Mini CAT – Summer 2018

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Clinical Scenario:

A G3P2002 woman who is currently 10 weeks pregnant has been recently diagnosed with hypothyroidism and was prescribed levothyroxine (synthroid) by her PMD.  Patient wants to know if there are adverse effects of the thyroid medication on her developing fetus.

 

Clinical Question:

In pregnant women diagnosed with subclinical hypothyroidism do the harms outweighs the benefits of managing hypothyroidism with levothyroxine?

 

PICO Question:

Identify the PICO elements – this should be a revision of whichever PICO you have already begun in a previous week

PICO search terms

 

P I C O
Subclinical hypothyroidism Levothyroxine placebo Adverse fetal outcome
pregnancy Synthroid No treatment Low IQ
  Thyroid hormone   Low birth weight
  Thyroxine   Preterm labor
      Fetal death
      Placental abruption
       
       
       

 

 

Search Strategy:

Outline the terms used, databases or other tools used, how many articles returned, and how you selected the final articles to base your CAT on.  This will likewise be a revision and refinement of what you have already done.

Search tools and strategy used:

Outline the terms used, databases or other tools used, how many articles returned, and how you selected the final articles to base your CAT on.  This will likewise be a revision and refinement of what you have already done.

Pubmed:

Search terms “subclinical hypothyroidism pregnancy fetal à search returned 158 results
Filters applied: Reviewsà 55 results
Filters applied: < 5 years à 23 results

 

Cochrane:

Search terms “subclinical hypothyroidism pregnancy fetal à search returned 965 results
Filters applied: Health Topics: Endocrine & Metabolic à 45 results
Filters applied: Type: Cochrane Evidence à 45 results

 

Trip Database:

Search terms “subclinical hypothyroidism pregnancy fetalà search returned 152 results
Filters applied: Systematic Review
à 6 results

 

 

Articles Chosen:

(3-5) for Inclusion (please copy and paste the abstract with link):

Please pay attention to whether the articles actually address your question and whether they are the highest level of evidence available.  If you cannot find high quality articles, be prepared to explain the extensiveness of your search and why there aren’t any better sources available.

 

Article 1

Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy.  Casey BM, Thom EA, Peaceman AM, Varner MW, Sorokin Y, Hirtz DG, Reddy UM, Wapner RJ, Thorp JM Jr, Saade G, Tita AT, Rouse DJ, Sibai B, Iams JD, Mercer BM, Tolosa J, Caritis SN, VanDorsten JP, Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network.  The New England Journal of Medicine. 2017 Mar 2;376(9):815-825. doi: 10.1056/NEJMoa1606205.

https://www.ncbi.nlm.nih.gov/pubmed/28249134?dopt=AbstractPlusAbstract

Background:

Subclinical thyroid disease during pregnancy may be associated with adverse outcomes, including a lower-than-normal IQ in offspring. It is unknown whether levothyroxine treatment of women who are identified as having subclinical hypothyroidism or hypothyroxinemia during pregnancy improves cognitive function in their children.

Methods:

We screened women with a singleton pregnancy before 20 weeks of gestation for subclinical hypothyroidism, defined as a thyrotropin level of 4.00 mU or more per liter and a normal free thyroxine (T4) level (0.86 to 1.90 ng per deciliter [11 to 24 pmol per liter]), and for hypothyroxinemia, defined as a normal thyrotropin level (0.08 to 3.99 mU per liter) and a low free T4 level (<0.86 ng per deciliter). In separate trials for the two conditions, women were randomly assigned to receive levothyroxine or placebo. Thyroid function was assessed monthly, and the levothyroxine dose was adjusted to attain a normal thyrotropin or free T4 level (depending on the trial), with sham adjustments for placebo. Children underwent annual developmental and behavioral testing for 5 years. The primary outcome was the IQ score at 5 years of age (or at 3 years of age if the 5-year examination was missing) or death at an age of less than 3 years.

Results:

A total of 677 women with subclinical hypothyroidism underwent randomization at a mean of 16.7 weeks of gestation, and 526 with hypothyroxinemia at a mean of 17.8 weeks of gestation. In the subclinical hypothyroidism trial, the median IQ score of the children was 97 (95% confidence interval [CI], 94 to 99) in the levothyroxine group and 94 (95% CI, 92 to 96) in the placebo group (P=0.71). In the hypothyroxinemia trial, the median IQ score was 94 (95% CI, 91 to 95) in the levothyroxine group and 91 (95% CI, 89 to 93) in the placebo group (P=0.30). In each trial, IQ scores were missing for 4% of the children. There were no significant between-group differences in either trial in any other neurocognitive or pregnancy outcomes or in the incidence of adverse events, which was low in both groups.

Conclusions:

Treatment for subclinical hypothyroidism or hypothyroxinemia beginning between 8 and 20 weeks of gestation did not result in significantly better cognitive outcomes in children through 5 years of age than no treatment for those conditions. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00388297.).

 

Article 2

Screening and subsequent management for thyroid dysfunction pre-pregnancy and during pregnancy for improving maternal and infant health.  Spencer L, Bubner T, Bain E, Middleton P.  The Cochrane Database of Systematic Reviews. 2015 Sep 21;(9):CD011263. doi: 10.1002/14651858.CD011263.pub2.

https://www.ncbi.nlm.nih.gov/pubmed/26387772

Abstract

Background:

Thyroid dysfunction pre-pregnancy and during pregnancy (both hyper- and hypothyroidism) is associated with increased risk of adverse outcomes for mothers and infants in the short- and long-term. Managing the thyroid dysfunction (e.g. thyroxine for hypothyroidism, or antithyroid medication for hyperthyroidism) may improve outcomes. The best method of screening to identify and subsequently manage thyroid dysfunction pre-pregnancy and during pregnancy is unknown.

Objectives:

To assess the effects of different screening methods (and subsequent management) for thyroid dysfunction pre-pregnancy and during pregnancy on maternal and infant outcomes.

Search Methods:

We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (14 July 2015) and reference lists of retrieved studies.

Selection Criteria:

Randomised or quasi-randomised controlled trials, comparing any screening method (e.g. tool, program, guideline/protocol) for detecting thyroid dysfunction (including hypothyroidism, hyperthyroidism, and/or thyroid autoimmunity) pre-pregnancy or during pregnancy with no screening, or alternative screening methods.

Data Collection and Analysis:

Two review authors independently assessed eligibility of studies, extracted and checked data accuracy, and assessed the risk of bias of included studies.

Main Results:

We included two randomised controlled trials (involving 26,408 women) – these trials were considered to be at low risk of bias. Universal screening (screening all women) versus case finding (screening only those at perceived increased risk) in pregnancy for thyroid dysfunction.  One trial (4562 women) compared universal screening with case finding for thyroid dysfunction. Before 11 weeks’ gestation, women in the universal screening group, and ‘high-risk’ women in the case finding group had their sera tested for TSH (thyroid stimulating hormone), fT4 (free thyroxine) and TPO-Ab (thyroid peroxidase antibody); women with hypothyroidism (TSH > 2.5 mIU/litre) received levothyroxine; women with hyperthyroidism (undetectable TSH and elevated fT4) received antithyroid medication.  In regards to this review’s primary outcomes, compared with the case finding group, more women in the universal screening group were diagnosed with hypothyroidism (risk ratio (RR) 3.15, 95% confidence interval (CI) 1.91 to 5.20; 4562 women; GRADE: high quality evidence), with a trend towards more women being diagnosed with hyperthyroidism (RR 4.50, 95% CI 0.97 to 20.82; 4562 women; P = 0.05; GRADE: moderate quality evidence). No clear differences were seen in the risks of pre-eclampsia (RR 0.87, 95% CI 0.64 to 1.18; 4516 women; GRADE: moderate quality evidence), or preterm birth (RR 0.99, 95% CI 0.80 to 1.24; 4516 women; GRADE: high quality evidence) between groups. This trial did not report on neurosensory disability for the infant as a child.  Considering this review’s secondary outcomes, more women in the universal screening group received pharmacological treatment for thyroid dysfunction (RR 3.15, 95% CI 1.91 to 5.20; 4562 women). No clear differences between groups were observed for miscarriage (RR 0.90, 95% CI 0.68 to 1.19; 4516 women; GRADE: moderate quality evidence), fetal and neonatal death (RR 0.92, 95% CI 0.42 to 2.02; 4516 infants; GRADE: moderate quality evidence), or other secondary outcomes: pregnancy-induced hypertension, gestational diabetes, congestive heart failure, thyroid storm, mode of birth (caesarean section), preterm labour, placental abruption, respiratory distress syndrome, low birthweight, neonatal intensive care unit admission, or other congenital malformations. The trial did not report on a number of outcomes including adverse effects associated with the intervention. Universal screening versus no screening in pregnancy for hypothyroidism.  One trial (21,846 women) compared universal screening with no screening for hypothyroidism. Before 15 + 6 weeks’ gestation, women in the universal screening group had their sera tested; women who screened ‘positive’ (TSH > 97.5th percentile, fT4 < 2.5th percentile, or both) received levothyroxine.  Considering primary review outcomes, compared with the no screening group, more women in the universal screening screened ‘positive’ for hypothyroidism (RR 998.18, 95% CI 62.36 to 15,978.48; 21,839 women; GRADE: high quality evidence). No data were provided for the outcome pre-eclampsia, and for preterm birth, the trial reported rates of 5.6% and 7.9% for the screening and no screening groups respectively (it was unclear if these percentages related to the entire cohort or women who screened positive). No clear difference was seen for neurosensory disability for the infant as a child (three-year follow-up IQ score < 85) (RR 0.85, 95% CI 0.60 to 1.22; 794 infants; GRADE: moderate quality evidence).More women in the universal screening group received pharmacological treatment for thyroid dysfunction (RR 1102.90, 95% CI 69.07 to 17,610.46; 1050 women); 10% had their dose lowered because of low TSH, high fT4 or minor side effects. No clear differences were observed for other secondary outcomes, including developmental delay/intellectual impairment at three years. Most of our secondary outcomes, including miscarriage, fetal or neonatal death were not reported.

Authors’ Conclusions:

Based on the existing evidence, though universal screening for thyroid dysfunction in pregnancy increases the number of women diagnosed with hypothyroidism who can be subsequently treated, it does not clearly impact (benefit or harm) maternal and infant outcomes.  While universal screening versus case finding for thyroid dysfunction increased diagnosis and subsequent treatment, we found no clear differences for the primary outcomes: pre-eclampsia or preterm birth. No clear differences were seen for secondary outcomes, including miscarriage and fetal or neonatal death; data were lacking for the primary outcome: neurosensory disability for the infant as a child, and for many secondary outcomes. Though universal screening versus no screening for hypothyroidism similarly increased diagnosis and subsequent treatment, no clear difference was seen for the primary outcome: neurosensory disability for the infant as a child (IQ < 85 at three years); data were lacking for the other primary outcomes: pre-eclampsia and preterm birth, and for the majority of secondary outcomes.  For outcomes assessed using the GRADE approach the evidence was considered to be moderate or high quality, with any downgrading of the evidence based on the presence of wide confidence intervals crossing the line of no effect.  More evidence is needed to assess the benefits or harms of different screening methods for thyroid dysfunction in pregnancy, on maternal, infant and child health outcomes. Future trials should assess impacts on use of health services and costs, and be adequately powered to evaluate the effects on short- and long-term outcomes.

 

Article 3

Interventions for clinical and subclinical hypothyroidism pre-pregnancy and during pregnancy.  Reid SM, Middleton P, Cossich MC, Crowther CA, Bain E. The Cochrane Database of Systematic Reviews. 2013 May 31;(5):CD007752. doi: 10.1002/14651858.CD007752.pub3.

https://www.ncbi.nlm.nih.gov/pubmed/23728666

Abstract

Background:

Over the last decade there has been enhanced awareness of the appreciable morbidity of thyroid dysfunction, particularly thyroid deficiency. Since treating clinical and subclinical hypothyroidism may reduce adverse obstetric outcomes, it is crucial to identify which interventions are safe and effective.

Objectives:

To identify interventions used in the management of hypothyroidism and subclinical hypothyroidism pre-pregnancy or during pregnancy and to ascertain the impact of these interventions on important maternal, fetal, neonatal and childhood outcomes.

Search Methods:

We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (31 March 2013).

Selection Criteria:

Randomised controlled trials (RCTs) and quasi-randomised controlled trials that compared a pharmacological intervention for hypothyroidism and subclinical hypothyroidism pre-pregnancy or during pregnancy with another intervention or placebo.

Data Collection and Analysis:

Two review authors assessed trial eligibility and quality and extracted the data.

Main Results:

We included four RCTs of moderate risk of bias involving 362 women. In one trial of 115 women, levothyroxine therapy to treat pregnant euthyroid (normal thyroid function) women with thyroid peroxidase antibodies was not shown to reduce pre-eclampsia significantly (risk ratio (RR) 0.61; 95% confidence interval (CI) 0.11 to 3.48) but did significantly reduce preterm birth by 72% (RR 0.28; 95% CI 0.10 to 0.80). Two trials of 30 and 48 hypothyroid women respectively compared levothyroxine doses, but both trials reported only biochemical outcomes. A trial of 169 women compared the trace element selenomethionine (selenium) with placebo and no significant differences were seen for either pre-eclampsia (RR 1.44; 95% CI 0.25 to 8.38) or preterm birth (RR 0.96; 95% CI 0.20 to 4.61). None of the four trials reported on childhood neurodevelopmental delay.  There was a non-significant trend towards fewer miscarriages with levothyroxine, and selenium showed some favourable impact on postpartum thyroid function and a decreased incidence of moderate to advanced postpartum thyroiditis.

Authors’ Conclusions:

This review found no difference between levothyroxine therapy and a control for treating pregnant euthyroid women with thyroid peroxidase antibodies for the outcome of pre-eclampsia, however a reduction in preterm birth and a trend towards reduced miscarriage with levothyroxine was shown. This review also showed no difference for pre-eclampsia or preterm birth when selenium was compared with placebo, however a promising reduction in postpartum thyroiditis was shown. Childhood neurodevelopmental delay was not assessed by any trial included in the review.  Given that this review is based on four trials of moderate risk of bias, with only two trials contributing data (n = 284), there is insufficient evidence to recommend the use of one intervention for clinical or subclinical hypothyroidism pre-pregnancy or during pregnancy over another, for improving maternal, fetal, neonatal and childhood outcomes.

 

Article 4

Subclinical Hypothyroidism in Pregnancy: A Systematic Review and Meta-Analysis.  Maraka S, Ospina NM, O’Keeffe DT, Espinosa De Ycaza AE, Gionfriddo MR, Erwin PJ, Coddington CC 3rd, Stan MN, Murad MH, Montori VMThyroid: The Official Journal of the American Thyroid Association. 2016 Apr;26(4):580-90. doi: 10.1089/thy.2015.0418. Epub 2016 Mar 3.

https://www.ncbi.nlm.nih.gov/pubmed/26837268

Abstract

Context: The impact of subclinical hypothyroidism (SCH) and of levothyroxine replacement in pregnant women with SCH is unclear.

Objective: To assess (a) the impact of SCH during pregnancy on maternal and neonatal outcomes and (b) the effect of levothyroxine replacement therapy in these patients.

Data Sources: Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, the Cochrane Controlled Trials Register, Ovid EMBASE, Web of Science, and Scopus were searched from inception to January 2015.

Study selection: Randomized trials and cohort studies of pregnant women with SCH that examined adverse pregnancy and neonatal outcomes were included.

Data extraction: Reviewers extracted data and assessed methodological quality in duplicate.

Data synthesis: Eighteen cohort studies at low-to-moderate risk of bias were included. Compared to euthyroid pregnant women, pregnant women with SCH were at higher risk for pregnancy loss (RR 2.01, CI 1.66 to 2.44), placental abruption (RR 2.14, CI 1.23 to 3.70), premature rupture of membranes (RR 1.43, CI 1.04 to 1.95), and neonatal death (RR 2.58, CI 1.41 to 4.73). One study at high risk of bias compared pregnant women with SCH who received levothyroxine to those who did not and found no significant decrease in the rate of pregnancy loss, preterm delivery, gestational hypertension, low birth weight, or low Apgar score.

Conclusions: SCH during pregnancy is associated with multiple adverse maternal and neonatal outcomes. The value of levothyroxine therapy in preventing these adverse outcomes remains uncertain.

 

 

 

Summary of the Evidence:

Author   (Date) Level   of Evidence Sample/Setting

(#   of subjects/ studies, cohort definition etc. )

Outcome(s)   studied Key   Findings Limitations   and Biases
Casey    et. al. (2017)

Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in   Pregnancy

Randomized   Control Trial   Pregnant   women < 20 weeks gestation with TSH thyrotropin level > 4.00 mU/L and a normal T4   level and  hypothyroxinemia with a   normal thyrotropin level  and a low   free T4

1203 women   were randomized to receive either levothyroxine or placebo.  Dosage were adjusted based on monthly   checks of TSH. 

-Children had   annual developmental and behavior testing for 5 years

Primary   outcome: IQ score at 5 years of age -children   born to women with subclinical hypothyroidism who   received levothyroxine had a median IQ score 97 and 94 in the placebo group.

-children born to women with hypothyroxinemia who   received levothyroxine had a median IQ score of 94 and 91 in the placebo   group. 

-small   study

-study   was conducted on children for only 5 years after birth

Spencer L et. al. (2015)

Screening and subsequent management for thyroid dysfunction pre-pregnancy   and during pregnancy for improving maternal and infant health 

Systematic   Review 2   RCTs selected with 26,408 participants and their babies were studied Primary outcomes:

Maternal

-thyroid dysfunction

-Pre-eclampsia

Infant

-preterm birth

Infant as child

-neurological   disorder

Secondary outcomes:

Maternal

-Clinical   improvement

-pharmacologic   treatment

-Miscarriage

-Pregnancy-induced   hypertension

-Gestational   diabetes

-HbA1 level

-Anemia

-Congestive   heart failure

-Thyroid storm

-Mode of birth

-Induction of   labor

-Preterm labor

-Placental   abruption

-Postpartum hemorrhage

-universal   screening leads to more diagnosis and treatment but no clear benefit of   maternal or fetal harms with treatment of levothyroxine

-no   clear differences of pre-eclampsia

-no   clear differences of pre-term birth

No clear differences   were observed for secondary outcomes (miscarriage and fetal or neonatal   death)

-low risk of bias

-no data on primary outcomes of   pre-eclampsia  and preterm birth

-no data on neurosensory   disabilities such as cerebral palsy, blindness, deafness, developmental   delay/intellectual impairment

-no data on adverse effects   associated with the intervention

-no data available on the   incidence of miscarriages

 

Reid SM et. al   (2013)

Interventions for clinical and subclinical hypothyroidism   pre-pregnancy and during pregnancy

Systematic Review 4 RCTs selected with a total of   362 participants Primary outcomes:

-pre-eclampsia

-Preterm birth

-Neuro-developmental delay as a   child

Secondary Outcomes:

-Placental abruption

-miscarriage

-Preterm labor

-Postpartum hemorrhage

-Small gestational age neonate

-reduced IQ

-Developmental delays

 

-levothyroxine was not shown to reduce pre-eclampsia   significantly (risk ratio (RR) 0.61; 95% confidence interval (CI) 0.11 to   3.48)

-Levothyroxine significantly reduced preterm birth by   72% (RR 0.28; 95% CI 0.10 to 0.80)

-reduced risk of miscarriage with levothyroxine   compared with no treatment (P = 0.07)

– No significant difference in the rate of gestational   hypertension between levothyroxine and no treatment groups (RR 0.65; 95% CI   0.22 to 1.92)

-No significant difference in the rate of placental   abruption between levothyroxine and no treatment groups (RR 0.30; 95% CI 0.01   to 7.29)

-small study

-Data from only 2 of RCTs were   used in systematic review

Childhood   neurodevelopmental delay was not assessed

-no data on miscarriages

-possible selection bias in primary trial

-3 RCTS selected for inclusion conducted in Italy   (moderate iodine deficiency and no compulsory law to supplement)

Maraka S et. al.   (2016)

Subclinical Hypothyroidism in Pregnancy: A Systematic Review and   Meta-Analysis

Systematic   Review and Meta-Analysis 18   studies at low-to-moderate risk of bias including 3995 pregnant women with   SCH Primary   outcome: pregnancy loss (miscarriage, intrauterine death, fetal loss).

Other   outcomes: preterm, preterm delivery, gestational hypertension, preeclampsia,   eclampsia,  gestational diabetes,   placental abruption, placenta previa, premature rupture of membranes,   caesarean delivery, intrauterine growth restriction (IUGR), low birth weight   (≤ 2500 gr), low Apgar score (≤ 7 at 5 min), small for gestational age, and   neonatal death

-pregnant   women with SCH were at higher risk for pregnancy loss, placental abruption,   PROM, and neonatal death compared to euthyroid pregnant women

-Levothyroxine   treatment had no effect on the mean offspring IQ at 3 years or the proportion   of children with IQ below 85

-no   association found for gestational diabetes, preterm labor, preterm delivery,   gestational hypertension, preeclampsia, placenta previa, caesarean delivery,   IUGR, low birth weight, low Apgar score, and small for gestational age

–   Incomplete searching and arbitrary study selection represent potential   limitations of systematic reviews

-selection   bias from primary study

-reporting   bias from RCTs

-no   data on eclampsia

-lack   of blinding when assessing the outcomes

-lack   of adjustment for confounders

-lack   of randomization and blinding when assessing the effect of levothyroxine   therapy in pregnant women with SCH

-paucity   of evidence regarding the effect of levothyroxine replacement therapy in   pregnant women with SCH

 

Conclusion(s):

Article 1: This article concluded that there is no statistically significant difference between the IQ levels of children born to women with subclinical hypothyroidism or hypothyroxinemia treated with levothyroxine or placebo.  This is an RCT which provides good quality evidence and this evidence is weighed higher as it is published by the New England Journal of Medicine which is a reputable source.  This evidence can be used as guidance in clinical practice especially for women who do not want to undergo pharmacologic treatment of subclinical hypothyroidism while they are pregnant.  

 

Article 2:  This article provides high quality evidence as it is published by the Cochrane Database of Systematic Reviews which is a reputable source.  The study showed that with the universal screening of thyroid dysfunction more women are diagnosed with hypothyroidism and treated.  However, there is no difference in maternal or fetal outcomes in women treated for hypothyroidism.  Also there needs to be more studies that assess the benefits and harms of different screening methods for thyroid dysfunction in pregnancy and the maternal and fetal outcomes. 

 

Article 3: This article provides high quality evidence as it is published by the Cochrane Database of Systematic Reviews which is a reputable source.  The study showed that there is a lower rate of preterm birth in the levothyroxine group as compared with the no treatment group.  In the levothyroxine group there was a preterm birth rate of 7.2% compared with a preterm rate of 26% in the untreated group (risk difference (RD) -0.19; 95% CI -0.33 to -0.05).  This study showed that there was no significant difference in the rates of gestational hypertension or placental abruption between levothyroxine and the no treatment group.  This article concluded that there is insufficient efficient based on the small sample size to recommend one treatment over another for clinical or subclinical hypothyroidism.  Even though this review is from the reputable Cochrane Database I would weigh this evidence lightly due to the small size of the study and the inconclusive conclusion on whether levothyroxine should be used in pregnancy to treat subclinical hypothyroidism. 

 

Article 4: This study was published in Thyroid: The Official Journal of the American Thyroid Association and it is a systematic review and meta-analysis which provides high quality evidence.  This review assessed the adverse outcomes in pregnant women diagnosed with subclinical hypothyroidism.  Subclinical hypothyroidism in pregnancy is associated with many adverse maternal and fetal outcomes such as pregnancy loss, placental abruption, PROM, and neonatal death.  The meta-analysis shows that pregnant women with SCH had a higher risk of pregnancy loss (RR 2.01, CI 1.66 to 2.44; I2= 0%), placental abruption (RR 2.14, CI 1.23 to 3.70; I2= 0%), PROM (RR 1.43, CI 1.04 to 1.95; I2= 9%), and neonatal death (RR 2.58, CI 1.41 to 4.73; I2= 0%). There is inconclusive evidence in support of levothyroxine in the treatment of SCH, the study also suggest that the dosage of levothyroxine should be adjusted according to the gestational period and laboratory findings.  I would weigh this evidence moderately, as it was a smaller study and there is no definitive conclusion for the use of levothyroxine in treating SCH in pregnancy.  

 

Clinical Bottom Line:

The clinical bottom line is that there is no robust conclusive evidence on the harms versus benefits of levothyroxine therapy for SCH during pregnancy.  Based on the current evidence in the meta-analysis, systematic reviews and RCTS on levothyroxine it seems to be a safe pharmacologic therapy and is the “go to” drug for the management of hypothyroidism.  I would recommend treating SCH with levothyroxine as it reduces the risk of adverse fetal outcomes and to date there are no evidence based studies of adverse effects of levothyroxine.  It is more beneficial to treat subclinical hypothyroidism in pregnancy because of its effects on maternal bradycardia which can have adverse effect on the developing fetus.  The fetus does not produce thyroid hormones until the 12-13 weeks of gestation, so it is important that maternal thyroid hormones are at sufficient levels in the first trimester as the fetal thyroid hormone supply comes from the maternal stores during the first trimester.  Even though there is no conclusive evidence on the harms or benefits of levothyroxine therapy, it would be important to discuss the adverse effects of untreated subclinical hypothyroidism with the patient and have the patient’s input in the decision process of whether or not to treat.   The adverse effects of untreated subclinical hypothyroidism is an increased risk of a fetus with a slightly lower IQ score, premature birth or low birth weight.  These effects are not statistically significant but should be discussed with the patient prior to treatment.