By: Ashlee Hawkins
Editor’s Note: The article published by Chen et al [1] on the importance of maternal hormones in fetal development and pregnancy outcomes was summarized by Ashlee Hawkins while on the FACTS elective. Among other findings, the study showed that even subclinical hypothyroidism or slight elevations in TSH can have detrimental maternal and neonatal effects. Pregnant women, particularly those with a history of thyroid disease, TPO antibody positivity, or autoimmune disease, must have early screening and prompt treatment of thyroid dysfunction. If you would like to learn more about the role of thyroid dysfunction in women’s health sample our CME and register today for the presentation on this topic in Part E delivered by Dr. Naomi Whittaker.
Introduction
Maternal hormones play a crucial role in fetal development and pregnancy maintenance, influencing outcomes such as fetal growth, organ development, and gestational length. Key maternal hormones involved in pregnancy maintenance and fetal development include progesterone, estrogen, insulin, and TSH. Progesterone supports implantation, prevents uterine contractions, and maintains pregnancy. On the other hand, insufficient levels of progesterone can lead to miscarriage or preterm labor. [2] Estrogen promotes placental development, regulates fetal organ growth, and enhances uterine blood flow. Low estrogen levels may contribute to fetal growth restriction and hypertensive disorders. [3] Maternal insulin regulates glucose availability for fetal growth. Gestational diabetes or persistently elevated blood glucose levels during pregnancy may lead to macrosomia (large for gestational age infants) and neonatal hypoglycemia. [4]
“Key maternal hormones involved in pregnancy maintenance and fetal development include progesterone, estrogen, insulin, and TSH.”
Ultimately, hormonal imbalances can lead to complications, including preterm birth, low birth weight, and neurodevelopmental disorders. Screening for maternal hormonal deficiencies before and during pregnancy could be essential to optimize maternal and neonatal outcomes. In the article [1] summarized below titled, “Preconception TSH and Pregnancy Outcomes: A Population-based Cohort Study in 184,611 Women,” Chen et al discuss their prospective study that specifically explored pre-pregnancy TSH levels and their potential impact on maternal and neonatal outcomes.
Methodology
Over a two-year period, researchers gathered a population of 248,501 rural Chinese couples planning to conceive within the next 6 months. Exclusion criteria included extreme maternal age, multiple prior pregnancies, extremely high baseline TSH (e.g., > 500), women with TSH < 0.48 or > 10, and couples lost to follow up. A total of 184,611 women were included in the analysis. TSH, hemoglobin, and glucose levels were measured preconception. All subjects were classified into three groups based on TSH levels: (1) the reference TSH group (0.48 – 2.49 mIU/L), (2) the upper limit group (2.5 – 4.28), and (3) the high TSH group (4.29 – 10). Pregnancy outcomes and neonatal outcomes were determined through face-to-face or telephone follow up; they focused primarily on pregnancy loss, gestational age, delivery modes, and birth weight.
Results
For the 184,611 pregnancies, researchers conducted a multivariable logical regression model to determine the association between preconception TSH levels and pregnancy outcomes. Compared to the reference TSH group, the study revealed the high normal group was associated with a higher likelihood of spontaneous abortion, preterm birth, and operative vaginal delivery. Similarly, the high TSH group had higher rates of spontaneous abortion, stillbirth, and preterm births.
“Compared to the reference TSH group (0.48 – 2.49 mIU/L), the study revealed the high normal group (2.5 – 4.28) was associated with a higher likelihood of spontaneous abortion, preterm birth, and operative vaginal delivery.”
The researchers conducted an additional regression analysis to explore a possible association between maternal lifestyle characteristics and TSH levels. Compared to the reference group, there was a significant finding revealing increased age, tobacco and alcohol use, hypertension, and pre-existing thyroid disease in both the high normal and the high TSH groups.
Discussion
Thyroid hormones play a crucial role in maternal and fetal outcomes, influencing various physiological processes essential for a healthy pregnancy. Maternal complications associated with thyroid dysfunction include an increased risk of miscarriage, preeclampsia, preterm birth, and gestational hypertension, while fetal complications range from stillbirth to impaired neurological development and cognitive deficits. [5] Even subclinical hypothyroidism or slight elevations in TSH can have detrimental effects on both the mother and fetus, as demonstrated by Chen et al. [1] Furthermore, studies have emphasized that untreated hypothyroidism during pregnancy can lead to lower birth weights and an increased risk of neurodevelopmental disorders in offspring. [6] The American Thyroid Association recommends early screening and intervention for thyroid dysfunction in pregnant women, especially those with risk factors such as autoimmune disease or a history of thyroid dysfunction. [5]
“Thyroid hormones play a crucial role in maternal and fetal outcomes.… Even subclinical hypothyroidism or slight elevations in TSH can have detrimental effects on both the mother and fetus.”
Ensuring hormonal balance before conception is critical, making preconception counseling and screening a vital component of maternal care. A holistic approach to hormonal enhancement can improve maternal and neonatal outcomes, promoting better long-term health for both mother and child. [7]
References
[1] Chen, S., Zhou, X., Zhu, H., Yang, H., Gong, F., Wang, L., Zhang, M., Jiang, Y., Yan, C., Li, J., Wang, Q., Zhang, S. and Pan, H. (2017), Preconception TSH and pregnancy outcomes: a population-based cohort study in 184 611 women. Clin Endocrinol, 86: 816-824. https://doi.org/10.1111/cen.13329
[2] Csapo AI et al. (1973). “The role of progesterone in the maintenance of pregnancy.” Am J Obstet Gynecol.
[3] Albrecht ED, Pepe GJ. (1990). “Placental steroid hormone biosynthesis in primate pregnancy.” Endocrine Reviews.
[4] McIntyre HD et al. (2019). “Gestational diabetes mellitus.” The Lancet Diabetes & Endocrinology.
[5] Alexander EK et al. (2017). “2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum.” Thyroid.
[6] Casey, B. M., Thom, E. A., Peaceman, A. M., Varner, M. W., Sorokin, Y., Reddy, U. M., … & Rouse, D. J. (2018). Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy. New England Journal of Medicine, 379 (12), 1141-1152.
[7] Mandel, S. J., Spencer, C. A., Hollowell, J. G., Blount, B. C., & Braverman, L. E. (2020). The impact of iodine and thyroid dysfunction on pregnancy outcomes. The Journal of Clinical Endocrinology & Metabolism, 105 (4), e1513-e1522.
ABOUT THE AUTHOR
Ashlee Hawkins, MD
Ashlee Hawkins, MD completed the FACTS elective as a fourth-year medical student at Georgetown University School of Medicine in Washington, DC. She earned her undergraduate and graduate degrees at Oklahoma State University in Stillwater, OK. Dr. Hawkins is now a resident in emergency medicine at Johns Hopkins Hospital and is interested in health equity. She enrolled in the FACTS elective to gain an in-depth understanding of natural family planning and to further promote such practices within the communities she will soon serve.
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