Impact of levothyroxine in women with positive thyroid antibodies on pregnancy outcomes: a systematic review and meta-analysis of randomised controlled trials

Lau, Lorraine; Benham, Jamie L; Lemieux, Patricia; Yamamoto, Jennifer M.; Donovan, Lois

doi:10.1136/bmjopen-2020-043751

Cited by 15 publications

(8 citation statements)

References 34 publications

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“…However, subsequent large-scale, multicenter, randomized controlled trials have shown that L-T4 treatment, in comparison to no L-T4 treatment, does not improve maternal and fetal outcomes in pregnant women with TPOAb-positive, subclinical hypothyroidism, or isolated hypothyroidism ( 23 , 24 ). The findings of the present study are also consistent with the results of two recent systematic reviews of TPOAb-positive women ( 25 , 26 ). Two randomized controlled trials investigated the effects of screening and treatment of hypothyroxinemia in pregnancy.…”

Section: Discussionsupporting

confidence: 93%

Effect of Levothyroxine on Pregnancy Outcomes in Pregnant Women With Hypothyroxinemia: An Interventional Study

Liu

et al. 2022

Front. Endocrinol.

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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.

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Section: Discussionsupporting

confidence: 93%

Effect of Levothyroxine on Pregnancy Outcomes in Pregnant Women With Hypothyroxinemia: An Interventional Study

Liu

et al. 2022

Front. Endocrinol.

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“…The general population in the long-term is mostly exposed to the environmental BPA in low doses [ 12 , 13 ]. As an endocrine disruptor, BPA has a significant impact on the reproduction of mammals and involves multiple reproductive links such as pregnancy, fertilization, and development [ 14 ]. The BPA can enter the human body through the respiratory tract, gastrointestinal tract, and skin and can accumulate in multiple organs and tissues, resulting in potential harm to human health through different molecular mechanisms [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Bisphenol A-Mediated RBP-4 on Pregnancy Outcomes in Nonobese Pregnant Female with Subclinical Hypothyroidism

Chen

Wang

Chen

et al. 2022

Contrast Media & Molecular Imaging

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Hypothyroidism is a systemic hypometabolic syndrome caused by the thyroxine resistance or a reduction in its extent. It is an endocrinopathy secondary to gestational diabetes and occurs usually without significant symptoms. This study explored the effect of bisphenol A (BPA)-mediated retinol-binding protein 4 (RBP-4) on pregnancy outcomes in a nonobese pregnant female with subclinical hypothyroidism. Three hundred nonobese pregnant females who had that established pregnancy files and had regular obstetric examinations from January 2021 to March 2022 were enrolled and classified with 100 cases in each group as early pregnancy (6–12 weeks of gestation), second-trimester (13–24 weeks of gestation), and third-trimester groups (25–36 weeks of gestation). Thirty pregnant women with subclinical hypothyroidism were selected as subjects, and another thirty pregnant women with normal thyroid function were selected as the normal control group. Thyroid function (thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free T4 (FT4), and thyroid peroxidase antibody (TPO-Ab)) was measured by immunoelectrochemiluminescence. The level of BPA in urine was determined by solid-phase extraction high-performance liquid chromatography-tandem mass spectrometry. Serum RBP4 levels were determined by enzyme-linked immunosorbent assay. The level of TSH in the third-trimester group was higher than that in the first- and second-trimester groups, while the levels of FT3, FT4, and TPO-Ab were lower than those in the other two groups ( P < 0.05). TSH in the second-trimester group was higher than that in the first-trimester group, while FT3, FT4, and TPO-Ab levels were lower than those in the first-trimester group ( P < 0.05). The levels of BPA and RBP4 in gestational diabetes mellitus and hypertension were higher than those in the nongestational period, and the levels of BPA and RBP4 in gestational intrahepatic cholestasis and anemia were higher than those in the nongestational period, and the levels of BPA and RBP4 in preterm delivery were higher than those in nongestational period ( P < 0.05). Also, the level of urinary BPA in the hypothyroidism group was higher than that in the normal control group ( P < 0.05) and the level of serum RBP4 in the hypothyroidism group was higher than that in the normal control group ( P < 0.05). According to multivariate logistic regression analysis, age ≥30 years and the ascending BPA and RBP4 were risk factors for subclinical hypothyroidism during pregnancy in the nonobese female. BPA and RBP-4 are closely related to the pregnancy outcome of nonobese subclinical hypothyroidism in the pregnant female. The degree of BPA and RBP-4 in adverse pregnancy outcomes is increased, which is the risk factor for nonobese subclinical hypothyroidism.

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“…In Di Girolamo et al' s meta-analysis, levothyroxine therapy in euthyroid anti-TPO + women was not associated with reduced risk of GH and PE (54). Also, Lau et al' systematic review showed that LT4 supplementation in women with thyroid autoimmunity without SCH or OH was not bene cial on pregnancy outcome (55). One reason for our nding is the higher elementary TSH values in TPO antibody positivity compared to TPOAb-subjects which may worsen during pregnancy.…”

Section: Discussionmentioning

confidence: 63%

Effect of levothyroxine on gestational hypertension and pre-eclampsia in subclinical hypothyroidism, hypothyroidism, and thyroid autoimmunity: a systematic review and meta-analysis

Goodarzi-Khoigani

Aminorroaya

Mohammadi

2022

Preprint

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Background We assessed the effect of levothyroxine (LT4) therapy on gestational hypertension (GH) and preeclampsia (PE) in subclinical hypothyroidism (SCH), overt hypothyroidism (OH), or thyroperoxidase antibody (TPOAb) positivity. Methods Scopus, Medline, Science Direct, ProQuest, Google Scholar, and Cochrane library were scientifically searched for randomized controlled trials (RCTs), cohorts, and case-control studies assessing the effect of levothyroxine on incidences of GH or/and PE compared to control or placebo up to November 2022. Results After LT4 therapy in women with SCH, the ORs of GH and PE were not significantly different from compared groups; also, in OH, and studies recruited both SCH or OH subjects. LT4 reduced GH in TPOAb + women compared with a non-treated group, while after treatment in TPOAb + versus TPOAb- women, the ORs of GH and PE did not change significantly. Conclusion After LT4 therapy, the ORs of GH and PE did not significantly change in SCH, OH, SCH or OH participants compared to controls; also, in TPOAb + compared to TPOAb- equivalents. Reduction of GH in treated TPOAb + versus non-treated TPOAb + women refers to the importance of TPOAb determination. Insignificant changes of both ORs in treated SCH compared to untreated indicates whether SCH increases the incidence of GH and PE.

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Impact of levothyroxine in women with positive thyroid antibodies on pregnancy outcomes: a systematic review and meta-analysis of randomised controlled trials

Cited by 15 publications

References 34 publications

Effect of Levothyroxine on Pregnancy Outcomes in Pregnant Women With Hypothyroxinemia: An Interventional Study

Effect of Levothyroxine on Pregnancy Outcomes in Pregnant Women With Hypothyroxinemia: An Interventional Study

Effect of Bisphenol A-Mediated RBP-4 on Pregnancy Outcomes in Nonobese Pregnant Female with Subclinical Hypothyroidism

Effect of levothyroxine on gestational hypertension and pre-eclampsia in subclinical hypothyroidism, hypothyroidism, and thyroid autoimmunity: a systematic review and meta-analysis

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