Maternal stress is a well-established risk factor for preterm birth and has been associated with adverse neonatal outcomes in the first and subsequent generations, including increased susceptibility to disease and lasting immunological changes. However, a causal link between prenatal maternal stress and preterm birth, as well as compromised neonatal immunity, has yet to be established. To fill this gap in knowledge, we used a murine model of prenatal maternal stress across three generations and high-dimensional flow cytometry to evaluate neonatal adaptive immunity. We report that recurrent prenatal maternal stress induced preterm birth in the first and second filial generations and negatively impacted early neonatal growth. Strikingly, prenatal maternal stress induced a systematic reduction in T cells and B cells, the former including regulatory CD4+ T cells as well as IL-4- and IL-17A-producing T cells, in the second generation. Yet, neonatal adaptive immunity gained resilience against prenatal maternal stress by the third generation. We also show that the rate of prenatal maternal stress-induced preterm birth can be reduced upon cessation of stress, though neonatal growth impairments persisted. These findings provide evidence that prenatal maternal stress causes preterm birth and affects neonatal immunity across generations, adverse effects that can be ameliorated upon cessation.

产妇压力是早产的公认危险因素，并已在第一代和后代与不良的新生儿结局相关，包括对疾病的易感性和持久的免疫学改变。但是，尚未确定产前产妇压力与早产之间的因果关系，以及新生儿免疫力受损。为了填补这一知识空白，我们使用了三代的产前产妇应激小鼠模型和高维流式细胞仪来评估新生儿适应性免疫。我们报告说，反复的产前产妇压力在第一代和第二代孝顺子代中引起早产，并对早期的新生儿生长产生负面影响。令人惊讶的是，产前产妇压力导致系统性地降低了T细胞和B细胞，前者在第二代中包括调节性CD4 + T细胞以及产生IL-4和IL-17A的T细胞。然而，第三代新生儿的适应性免疫获得了抵抗产前产妇压力的弹性。我们还表明，尽管新生儿生长障碍持续存在，但停止压力后可以降低产前产妇压力导致的早产率。这些发现提供了证据，表明产前产妇的压力会导致早产并影响各代人的新生儿免疫力，戒烟后可减轻不良反应。我们还表明，尽管新生儿生长障碍持续存在，但停止压力后可以降低产前产妇压力导致的早产率。这些发现提供了证据，表明产前母亲的压力会导致早产并影响各代人的新生儿免疫力，戒烟后可减轻不良反应。我们还表明，尽管新生儿生长障碍持续存在，但停止压力后可以降低产前产妇压力导致的早产率。这些发现提供了证据，表明产前产妇的压力会导致早产并影响各代人的新生儿免疫力，戒烟后可减轻不良反应。