Levothyroxine for subclinical hypothyroidism during pregnancy: an updated systematic review and meta-analysis of randomized controlled trials.

PURPOSE: We aimed to perform a systematic review and meta-analysis addressing the efficacy of levothyroxine therapy in pregnant women with subclinical hypothyroidism considering most recent evidence and subgroups of interest for clinical practice. METHODS: PubMed, Embase, and Cochrane Central were searched from inception for randomized controlled trials (RCTs) comparing levothyroxine with placebo or no intervention in pregnant women with subclinical hypothyroidism. We used a random-effects model and conducted subgroup analyses based on thyroid peroxidase antibody status, thyroid stimulating hormone levels, fertility treatment, and recurrent miscarriage. RESULTS: We included 11 RCTs comprising 2,749 pregnant women with subclinical hypothyroidism. Patients treated with levothyroxine (1,439; 52.3%) had significantly lower risk of pregnancy loss (risk ratio 0.69; 95% confidence interval 0.52-0.91; p < 0.01; 6 studies). However, there was no significant association between levothyroxine and live birth (risk ratio 1.01; 95% confidence interval 0.99-1.03; p = 0.29; 8 studies). No statistically significant interaction was observed across subgroups (p > 0.05). CONCLUSION: Levothyroxine replacement therapy for subclinical hypothyroidism during pregnancy may decrease pregnancy loss when early prescribed. Nevertheless, further investigation is needed in patients with thyroid stimulating hormone above four milliunits per liter, especially when associated with recurrent miscarriage or infertility.

Prophylactic tranexamic acid in Cesarean delivery: an updated meta-analysis with a trial sequential analysis.

PURPOSE: Postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. Although several studies on the prophylactic use of tranexamic acid (TXA) in parturients undergoing Cesarean delivery have been published, conflicting results raise questions regarding its use. Thus, we aimed to investigate the safety and efficacy of PPH prophylaxis with TXA. SOURCE: We searched PubMed®, Embase, Cochrane Central, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing prophylactic TXA with placebo or no treatment in parturients undergoing Cesarean delivery. Our main outcomes were PPH, any blood transfusion, need for additional uterotonics, and adverse events. We performed a trial sequential analysis (TSA) of all outcomes to investigate the reliability and conclusiveness of findings. PRINCIPAL FINDINGS: We included 38 RCTs including 22,940 parturients, 11,535 (50%) of whom were randomized to receive prophylactic TXA. Patients treated with TXA had significantly fewer cases of PPH (risk ratio [RR], 0.51; 95% confidence interval [CI], 0.38 to 0.69; P < 0.001); less blood transfusion (RR, 0.43; 95% CI, 0.30 to 0.61; P < 0.001), and less use of additional uterotonics (RR, 0.52; 95% CI, 0.40 to 0.68; P < 0.001). No significant differences were found between the groups in terms of adverse effects and thromboembolic events. CONCLUSION: Prophylactic TXA administration for parturients undergoing Cesarean delivery significantly reduced blood loss, without increasing adverse events, supporting its use as a safe and effective strategy for reducing PPH in this population. STUDY REGISTRATION: PROSPERO (CRD42023422188); first submitted 27 April 2023.

RéSUMé: OBJECTIF: L'hémorragie du post-partum (HPP) est l'une des principales causes de mortalité maternelle dans le monde. Bien que plusieurs études sur l'utilisation prophylactique d'acide tranexamique (TXA) chez les personnes parturientes ayant accouché par césarienne aient été publiées, des résultats contradictoires soulèvent des questions quant à son utilisation. Ainsi, nous avons cherché à étudier l'innocuité et l'efficacité de la prophylaxie à base de TXA pour l'HPP. SOURCES: Nous avons fait une recherche sur PubMed®, Embase, Cochrane Central et ClinicalTrials.gov pour en tirer les études randomisées contrôlées (ERC) comparant le TXA prophylactique à un placebo ou à l'absence de traitement chez les personnes parturientes accouchant par césarienne. Nos principaux critères d'évaluation étaient l'HPP, toute transfusion sanguine, la nécessité d'un utérotonique supplémentaire et les événements indésirables. Nous avons effectué une analyse séquentielle des études pour tous les résultats afin d'examiner la fiabilité et le caractère concluant des conclusions. CONSTATATIONS PRINCIPALES: Nous avons inclus 38 ERC comprenant 22 940 personnes parturientes, dont 11 535 (50 %) ont été randomisées pour recevoir du TXA prophylactique. La patientèle traitée par TXA présentait significativement moins de cas d'HPP (risque relatif [RR], 0,51; intervalle de confiance [IC] à 95 %, 0,38 à 0,69; P < 0,001); moins de transfusion sanguine (RR, 0,43; IC 95 %, 0,30 à 0,61; P < 0,001) et moins d'utilisation d'utérotoniques supplémentaires (RR, 0,52; IC 95 %, 0,40 à 0,68; P < 0,001). Aucune différence significative n'a été constatée entre les groupes en termes d'effets indésirables et d'événements thromboemboliques. CONCLUSION: L'administration prophylactique de TXA pour les personnes parturientes accouchant par césarienne a considérablement réduit les pertes de sang sans augmenter les événements indésirables, ce qui soutient son utilisation comme stratégie sécuritaire et efficace pour réduire l'HPP dans cette population. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42023422188); première soumission le 27 avril 2023.

The role of pravastatin in preventing preeclampsia in high-risk pregnant women: a meta-analysis with trial sequential analysis.

OBJECTIVE: We aimed to perform a systematic review and meta-analysis of randomized controlled trials to evaluate the prophylactic use of pravastatin in pregnant women with high-risk of preeclampsia. DATA SOURCES: PubMed, Embase, Cochrane Central, and Web of Science were searched from inception to August 2023 with no language or filters restriction. The references from included studies, previous systematic reviews, and meta-analyses were manually searched for any additional studies. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing pravastatin in any dose with placebo or no treatment in pregnant women with high risk for preeclampsia and up to 20 weeks of gestation were included in this meta-analysis. METHODS: We used RStudio version 4.2.2 with random effects models to compute pooled risk ratios for prespecified outcomes data. The quality assessment was conducted using version 2 of the Cochrane Risk of Bias Assessment Tool. We also performed a trial sequential analysis to evaluate the reliability of our findings. RESULTS: We included 3 randomized controlled trials comprising 213 patients, of whom 106 (49.8%) were allocated to the pravastatin group. There was no significant effect of pravastatin on the incidence of preeclampsia (risk ratio, 0.62; 95% confidence interval, 0.33-1.14; P=.12). CONCLUSION: Our study was unable to demonstrate the benefit of pravastatin for preventing preeclampsia in high-risk pregnant women. Nevertheless, these findings comprised only preliminary studies with a small number of subjects, highlighting the need of well-designed, and adequately powered clinical trials.