinical hypothyroidism (P=0.309). In offspring’s Gesell assessment at six-month old, children in controlled hypothyroidism group performed a better adaptive ability compared to those firstly diagnosed during pregnancy (104.45±13.93 vs 99.38±17.71, P=0.022). At one-year old, children in preconception uncontrolled group performed inferior to those those firstly diagnosed during pregnancy, in the GDDS full-scale DQ (100.61±5.96 vs 105.14±7.40, P=0.001), and fine motor, adaptability, language and social emotional response category. Conclusions: Maternal hypothyroidism before conception and during pregnancy possibly shares different effect on offspring’s neurodevelopment. Impaired offspring’s neurocognitive function suggested the necessity of preconception hypothyroidism screening and close follow up of offspring’s neurodevelopment in early infancy. Trial Registration: The registered ClinicalTrials ID was NCT01744743. Funding Statement: This study was funded by the grants from Health industry special funds for Public Benefit Research Foundation from the Ministry of Health, People's Republic of China (201002013), the National Science Fund of China (81270712), National Science Foundation for Young Scholars of China (81200449), National Science Foundation for Young Scholars of China (81300506), National Key Basic Research Plan of China (973 Plan) (2010CB529500), National Science Foundation for Young Scholars of Shanghai (13ZR1452000), the Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, and the Key Specialty Project of the Ministry of Health, People's Republic of China. Declaration of Interests: The authors report no conflict of interest. Ethics Approval Statement: The study was reviewed and approved by the Ethics and Research Committee of Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. All the women have signed the consent.