Background: Women positive for thyroid peroxidase antibodies (TPO-Ab) have a higher risk of recurrent pregnancy loss. Evidence on whether levothyroxine treatment improves pregnancy outcomes in... Show moreBackground: Women positive for thyroid peroxidase antibodies (TPO-Ab) have a higher risk of recurrent pregnancy loss. Evidence on whether levothyroxine treatment improves pregnancy outcomes in women who are TPO-Ab positive women with recurrent pregnancy loss is scarce. The aim of this study was to determine if levothyroxine increases live birth rates in women who were TPO-Ab positive with recurrent pregnancy loss and normal thyroid function. Methods: The T4LIFE trial was an international, double-blind, placebo-controlled, phase 3 study done in 13 secondary and tertiary hospitals in the Netherlands, one tertiary hospital in Belgium, and one tertiary hospital in Denmark. Women (18-42 years) who were TPO-Ab positive, had two or more pregnancy losses, and had a thyroid stimulating hormone (TSH) concentration within the institutional reference range were eligible for inclusion. Women were excluded if they had antiphospholipid syndrome (lupus anticoagulant, anticardiolipin IgG or IgM antibodies, or beta 2-glycoprotein-I IgG or IgM antibodies), other autoimmune diseases, thyroid disease, previous enrolment in this trial, or contraindications for levothyroxine use. Before conception, women were randomly assigned (1:1) to receive either levothyroxine or placebo orally once daily. The daily dose of levothyroxine was based on preconception TSH concentration and ranged from 0.5-1.0 mu g/kg bodyweight. Levothyroxine or placebo was continued until the end of pregnancy. The primary outcome was live birth, defined as the birth of a living child beyond 24 weeks of gestation measured in the intention-to-treat population. The trial was registered within the Netherlands Trial Register, NTR3364 and with EudraCT, 2011-001820-39. Results: Between Jan 1, 2013, and Sept 19, 2019, 187 women were included in the study: 94 (50%) were assigned to the levothyroxine group and 93 (50%) were assigned to the placebo group. The trial was prematurely stopped when 187 (78%) of the 240 predefined patients had been included because of slow recruitment. 47 (50%) women in the levothyroxine group and 45 (48%) women in the placebo group had live births (risk ratio 1.03 [95% CI 0.77 to 1.38]; absolute risk difference 1.6% [95% CI -12.7 to 15.9]). Seven (7%) women in the levothyroxine group and seven (8%) in the placebo group reported adverse events, none of them were directly related to the study procedure. Interpretation: Compared with placebo, levothyroxine treatment did not result in higher live birth rates in euthyroid women with recurrent pregnancy loss who were positive for TPO-Ab. On the basis of our findings, we do not advise routine use of levothyroxine in women who are TPO-Ab positive with recurrent pregnancy loss and normal thyroid function. Copyright (C) 2022 Elsevier Ltd. All rights reserved. Show less
Purpose To investigate the effects of the antenatal administration of betamethasone on fetal Doppler and short term fetal heart rate variation (CTG-STV) in early growth restricted (FGR) fetuses... Show morePurpose To investigate the effects of the antenatal administration of betamethasone on fetal Doppler and short term fetal heart rate variation (CTG-STV) in early growth restricted (FGR) fetuses.Materials and Methods Post hoc analysis of data derived from the TRUFFLE study, a prospective, multicenter, randomized management trial of severe early onset FGR. Repeat Doppler and CTG-STV measurements between the last recording within 48 hours before the first dose of betamethasone (base-line value) and for 10 days after were evaluated. Multilevel analysis was performed to analyze the longitudinal course of the umbilico-cerebral ratio (UC ratio), the ductus venosus pulsatility index (DVPIV) and CTG-STV.Results We included 115 fetuses. A significant increase from baseline in CTG-STV was found on day + 1 (p = 0.019) but no difference thereafter. The DVPIV was not significantly different from baseline in any of the 10 days following the first dose of betamethasone (p = 0.167). Multilevel analysis revealed that, over 10 days, the time elapsed from antenatal administration of betamethasone was significantly associated with a decrease in CTG-STV (p = 0.045) and an increase in the DVPIV (p = 0.001) and UC ratio (p < 0.001).Conclusion Although steroid administration in early FGR has a minimal effect on increasing CTG-STV one day afterwards, the effects on Doppler parameters were extremely slight with regression coefficients of small magnitude suggesting no clinical significance, and were most likely related to the deterioration with time in FGR. Hence, arterial and venous Doppler assessment of fetal health remains informative following antenatal steroid administration to accelerate fetal lung maturation. Show less
Wyk, L. van; Boers, K.E.; Wassenaer-Leemhuis, A.G. van; Post, J.A.M. van der; Bremer, H.A.; Delemarre, F.M.C.; ... ; DIGITAT Study Grp 2019
