SYSTEMATIC REVIEW article
Front. Pediatr.
Sec. Neonatology
Volume 13 - 2025 | doi: 10.3389/fped.2025.1530859
This article is part of the Research TopicEnhancing Drug Safety for Pregnant and Lactating Women: Addressing Perinatal Pharmacotherapy ChallengesView all 5 articles
Meta-Analysis of the effects of levothyroxine therapy for subclinical hypothyroidism during pregnancy on offspring outcomes
Provisionally accepted
- 1The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
- 2Department of Neonatology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
- 3Department of Ultrasound, The Inner Mongolia Hospital of Peking University Cancer Hospital, Hohhot, China
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Objective: To conduct a systematic evaluation of the impact of L-T4 therapy on birth outcomes in pregnancies complicated by SCH. Methods: A thorough literature review was conducted across several databases, including PubMed, Embase, Cochrane Library, Web of Science, Sinomed, Wanfang Data Knowledge Service Platform, CNKI, and VIP, to investigate the impact of L-T4 treatment of SCH during pregnancy on birth outcomes in offspring. Based on predefined inclusion and exclusion criteria, two researchers were appointed to extract data and assess the quality of the literature. Subsequently, meta-analysis was performed using RevMan 5.4 and Stata 14 software. Results：The study incorporated a total of thirty randomized controlled trials (RCTs) and cohort studies, encompassing four countries and regions. The sample included 18568 pregnant women with SCH and 5578 pregnant women undergoing L-T4 treatment. The meta-analysis indicated that L-T4 treatment for SCH during pregnancy may reduce the incidence of preterm birth (RCTs (RR=0.56, 95%CI=0.41~0.77), cohort studies (RR=0.71, 95%CI=0.51~0.99)) and LBWI (RCTs (RR=0.56, 95%CI=0.35~0.89), cohort studies (RR=0.71, 95%CI=0.58~0.88)) , while it does not significantly affect the risk of macrosomia (RCTs (RR=0.29, 95%CI=0.06~1.38), cohort studies (RR=0.70, 95%CI=0.30~1.62)) , SGA (RCTs (RR=1.18, 95%CI=0.74~1.90)) , or congenital hypothyroidism (CH) (cohort studies (RR=1.27, 95%CI=0.16~10.07)) in children. No significant difference in birth weight (RCTs (RR=0.10, 95%CI=-0.04~0.24), cohort studies (RR=0.10, 95%CI=-0.08~0.28)) was observed between the L-T4 treatment group and the non L-T4 treatment group. Regarding neonatal cord blood thyroid function, the TSH levels in the L-T4 treatment group were lower compared to the non L-T4 group (RCTs (RR=-2.48, 95%CI=-4.51~-0.45), cohort studies (RR=-3.53, 95%CI=-4.27~-2.79)); however, no significant differences were found in FT3 (RCTs (RR=0.06, 95%CI=-0.24~0.36), cohort studies (RR=0.08, 95%CI=-0.72~0.88)) and FT4 levels (RCTs (RR=0.07, 95%CI=-0.41~0.56), cohort studies (RR=0.03, 95%CI=-1.18~1.24)) between the two groups. Conclusion: L-T4 treatment appears to reduce the incidence of preterm birth and LBWI in pregnant mothers with SCH, but it does not significantly affect the incidence of macrosomia, SGA, CH, or birth weight. Regarding the thyroid function in neonatal umbilical cord blood, L-T4 treatment in SCH pregnant women can reduce TSH levels in the umbilical cord blood of their newborns, while having no significant effect on FT3 and FT4 levels.
Keywords: Pregnancy, subclinical hypothyroidism, SCH, L-T4, offspring, neonate, metaanalysis
Received: 19 Nov 2024; Accepted: 25 Jun 2025.
Copyright: © 2025 You, Zhang, Liu, Li, Xu and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yayu Zhang, Department of Neonatology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
Dan Song, Department of Neonatology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
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