Hypothyroidism in Pregnancy: A High-Stakes Protocol for Optimal Maternal and Fetal Outcomes

Dr Neeraj Manikath , claude.ai

Abstract

Pregnancy represents a profound physiological stress test for the hypothalamic-pituitary-thyroid (HPT) axis, with maternal thyroid dysfunction carrying significant implications for both maternal health and fetal neurodevelopment. Maternal hypothyroidism, even in its subclinical form, has been consistently linked to adverse obstetric outcomes and irreversible fetal intellectual impairment. This state-of-the-art review synthesizes current evidence and provides practical, evidence-based protocols for the management of hypothyroidism across the preconception, antenatal, and postpartum continuum. We emphasize the critical importance of early intervention, appropriate dose adjustments, vigilant monitoring, and postpartum surveillance to optimize outcomes in this high-stakes clinical scenario.

Introduction

The intricate relationship between thyroid function and pregnancy has fascinated endocrinologists and obstetricians for decades. Thyroid hormones are essential for normal fetal brain development, particularly during the first trimester when the fetus is entirely dependent on maternal thyroid hormone supply. The fetal thyroid gland begins functioning only after 10-12 weeks of gestation, making the first trimester a critical window of vulnerability. Even modest maternal hypothyroidism during this period can result in irreversible neurodevelopmental deficits in offspring, with studies demonstrating IQ reductions of 7-10 points in children born to mothers with inadequately treated hypothyroidism.

The prevalence of hypothyroidism in pregnancy varies geographically, ranging from 2-3% for overt hypothyroidism to 10-15% for subclinical hypothyroidism in iodine-sufficient populations. In iodine-deficient regions, these figures can be substantially higher. Given the potentially devastating consequences of untreated maternal hypothyroidism and the relative simplicity of treatment with levothyroxine (LT4), mastering the management of this condition represents a fundamental competency for all clinicians caring for pregnant women.

Physiological Changes in Thyroid Function During Pregnancy

Understanding the normal physiological adaptations of the HPT axis during pregnancy is essential for appropriate clinical management. Multiple interconnected mechanisms drive increased thyroid hormone requirements during gestation:

Human Chorionic Gonadotropin Effect

Human chorionic gonadotropin (hCG), which shares structural homology with thyroid-stimulating hormone (TSH), exerts mild thyroid-stimulating effects, particularly during the first trimester when hCG levels peak at 10-12 weeks. This physiological phenomenon typically results in TSH suppression to the lower end of the normal range or even below it in the first trimester, with approximately 15-20% of healthy pregnant women exhibiting TSH values below 0.4 mIU/L during this period.

Increased Thyroid Hormone Binding

Estrogen-mediated increases in hepatic synthesis of thyroid-binding globulin (TBG) result in a 50% rise in TBG concentrations by approximately 20 weeks of gestation. This increased binding capacity necessitates greater thyroid hormone production to maintain adequate free hormone levels, typically increasing total T4 requirements by 30-50%.

Increased Renal Iodide Clearance

Pregnancy-related increases in glomerular filtration rate result in enhanced renal iodide clearance, effectively reducing the iodide pool available for thyroid hormone synthesis. This effect is particularly relevant in areas of marginal iodine sufficiency.

Placental Deiodinase Activity

Type 3 deiodinase (D3) expression in the placenta increases dramatically during pregnancy, catalyzing the conversion of T4 to reverse T3 (rT3) and T3 to T2, thereby increasing maternal thyroid hormone degradation and requirements.

Transplacental Thyroid Hormone Transfer

Throughout pregnancy, but particularly during the first trimester, maternal thyroid hormones cross the placenta to support fetal development. Even at term, approximately 30-50% of fetal thyroid hormone content is of maternal origin.

Pearl: The TSH reference range shifts during pregnancy. First-trimester TSH upper limit should be approximately 2.5 mIU/L, second trimester 3.0 mIU/L, and third trimester 3.5 mIU/L. Using standard non-pregnant reference ranges will miss cases of gestational hypothyroidism.

Clinical Consequences of Maternal Hypothyroidism

Fetal and Neonatal Outcomes

The fetal consequences of maternal hypothyroidism represent the most compelling rationale for aggressive treatment. Multiple large-scale prospective studies have documented the neurodevelopmental implications:

Neurodevelopmental Impairment: The landmark study by Haddow and colleagues demonstrated that children born to mothers with untreated hypothyroidism (TSH >99th percentile) during pregnancy had mean IQ scores 7 points lower than controls, with 19% scoring two or more standard deviations below the mean compared to 5% of controls. Subsequent meta-analyses have confirmed these findings, establishing a dose-response relationship between maternal TSH elevation and offspring cognitive impairment.

Timing Criticality: The first trimester represents the most vulnerable period for fetal brain development. Thyroid hormones regulate neuronal migration, dendritic and axonal outgrowth, synaptogenesis, and myelination. Even transient first-trimester hypothyroidism may result in permanent structural brain alterations detectable on neuroimaging.

Additional Fetal Risks: Beyond neurodevelopmental effects, maternal hypothyroidism increases risks of low birth weight, prematurity, congenital anomalies, and fetal/neonatal death. The severity of these risks correlates with the degree and duration of thyroid hormone insufficiency.

Maternal Outcomes

Inadequately treated maternal hypothyroidism increases risks of:

Pregnancy-induced hypertension and preeclampsia (risk increased 2-3 fold)
Gestational diabetes
Placental abruption (risk increased 2-fold)
Postpartum hemorrhage
Spontaneous miscarriage (risk increased 2-4 fold)
Anemia

Oyster: Subclinical hypothyroidism (elevated TSH with normal free T4) carries similar risks to overt hypothyroidism when TSH exceeds 4-5 mIU/L. The traditional distinction between "subclinical" and "overt" becomes less meaningful in pregnancy, where even modest TSH elevation warrants treatment.

Pre-Conception Management: Setting the Stage for Success

Pre-conception counseling and optimization represent the ideal starting point for hypothyroid women planning pregnancy. This phase allows clinicians to achieve optimal thyroid function before the critical first trimester, when many women may not yet recognize they are pregnant.

Target TSH Level

The 2017 American Thyroid Association (ATA) guidelines recommend a pre-conception TSH target of less than 2.5 mIU/L for women with hypothyroidism planning pregnancy. This recommendation is based on several considerations:

The predictable 30-50% increase in LT4 requirements during pregnancy
The critical importance of adequate thyroid hormone during early embryogenesis
Evidence suggesting improved pregnancy outcomes with pre-conception TSH optimization
The pregnancy-specific TSH reference range, with first-trimester upper limit of 2.5 mIU/L

Dose Optimization Strategy

For women with baseline TSH above 2.5 mIU/L, systematic dose escalation is required. The typical approach involves:

Increasing LT4 dose by 12.5-25 mcg increments
Rechecking TSH after 4-6 weeks at each new dose
Continuing adjustments until TSH is consistently below 2.5 mIU/L
Ensuring stable dosing for at least 2-3 months before conception attempt

Counseling Content

Pre-conception counseling should address:

The critical importance of early pregnancy notification to the healthcare team
The need for immediate dose adjustment upon pregnancy confirmation
The requirement for frequent monitoring during pregnancy
Expected postpartum dose adjustments
Medication compliance importance
Proper LT4 administration (30-60 minutes before food, separated from supplements)

Hack: For women planning pregnancy within 6-12 months, consider empirically increasing LT4 dose by one additional tablet weekly (approximately 15% increase) even if current TSH is between 2.5-4.0 mIU/L. This creates a "buffer" against the predictable pregnancy-related increase in thyroid hormone requirements and may prevent first-trimester hypothyroidism.

First Trimester Management: The Critical Window

Immediate Dose Adjustment Protocol

Upon confirmation of pregnancy, immediate LT4 dose escalation is imperative. The traditional "wait and monitor" approach is obsolete given our understanding of first-trimester fetal thyroid hormone dependence.

The Two-Tablet Weekly Rule: The most practical and widely applicable approach involves instructing patients to take two additional tablets per week beyond their current regimen. For example, a patient taking 100 mcg daily would take 100 mcg daily plus two additional 100 mcg tablets per week (on Sundays and Wednesdays, for instance), resulting in a total weekly dose of 900 mcg versus the pre-pregnancy 700 mcg—approximately a 29% increase.

This method offers several advantages:

Simple patient instructions that minimize confusion
Approximately 25-30% dose increase, matching physiological requirements
Uses existing tablet strength, avoiding prescription changes
Immediately implementable without waiting for laboratory results

Alternative approaches include:

Calculating a precise 30% increase and prescribing appropriate combination dosing
Empirically increasing to the next higher dose strength daily (e.g., 100 mcg to 125 mcg)

Early Monitoring Protocol

TSH monitoring should occur approximately 4 weeks after the initial dose increase, then every 4 weeks through 16-20 weeks of gestation. This intensive monitoring reflects:

Rapid changes in thyroid hormone requirements during this period
The critical nature of adequate thyroid hormone for ongoing fetal development
Individual variability in dose requirements (ranging from 20% to 85% increases)

Pearl: Measure TSH and free T4 together during pregnancy. Isolated TSH measurement may miss cases of over-replacement (normal TSH with elevated free T4), which carries its own risks including low birth weight and maternal cardiac arrhythmias.

Management of Newly Diagnosed Hypothyroidism

For women diagnosed with hypothyroidism during pregnancy, aggressive treatment initiation is warranted:

Overt Hypothyroidism (elevated TSH, low free T4):

Initiate full replacement dose immediately: 1.6-2.0 mcg/kg/day
Do not employ gradual titration protocols used outside pregnancy
Check TSH after 2-4 weeks and adjust accordingly
Target TSH below 2.5 mIU/L in first trimester, below 3.0 mIU/L subsequently

Subclinical Hypothyroidism (elevated TSH, normal free T4): The management of subclinical hypothyroidism in pregnancy has evolved significantly. While universal screening remains controversial, most experts recommend treatment when:

TSH exceeds 4.0 mIU/L (some advocate 2.5 mIU/L threshold)
TPO antibodies are positive (present in 10-15% of pregnant women)
Prior history of miscarriage or subfertility
Symptoms suggestive of hypothyroidism

Initial dosing for subclinical hypothyroidism typically ranges from 50-75 mcg daily, with adjustments based on repeat TSH measurement after 4 weeks.

Hack: For urgent situations where same-day LT4 initiation is required but the patient cannot obtain medication immediately, intravenous levothyroxine can be administered at 70-80% of the calculated oral dose. This is particularly relevant for newly diagnosed overt hypothyroidism in early pregnancy.

Second and Third Trimester Management: Maintaining Stability

Monitoring Frequency

After achieving TSH stability (target below 3.0 mIU/L) by 16-20 weeks, monitoring frequency can decrease to once per trimester. However, maintain vigilance for:

Medication non-compliance
Introduction of interfering medications (iron, calcium, proton pump inhibitors)
Gastrointestinal disturbances affecting absorption
Intercurrent illness

Some studies suggest thyroid hormone requirements may plateau or even slightly decrease in the third trimester, possibly related to declining hCG levels and reduced fetal growth velocity. However, maintain the elevated pregnancy dose rather than attempting late-pregnancy reductions.

Managing Inadequate Response

If TSH remains elevated despite dose increases, consider:

Absorption issues: Ensure proper LT4 administration technique. Consider bedtime dosing if morning ingestion proves difficult. Separate LT4 from prenatal vitamins by at least 4 hours (iron and calcium substantially impair absorption).
Compliance assessment: Use non-judgmental inquiry about medication adherence. Simplify regimen if possible.
Inadequate dosing: Some women require 60-80% dose increases during pregnancy. Do not hesitate to escalate aggressively if TSH remains elevated.
Gastrointestinal disorders: Hyperemesis gravidarum, celiac disease, or inflammatory bowel disease may impair LT4 absorption.

Oyster: Gestational transient thyrotoxicosis (GTT) occurs in 1-3% of pregnancies, typically in the first trimester with multiple gestation or hyperemesis. It manifests with suppressed TSH and elevated free T4 but without thyroid autoantibodies, and resolves spontaneously by 14-18 weeks. Distinguish this from Graves' disease through history, physical examination (ophthalmopathy, goiter), and antibody testing. Women with hypothyroidism on LT4 replacement who develop first-trimester TSH suppression may have GTT superimposed on their baseline condition—maintain their LT4 rather than reducing dose, as this represents physiological adaptation.

Postpartum Management: Navigating the Transition

Immediate Postpartum Dose Adjustment

Following delivery, the physiological drivers of increased thyroid hormone requirements resolve rapidly. Instruct patients to return to their pre-pregnancy LT4 dose immediately after delivery. This typically represents a 25-30% dose reduction from the pregnancy dose.

The Reverse Two-Tablet Rule: For women who added two tablets weekly during pregnancy, simply discontinue those additional tablets and return to the pre-pregnancy daily regimen.

Postpartum Monitoring

Check TSH approximately 6 weeks postpartum to confirm adequate dose adjustment. This timing allows:

Physiological stabilization after delivery
Assessment before potential subsequent pregnancy
Identification of postpartum thyroiditis

Postpartum Thyroiditis: The Hidden Risk

Postpartum thyroiditis (PPT) affects approximately 5-10% of all postpartum women and up to 20-25% of women with positive TPO antibodies. The condition follows a characteristic triphasic pattern:

Phase 1: Thyrotoxic Phase (1-4 months postpartum)

Transient hyperthyroidism due to destructive thyroiditis
Presents with anxiety, palpitations, heat intolerance, weight loss
Differentiate from Graves' disease through low radioiodine uptake (contraindicated during breastfeeding, use TSH receptor antibodies instead)
Management is symptomatic (beta-blockers); avoid antithyroid drugs

Phase 2: Hypothyroid Phase (4-8 months postpartum)

Occurs in approximately 70% of women who had thyrotoxic phase
Manifests with fatigue, depression, cold intolerance, weight gain
May be misattributed to postpartum depression or "normal" postpartum fatigue
Requires LT4 treatment if TSH exceeds 10 mIU/L or if symptomatic with TSH 4-10 mIU/L

Phase 3: Recovery Phase (12-18 months postpartum)

Thyroid function normalizes in approximately 80% of women
20-30% develop permanent hypothyroidism requiring ongoing treatment

Pearl: Women with postpartum thyroiditis have a 70% recurrence risk in subsequent pregnancies and 20-50% risk of developing permanent hypothyroidism within 5-10 years. Recommend annual TSH screening for these women.

For women with pre-existing hypothyroidism, distinguishing true PPT from simple over-replacement after dose reduction can be challenging. Clues favoring PPT include:

Symptoms of thyrotoxicosis rather than simple biochemical changes
TSH suppression below 0.1 mIU/L with elevated free T4
Positive TPO antibodies (if not previously documented)
Subsequent development of hypothyroid phase

Breastfeeding Considerations

LT4 therapy is completely compatible with breastfeeding. Only minute amounts of thyroid hormone are secreted in breast milk, insufficient to affect infant thyroid function. Emphasize continuation of LT4 therapy to breastfeeding mothers, as maternal hypothyroidism may reduce milk production and maternal energy for infant care.

Hack: For breastfeeding mothers struggling with multiple medications and nighttime infant care, consider recommending once-weekly LT4 dosing schedule for several weeks postpartum. While unconventional, once-weekly dosing with 7 times the daily dose has been shown effective in ensuring compliance during this chaotic period. The long half-life of LT4 (approximately 7 days) makes this pharmacologically reasonable.

Special Scenarios and Complex Cases

Thyroid Cancer Survivors

Women with history of thyroid cancer typically require TSH suppression below normal ranges. During pregnancy, this creates a management dilemma. Current recommendations suggest:

High-risk patients: Maintain TSH suppression (target 0.1-0.5 mIU/L)
Low-risk patients in remission: Accept TSH in low-normal range (0.5-2.5 mIU/L) during pregnancy
Collaborate closely with oncology/endocrinology teams

Multiple Gestation

Twin and higher-order multiple pregnancies impose even greater demands on maternal thyroid function due to:

Higher hCG levels
Greater placental mass and D3 activity
Increased fetal thyroid hormone requirements

Consider:

More aggressive initial dose increases (35-40% rather than 25-30%)
More frequent monitoring
Anticipation of higher final dose requirements

Infertility Treatment

Women undergoing assisted reproductive technology often have thyroid function assessment as part of fertility evaluation. Optimize TSH to below 2.5 mIU/L before initiating treatment. The supraphysiological estrogen levels during ovarian hyperstimulation may transiently increase TBG and thyroid hormone requirements.

Hyperemesis Gravidarum

Severe hyperemesis may complicate oral LT4 absorption. Strategies include:

Attempting different administration times when nausea is minimized
Using liquid LT4 formulations (may be better absorbed with gastric upset)
In extreme cases, consider intravenous LT4 administration (70-80% of oral dose)
Some women find rectal LT4 administration effective, though evidence is limited

Oyster: Paradoxically, women with hyperemesis often have biochemical hyperthyroidism (low TSH, elevated free T4) due to hCG-mediated thyroid stimulation. Women with pre-existing hypothyroidism and hyperemesis may require no dose increase or even temporary dose reduction during the hyperemesis period, with resumption of full pregnancy dosing once hyperemesis resolves.

Monitoring Beyond TSH: When to Measure Additional Parameters

While TSH remains the primary monitoring parameter, certain situations warrant expanded testing:

Free T4 Measurement

Initial pregnancy assessment in women on LT4
Suspected over-replacement (symptoms with normal or low TSH)
Central hypothyroidism (rare in pregnancy)
Rapid TSH changes requiring confirmation

Thyroid Antibodies

Initial pregnancy assessment in women with hypothyroidism
Newly diagnosed subclinical hypothyroidism
History of recurrent miscarriage
Personal or family history of autoimmune disease
Suspicion for postpartum thyroiditis

Total T3 Measurement

Rarely necessary during pregnancy
May help assess adequacy of replacement in rare cases of poor T4-to-T3 conversion

Hack: If laboratory turnaround time for free T4 is prolonged in your setting, you can use a clinical heuristic: If TSH is below 0.1 mIU/L, consider dose reduction; if TSH is 0.1-0.5 mIU/L, maintain current dose; if TSH is above 2.5 mIU/L in first trimester or above 3.0 mIU/L later, increase dose by 12.5-25 mcg. This allows more timely dose adjustments while awaiting confirmatory free T4 results.

Controversies and Areas of Ongoing Research

Universal Screening Debate

Whether to perform universal thyroid function screening in early pregnancy remains contentious. Arguments favoring screening include:

High prevalence of thyroid dysfunction
Substantial consequences of untreated hypothyroidism
Availability of safe, effective treatment
Potential cost-effectiveness

Arguments against universal screening:

Lack of randomized controlled trial evidence for improved outcomes with screening-detected subclinical hypothyroidism treatment
Resource utilization concerns
Risk of overtreatment and associated anxiety

Major guidelines differ: ATA recommends aggressive case-finding rather than universal screening, while ACOG does not recommend universal screening. Practically, many institutions have adopted universal first-trimester TSH screening given its low cost and high-stakes consequences.

Subclinical Hypothyroidism Treatment Threshold

The optimal TSH threshold for initiating treatment in pregnancy remains debated, with various cutoffs proposed (2.5, 3.0, 4.0, 10.0 mIU/L). Recent randomized trials showed no benefit of LT4 treatment for subclinical hypothyroidism with TSH 4.0-10.0 mIU/L and negative antibodies regarding child IQ at age 5 years. However, these trials had limitations:

Treatment often initiated after 12-14 weeks
Target TSH may have been suboptimal
Primary outcome (child IQ) may not capture all relevant endpoints

Most experts continue to recommend treatment for TSH above 4.0 mIU/L, especially if TPO antibodies are positive or in the first trimester.

Isolated Hypothyroxinemia

Isolated hypothyroxinemia (low free T4 with normal TSH) occurs in 1-2% of pregnancies. Its clinical significance remains uncertain, with some studies suggesting associations with adverse outcomes and others showing no effect. Current guidelines do not recommend treatment, but this remains an area of active investigation.

Practical Clinical Pearls and Protocols

The Complete Management Checklist

Pre-conception:

[ ] Check TSH in all women with hypothyroidism planning pregnancy
[ ] Target TSH below 2.5 mIU/L
[ ] Ensure compliance and proper medication administration
[ ] Provide anticipatory guidance about pregnancy management

First prenatal visit:

[ ] Check TSH (and free T4) in all women on LT4 or with thyroid disease history
[ ] Immediately increase LT4 by two tablets weekly
[ ] Schedule repeat TSH in 4 weeks
[ ] Review proper medication administration

First trimester monitoring:

[ ] Check TSH every 4 weeks until 16-20 weeks
[ ] Target TSH below 2.5 mIU/L
[ ] Adjust dose by 12.5-25 mcg increments as needed

Second and third trimester:

[ ] Check TSH at least once per trimester after achieving stability
[ ] Maintain pregnancy dose throughout gestation

Postpartum:

[ ] Reduce to pre-pregnancy dose immediately after delivery
[ ] Check TSH at 6 weeks postpartum
[ ] Screen for postpartum thyroiditis symptoms
[ ] Plan long-term follow-up

Patient Education Points

Ensure patients understand:

Medication must be taken daily without interruption
Proper administration technique (30-60 minutes before food, especially coffee)
Separate from iron, calcium, and multivitamins by 4 hours
Notify healthcare team immediately upon positive pregnancy test
Do not adjust dose independently
Breastfeeding is safe and encouraged while on LT4
Postpartum dose reduction is expected and normal

Hack: Create pre-printed patient instruction sheets for each phase of management (preconception, first trimester, postpartum). This ensures consistency of messaging and reduces time spent explaining at each visit. Include your contact information for urgent questions.

Quality Improvement and Systems Approaches

Given the high stakes and time-sensitive nature of hypothyroidism management in pregnancy, consider implementing systems-level approaches:

Electronic Health Record Tools

Best-practice alerts for pregnant women on LT4 without recent TSH
Automatic dose-increase orders triggered by pregnancy diagnosis
Standardized postpartum dose-reduction protocols

Care Coordination

Establish clear communication pathways between endocrinology, obstetrics, and primary care
Define which specialist manages thyroid dose adjustments
Create protocols for urgent dose changes and monitoring

Patient Engagement

Automated reminders for medication refills and laboratory monitoring
Patient portals with educational materials
Peer support groups for women managing hypothyroidism in pregnancy

Conclusion

Hypothyroidism in pregnancy represents a uniquely high-stakes clinical scenario where the consequences of under-treatment can be devastating and irreversible, yet appropriate management is straightforward and highly effective. The key principles bear repeating:

Anticipate and prevent: Optimize thyroid function before conception whenever possible
Act immediately: Increase LT4 dose by 25-30% upon pregnancy confirmation
Monitor vigilantly: Check TSH every 4 weeks in first half of pregnancy
Target appropriately: TSH below 2.5 mIU/L in first trimester, below 3.0 mIU/L subsequently
Transition carefully: Return to pre-pregnancy dose postpartum and monitor for thyroiditis

The physiological stress test that pregnancy imposes on the maternal thyroid provides a window into the remarkable adaptability of human endocrine systems and the critical importance of thyroid hormones for neurodevelopment. As clinicians, our obligation is to ensure that every woman with hypothyroidism receives the knowledge, monitoring, and treatment necessary to optimize outcomes for herself and her child.

The protocols outlined in this review synthesize current evidence and expert consensus to provide a practical framework for management. However, medicine remains both art and science—individualize care based on patient-specific factors, maintain communication with multidisciplinary teams, and stay current with evolving evidence. The stakes are high, but with appropriate attention and systematic management, excellent outcomes are achievable for the vast majority of pregnancies complicated by hypothyroidism.

References

Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid. 2017;27(3):315-389.
Haddow JE, Palomaki GE, Allan WC, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med. 1999;341(8):549-555.
De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(8):2543-2565.
Casey BM, Thom EA, Peaceman AM, et al. Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy. N Engl J Med. 2017;376(9):815-825.
Lazarus JH, Bestwick JP, Channon S, et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med. 2012;366(6):493-501.
Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21(10):1081-1125.
Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy. J Clin Endocrinol Metab. 2010;95(9):E44-48.
Yassa L, Marqusee E, Fawcett R, Alexander EK. Thyroid hormone early adjustment in pregnancy (the THERAPY) trial. J Clin Endocrinol Metab. 2010;95(7):3234-3241.
Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev. 1997;18(3):404-433.
Korevaar TI, Muetzel R, Medici M, et al. Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study. Lancet Diabetes Endocrinol. 2016;4(1):35-43.
Mannisto T, Mendola P, Grewal J, et al. Thyroid diseases and adverse pregnancy outcomes in a contemporary US cohort. J Clin Endocrinol Metab. 2013;98(7):2725-2733.
Nicholson WK, Robinson KA, Smallridge RC, Ladenson PW, Powe NR. Prevalence of postpartum thyroid dysfunction: a quantitative review. Thyroid. 2006;16(6):573-582.
Pearce EN. Thyroid disorders during pregnancy and postpartum. Best Pract Res Clin Obstet Gynaecol. 2015;29(5):700-706.
Pop VJ, Brouwers EP, Vader HL, Vulsma T, van Baar AL, de Vijlder JJ. Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year follow-up study. Clin Endocrinol (Oxf). 2003;59(3):282-288.
Springer D, Zima T, Limanova Z. Reference intervals in evaluation of maternal thyroid function during the first trimester of pregnancy. Eur J Endocrinol. 2009;160(5):791-797.