Ramadan during pregnancy: effects on health and fertility across the generations

当我们开始最初的项目时，关于怀孕期间斋月对后代生命过程的健康影响的证据很少。我们的研究有助于了解怀孕期间斋月对整个生命过程的影响，从出生到成年后的健康。此外，我们发现，德国许多怀孕的穆斯林坚持斋月禁食，这突显了这项研究在穆斯林人口占少数的国家也具有公共卫生相关性。在世界范围内，大多数穆斯林妇女的怀孕与斋月重叠，怀孕的穆斯林中有很高比例的人禁食，从而使大量穆斯林在宫内斋月禁食。因此，进一步的研究非常重要，因为充分了解怀孕期间斋月如何对后代产生影响，对于穆斯林妇女做出明智的决定以及卫生保健工作者提供有充分根据的建议是必要的。我们之前工作中一个特别值得注意的发现是，我们的结果表明，产前接触斋月可能会导致表观遗传变化。我们发现，有迹象表明，生育能力改变的表型，特别是快速成熟的表型，可能会出现在出生前接触斋月的反应中。这可能是因为暴露于斋月的孕妇的生育时间窗口被转移到了更年轻的年龄，以应对因产前暴露于斋月而增加的高死亡率压力。从对其他类型的产前暴露的研究中，有迹象表明，这种表观遗传适应确实可能发生，但迄今为止，从斋月的背景来看，还没有关于这方面的任何信息。对其他产前暴露的研究也表明，表观遗传变化可以遗传给后代，怀孕期间的斋月为研究这一现象提供了一个独特的机会，以应对相对轻微的产前休克。鉴于我们的背景，我们不打算对这些表观遗传变化本身进行生物医学研究。相反，我们关注的是跨越大人口群体的结果和影响。这项更新提案中提出的研究包括两个主要项目。首先，我们研究了宫内斋月引起的潜在表观遗传学变化对人类生殖的影响，重点是生育窗口是否发生变化(表现为更早的月经初潮/更晚的绝经，或更早的初产年龄)，以及对完全生育力的改变(一生中的孩子数量)。其次，我们研究表观遗传变化对后代的影响，即我们分析孙辈的健康结果是否受到影响，例如，关注出生时的健康或认知测试分数。如果我们确实发现了对生育率和跨代健康结果的影响，那么怀孕期间遵守斋月的后果可能比目前认为的更深远，而且跨越不止一代人。

The evidence on health effects of Ramadan during pregnancy along the offspring’s life course was scarce when our work on the original project started. Our research has contributed to a body of knowledge on the effects of Ramadan during pregnancy along the entire life course, from health at birth to later adulthood. Moreover, we found that many pregnant Muslims in Germany adhere to the Ramadan fast, which underlines the public health relevance of this research also in countries with minority Muslim populations. Worldwide, a majority of pregnancies of Muslim women overlap with a Ramadan and a high share of pregnant Muslims fast, thereby exposing substantial numbers of Muslims to Ramadan fasting in utero. Further research is therefore highly relevant, as a full understanding of how Ramadan during pregnancy exerts effects on the offspring is necessary for Muslim women to make well-informed decisions, and for health care workers to give well-founded advice. One particularly noteworthy finding of our previous work is that our results suggest that prenatal exposure to Ramadan might lead to epigenetic changes. We found indications that phenotypes with an altered fertility, in particular with rapid maturation, may emerge in response to prenatal exposure to Ramadan. It might be that the fertility window of the exposed are shifted to a younger age, as a response to the increased high mortality pressure that is induced by prenatal exposure to Ramadan. From research on other types of prenatal exposures, there are indications that such epigenetic adaptations may indeed occur, yet nothing is to date known about this from the context of Ramadan. Research on other prenatal exposures has also shown that epigenetic changes can carry over to subsequent generations and Ramadan during pregnancy provides a unique opportunity to study this phenomenon in response to a comparatively mild prenatal shock. Given our background, we do not plan to do biomedical research into these epigenetic changes themselves. Rather, we focus on the outcomes and effects that span across large population groups.The research proposed in this renewal proposal consists of two main projects. First, we study the implications of potential epigenetic changes caused by in utero exposure to Ramadan on human reproduction, focusing on whether the fertility window shifts (as expressed by earlier menarche / later menopause, or an earlier age at first childbirth), as well as on altered completed fertility (number of children over lifetime). Second, we study the implications of epigenetic changes on the subsequent generation, i.e. we analyze whether health outcomes of the grandchildren generation are affected, for instance focusing on health at birth or cognitive test scores. If we indeed find effects on fertility and transgenerational health outcomes, the consequences of Ramadan observance during pregnancy may be even more far-reaching than is currently thought, and span across more than one generation.