Dataset Information

Early Levothyroxine Treatment for Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy: The St Carlos Gestational and Thyroid Protocol.

ABSTRACT: The optimal maternal levels of thyroid hormones (TH) during the first trimester of gestation have not been established, nor has the ideal moment to initiate levothyroxine treatment (LT) to improve the evolution of gestation and fetal development. Cut-off points for Thyroid-stimulating hormone (TSH) <2.5 µIU/mL and free thyroxine (FT4)>7.5 pg/mL have been recommended. There are no data on whether initiation of LT <9th Gestational Week (GW) can have a favourable impact.

Objective

To define the TSH/FT4 percentiles corresponding with 2.5 µIU/mL and 7.5 pg/mL levels, respectively, at GW8 (Study 1), and evaluate the effects of protocol-based LT before GW9 on gestation evolution, in women with TSH ≥2.5 µIU/mL and/or FT4≤ 7.5 pg/mL (study 2).

Subjects

2768 consecutive pregnant women attending the first gestational visit from 2013-2014 and 3026 from 2015-2016 were eligible for Study I and 2 respectively. A final 2043 (study 1) and 2069 (study 2) women were assessed in these studies.

Results

Study 1: The FT4 level of 7.5 pg/mL corresponds with the 17.9th percentile, a TSH level of 2.5 µIU/mL with the 75.8^th. Women with TSH ≥2.5 µIU/mL had a history of fetal losses more frequently than those <2.5 (OR 2.33 (95%CI): 1.58-3.12), as did those with FT4 ≤7.5 pg/ml compared to those >7.5 (OR 4.81; 3.25-8.89). Study 2: A total of 1259 women had optimal TSH/FT4 levels (Group 1), 672 (32.4%, Group 2) had suboptimal TSH or T4l, and 138 (6.7%, Group 3) had suboptimal values of both. 393 (58.5%) in Group 2 and 88 (63.8%) in Group 3 started LT before GW9. Mean (SD) GW24 levels were TSH: 1.96 ± 1.22 µIU/mL and FT4: 7.07 ± 1.25 pg/mL. The highest FT4 value was 12.84 pg/mL. The adjusted risk for an adverse event if LT was started early was 0.71 (0.43-0.91) for Group 2 and 0.80 (0.66-0.94) for Group 3.

Conclusions

Early LT in women with suboptimum levels of TSH/FT4 (≥2.5µIU/mL/≤7.5 pg/ml) at or before GW9 is safe and improves gestation progression. These data support the recommendation to adopt these cut-off points for LT initiation, which should be started as early as possible.

SUBMITTER: Runkle I

PROVIDER: S-EPMC8560890 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Early Levothyroxine Treatment for Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy: The St Carlos Gestational and Thyroid Protocol.

Runkle Isabelle I de Miguel María Paz MP Barabash Ana A Cuesta Martin M Diaz Ángel Á Duran Alejandra A Familiar Cristina C de la Torre Nuria García NG Herraiz Miguel Ángel MÁ Izquierdo Nuria N Diaz Ángel Á Marcuello Clara C Matia Pilar P Melero Verónica V Montañez Carmen C Moraga Inmaculada I Perez-Ferre Natalia N Perez Noelia N Assaf-Balut Carla C Rubio Miguel Ángel MÁ Ruiz-Sanchez Jorge Gabriel JG Sanabria Concepción C Torrejon María José MJ Valerio Johanna J Del Valle Laura L Calle-Pascual Alfonso A

Frontiers in endocrinology 20211019

The optimal maternal levels of thyroid hormones (TH) during the first trimester of gestation have not been established, nor has the ideal moment to initiate levothyroxine treatment (LT) to improve the evolution of gestation and fetal development. Cut-off points for Thyroid-stimulating hormone (TSH) <2.5 µIU/mL and free thyroxine (FT4)>7.5 pg/mL have been recommended. There are no data on whether initiation of LT <9th Gestational Week (GW) can have a favourable impact.<h4>Objective</h4>To define ...[more]

PMID: 34737722

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Project description:BackgroundSubclinical 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.MethodsWe 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.ResultsA 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.ConclusionsTreatment 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 .).

Project description:ImportanceIt is unclear whether levothyroxine treatment provides clinically important benefits in adults aged 80 years and older with subclinical hypothyroidism.ObjectiveTo determine the association of levothyroxine treatment for subclinical hypothyroidism with thyroid-related quality of life in adults aged 80 years and older.Design, setting, and participantsProspectively planned combined analysis of data involving community-dwelling adults aged 80 years and older with subclinical hypothyroidism. Data from a randomized clinical trial were combined with a subgroup of participants aged 80 years and older from a second clinical trial. The trials were conducted between April 2013 and May 2018. Final follow-up was May 4, 2018.ExposuresParticipants were randomly assigned to receive levothyroxine (n = 112; 52 participants from the first trial and 60 from the second trial) or placebo (n = 139; 53 participants from the first trial and 86 from the second trial).Main outcomes and measuresCo-primary outcomes were Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire scores for the domains of hypothyroid symptoms and tiredness at 1 year (range, 0-100; higher scores indicate worse quality of life; minimal clinically important difference, 9).ResultsOf 251 participants (mean age, 85 years; 118 [47%] women), 105 were included from the first clinical trial and 146 were included from the second clinical trial. A total of 212 participants (84%) completed the study. The hypothyroid symptoms score decreased from 21.7 at baseline to 19.3 at 12 months in the levothyroxine group vs from 19.8 at baseline to 17.4 at 12 months in the placebo group (adjusted between-group difference, 1.3 [95% CI, -2.7 to 5.2]; P = .53). The tiredness score increased from 25.5 at baseline to 28.2 at 12 months in the levothyroxine group vs from 25.1 at baseline to 28.7 at 12 months in the placebo group (adjusted between-group difference, -0.1 [95% CI, -4.5 to 4.3]; P = .96). At least 1 adverse event occurred in 33 participants (29.5%) in the levothyroxine group (the most common adverse event was cerebrovascular accident, which occurred in 3 participants [2.2%]) and 40 participants (28.8%) in the placebo group (the most common adverse event was pneumonia, which occurred in 4 [3.6%] participants).Conclusions and relevanceIn this prospectively planned analysis of data from 2 clinical trials involving adults aged 80 years and older with subclinical hypothyroidism, treatment with levothyroxine, compared with placebo, was not significantly associated with improvement in hypothyroid symptoms or fatigue. These findings do not support routine use of levothyroxine for treatment of subclinical hypothyroidism in adults aged 80 years and older.Trial registrationClinicalTrials.gov Identifier: NCT01660126; Netherlands Trial Register: NTR3851.

Project description:ContextAdverse maternal outcomes and perinatal complications are associated with maternal hypothyroidism. However, the utility of levothyroxine (L-T4) in the treatment of pregnant women with hypothyroxinemia is unclear.ObjectiveThis study aimed to evaluate the effects of L-T4 on maternal and perinatal outcomes in pregnant women with hypothyroxinemia.MethodsThe nonrandomized interventional study was conducted at Shanghai First Maternity and Infant Hospital, Punan Hospital of Shanghai, and Beicai Community Health Center of Shanghai. The pregnant women with hypothyroxinemia from the first trimester were enrolled and divided into treatment and control groups. 463 taking L-T4 and 501 not administering L-T4 were analyzed in the study. All participants were screened for TPOAB/TGAB antibody status.Main outcomeThe primary outcome of the study was the hypertensive disorder of pregnancy (HDP), measured as the proportion of HDP. In addition to this primary outcome, some secondary outcomes will be measured: miscarriage, gestational diabetes mellitus, premature rupture of membranes, placental abruption, intrahepatic cholestasis of pregnancy, fetal distress, macrosomia, and neonates admitted to the neonatal intensive care unit (NICU). The effects of L-T4 on the incidence of adverse pregnancy outcomes and perinatal complications were compared.ResultsMultivariate logistic regression analysis showed that L-T4 treatment (adjusted odds ratio = 1.78 [95% CI = 1.00-3.16], p = 0.04) significantly reduced the incidence of miscarriage. Otherwise, lower neonates admitted to the NICU were strongly associated with the L-T4 group (adjusted odds ratio = 1.36 [95% CI = 1.01 - 1.83], p = 0.04). There were no significant differences in the incidence rates of other adverse maternal outcomes and perinatal complications between pregnant women with hypothyroxinemia receiving and those not receiving L-T4 treatment.ConclusionThe incidence of HDP was not significantly reduced using L-T4 in pregnant women with hypothyroxinemia. The results of this study also showed that L-T4 treatment significantly reduced the miscarriages rate and the proportion of newborns admitted to the NICU.

Project description:BackgroundLevothyroxine replacement therapy may decrease the risk of adverse pregnancy outcomes among women with subclinical hypothyroidism (SCH). The aim of this study is to conduct a systematic review and meta-analysis to examine the risk of adverse pregnancy, perinatal, and early childhood outcomes among women with SCH treated with levothyroxine.MethodsA systematic literature search was conducted using Ovid-Medline, Ovid-EMBASE, Pubmed (non-Medline), Ebsco-CINAHL Plus with full text and Cochrane Library databases. Randomized controlled studies (RCTs) and observational studies examining the association between treatment of SCH during pregnancy and our outcomes of interest were included. Studies that compared levothyroxine treatment versus no treatment were eligible for inclusion. Data from included studies were extracted and quality assessment was performed by two independent reviewers.ResultsSeven RCTs and six observational studies met our inclusion criteria. A total of 7342 individuals were included in these studies. RCTs demonstrated several sources of bias, with lack of blinding of the participants or research personnel; only one study was fully blinded. In the observational studies, there was moderate to serious risk of bias due to lack of adjustment for certain confounding variables, participant selection, and selective reporting of results. Pooled analyses showed decreased risk of pregnancy loss (RR: 0.79; 95% CI: 0.67 to 0.93) and neonatal death (RR: 0.35; 95% CI: 0.17 to 0.72) associated with levothyroxine treatment during pregnancy among women with SCH. There were no associations between levothyroxine treatment and outcomes during labour and delivery, or cognitive status in children at 3 or 5 years of age.ConclusionTreatment of SCH with levothyroxine during pregnancy is associated with decreased risks of pregnancy loss and neonatal death. Given the paucity of available data and heterogeneity of included studies, additional studies are needed to address the benefits of levothyroxine use among pregnant women with SCH.

Project description:BackgroundSome clinicians used levothyroxine (LT4) treatment for mild subclinical hypothyroidism (SCH) pregnant women (2.5 < thyroid-stimulating hormone (TSH) ≤ the pregnancy-specific reference range with normal free thyroxine (FT4) level) with thyroid peroxidase antibody negative (TPOAb-), although the recent clinical guideline did not recommend it. It is unknown whether LT4 treatment for pregnant women with mild SCH and TPOAb- have impact on fetal growth. Therefore, the aim of the study was to investigate the effect of LT4 treatment on fetal growth and birth weight among mild SCH pregnant women with TPOAb-.MethodsThis was a birth cohort study including 14,609 pregnant women between 2016 and 2019 in Tongzhou Maternal and Child Health Hospital of Beijing, China. Pregnant women were divided into 3 groups as follows: Euthyroid (n = 14,285, 0.03 ≤ TSH ≤ 2.5mIU/L, normal FT4), TPOAb-; Untreated mild SCH with TPOAb- (n = 248, 2.5 < TSH ≤ 2.9mIU/L, normal FT4, without LT4 treatment); Treated mild SCH with TPOAb- (n = 76, 2.5 < TSH ≤ 2.9mIU/L, normal FT4, with LT4 treatment). The main outcome measures were Z-scores of fetal growth indicators (abdominal circumference (AC), biparietal diameter (BPD), femur length (FL), head circumference (HC), estimated fetal weight (EFW)), fetal growth restriction (FGR) and birth weight.ResultsThere was no difference in fetal growth indicators and birth weight between the untreated mild SCH women with TPOAb- and the euthyroid pregnant women. But the HC Z-score was lower in the LT4 treated mild SCH women with TPOAb-, compared with the euthyroid pregnant women (β = -0.223, 95%CI: -0.422, -0.023). The LT4 treated mild SCH women with TPOAb- had lower fetal HC Z-score (β = -0.236, 95%CI: -0.457, -0.015), compared with the untreated mild SCH women with TPOAb-.ConclusionsWe observed that LT4 treatment for mild SCH with TPOAb- was associated with decreased fetal HC, which was not observed for untreated mild SCH women with TPOAb-. The adverse effect of LT4 treatment for mild SCH with TPOAb- provided new evidence for the recent clinical guideline.

Dataset Information

Early Levothyroxine Treatment for Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy: The St Carlos Gestational and Thyroid Protocol.

Objective

Subjects

Results

Conclusions

Publications

Early Levothyroxine Treatment for Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy: The St Carlos Gestational and Thyroid Protocol.

Similar Datasets

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