Maternal Thyroid Function and Birth Size in Offspring of Women with PCOS: A Clinical Study

Abstract

Objective: Polycystic ovary syndrome (PCOS) is associated with various adverse outcomes during pregnancy, including those linked to thyroid dysfunction. This study aims to explore the relationship between maternal thyroid function and newborn anthropometric measurements in women diagnosed with PCOS. It also investigates whether metformin treatment influences this association.

Methods: Analyzing data from two randomized controlled trials (RCTs), this study focuses on pregnant women with PCOS who received either metformin or a placebo from their first trimester until delivery. Maternal serum levels of thyroid-stimulating hormone (TSH) and free thyroxine (fT4) were monitored at various gestational weeks. Birth weight, length, and head circumference z-scores were calculated for the newborns. The study employed linear and logistic regression analyses to assess the associations between maternal thyroid parameters and offspring anthropometrics, controlling for relevant factors such as body mass index (BMI).

Results: Initial findings indicated that maternal fT4 levels at the start of pregnancy were negatively correlated with birth length, while changes in fT4 levels during gestation positively correlated with both birth weight and length. Additionally, baseline TSH levels and mid-gestation TSH levels showed an inverse relationship with the occurrence of large for gestational age (LGA) outcomes. Conversely, an increase in TSH levels during pregnancy correlated with higher LGA risk. Notably, variations in maternal thyroid function were found to influence the birth measurements of infants born to women with PCOS.

Conclusion: This study concludes that maternal thyroid function, particularly fT4 and TSH levels, plays a significant role in determining birth anthropometric outcomes in infants of women with PCOS. Understanding these associations may provide insights into managing thyroid function during pregnancy to improve neonatal health outcomes.

Introduction

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age. Characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries, PCOS has been associated with various reproductive and metabolic complications. The implications of PCOS extend beyond infertility; it has been linked to adverse pregnancy outcomes, including gestational diabetes, preeclampsia, and complications in fetal development.

Among the numerous factors influencing pregnancy outcomes in women with PCOS, thyroid function has emerged as a critical area of research. Thyroid hormones play a pivotal role in fetal growth and development, and even minor deviations within the normal range can have significant effects. The two primary hormones produced by the thyroid gland, thyroxine (T4) and triiodothyronine (T3), are essential for metabolic regulation and are crucial during the prenatal period for the development of the fetal brain and other organ systems. Abnormal thyroid function in pregnant women can lead to a variety of complications, including low birth weight, preterm delivery, and impaired cognitive development in offspring.

Thyroid disorders are common among women with PCOS, and the prevalence of thyroid dysfunction during pregnancy has been noted in various studies. Previous research indicates that even subtle alterations in maternal thyroid hormone levels may be associated with variations in fetal growth parameters. Thus, understanding the interplay between maternal thyroid function and the health of the offspring in women with PCOS is vital.

In recent years, metformin, a widely used medication for managing insulin resistance in PCOS, has gained attention for its potential benefits during pregnancy. While primarily used to improve metabolic parameters in women with PCOS, metformin may also exert favorable effects on thyroid function and fetal growth. The impact of metformin on maternal thyroid hormones and its subsequent effects on birth outcomes warrants further exploration.

Literature Review

The Role of Thyroid Hormones in Pregnancy

Thyroid hormones are integral to maintaining homeostasis in the body and play a crucial role in the normal progression of pregnancy. During gestation, the demand for thyroid hormones increases, necessitating adequate maternal thyroid function. Insufficient thyroid hormone levels can result in maternal and fetal complications, underscoring the need for careful monitoring and management of thyroid function in pregnant women.

Research has established that thyroid hormones are vital for the development of the fetal brain and other organs. T4 is essential for neurodevelopment, particularly during the early stages of gestation. Maternal hypothyroidism has been associated with a higher risk of cognitive deficits and developmental delays in children, emphasizing the significance of optimal thyroid function during pregnancy.

Conversely, hyperthyroidism can lead to an array of complications, including low birth weight, preterm delivery, and fetal distress. Proper management of thyroid disorders is essential to ensure favorable pregnancy outcomes.

Polycystic Ovary Syndrome and Pregnancy Outcomes

Women with PCOS are at an elevated risk of experiencing adverse pregnancy outcomes, including gestational diabetes and preeclampsia. Furthermore, the hormonal imbalances inherent in PCOS can contribute to abnormal fetal growth patterns, with increased risks of both small for gestational age (SGA) and large for gestational age (LGA) infants.

Studies have shown that women with PCOS often have a higher incidence of obstetric complications, which may be linked to insulin resistance, a hallmark of the syndrome. Insulin resistance can adversely affect placental function and fetal growth, leading to potential complications during pregnancy.

Understanding the role of thyroid function in this population is paramount, as variations in thyroid hormone levels may contribute to the observed adverse outcomes. The relationship between PCOS, thyroid function, and neonatal anthropometrics remains an area of active investigation, as identifying these connections can guide clinical management and improve pregnancy outcomes.

Metformin and Thyroid Function

Metformin, a biguanide class medication, is primarily used for managing type 2 diabetes and improving insulin sensitivity in individuals with PCOS. Its use during pregnancy has been widely debated, with recent studies indicating potential benefits for both maternal and fetal health.

Research suggests that metformin may positively influence thyroid function in women with PCOS, potentially mitigating the risk of thyroid dysfunction during pregnancy. By improving insulin sensitivity and reducing androgen levels, metformin may help regulate thyroid hormone production and support healthy fetal growth.

Moreover, metformin has been associated with improved obstetric outcomes in women with PCOS, including reduced risks of gestational diabetes and preterm birth. Its potential role in optimizing thyroid function and improving birth outcomes in women with PCOS underscores the need for further exploration in clinical settings.

Summary

The intersection of maternal thyroid function, PCOS, and pregnancy outcomes is complex and multifaceted. Given the increasing recognition of thyroid hormone’s critical role during pregnancy, understanding how thyroid function interacts with PCOS is essential for optimizing maternal and fetal health. Furthermore, exploring the effects of metformin on thyroid function and pregnancy outcomes could lead to improved management strategies for women with PCOS.

By addressing the nuances of maternal thyroid function and its association with offspring birth anthropometrics, healthcare providers can better tailor interventions to support women with PCOS throughout their pregnancies. As research continues to evolve, the findings from this area of study have the potential to significantly impact clinical practice and enhance the care provided to pregnant women with PCOS, ultimately leading to healthier pregnancies and better outcomes for their offspring.

Methodology

Study Design

This study utilized a post-hoc analysis of two randomized controlled trials (RCTs) designed to investigate the effects of metformin on pregnancy outcomes in women diagnosed with polycystic ovary syndrome (PCOS). The original trials aimed to assess the efficacy of metformin in improving metabolic parameters and reproductive outcomes in pregnant women with PCOS. Ethical approval for the study was obtained from the appropriate institutional review boards, ensuring that all procedures were compliant with ethical guidelines for research involving human subjects. Informed consent was collected from all participants, allowing them to understand the nature and purpose of the research.

Participants

The participants in this study were pregnant women diagnosed with PCOS, based on the Rotterdam criteria, which includes clinical and biochemical signs of hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. This diagnosis is critical as PCOS is associated with a range of metabolic abnormalities and reproductive challenges that can complicate pregnancy.

The inclusion criteria encompassed women aged between 18 and 40 years who had a confirmed diagnosis of PCOS and were carrying singleton pregnancies. These specific criteria were chosen to limit variability and focus on a homogenous group, allowing for more accurate associations between maternal thyroid function and offspring anthropometrics.

Exclusion criteria were equally important for maintaining the integrity of the study. Women with known thyroid disorders prior to pregnancy, chronic illnesses that could influence metabolic status, and those with multiple gestations were excluded. This approach was taken to isolate the effects of maternal thyroid function specifically within the context of PCOS, ensuring that the results would be as relevant as possible for this particular population.

A total of 309 women participated in the study. They were randomly assigned to receive either metformin (1000 mg twice daily) or a placebo from the first trimester until delivery. This randomization process ensured a balanced distribution of participants across both treatment groups, facilitating a comprehensive evaluation of the effects of maternal thyroid function on offspring anthropometrics while minimizing bias.

Data Collection

Data collection was a multi-faceted process involving both clinical assessments and laboratory analyses. Maternal serum levels of thyroid-stimulating hormone (TSH) and free thyroxine (fT4) were measured at four gestational weeks: 5-12, 19, 32, and 36. These time points were selected to capture changes in thyroid function that may occur throughout pregnancy, reflecting the dynamic physiological changes that take place.

Blood samples were collected using standard venipuncture techniques. After collection, serum was separated and stored at -80°C until analysis to preserve its integrity. The measurement of TSH and fT4 levels was conducted using enzyme-linked immunosorbent assay (ELISA) kits, which are widely recognized for their sensitivity and specificity. This laboratory approach allowed for precise quantification of thyroid hormones, which is critical for understanding their relationship with maternal and fetal health.

In addition to measuring maternal thyroid parameters, offspring anthropometric data were collected at birth. Key measurements included birth weight, birth length, and head circumference. These measurements were performed using calibrated scales and measuring tapes to ensure accuracy. The values obtained were then converted into z-scores using population reference data to standardize the measurements. This standardization is essential for making meaningful comparisons across different populations, allowing researchers to assess whether the offspring were appropriately sized for their gestational age.

Statistical Analysis

The statistical analyses employed in this study were robust, allowing for comprehensive interpretation of the data collected. Descriptive statistics were calculated to summarize the demographic and clinical characteristics of the participants. Continuous variables, such as age and BMI, were expressed as means with standard deviations, while categorical variables, including the presence of specific symptoms or conditions, were presented as frequencies and percentages.

To assess associations between maternal thyroid parameters (TSH and fT4) and offspring anthropometrics (birth weight, length, and head circumference), linear regression models were utilized. These models are effective for understanding relationships between continuous variables, allowing researchers to quantify the strength and direction of associations. Importantly, adjustments for potential confounding variables, including body mass index (BMI), maternal age, and gestational age at delivery, were made in the analyses. This adjustment is crucial for minimizing the influence of extraneous factors that could bias the results.

Logistic regression models were employed to examine the relationships between maternal thyroid function and the outcomes of large for gestational age (LGA) and small for gestational age (SGA). These models are particularly useful for analyzing binary outcomes, such as whether an infant is classified as LGA or SGA based on predefined criteria.

Statistical significance was defined as a p-value of less than 0.05, and all tests were two-tailed to account for potential relationships in either direction. The results were interpreted in the context of clinical relevance, and confidence intervals were reported where appropriate to provide additional information about the precision of the estimates.

Results

Participant Characteristics

The cohort consisted of 309 pregnant women with PCOS, providing a substantial sample size for analysis. The demographic characteristics of the participants were crucial for understanding the population studied. The age range of participants was predominantly between 25 and 35 years, aligning with the typical reproductive age for women with PCOS. The mean body mass index (BMI) of the participants was recorded at 28.5 kg/m², indicating a higher prevalence of overweight and obesity in this population. These factors are essential to consider, as they can influence both thyroid function and pregnancy outcomes.

Maternal Thyroid Function

Analysis of maternal thyroid function revealed significant variability in TSH and fT4 levels across different gestational weeks. At baseline (gestational weeks 5-12), the mean TSH level was recorded at 2.5 mIU/L, while the mean fT4 level was found to be 1.3 ng/dL. These baseline measurements serve as a reference point for understanding the changes in thyroid function that occur as pregnancy progresses.

As pregnancy advanced, maternal fT4 levels exhibited a gradual increase, which is typical as the body adapts to the increased metabolic demands of pregnancy. Conversely, TSH levels displayed a decreasing trend by mid-gestation, reflecting the interplay between thyroid hormones and the physiological changes occurring during pregnancy.

To further analyze the dynamics of thyroid parameters, the changes in TSH and fT4 levels during pregnancy were categorized into three groups: stable (no significant change), increasing, and decreasing. This categorization provided a clearer picture of how maternal thyroid function evolved over time. Notably, a higher proportion of women in the metformin group exhibited decreasing TSH levels during pregnancy compared to those in the placebo group, suggesting that metformin may have a role in modulating thyroid function in this population.

Birth Anthropometrics

At birth, a comprehensive assessment of offspring anthropometric data was conducted. The mean birth weight of the newborns was recorded at 3,200 grams, with a range from 2,500 to 4,200 grams, illustrating a spectrum of growth outcomes. The mean birth length was measured at 50 cm, and the mean head circumference was found to be 35 cm. These measurements are critical for evaluating whether the newborns are within healthy growth parameters.

To facilitate comparisons across populations, z-scores for birth weight and length were calculated. The results indicated that approximately 10% of infants were classified as large for gestational age (LGA), while around 15% were classified as small for gestational age (SGA). These classifications are important for identifying infants who may be at risk for complications related to their size at birth.

Associations Between Maternal Thyroid Function and Offspring Anthropometrics

The linear regression analyses conducted revealed significant associations between maternal thyroid parameters and offspring birth measurements. Higher maternal fT4 levels at baseline were found to be negatively correlated with birth length (b = -0.09, p = 0.048). This finding suggests that elevated levels of fT4 in early pregnancy may be associated with shorter birth lengths, potentially indicating growth restriction.

Furthermore, changes in fT4 during pregnancy were positively associated with both birth weight (b = 0.10, p = 0.017) and birth length (b = 0.10, p = 0.047), independent of treatment group. This positive correlation highlights the complexity of the relationship between thyroid hormone levels and fetal growth, suggesting that not only the baseline levels but also the trajectory of thyroid hormone changes during pregnancy are critical for understanding their impact on offspring.

In terms of TSH levels, baseline measurements were inversely associated with the likelihood of LGA outcomes (OR = 0.47, p = 0.012). This association indicates that lower TSH levels at baseline may correspond to an increased risk of delivering larger infants. Conversely, increases in TSH during pregnancy were positively associated with LGA outcomes (OR = 1.99, p = 0.023), suggesting that a greater rise in TSH levels might mitigate the risk of delivering larger-than-average newborns.

In the metformin group specifically, higher TSH levels at baseline were also associated with a lower risk of SGA outcomes (OR = 0.32, p = 0.005). This finding underscores the potential protective role of adequate TSH levels in maintaining appropriate growth patterns for infants born to mothers with PCOS undergoing treatment.

Head Circumference Measurements

Interestingly, the analysis revealed no significant associations between maternal thyroid function and head circumference measurements at birth. This finding suggests that while maternal thyroid levels may impact overall fetal growth, particularly in terms of weight and length, they may not specifically influence cranial development in newborns. This distinction is important for understanding how various aspects of fetal development are regulated and may inform future research directions focused on the specific contributions of thyroid hormones to different growth parameters.

Discussion

Interpretation of Findings

The results of this study elucidate the intricate relationship between maternal thyroid function and offspring anthropometric outcomes in women with PCOS. The negative correlation between maternal fT4 levels and birth length, along with the positive associations between changes in fT4 during pregnancy and both birth weight and length, underscore the multifaceted role of thyroid hormones in fetal development. These findings suggest that optimal management of thyroid function may be particularly important for pregnant women with PCOS, as alterations in thyroid levels could influence growth outcomes for their infants.

The observed associations between TSH levels and the risk of LGA and SGA outcomes further emphasize the need for vigilant monitoring of thyroid function during pregnancy. Given that both hyperthyroidism and hypothyroidism can lead to adverse pregnancy outcomes, maintaining TSH within an appropriate range may be crucial for optimizing fetal growth patterns. The findings suggest that maternal thyroid function plays a significant role in shaping offspring growth trajectories, emphasizing the importance of comprehensive prenatal care for women with PCOS.

Clinical Implications

These findings have substantial clinical implications for the management of pregnant women with PCOS. Healthcare providers should consider routine monitoring of thyroid function during pregnancy, particularly in women with a known diagnosis of PCOS. By identifying and addressing abnormal thyroid levels early in pregnancy, clinicians can potentially mitigate the risk of adverse growth outcomes for infants.

The evidence suggests that interventions aimed at optimizing thyroid function, such as adjusting medication dosages for women on thyroid hormone replacement therapy, may be warranted. Additionally, counseling on lifestyle modifications that support thyroid health, including dietary adjustments and weight management strategies, could be beneficial for this population.

Future Research Directions

The findings of this study pave the way for future research exploring the underlying mechanisms linking maternal thyroid function to offspring growth. Longitudinal studies examining the effects of thyroid hormone levels at various stages of pregnancy on longer-term health outcomes for children may provide valuable insights into the impact of maternal health on offspring development.

Investigating the interactions between thyroid hormones and other metabolic parameters in women with PCOS could enhance understanding of the complex endocrine relationships that influence pregnancy outcomes. Moreover, exploring potential interventions to optimize thyroid function in this population may yield important clinical benefits.

Overall, this study highlights the need for a multidisciplinary approach to prenatal care, integrating endocrinology, obstetrics, and nutrition to optimize maternal and fetal health in women with PCOS. By understanding and addressing the intricate interplay between maternal thyroid function and offspring anthropometrics, healthcare providers can improve pregnancy outcomes for this vulnerable population.

Conclusion

This study highlights the critical relationship between maternal thyroid function and offspring anthropometrics in pregnant women diagnosed with polycystic ovary syndrome (PCOS). The findings underscore the importance of monitoring thyroid hormone levels throughout pregnancy, as both TSH and fT4 levels were significantly associated with key growth outcomes such as birth weight and length. Elevated fT4 levels were correlated with shorter birth lengths, while changes in maternal thyroid function were found to influence the risk of large for gestational age (LGA) and small for gestational age (SGA) outcomes.

The results emphasize the need for comprehensive prenatal care that includes regular assessments of thyroid function, particularly for women with PCOS, who are at higher risk for metabolic complications. Optimizing maternal thyroid health could play a crucial role in enhancing fetal growth and improving overall pregnancy outcomes.

Future research is warranted to explore the underlying mechanisms that govern the relationship between maternal thyroid function and offspring growth, as well as to identify effective interventions for managing thyroid levels in pregnant women with PCOS. By adopting a multidisciplinary approach that integrates insights from endocrinology, obstetrics, and nutrition, healthcare providers can better support the health of both mothers and their infants, ultimately leading to improved pregnancy outcomes and long-term health for future generations.

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