Department of Development and Regeneration, Cluster Woman and Child, Group Biomedical Sciences, KU Leuven, Herestraat 49 - Box 805, B-3000, Leuven, Belgium.
Fetal Medicine Research Center, BCNatal - Barcelona Center for Maternal, Fetal, and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Déu), IDIBAPS, University of Barcelona, Barcelona, 08028, Spain; Clinical Sciences Lund, Department of Pediatrics, Lund University, 221 85, Lund, Sweden.
Placenta. 2022 Aug;126:90-113. doi: 10.1016/j.placenta.2022.06.007. Epub 2022 Jun 27.
Fetal growth restriction (FGR) in human pregnancy is associated with perinatal mortality, short- and long-term morbidities. No prenatal therapy is currently established despite decades of research. We aimed to review interventions in animal models for prenatal FGR treatment, and to seek the next steps for an effective clinical therapy. We registered our protocol and searched MEDLINE, Embase, and The Cochrane Library with no language restrictions, in accordance with the PRISMA guideline. We included all studies that reported the effects of any prenatal intervention in animal models of induced FGR. From 3257 screened studies, 202 describing 237 interventions were included for the final synthesis. Mice and rats were the most used animals (79%) followed by sheep (16%). Antioxidants (23%), followed by vasodilators (18%), nutrients (14%), and immunomodulators (12%) were the most tested therapy. Two-thirds of studies only reported delivery or immediate neonatal outcomes. Adverse effects were rarely reported (11%). Most studies (73%), independent of the intervention, showed a benefit in fetal survival or birthweight. The risk of bias was high, mostly due to the lack of randomization, allocation concealment, and blinding. Future research should aim to describe both short- and long-term outcomes across various organ systems in well-characterized models. Further efforts must be made to reduce selection, performance, and detection bias.
人类妊娠中的胎儿生长受限（FGR）与围产期死亡率、短期和长期发病率有关。尽管经过几十年的研究，但目前仍没有产前治疗方法。我们旨在综述动物模型中治疗产前 FGR 的干预措施，并寻找有效的临床治疗方法的下一步。我们按照 PRISMA 指南，对 MEDLINE、Embase 和 The Cochrane Library 进行了无语言限制的检索，并注册了我们的方案。我们纳入了所有报告在诱导性 FGR 动物模型中任何产前干预效果的研究。在 3257 项筛选研究中，有 202 项研究描述了 237 项干预措施，最终用于综合分析。小鼠和大鼠（79%）是最常用的动物，其次是绵羊（16%）。抗氧化剂（23%）、血管扩张剂（18%）、营养素（14%）和免疫调节剂（12%）是研究最多的治疗方法。三分之二的研究仅报告了分娩或新生儿即刻结局。很少有研究（11%）报告了不良反应。大多数研究（73%），无论干预措施如何，都显示出胎儿存活率或出生体重的获益。偏倚风险较高，主要是由于缺乏随机化、分配隐匿和盲法。未来的研究应旨在描述在各种特征明确的模型中，各种器官系统的短期和长期结局。还必须进一步努力减少选择、表现和检测偏倚。
