Low Thyroid, Hashimotos and Pregnancy

by Jeffrey Dach MD

Today is a happy day for Susan.  She just delivered a healthy baby girl, and mailed me a cute photo of the baby from her hospital bed,  Six months before, Susan was weeping in my office, recounting her story of repeated miscarriages and fertility problems.  Her lab panel showed a borderline low thyroid status and elevated anti-thyroid antibodies indicating Hashimoto’s Autoimmune Thyroiditis.  Upper Left Image courtesy of wikimedia commons.

After a complete evaluation, we started Susan on our usual program including natural desiccated thyroid One and a Half Grains per day, selenium 400 mcg/day, iodine 450 mcg per day and a good prenatal multivitamin.  That must have done the trick, and Susan’s thank you card has the “pitter patter of little feet” on the cover.

A Common Scenario

Since ten to twenty per cent of all women of reproductive age have elevated anti thyroid antibodies, we see this scenario quite often.

There are literally thousands of low thyroid Susans ignored by mainstream medicine, left to suffer through repeated miscarriages and other fertility problems, representing yet another tragic error by conventional endocrinology.  Left image mother and baby courtesy of wikimedia commons.

Dr Peter Taylor Makes a Plea

Dr Peter Taylor made exactly this point at a recent Endocrine Society Meeting when he said that more pregnant women would benefit from thyroid hormone treatment to prevent miscarriages and stillborn babies.(8)  His pleas to screen all pregnant women were ignored, as they have been for many years.(9)  Further studies show that many women with thyroid anti-bodies have better pregnancy outcomes when treated with thyroid hormones.(10,11)

The New York Times Gets the Story Right

A few years back in 2009,  Dr Alex Stagnaro-Green gave the New York Times an accurate accounting of the role of thyroid in pregnancy. (1) These are Dr Green’s points:

1)  Pregnancy is like a stress test for the thyroid. increasing thyroid hormone requirement by 50%

2) Hypothyroidism during pregnancy is linked to miscarriage (5), and preterm delivery. (5)  Compared to aged matched controls, children of hypothyroid mothers have lower I.Q.s by seven points on average when tested  seven to nine years later. (3)  Nineteen per cent of these children had IQ’s of 85 or less.(3)

3) Even though thyroid hormone levels may be completely normal, the presence of Hashimoto’s anti-thyroid antibodies is associated with a 200-300% increase of miscarriage.

Dr. Roberto Negro from Italy published a study in 2006 of women who were thyroid antibody-positive.  Treatment of these women with thyroid hormone resulted in a dramatic reduction of stillbirths and preterm deliveries.(4)  Upper left image courtesy of wikimedia commons.

How to Make Smarter Babies

As mentioned above, children born to hypothyroid mothers, have lower IQ when tested 7-9 years later.  Giving thyroid hormones to the mother makes smarter babies.(3)  In addition, maternal iodine deficiency is associated with reduced educational outcomes in the offspring.(14)  This is precisely why we screen women for iodine levels, and make sure they have adequate iodine supplementation. In  Hashimotos patients, we use low-dose iodine supplementation of 225-450 mcg per day which is a safe level.

Hypothyroid MOM

Perhaps the one person most dedicated to getting this message out is Dana Trentini who runs HypoThyroid Mom.  (left image courtesy of Dana Trentini Hypothyroid MOM.

After suffering through a miscarriage herself, she discovered the importance of thyroid in pregnancy,  and has been a tireless advocate ever since.   Regretting her misplaced trust in doctors who failed to treat her low thyroid condition, HypothyroidMom now encourages all women to take charge of their thyroid health.  The EcoFeminist Blog run by Aimee picks up and amplifies this message in her article,  hypothyroidism and miscarriage.

Conclusion: Another tragedy of modern endocrinology is the manner in which the hypothyroid mom is ignored, leading to unnecessary suffering.  All pregnant women should be screened for thyroid antibodies and more pregnant women should be treated with thyroid hormones which will result in reduction in miscarriages, reduction in preterm infants, and improvement in IQ and educational outcomes in the newborn

Jeffrey Dach MD
7450 Griffin Road Suite 190
Davie, Fl 33314
954-792-4663

Articles with Related Interest

Why Natural Thyroid is Better than Synthetic

TSH SUppression Benefits and Adverse Effects

How to Make Smarter Children with Iodine Supplementation

The Unreliable TSH Part One

The Unreliable TSH Part Two

Hashimotos, Iodine and Selenium

Links and references

1)  http://www.nytimes.com/ref/health/healthguide/esn-hypothyroidism-expert.html?pagewanted=all
Pregnancy and the Thyroid New York Times  3/13/2009
By INGFEI CHEN  Dr. Alex Stagnaro-Green is a professor of medicine and obstetrics and gynecology at Touro University College of Medicine in Hackensack, N. J. He was a member of an international panel of experts convened by the Endocrine Society that issued a clinical practice guideline in 2007 on managing thyroid dysfunction during pregnancy and after childbirth.
It turns out that pregnancy is like a stress test for the thyroid: the amount of thyroid hormone that needs to be released during pregnancy is increased by about 50 percent, and that’s because of some of the hormones related to pregnancy. If there is a dysfunction with the thyroid, it has been linked — especially hypothyroidism — to miscarriage, preterm delivery, and also with decreased I.Q. in the unborn child when tested at 7 to 9 years old. Furthermore, if a woman has Hashimoto’s disease with antibodies, but with the thyroid hormone levels still being normal, that’s also been associated with a two- to threefold increase of miscarriage. So that’s why all this is very important.
But the women who were antibody-positive who didn’t get the thyroid hormone had a miscarriage rate that was four times higher.
First I educate her that about 50 to 60 percent of women who have thyroid disease and are on thyroid hormone replacement therapy will need an increase in the hormone very early in the first trimester. I explain that this is extremely important so as to prevent complications like miscarriage. And therefore we try to adjust the thyroid hormone level before a woman gets pregnant so that she’s clearly in the normal range.
Secondly, as soon as they get pregnant, I have my patients call me immediately to get thyroid function tests so that I can modify their dose as early as possible in the pregnancy. Bottom line is that as soon as a woman knows she is pregnant she should be tested and see her doctor.

2) https://www.ncbi.nlm.nih.gov/pubmed/2118190
JAMA. 1990 Sep 19;264(11):1422-5.
Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies.
Stagnaro-Green A1, Roman SH, Cobin RH, el-Harazy E, Alvarez-Marfany M, Davies TF. Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029.
We screened 552 women who presented to their obstetrician in the first trimester of pregnancy using highly sensitive enzyme-linked immunosorbent assays for the presence of thyroglobulin and thyroid peroxidase autoantibodies and found an incidence of positivity of 19.6%. The tendency to secrete detectable levels of thyroid autoantibodies was significantly correlated with an increased rate of miscarriage. Thyroid autoantibody-positive women miscarried at a rate of 17%, compared with 8.4% for the autoantibody-negative women. Individual levels of thyroglobulin and thyroid peroxidase autoantibodies were similarly related to this increased miscarriage rate, with no evidence of autoantibody specificity in the relationship. Furthermore, the increase in miscarriages could not be explained by differences in thyroid hormone levels, the presence of cardiolipin autoantibodies, maternal age, gestational age at the time of maternal entry into the study, or previous obstetric history. We conclude that thyroid autoantibodies are an independent marker of “at-risk” pregnancy.

3) https://www.ncbi.nlm.nih.gov/pubmed/10451459
N Engl J Med. 1999 Aug 19;341(8):549-55.
Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child.
Haddow JE1, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, O’Heir CE, Mitchell ML, Hermos RJ, Waisbren SE, Faix JD, Klein RZ.
When thyroid deficiency occurs simultaneously in a pregnant woman and her fetus, the child’s neuropsychological development is adversely affected. Whether developmental problems occur when only the mother has hypothyroidism during pregnancy is not known.
METHODS:In 1996 and 1997, we measured thyrotropin in stored serum samples collected from 25,216 pregnant women between January 1987 and March 1990. We then located 47 women with serum thyrotropin concentrations at or above the 99.7th percentile of the values for all the pregnant women, 15 women with values between the 98th and 99.6th percentiles, inclusive, in combination with low thyroxine levels, and 124 matched women with normal values. Their seven-to-nine-year-old children, none of whom had hypothyroidism as newborns, underwent 15 tests relating to intelligence, attention, language, reading ability, school performance, and visual-motor performance.
RESULTS:The children of the 62 women with high serum thyrotropin concentrations performed slightly less well on all 15 tests. Their full-scale IQ scores on the Wechsler Intelligence Scale for Children, third edition, averaged 4 points lower than those of the children of the 124 matched control women (P= 0.06); 15 percent had scores of 85 or less, as compared with 5 percent of the matched control children. Of the 62 women with thyroid deficiency, 48 were not treated for the condition during the pregnancy under study. The full-scale IQ scores of their children averaged 7 points lower than those of the 124 matched control children (P=0.005); 19 percent had scores of 85 or less. Eleven years after the pregnancy under study, 64 percent of the untreated women and 4 percent of the matched control women had confirmed hypothyroidism.
CONCLUSIONS:Undiagnosed hypothyroidism in pregnant women may adversely affect their fetuses; therefore, screening for thyroid deficiency during pregnancy may be warranted.

4) https://www.ncbi.nlm.nih.gov/pubmed/16621910
J Clin Endocrinol Metab. 2006 Jul;91(7):2587-91.
Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications.
Negro R1, Formoso G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H.

Euthyroid women with autoimmune thyroid disease show impairment of thyroid function during gestation and seem to suffer from a higher rate of obstetrical complications.
OBJECTIVE:We sought to determine whether these women suffer from a higher rate of obstetrical complications and whether levothyroxine (LT(4)) treatment exerts beneficial effects.
DESIGN:This was a prospective study.
SETTING:The study was conducted in the Department of Obstetrics and Gynecology.
PATIENTS:A total of 984 pregnant women were studied from November 2002 to October 2004; 11.7% were thyroid peroxidase antibody positive (TPOAb(+)).
INTERVENTION:TPOAb(+) patients were divided into two groups: group A (n = 57) was treated with LT(4), and group B (n = 58) was not treated. The 869 TPOAb(-) patients (group C) served as a normal population control group.
MAIN OUTCOME MEASURES:Rates of obstetrical complications in treated and untreated groups were measured.
RESULTS:At baseline, TPOAb(+) had higher TSH compared with TPOAb(-); TSH remained higher in group B compared with groups A and C throughout gestation. Free T(4) values were lower in group B than groups A and C after 30 wk and after parturition. Groups A and C showed a similar miscarriage rate (3.5 and 2.4%, respectively), which was lower than group B (13.8%) [P < 0.05; relative risk (RR), 1.72; 95% confidence interval (CI), 1.13-2.25; and P < 0.01; RR = 4.95; 95% CI = 2.59-9.48, respectively]. Group B displayed a 22.4% rate of premature deliveries, which was higher than group A (7%) (P < 0.05; RR = 1.66; 95% CI = 1.18-2.34) and group C (8.2%) (P < 0.01; RR = 12.18; 95% CI = 7.93-18.7).
CONCLUSIONS:Euthyroid pregnant women who are positive for TPOAb develop impaired thyroid function, which is associated with an increased risk of miscarriage and premature deliveries. Substitutive treatment with LT(4) is able to lower the chance of miscarriage and premature delivery.

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5) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229690/
Maternal Subclinical Hypothyroidism, Thyroid Autoimmunity, and the Risk of Miscarriage: A Prospective Cohort Study
Liu Haixia, Shan Zhongyan, Li Chenyan, Mao Jinyuan, Xie Xiaochen, Wang Weiwei, Fan Chenling, Wang Hong, Zhang Hongmei,
Han Cheng, Wang Xinyi, Liu Xin, Fan Yuxin, Bao Suqing, and Teng Weiping.  Thyroid. November 2014, 24(11): 1642-1649.

ABSTRACT Background: Increasing data suggest that subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) are associated with adverse pregnancy outcomes, but there are limited data on the association of these conditions in early pregnancy with subsequent miscarriage.
Methods: In this prospective cohort study, we screened 3315 women at low risk for thyroid dysfunction at four to eight weeks’ gestation from iodine-sufficient areas of China between January 2012 and September 2012. Thyrotropin (TSH), free thyroxine (fT4), and the autoantibodies thyroid-peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) were measured. Based on these results, women were divided into four groups for comparison: euthyroidism (ET), isolated SCH, isolated TAI (positive TPOAb or/and TgAb), and SCH with TAI (SCH+TAI). The SCH group was stratified into two subgroups (SCH 1 and SCH 2) on the basis of the level of TSH (2.5≤TSH<5.22 or 5.22≤TSH<10 respectively). Accordingly, the SCH+TAI group was also stratified into two subgroups (SCH+TAI 1 and SCH+TAI 2). The outcome of interest was miscarriage, defined as spontaneous pregnancy loss prior to 20 weeks.
Results: Compared to women with ET, the risk of miscarriage was significantly higher among women with SCH 2 (7.1% vs. 2.2%, aOR 3.40 [CI 1.62–7.15]; p=0.002), isolated TAI (5.7% vs. 2.2%, aOR 2.71 [CI 1.43–5.12]; p=0.003), SCH+TAI 1 (10.0% vs. 2.2%, aOR 4.96 [CI 2.76–8.90]; p=0.000), and SCH+TAI 2 (15.2% vs. 2.2%, aOR 9.56 [CI 3.76–24.28]; p=0.000). The gestational ages of 110 women at miscarriage were lower among women with subclinical thyroid abnormalities compared to ET (11.13±3.21 weeks with subclinical thyroid abnormalities vs. 9.33±1.71 weeks with ET; p=0.024). In parallel with the higher TSH levels, there were earlier gestation ages at miscarriage between subgroups of SCH and SCH+TAI (SCH 1 vs. SCH 2: 10.79±1.77 vs. 9.70±1.47 weeks, p=0.039; SCH+TAI 1 vs. SCH+TAI 2: 9.59±1.97 vs. 8.88±1.24 weeks, p=0.031).
Conclusions: Women with SCH and TAI are at an increased risk of miscarriage between four and eight gestational weeks. Women with a combination of SCH and TAI were found to have the highest risk and earlier gestational ages of miscarriage.

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6) http://hypothyroidmom.com/what-every-pregnant-woman-needs-to-know-about-hypothyroidism/
What Every Pregnant Woman Needs To Know About Hypothyroidism
October 8, 2012 by Dana Trentini
The launch of my blog Hypothyroid Mom is intentionally timed this October 2012 during Miscarriage Awareness Month in memory of the baby I lost to hypothyroidism and in dedication to my two boys who beat the odds and made it to the world. This is Part 2 of my 5-part series entitled Miscarriage Awareness Month: The Dangers of Hypothyroidism And Pregnancy.

7) https://theecofeminist.com/2016/08/30/hypothyroidism-and-miscarriage/
Hypothyroidism and Miscarriage August 30, 2016     Eco Feminist

Nov 9, 2016  Peter Taylor

8) https://www.sciencedaily.com/releases/2016/11/161109090353.htm
Giving more pregnant women common thyroid medicine may reduce risk of complications.  Date:    November 9, 2016
Source:    Society for Endocrinology
Summary:    Extending the number of pregnant women given the common drug levothyroxine to boost thyroid hormone levels may lead to a reduced number of stillbirths, early caesarean sections and low-weight babies, according to a new study.
In this study, researchers from the University of Cardiff investigated whether pregnant women with mild hypothyroidism and their babies would also benefit from levothyroxine treatment. They combined data from a thyroid screening study and linked it to routinely collected clinical data to study the effect of correcting borderline thyroid function on obstetric outcomes.
The researchers analysed over 13,000 women who were 12-16 weeks pregnant, 518 of whom had mild hypothyroidism. Of these, 263 women received levothyroxine and the rest received no treatment. They assessed the women’s pregnancy outcomes by measuring stillbirth rates, preterm delivery, length of stay at hospital, birth weight and the number of early caesarean sections.
They found that women with mild hypothyroidism treated with levothyroxine had a lower risk of giving birth to low weight babies and were also less likely to undergo an early caesarean. Untreated women with mild hypothyroidism were more likely to have a stillbirth than women with normal thyroid function and no stillbirths occurred in the treated group. However, there was no significant difference between the other obstetric outcomes or when all outcomes were combined.
“Our work raises the possibility of providing real benefits from using a safe, cheap and well established treatment by simply extending it to the number of pregnant women we treat,” said Dr Peter Taylor, lead author of the study.
Dr Taylor believes more substantial benefits might be found by treating the pregnant women at an earlier stage than used in this study. “We should consider universal thyroid screening in pregnancy as it compares favourably in terms of cost-effectiveness with other conditions that we currently screen for,” he added.

9) http://www.futuremedicine.com/doi/abs/10.2217/whe.15.7?journalCode=whe
Taylor, Peter N., et al. “Should all women be screened for thyroid dysfunction in pregnancy?.” Women’s Health 11.3 (2015): 295-307.
The subject of universal thyroid screening in pregnancy generates impassioned debate. Thyroid dysfunction is common, has significant adverse implications for fetal and maternal well-being, is readily detectable and can be effectively and inexpensively treated. Furthermore, the currently recommended case-finding strategy does not identify a substantially proportion of women with thyroid dysfunction thus favoring universal screening. On the other hand subclinical thyroid dysfunction forms the bulk of gestational thyroid disorders and the paucity of high-level evidence to support correction of these asymptomatic biochemical abnormalities weighs against universal screening. This review critically appraises the literature, examines the pros and cons of universal thyroid screening in pregnancy, highlighting the now strong case for implementing universal screening and explores strategies for its implementation.

10) http://www.endocrine-abstracts.org/ea/0044/ea0044OC6.3.htm
Endocrine Abstracts (2016) 44 OC6.3
Controlled Antenatal ; Obstetric Outcomes
Peter Taylor1, Arron Lacey2, Daniel Thayer2, Mohd Draman1, Arshiya Tabasum1,3, Ilaria Muller1, Luke Marsh1, Arwel Poacher1, Aled Roberts3, Marian Ludgate1, Alex Rees3, Kristien Boelaert4, Aled Rees1, Shiao Chan4,5, John Lazarus1, Scott Nelson6, Bijay Vaidya7 & Onyebuchi Okosieme1
Context: Suboptimal thyroid function in pregnancy is associated with adverse obstetric outcomes but it is unclear whether levothyroxine treatment, initiated during pregnancy is beneficial.
Design & Participants: Retrospective analysis of the Controlled Antenatal Thyroid Screening (CATS) study with obstetric outcomes obtained through data-linkage in the Secure Anonymised Information Linkage (SAIL) databank. We studied 13,224 pregnant women; 12,608 had normal thyroid function, 340 had subclinical hypothyroidism (SCH), 305 had isolated hypothyroxinemia (IH). 518 women with abnormal thyroid function were randomized to receive levothyroxine (N=263) or no treatment (N=255) at the end of the first trimester.
Main Outcome Measures: Composite measure (primary outcome) of stillbirth, neonatal death, preterm delivery <34 weeks, APGAR score at 5 minutes <7, length of hospital stay >5 days. Secondary analyses included early gestational age (<37 weeks), early caesarean sections (<37 weeks).
Results: In individuals with abnormal thyroid function randomized to treatment or control, treatment had no discernible effect on the composite outcome. 29 events occurred in the untreated group vs 22 in the treated. OR (treated) = 0.75 95%CI (0.40, 1.40). Untreated women with SCH had increased odds of stillbirth compared to women with normal thyroid function OR=4.37 (95%CI 1.04, 18.3). No stillbirths occurred in women on levothyroxine. Untreated women with IH had increased odds of an early gestational age at delivery (<37 weeks) than women with normal thyroid function OR=1.58 (95%CI 1.04, 2.50). Women with IH randomized to receive treatment with levothyroxine had reduced odds of early gestational age at delivery OR=0.37 (95%CI 0.14, 0.99) and early caesarean sections (0% vs 4%) p=0.04 than untreated women.
Conclusion: Both SCH and IH were associated with key adverse obstetric outcomes. Although there was no difference in composite outcome there were some benefits observed with levothyroxine therapy. Larger studies are required to confirm the benefits of screening and treatment in pregnancy.

11) http://www.bmj.com/content/342/bmj.d2616
Thangaratinam, Shakila, et al. “Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence.” Bmj 342 (2011): d2616.
This systematic review was conducted with a prospective protocol with widely recommended methods.15
Conclusion The presence of maternal thyroid autoantibodies is strongly associated with miscarriage and preterm delivery. There is evidence that treatment with levothyroxine can attenuate the risks.

What is already known on this topic
Thyroid autoantibodies are relatively common in women of reproductive age
Thyroid autoimmunity might be associated with adverse pregnancy outcomes
What this study adds
In women with normal thyroid function and thyroid autoantibodies the risk of miscarriage is more than tripled and the risk of preterm birth is doubled
Treatment with levothyroxine can halve the risk of miscarriage in women with normal thyroid function and thyroid autoantibodies

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12) http://acb.sagepub.com/content/53/4/421.short
Thyroxine replacement: a clinical endocrinologist’s viewpoint

V Eligar1     PN Taylor1     OE Okosieme1,2⇑     GP Leese3     CM Dayan1  1Thyroid Research Group, Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, UK  2Endocrine and Diabetes, Department Prince Charles Hospital, Cwm Taf University Health Board Merthyr Tydfil, UK
3Department of Medicine, University of Dundee, Ninewells Hospital, Dundee, UK
OE Okosieme, University Hospital of Wales Cardiff, UK. Email: OkosiemeOE@Cardiff.ac.uk
Background Hypothyroidism affects 2–5% of the general population. Patients with uncorrected disease suffer significant morbidity and have an increased risk of cardiovascular disease and neurocognitive impairment. Levothyroxine, the treatment of choice, is inexpensive, easy to administer and in most cases restores well-being while normalizing thyroid function. However, 30–50% of individuals on levothyroxine are either over-treated or under-treated and others remain dissatisfied with treatment despite achieving thyroid hormone concentrations within the laboratory reference interval.
Methods This review is based on a systematic search of the literature for controlled trials, systematic reviews, guideline papers and cohort studies addressing best practice in thyroid hormone replacement.
Results Recent decades have seen improvements in patient management strategies driven by a better appreciation of levothyroxine pharmacokinetics. However, aspects of therapy such as the optimal timing of medication, strategies to overcome treatment non-adherence and target thyroid stimulating hormone concentrations in pregnancy and in patients with differentiated thyroid cancer remain challenging. Furthermore, there is now a substantial body of literature on common genetic variations in the deiodinases and thyroid hormone transporters and their role in the local regulation of thyroid hormone delivery. The benefits of combination therapy with liothyronine and levothyroxine are uncertain, and while it is theoretically probable that subsets of genetically predisposed individuals will benefit from combination therapy the existing evidence is as yet limited.
Conclusion Despite the availability of thyroid hormone replacement for more than a century, there are still substantial challenges in practice and opportunities to improve treatment outcomes.

13) http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/thyroid_preg.html
Thyroid Hormones: Pregnancy and Fetal Development

Thyroid hormones are critical for development of the fetal and neonatal brain, as well as for many other aspects of pregnancy and fetal growth. Hypothyroidism in either the mother or fetus frequently results in fetal disease; in humans, this includes a high incidence of mental retardation.
Isolated maternal hypothyroidism: Overt maternal hypothyroidism typically is not a significant cause of fetal disease because it usually is associated with infertility. When pregnancy does occur, there is increased risk of intrauterine fetal death and gestational hypertension. Subclincial hypothyroidism is increasingly being recognized as a cause of developmental disease – this is a rather scary situation. Several investigators have found that mild maternal hypothyroidism, diagnosed only retrospectively from banked serum, may adversely affect the fetus, leading in children to such effects as slightly lower performance on IQ tests and difficulties with schoolwork. The most common cause of subclinical hypothyroidism is autoimmune disease, and it is known that anti-thyroid antibodies cross the human placenta. Thus, the cause of this disorder may be a passive immune attack on the fetal thyroid gland.

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14) http://press.endocrine.org/doi/full/10.1210/jc.2012-4249
http://ecite.utas.edu.au/99264
Hynes, Kristen L., et al. “Mild iodine deficiency during pregnancy is associated with reduced educational outcomes in the offspring: 9-year follow-up of the gestational iodine cohort.” The Journal of Clinical Endocrinology & Metabolism 98.5 (2013): 1954-1962.

Iodine is essential for neurodevelopment in utero and in childhood, with deficiency being a major cause of preventable intellectual impairment (1). The serious neurodevelopmental consequences of severe iodine deficiency (ID) on the fetus are well documented and include cretinism, which manifests as motor, cognitive, and auditory defects (2). ID, however, results in a spectrum of disorders with many speculating that even mild maternal ID has subtle impacts on fetal development. Recent reviews are not conclusive as to whether low maternal dietary iodine intake in areas of mild deficiency leads to measurable effects on cognition and neurodevelopment of the offspring (3, 4).
Clinical trials of iodine supplementation in pregnancy in regions of mild ID have typically focused on positive changes in maternal and fetal thyroid function and volumes but have not examined long-term developmental consequences in the offspring. To our knowledge, there are only three studies reporting neurodevelopmental outcomes in offspring after supplementation of mothers with mild ID. Berbel et al (5) reported significantly delayed neurobehavioral performance in children (aged 18 months) if their mothers did not receive iodine supplementation by 4 to 6 weeks of gestation. Similarly, Velasco et al (6) found that children (aged 3–18 months) had higher psychomotor development scores if their mothers were given supplements from the first trimester. Both interventions provide preliminary evidence that even mild gestational ID may have an adverse impact on fetal neurodevelopment and subsequent infant functioning. In contrast, Murcia et al (7) reported that higher maternal intake of iodine-containing supplements was associated with lower scores on the Psychomotor Development Index of the Bayley Scales of Infant Development in their children (aged 1 year).
In addition to gestational studies, there is increasing evidence from observational population studies that less severe cognitive and motor impairment occurs in apparently normal individuals from areas of ID (8). Children without cretinism from iodine-deficient regions of Iran were found to have growth retardation and neurological, auditory, and psychomotor impairments (9). Boyages et al (10) reported impaired intellectual and neuromotor development in apparently normal Chinese children, with a shift in the distribution of cognitive skills to a lower level. Furthermore, randomized controlled trial data show that postgestational supplementation can lead to significantly improved mental performance of children from areas of mild (11), moderate (12), and severe ID (13).
We compared educational outcomes of children (aged 9 years) born to women assessed as being iodine deficient (urinary iodine concentration [UIC] <150 μg/L) or sufficient (UIC ≥150 μg/L) during pregnancy. Gestation occurred during 1999–2001, a documented period of mild ID (median UIC, 77.5 μg/L) in the Tasmanian population (14), with the children subsequently growing up in an environment considered to be replete (14, 15) (median UIC, 108.0 μg/L) after introduction of voluntary iodine fortification (16). We investigate whether mild gestational ID has long-term effects on educational outcomes.

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15) http://www.thyroidmanager.org/question/repeated-miscarriages-in-a-young-woman-with-hashimoto%E2%80%99s-thyroiditis-and-antibodies/
Repeated Miscarriages in a Young Woman with Hashimoto’s Thyroiditis and Antibodies  Last Updated: March 5, 2008 ·   Leslie J. DeGroot, M.D.

Question

This is a 32 yr old female who first saw me 3/7/7 when she was 8 weeks IUP, G4M3. First pregnacy was 5yrs ago FTND. Subsequent 3 miscarriages at 6-8wks IUP. Hypothyroidism diagnosed 3yrs ago, not treated for reasons unclear. 6/06 she was started on LT4 50 mcg, gradually increased to 100mcg by 2/07. When I saw her 3/7/7 – TSH was 6.9 (1st trim N- 0.3-4.5), FT4-1.3, TPO> 1000, TGAb>3000, TSI – 132 (N<125), TBII -30%(n<16%). I increased her LT4 to 112mcg, but she went on to have a miscarriage 5/07 at 12 weeks IUP. Her TSH on f/u post miscarriage was – 0.03, FT41.8, T3 185, TPO> 1000, TGAb1050. I reduced her LT4 back to 100mcg/day.

She also had a tennis ball sized fibroid which was subsequently removed. She has also had extensive testing by her reproductive endo, for etiology for her miscarriages, all which seem negative.

She wants to conceive again.

Since 11/07 her TFT have been normal on LT4 88mcg/day. 2/07 – TSH- 2.87, FT4 1.4, T3-122, TPO>1000, TGAb> 3000.

She weighs 123lbs, and was hyperthyroid on 100mcg LT4.So, I have not changed her current dose.

Is she a candidate for IVIG? Is there anything else I can do from endo standpoint to reduce her risk for miscarriage? What would you advice her?

Radha Reddy, MD
Rancho Cucamonga CA
Response

I am not too familiar with the medical phraseology used in the U.S. when presenting case histories, but I think I understood correctly that this patient has been pregnant 4 times, with three previous miscarriages, and a fourth – and last miscarriage – during her most recent pregnancy in 2007. Obviously, she also has chronic autoimmune thyroiditis, with hypothyroidism diagnosed a couple of years ago. It is not clear to me whether the 3 previous miscarriages took place while she was an untreated hypothyroid patient or whether the obstetrical history occurred before that period (where, by the way, she may also have already been hypothyroid, without a diagnosis). In her most recent pregnancy, the patient received L-thyroxine ‘almost’ from the onset of gestation. However, and despite increasing her l-T4 dosage, the “best” TSH obtained was still clearly suboptimal in the first trimester (6.9 mU/L). After that, she miscarried once again. Finally, the antibody data indicate high titers of anti-Tg (>1000-3000) and anti-TPO (>1000) Abs and a positive TBII value (30% TSH binding inhibition).

Comments:

1) This is the sad – but not unusual – story of those patients who miscarry early (in the first trimester) and repeatedly, who have autoimmune thyroiditis and a not well-controlled thyroid function. Most studies on recurrent abortion in such ‘thyroid’ cases indicate that the best that can be done to help them is to make sure that their thyroid function is perfectly equilibrated before they become pregnant (serum TSH below 2.5 mU/L is probably the best target). In my own practice, I tend to titrate them even ‘higher’, to obtain a serum TSH around 1 mU/L. As soon as they become pregnant (spontaneously or medically-assisted), their thyroid function tests need to be monitored extremely closely to make sure that thyroid function remains entirely normal. This can only be achieved by sequential monitoring (every three-four weeks) of serum free T4 and TSH, with rapid (or even anticipated, as I like to do) increments in L-T4 dosage, and a close follow up until 24 weeks gestation, at least.

2) If this Hashimoto patient also has TSH-receptor antibodies (again from my understanding of the data presented), she may well be one of those rare cases with blocking-type TSHR-Abs. In principle, this should not affect the mother other than enhancing the risk of hypothyroidism, but could constitute a risk for fetal thyroid function during the second half of pregnancy (if she ever gets to that point !).

3) She may well be a candidate for IVIG (in addition to L-T4?). This decision is usually taken by our Ob-Gyn colleagues. The rate of pregnancy success with IVIG in the study by E. Vaquero (Amer J Reproductive Immunology in 2000) was improved (54.5%) but less than with l-T4 administration (81.2%). However, that study was not randomized nor controlled and the number of cases in each branch was small (see my Editorial with this article on pages 202-203).

4) I have followed personally a small number of women with the similar difficult medical conditions. Some have undergone medically-assisted procreation, some have even eventually adopted children, and despite these heavy antecedents, we have witnessed a few (but remarkable) successes since some women finally achieved natural conception and successful outcome of pregnancy (after many failed attempts) by treating adequately their Hashimoto’s disease. Thus, there is still hope since the patient is only 32 years of age, but this of course is not to say that success is obtained in all those cases !!

I hope my comments will be helpful to you.

Prof Daniel Glinoer
University of Brussels

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16) https://www.holtorfmed.com/thyroid-miscarriage/
Subclinical Hypothyroidism and Thyroid Antibodies Increase Risk of Early Miscarriage  .  by Holtorf Medical Group

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17) http://www.stopthethyroidmadness.com/2012/11/28/hypothyroidism-pregnancy-dangerous/
Ladies: Hypothyroidism in pregnancy can be dangerous, says this woman who suffered a miscarriage
November 28, 2012  By Janie Bowthorpe

18) Endocrine Society (2012, June 23). Mild thyroid dysfunction in early pregnancy linked to serious complication. Newswise. Retrieved July 3, 2012 from http://www.newswise.com/articles/mild-thyroid-dysfunction-in-early-pregnancy-linked-to-serious-complications

19) Allan, W.C., J.E. Haddow, G.E. Palomaki, J.R. Williams, M.L. Mitchell, R.J. Hermos, J.D. Faix, R.Z. Klein. Maternal thyroid deficiency and pregnancy complications: implications for population screening. J Med Screen 2000; 7:127-130. Retrieved from http://171.66.127.126/content/7/3/127.full.pdf

20) Rao VR, Lakshmi A, Sadhnani MD. Prevalence of hypothyroidism in recurrent pregnancy loss in first trimester. Indian J Med Sci 2008;62:357-61. Retrieved from http://www.indianjmedsci.org/text.asp?2008/62/9/357/43122

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21) http://drclark.typepad.com/dr_david_clark/2011/11/thyroid-antibodies-and-risk-of-miscarriage-premature-birth.html
Thyroid Antibodies and Risk of Miscarriage, Premature Birth
TriangleThyroidDoctor.com
Dr. David Clark, DC -Center for Low Thyroid Solutions Durham, NC- explains a hidden cause of why many women suffer miscarriages and premature births.

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