Normal maternal thyroid function is crucial for a normal pregnancy and fetal growth. During pregnancy, maternal thyroid dysfunction induces pregnancy complications and influences fetal development in utero and later in life [1, 2, 3]. According to the levels of thyroid stimulating hormone (TSH) and free tetraiodothyronine (fT4), thyroid disorders in pregnancy are classified as subclinical hypothyroidism (SCH), overt hypothyroidism, isolated maternal hypothyroxinemia (IMH), subclinical hyperthyroidism, and thyrotoxicosis [4, 5, 6]. On this basis, thyrotoxicosis can be divided into overt hyperthyroidism and gestational transient thyrotoxicosis (GTT) according to its etiology [5].

Thyroid dysfunction is one of the most common complications of pregnancy. The reported frequencies of various thyroid dysfunctions in pregnancy are varied because of difference between research objectives and methods in previous studies [6, 7, 8, 9]. The influence induced by different types of maternal thyroid dysfunction on pregnancy complications and outcomes is still controversial [5, 10]. For example, a meta-analysis of 18 studies, including 3995 pregnant women with SCH, has found no association between SCH and preeclampsia, preterm birth (PTB) and low birth weight [11], but the other studies have reported SCH increased the risk of PTB, preeclampsia and small for gestational age (SGA) [12, 13]. Therefore, more clinical observation and data are necessary for research.

The effects of IMH on pregnant complications are indeterminate, and there is no consensus on whether they should receive levothyroxine. According to the American Thyroid Association (ATA) pregnancy guidelines in 2017 [6], IMH should not be treated. However, an opposite conclusion was made in the European Thyroid Association (ETA) guidelines for the management of SCH in pregnancy and children [14]. In China, the guidelines neither recommend nor are opposed to treatment with levothyroxine for pregnant women with IMH in early pregnancy [15].

In this study, we performed a survey of the prevalence of thyroid dysfunction in early pregnancy in the local region of southern China. We also analyzed the incidence of obstetrical complications and pregnancy adverse outcomes among different thyroid function groups. In additional, we assessed the effects of levothyroxine replacement on adverse outcomes in pregnant women with IMH.

This study demonstratedthat thyroid dysfunction is a prevalent issue among local pregnant women, with at least 1 in 7 having some form of thyroid dysfunction. While our results are generally consistent with a meta-analysis reporting the prevalence of overt hypothyroidism (0.5%), subclinical hypothyroidism (IMH, 2.05%), and subclinical hyperthyroidism (2.18%) [16], our study revealed a significantly higher prevalence of subclinical hyperthyroidism (SCH, 6.68%) and a lower prevalence of overt hyperthyroidism (0.45%) compared to the meta-analysis (3.47% and 0.91%, respectively). These figures contrast with those reported in Denmark (SCH 5.3%, overt hyperthyroidism 1.6%) [17] and vary across studies conducted in China, with a reported prevalence of SCH and overt hypothyroidism ranging from 0.24% to 8.26% [13, 18]. This discrepancy warrants further investigation. Several factors may contribute to these variations. Differences in iodine intake, although mitigated by China’s universal salt iodization program, could still influence thyroid hormone levels across various regions. Heterogeneity in diagnostic criteria, particularly the threshold values for TSH and free T4 used to define thyroid dysfunction, can significantly impact prevalence estimates. Furthermore, the absence of routine TPOAb testing in our cohort, unlike some other studies, may have influenced our findings, as TPOAb positivity is associated with altered thyroid function and pregnancy outcomes. Future studies should standardize diagnostic criteria and routinely assess TPOAb status to enhance comparability and reduce bias.

We collaboratively determined the prevalence of GTT with endocrinologists to be 3.26%. Differentiating GTT from hyperthyroidism can be challenging and requires consideration of various clinical and laboratory findings [5]. GTT is associated with elevated levels of human chorionic gonadotropin (hCG), a hormone secreted by the placenta, and is often characterized by hyperemesis gravidarum, which typically does not necessitate intervention. This condition is a physiological phenomenon rather than an immune disorder, and individuals with GTT typically exhibit negative TRAb test results [19].

In this study, various impacts on adverse pregnancy outcomes among different thyroid dysfunction groups were observed. It is well established that subclinical hyperthyroidism and GTT have minimal adverse effects on pregnancy outcomes and obstetric complications [20, 21], and the present results are consistent with these conclusions. Compared to the euthyroid group, pregnant women with overt hypothyroidism exhibited a higher incidence of preeclampsia and PPH, with nearly a threefold increased risk. However, logistic regression analysis revealed no significant relationship between overt hypothyroidism and other adverse pregnancy outcomes (all p $>$ 0.05). Additionally, no associations were found between overt hyperthyroidism and any of the observed pregnancy outcomes (all p $>$ 0.05). The main reasons for these findings may be related to the use of levothyroxine or propylthiouracil (PTU) once hypothyroidism or hyperthyroidism is diagnosed. Previous studies have shown that untreated hypothyroidism and hyperthyroidism can lead to serious adverse consequences for both pregnant women and their fetuses [5, 11, 20, 22]. However, if maternal hyperthyroidism is adequately treated, the prognosis tends to be favorable. According to existing guidelines [6], all participants identified with overt hyperthyroidism and hypothyroidism in the present study were treated immediately and maintained TSH levels within the normal range. The results reflect the obstetrical outcomes of pregnant women with treated hypothyroidism and hyperthyroidism.

In Regard to SCH and IMH, the findings suggest that SCH increases the risk of preeclampsia, PROM, and therapeutic abortion due to fetal anomalies, while decreasing the risk of GDM. IMH, conversely, was associated with increased risks of preeclampsia and GDM. These findings are partially consistent with, but also diverge from, previous literature [12, 13, 23, 24, 25, 26], highlighting the potential influence of factors such as timing of levothyroxine initiation, TPOAb status, and gestational age at diagnosis. Liu et al. [13] demonstrated that late-pregnancy SCH is associated with increased risks of preterm birth, preeclampsia, and fetal demise, unlike early-pregnancy SCH.

The data of this study consistently showed an increased risk of preeclampsia across all hypothyroid groups (overt hypothyroidism, SCH, and IMH). This warrants further investigation into the underlying pathophysiological mechanisms. Emerging evidence suggests that hypothyroxinemia interferes with trophoblast migration and the expression of matrix metalloproteinases, both of which are pivotal for placental restructuring and maternal-fetal blood supply, thereby elevating the risk for preeclampsia [27]. Additionally, hypothyroidism is associated with endothelial dysfunction, culminating in compromised vasorelaxation, increased vascular resistance, and the onset of hypertension—pathognomonic features of preeclampsia [28]. Moreover, previous studies have indicated a correlation between elevated levels of soluble fms-like tyrosine kinase 1 (sFlt-1), a pregnancy-specific angiogenic factor central to the pathophysiology of preeclampsia, and increased TSH concentrations, which in turn is associated with an increased risk of SCH [29, 30].

This study identified a 33% reduced OR (0.67, 95% CI: 0.57–0.79) for gestational GDM in women with SCH. This finding aligns with a comparable OR (0.63, 95% CI: 0.50–0.81) reported by Liu et al. [13], as well as trends observed in other studies indicating a decreased incidence of GDM among women with SCH [31, 32]. It has been hypothesized that elevated TSH levels may negatively influence the development and occurrence of GDM by binding to TSH receptors present on extrathyroidal tissues [13].

There is no consensus on treating IMH, and treatment decisions often rely on clinical judgment or patient preference due to a lack of definitive evidence. With an incidence rate of 1.95%, the effectiveness of levothyroxine in IMH must be established. This study found that levothyroxine did not significantly improve pregnancy outcomes or reduce obstetric complications (p $>$ 0.05). It might be more beneficial to address underlying maternal issues, such as iodine nutrition or iron deficiency [33], rather than administering levothyroxine without further consideration. However, it did show a non-significant trend towards lower rates of spontaneous abortion, preterm birth, and preeclampsia in the treated IMH group, and a notable exception was observed in neonatal birth weight: infants born to levothyroxine-treated mothers exhibited a higher mean birth weight compared to the untreated group. It had been reported that there was an inverse, dose-response association of maternal TSH and fT4 (even within the normal range) with birthweight [34]. Therefore, further research is required to carefully assess the potential risks and benefits of levothyroxine therapy during pregnancy.

This study has certain limitations: firstly, we failed to gather certain crucial maternal demographic characteristics pertinent to thyroid dysfunction, including pregestational body mass index (BMI), smoking habits, and alcohol consumption during pregnancy. Second, additionally data on thyroid conditions during the second and third trimesters were not available, which implies that some individuals with normal thyroid function in the first trimester might have developed thyroid dysfunction later in pregnancy [13]. This lack of these data could potentially skew the results. Third, during the period of our study, TPOAb was not commonly included in thyroid function assessment for pregnant women, especially those with normal TSH levels. The absence of TPOAb data for many subjects led to our decision to exclude this marker from our analysis. This exclusion might have influenced the interpretation of findings in this study, as TPOAb positivity can significantly affect thyroid function and pregnancy outcomes [13, 18]. Finally, the study did not include an assessment of iodine nutrition, which is a critical factor in thyroid function. However, universal salt iodization is mandatory in mainland China, and according to World Health Organization (WHO) guidelines, in countries where salt iodization is prevalent and covers over 90% of the general population, including pregnant women, additional iodine supplementation is not necessary. Therefore, we did not conduct iodine nutrition assessment for all pregnant women included in the study.

In conclusion, our study revealed the incidence of thyroid disorders during pregnancy in the local area of southern China, showing a high frequency of SCH but a low frequency of overt hypothyroidism and overt hyperthyroidism. Generally, pregnant women with hypothyroidism are at a higher risk for pregnancy complications, including those with IMH, who require careful monitoring and medical intervention. However, treatment with levothyroxine did not improve pregnancy outcomes or obstetric complications. It may be more beneficial to investigate and address underlying maternal issues, such as inadequate iodine nutrition or iron deficiency, rather than simply adding levothyroxine.

ATA, American Thyroid Association; ETA, European Thyroid Association; fT4, free tetraiodothyronine; GDM, gestational diabetes mellitus; GTT, gestational transient thyrotoxicosis; hCG, human chorionic gonadotropin; IH, isolated hypothyroxinemia; PPH, postpartum hemorrhage; PROM, premature rupture of membranes; PTU, propylthiouracil; SCH, subclinical hypothyroidism; TPOAb, thyroid peroxidase antibody; TRAb, thyroid stimulating hormone receptor antibody; TSH, thyroid stimulating hormone.

The datasets generated and analysed during the current study are not publicly available due hospital regulations but are available from the corresponding author on reasonable request.

MS: data collection and manuscript writing. HZ: data collection and analysis. JLiang: data analysis. YF: study design and manuscript revision. JLou: interpretation of data for the work. BD: interpretation of data for the work. XW: supervision; substantial contributions to the conception. JC: supervision and substantial contributions to the conception or design of the work. All authors contributed to editorial changes in the manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

Written informed consent was obtained from each participant and the program was approved by the Research Ethics Committee of Dongguan Maternal and Children Hospital on 1 July 2021 (reference: No. 202133). The study was conducted in accordance with the Declaration of Helsinki.

The study was funded by Basic and Applied Basic Research Program of Guangdong Province (2020A1515110308); Key Social Development Program of Dongguan City (20211800904772).

The authors declare no conflict of interest.