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bioRxiv · 10.1101/446997

A Mathematical Model Relating Pitocin Use During Labor with Offspring Autism Development in Terms of Oxytocin Receptor Desensitization in the Fetal Brain

Gottlieb, M.
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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 D equal to 1.8E6 (pg-min)/ml is employed to establish a desensitization threshold, and by extension; a down-regulation 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 (S.G. Gregory, 2013), Yale University (O. Weisman, 2015) and Harvard University (A.S. Oberg, 2016) 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 re-interpreted 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, that may mitigate possible offspring autism development.\n\nHIGHLIGHTSO_LIBuildup of oxytocin (OT) in the maternal circulation mathematically modeled.\nC_LIO_LIRelationship of OT half-life and OT concentration in maternal circulation identified.\nC_LIO_LIOTR Desensitization related to Pitocin infusion time and OT override concentration.\nC_LIO_LIWeak correlations for autism development in epidemiological studies explained.\nC_LIO_LIExamination called for of medical records of Pitocin use in epidemiological studies.\nC_LI\n\nOUTLINE OF PAPERIntroduction\n\nO_LIDevelopment and application of mathematical model - Sections 1 through 6, notably: Figures 1 through 4\nC_LIO_LIDiscussion of oxytocin receptor desensitization as it pertains to mathematical model - Sections 7 and 8\nC_LIO_LIInfluence of mathematical model on interpretation of epidemiological studies - Sections 9 and 10\nC_LIO_LIResearch considerations - Section 11, notably:Subsection 11.1 - Call for detailed epidemiological analysis of selected medical information indicated by mathematical model Subsection 11.2 - Review of pulsatile Pitocin infusion to mitigate possible offspring autism development indicated by mathematical model\nC_LI\n\nO_FIG O_LINKSMALLFIG WIDTH=145 HEIGHT=200 SRC=\"FIGDIR/small/446997_fig1.gif\" ALT=\"Figure 1\">\nView larger version (62K):\norg.highwire.dtl.DTLVardef@1704563org.highwire.dtl.DTLVardef@1db729aorg.highwire.dtl.DTLVardef@41035eorg.highwire.dtl.DTLVardef@442b1f_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO Percent Oxytocin Removal by Liver and Kidneys and Percent Oxytocin Remaining in Blood with One-Minute Circulation Time as a Function of Oxytocin Half-Life in the Blood.\n\nC_FIG

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Gottlieb, M.. 2018-10-18. A Mathematical Model Relating Pitocin Use During Labor with Offspring Autism Development in Terms of Oxytocin Receptor Desensitization in the Fetal Brain. https://doi.org/10.1101/446997

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