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胎儿大脑中催产素受体脱敏与分娩时使用催产素与后代自闭症发展关系的数学模型。

A Mathematical Model Relating Pitocin Use during Labor with Offspring Autism Development in terms of Oxytocin Receptor Desensitization in the Fetal Brain.

机构信息

1700 Shattuck Avenue, #114, Berkeley, CA 94709, USA.

出版信息

Comput Math Methods Med. 2019 Jul 11;2019:8276715. doi: 10.1155/2019/8276715. eCollection 2019.

Abstract

This paper develops a mathematical model describing the potential buildup of high oxytocin concentrations in the maternal circulation during labor in terms of continuous Pitocin infusion rate, half-life, and maternal weight. Oxytocin override of the degradation of oxytocin by placental oxytocinase is introduced to model the potential transfer of oxytocin from the maternal circulation across the placenta into the fetal circulation and from there into the brain of the fetus. The desensitization unit equal to 1.86 (pg·min)/ml is employed to establish a desensitization threshold and by extension, a downregulation threshold as a function of oxytocin override concentration and continuous Pitocin infusion time, that could be a factor in the subsequent development of autism among offspring. Epidemiological studies by Duke University [1], Yale University [2], and Harvard University [3] are discussed regarding Pitocin use and offspring autism development for an explanation of the weak correlations they identified. The findings of the Harvard epidemiological study are reinterpreted regarding Pitocin use and its conclusion questioned. Further evaluations of the findings of these three epidemiological studies are called for to incorporate medical information on quantity of Pitocin used, continuous Pitocin infusion rate, length of labor, and maternal weight to determine if a correlation can be established with offspring autism development above an empirically determined desensitization threshold for Pitocin use. Suggestions for research are discussed, including an alternative to continuous Pitocin infusion, pulsatile infusion of Pitocin during labor induction, which may mitigate possible offspring autism development.

摘要

本文开发了一个数学模型,根据持续垂体后叶素输注率、半衰期和产妇体重来描述分娩期间母体循环中高催产素浓度的潜在积累。引入了胎盘催产素酶对催产素的降解的催产素超越,以模拟催产素从母体循环穿过胎盘进入胎儿循环,并从那里进入胎儿大脑的潜在转移。采用脱敏单位等于 1.86(pg·min)/ml 来建立脱敏阈值,并扩展为作为催产素超越浓度和持续垂体后叶素输注时间的函数的下调阈值,这可能是后代自闭症随后发展的一个因素。杜克大学[1]、耶鲁大学[2]和哈佛大学[3]的流行病学研究讨论了垂体后叶素的使用和后代自闭症的发展,以解释他们确定的弱相关性。重新解释了哈佛流行病学研究的发现,对垂体后叶素的使用提出了质疑。需要进一步评估这三项流行病学研究的发现,以纳入有关垂体后叶素使用量、持续垂体后叶素输注率、分娩时间和产妇体重的医学信息,以确定是否可以在经验确定的垂体后叶素使用脱敏阈值之上建立与后代自闭症发展的相关性。讨论了研究建议,包括替代持续垂体后叶素输注的方法,即在分娩诱导期间脉冲式输注垂体后叶素,这可能减轻后代自闭症发展的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6592/6657633/491fd27d9247/CMMM2019-8276715.001.jpg

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