Thyroid Hormone, Birth Defects, and the Developing Brain

I miscarried my child at 12 weeks needlessly from maternal hypothyroidism. I knew deep inside me that something was wrong with my pregnancy. I should have gone for a second medical opinion but I didn’t. I was of the belief that doctor knows best and I have to live with that regret for the rest of my life.

Despite mounting evidence of the dangers of maternal thyroid dysfunction in pregnancy, there is still NO universal thyroid screening in pregnancy and this enrages me.

Written by Eugene L. Heyden, RN

Pregnancy is a period that places great physiological stress on both the mother and the fetus. When pregnancy is complicated by endocrine disorders such as hypothyroidism, the potential for maternal and fetal adverse outcomes can be immense. ~Sahay and Sir Negesh, 2012

It is quite remarkable that the fate of a new little life will depend on the availability of a small little molecule made by a tiny little gland. The small little molecule is a hormone called thyroxin; the tiny little gland is, of course, the thyroid. During fetal development, a baby will make some thyroxin, starting around mid-gestation, but it will be Mom who supplies her baby with most of the thyroxin he or she will ever know until sometime after birth. Then it will be Baby’s turn to supply all the thyroxin he or she will ever know. Given all the information available regarding the requirements of thyroxin for proper fetal development, we pay surprisingly little attention to the thyroid hormone status of those who are pregnant or may become pregnant at a moment’s notice. According to one study: “Consistently, over half of women with thyroid laboratory abnormalities would be missed if only high-risk women were examined.” (Jiskra et al., 2011) As a result, babies are lost, babies are damaged. Why are they lost? Why are they damaged? Why is thyroxin so important?

It all has to do with genes and the genetic programs that are unleashed following conception. Think about it for a moment. The eye, the ear, the heart, brain—how about everything!—will need to be formed according to plan. The genes tucked safely within the nucleus of the cell are the plan! This is where thyroxin comes in. Thyroxin is the hormone of fetal development. It orchestrates the genetic events that precisely form a new little life. Apparently, there are between 2,000 and 10,000 receptors responsive to thyroid hormone within the nucleus of any given cell, making thyroid hormone intimately involved in initiating and regulating genetic events (Neves et al., 2002). When supplies are low for any length of time, genetic programs may not fulfill their mission, and birth defects can emerge.

By birth defects, I don’t necessarily mean physical birth defects. Under this banner, I also include defects that occur within the developing brain. Indeed, the brain is very sensitive to low thyroid hormone levels during gestation. It may not form as intended when the supply of thyroid hormone is low.

Epidemiological studies have indicated that even a marginally low thyroxin [T4] level in a pregnant woman may give rise to reduction in cognitive function of the offspring. Thus, even minor changes in the thyroid homeostasis may affect neurological development. (Boas et al., 2012, emphasis added)

Well, we wouldn’t want any of this altered neurologic development around, now would we? But it’s everywhere! Have you heard of autism? When I first started paying attention to autism some 6 or 7 years ago, I was alarmed at the statistic that 1 in 150 children was being diagnosed with this disorder, per year. A few years later, the statistic was 1 in 88. Now, in 2014, 1 in 68 children will receive this diagnosis. Hearts will be broken. And if you doubt whether autism is related to the thyroid hormone status in Mom during gestation, you may want to reconsider. You may need to have a lively little discussion with Dr. Román.

Maternal hypothyroidism causes pregnancy complications, including postpartum hemorrhage, placental abruption, and preterm labor; some of these are risk factors for autism. (Román et al., 2013)

Of related interest is the finding that a family history of autoimmune thyroiditis doubled the risk of autism. (Román, 2007)

If Dr. Román is out of the office, see if you can find Dr. Hendricks around somewhere. Ask him how important thyroxin is to the developing brain. He will probably say something like:

Animal models confirm that the first half of pregnancy may constitute a sensitive period in which maternal hypothyroxinemia alters neurogenesis and causes neuronal migration errors in the developing fetal brain. (Hendricks et al., 2013)

Oh, I’ve somehow slipped a new word into the conversation, hypothyroxinemia. What is this? Hypothyroxinemia is a low level of thyroxin in the blood stream (in Mom) when the TSH, a laboratory test used to detect thyroid abnormalities, says, “All is well!” Hypothyroxinemia is just another way for the developing baby to become hypothyroid during gestation, and the mother (and the physician) will be so unaware of its existence. You don’t feel hypothyroxinemia like you may feel hypothyroidism. Most often, it is silent, but ever ready to harm. It may be comforting to have normal TSH result in hand, but you will be missed, your baby will be missed, if a free T4 (and free T3) are not part of the prenatal evaluation. “Oh, I’ve never heard of hypothyroxinemia before, it must be rare!” You shouldn’t have said that. “While the incidence of hypothyroidism in pregnant women is around 2.5%, hypothyroxinemia is much more prevalent, up to 30%, and it is usually due to mild iodine deficiency.” (Bernal, 2014, emphasis added) Notice the words “mild iodine deficiency”—very important. Mildly iodine-deficient women are everywhere!

I knew someone would go and slip the words iodine deficiency into the conversation. (I think it was me.) “Oh, but that’s probably rare, too!” (You keep saying the silliest of things.) Just admit it, you were totally unaware that the USA is an iodine-deficient region (Stagnaro-Green and Pearce, 2012). Sure, iodized salt has saved us from goiter—that is, big ugly goiter—but iodine deficiency still remains a big problem in our corner of the globe. And pregnancy, due to an increased demand for iodine and an increased renal secretion of iodine that automatically occurs during pregnancy, will easily convert an iodine-sufficient woman into an iodine-deficient woman as the pregnancy progresses. (It will also convert an iodine deficient woman into a more iodine deficient woman.) And just for the record, iodine deficiency leads to hypothyroxinemia. So, as you can see, iodine deficiency is just another way for Baby to become hypothyroid and at great risk for improper development.

In the United States, a seven-fold increase in the frequency of moderate iodine deficiency among pregnant women has occurred since the 1970s, along with a four-fold increase in the frequency of moderate iodine deficiency in the total population, coincident with a greater than 50% decline in urinary iodine excretion, along with subclinical signs of thyroid deficiency. (Román, 2007)

I’d better bring this discussion to a close before I go and introduce another new word or concept that will require me to go on and on to explain. And believe me, I could go on and on. There are babies at risk here! They must be found.

When the potential adverse outcomes are so significant and the tools to diagnose and intervene are easily accessible, however, leaving maternal thyroid disease underdiagnosed, even in one third of pregnant women, is no longer acceptable. (Brent, 2007)

I think you are getting the idea here. Maternal thyroid dysfunction is not benign. It has serious consequences. A war should be declared against it. Let’s close with this: Hypothyroidism, imposed on the developing fetus, impairs development . . . period! The results could range from “Why is my child having such a difficult time learning to put the right shoe on the right foot?” to “Why does my child have autism?” or “Why does my child have cerebral palsy?” Of course, there is this haunting question: “Why, oh why, did I lose my baby?” These questions are asked all too frequently. Universal screening for thyroid dysfunction, both before and during pregnancy, will save many babies from defects of body and of mind. It is certain to save many babies from death before birth.

About Eugene L. Heyden, RN

Eugene L. Heyden, RN is a registered nurse with nearly 35 years of clinical experience, and in a variety of clinical settings. His passions include medical research and patient education. impactofvitamind.com

References

Ares S, Escobar-Morreale HF, Quero J, Durán S, Presas MJ, Hurruzo J, Morreale de Escobar G 1997 Neonatal Hypothyroxinemia: Effects of Iodine Intake and Premature Birth. The Journal of Clinical Endocrinology & Metabolism 82(6)1704–1712

Boas M, Feldt-Rasmussen U, Main KM 2012 Thyroid Effects of Endocrine Disrupting Chemicals. Molecular and Cellular Endocrinology 355:240–248

Brent GA 2007 Diagnosing Thyroid Dysfunction in Pregnant Women: Is Case Finding Enough? The Journal of Clinical Endocrinology & Metabolism 92(1):39–41

Hendricks J, Ghassabiant A, Peeters RP, Tiemeiert H 2013 Maternal Hypothyroxinemia and Effects on Cognitive Functioning in Childhood: How and Why? Clinical Endocrinology 79:152–162

Jiskra J, BartáKová J, Holomka Š, Límanová Z, Springer D, Antošová M, Telička Z, Potluková E 2011 Low Prevalence of Clinically High-Risk Women and Pathological Thyroid Ultrasound among Pregnant Women Positive in Universal Screening for Thyroid Disorders. Experimental and Clinical Endocrinology and Diabetes 119(9):530

Neves FA, Cavalieri RR, Simeoni LA, Gardner DG, Baxter JD, Scharschmidt BF, Lomri N, Ribeiro RC 2002 Thyroid Hormone Export Varies Among Primary Cells and Appears to Differ from Hormone Uptake. Endocrinology 143(2):476–483

Román GC 2007 Autism: Transient In Utero Hypothyroxinemia Related to Maternal Flavonoid Ingestion During Pregnancy and to Other Environmental Antithyroid Agents. Journal of Neurological Sciences 262:15–26

Román GC, Ghassabian A, Bingers-Schokking JJ, Jaddoe V, Hofman A, de Rijke YB, Verhuslt FC, Tiemeier H 2013 Association of Gestational Maternal Hypothyroxinemia and Increased Autism Risk. Ann Neurol 74:733–742

Sahay RK, Sir Nagesh VS 2012 Hypothyroidism in Pregnancy. Indian J Endocrinol Metab; May–June; 16(3):364–370

Stagnaro-Green A, Pearce E 2012 Thyroid Disorders in Pregnancy. Nat. Rev. Endocrinol 8:650–658