The incidence of spontaneous pregnancy/infant losses is highly variable in long-tailed macaques (cynomolgus monkey), making it potentially difficult to ascertain test item-related effects in developmental toxicity studies. Therefore, pregnancy normograms had been developed by Jarvis et al. [1] to aid in the distinction of normal (e.g. test facility background) versus non-normal pregnancy outcomes. These normograms were mostly derived from embryo-fetal development studies and from PPND studies with a postnatal phase limited to seven days. However, the enhanced pre- and postnatal developmental (ePPND) study paradigm has essentially replaced these former study types. This work aims at providing enhanced normograms (e-normograms) in the context of regulatory ePPND studies. Survival functions for the prenatal phase (286 control pregnancies) and the postnatal phase (222 live infants) were estimated using the Kaplan-Meier estimator. Normograms were generated from survival curves and pseudo-study simulations. Data were available from two test facilities with comparable EU-compliant animal husbandry. Pregnancy duration/outcome as well as survival functions did not differ significantly between test facilities indicating that this husbandry system yields comparable developmental observations across different test facilities, at least in this NHP species. These novel e-normograms were developed for pregnant long-tailed macaques and provide an extended postnatal period up to three months, a new concept of separate normograms for the prenatal and the postnatal period, specific information on the perinatal phase events, a prediction of expected number of live infants for group size management, and the option to evaluate effects on pregnancy duration through distinction of live births and infant losses.

中文翻译：

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非人灵长类动物发育毒性研究中的增强范数图和妊娠结局分析。

在长尾猕猴（食蟹猴）中，自然怀孕/婴儿流产的发生率变化很大，因此潜在地难以确定发育毒性研究中与测试项目相关的影响。因此，Jarvis等人开发了怀孕规范图。[1]有助于区分正常（例如测试机构背景）与非正常妊娠结局。这些范数图主要来自胚胎胎儿发育研究和PPND研究，其产后阶段限于7天。但是，增强的产前和产后发育（ePPND）研究范例已基本上取代了这些以前的研究类型。这项工作旨在在监管性ePPND研究的背景下提供增强的规范图（e-normograms）。使用Kaplan-Meier估计量估计产前阶段（286例妊娠）和产后阶段（222例活婴儿）的生存功能。从生存曲线和伪研究模拟生成范数图。数据可从两家具有类似欧盟标准的畜牧业的测试机构获得。各测试设施之间的怀孕持续时间/结果以及生存功能均无显着差异，这表明该畜牧系统至少在该NHP物种中在不同的测试设施上产生了可比的发育观察结果。这些新颖的电子规范图是为怀孕的长尾猕猴开发的，可将产后延长到三个月，为产前和产后提供了单独的规范图的新概念，有关围产期事件的具体信息，