An association of intrapartum synthetic oxytocin dosing and the odds of developing autism

Abstract

A case-control study was performed to determine whether an association exists between exposure to synthetic oxytocin and a subsequent autism spectrum disorder diagnosis; 171 children under age 18 meeting Diagnostic and Statistical Manual of Mental Disorders (5th ed.) autism spectrum disorder criteria were compared to 171 children without autism spectrum disorder diagnosis matched by gender, birth year, gestational age, and maternal age at birth. A conditional logistic regression model was used to examine the association of clinical variables and autism spectrum disorder. Significantly elevated odds ratios for autism spectrum disorder were associated with first-time Cesarean section (odds ratio = 2.56), but not a repeat Cesarean section. Odds ratios were also significantly elevated for subjects whose mother’s body mass index was 35 or higher at birth (odds ratio = 2.34) and subjects in which the reason for delivery was categorized as “fetal indication” (odds ratio = 2.00). When controlling for these and other variables, the odds of developing autism spectrum disorder were significantly elevated in males with long duration of exposure (odds ratio = 3.48) and high cumulative dose of synthetic oxytocin (odds ratio = 2.79). No significant associations of synthetic oxytocin dosing and autism spectrum disorder were noted in female subjects. The association of elevated autism spectrum disorder odds found with high duration and high cumulative dose synthetic oxytocin in male subjects suggests the need for further investigation to fully elucidate any cause and effect relationship. Lay abstract Oxytocin is a hormone naturally produced in the human body that can make the womb (uterus) contract during labor. Manufactured oxytocin is frequently given to mothers in labor to strengthen the contractions or in some cases to start labor. This study compared children with a diagnosis of autism and children without autism to see whether children with autism received more oxytocin during labor. The odds of a child having an autism diagnosis were significantly higher if the delivery was a first-time Cesarean section, if the mother had a body mass index of 35 or higher, or if the reason for delivery were a range of fetal problems that made delivery necessary. It was found that boys who were exposed to oxytocin for longer periods of time during labor and received higher total doses of oxytocin had significantly higher odds of developing autism. There were no significant associations of oxytocin dosing and autism noted in female children. As this is the first study to look at any relationship between the dose of oxytocin received during labor and the odds of developing autism, further study needs to be done to determine whether there is any cause and effect relationship. Thus, at this time, there is no recommended change in clinical practice.

Is Oxytocin “Nature’s Medicine”?

“…However, oxytocin appears to have dose-dependent effects at birth, particularly when administered exogenously, with higher doses conferring less neuroprotection in vitro ( Ceanga et al, 2010 ) as well as an increased risk for autism for male offspring ( Soltys et al, 2020 ). Possible explanations to explain the loss of oxytocin’s protection when administered exogenously at high concentrations are oxytocin-induced receptor desensitization ( Plested and Bernal, 2001 ; Robinson et al, 2003 ) and/or oxygen desaturation of the fetal blood supply (i.e., greater hypoxia) that can occur after synthetic oxytocin-induced uterine hyperstimulation ( Simpson and James, 2008 ).…”

Maternal Diabetes-Induced Suppression of Oxytocin Receptor Contributes to Social Deficits in Offspring

“…OXTR is widely expressed in human tissues, with particularly high levels being located in limbic brain regions ( Kudwa et al, 2014 ). In conjunction with OXT, OXTR has been reported to regulate diverse social behaviors ( Maejima et al, 2018 ; Gulliver et al, 2019 ; Resendez et al, 2020 ; Soltys et al, 2020 ) and play a role in ASD etiology ( Jacob et al, 2007 ; LoParo and Waldman, 2015 ; Uzefovsky et al, 2019 ), although there has been some controversy with these conclusions ( Tansey et al, 2010 ). Epigenetic modification of OXTR has been widely reported to be associated with ASD development ( Jack et al, 2012 ; Maud et al, 2018 ; Krol et al, 2019 ; Tops et al, 2019 ), although the detailed mechanism remains unclear.…”

A Novel Pregnant Rat Model for Labor Induction and Augmentation With Oxytocin

“…Our contextually relevant animal model, by providing unrivaled access to maternal and fetal tissue, has wide-ranging implications for translational research related to perinatal Oxt exposure. This makes our model well suited to investigate lingering concerns about the impact of Oxt on neurobehavioral development of the offspring (8,14,41,42), epigenetic regulation of OxtR in the fetal brain (18), relationship between intrapartum Oxt use and breastfeeding success (43)(44)(45), and the complex association between Oxt and postpartum depression (46)(47)(48). Furthermore, by scaling down with appropriate equipment (iPRECIO ® SMP 310-R with a dedicated wireless communication device), transgenic mouse models could be used to investigate complex gene-environment interaction studies in the perinatal period.…”

“…Despite widespread use for over 50 years, most research has focused on the contractile effects of Oxt and associated obstetric outcomes(4–7). Whether Oxt affects the fetus remains sparsely studied, despite controversial epidemiological evidence suggesting a link between the use of Oxt and neurodevelopmental disorders (8–14). Importantly, most preclinical studies that examine this question do so without inducing birth(15–18), making them contextually less germane.…”

“…Whether Oxt affects the fetus remains sparsely studied, despite controversial epidemiological evidence suggesting a link between the use of Oxt and neurodevelopmental disorders (8)(9)(10)(11)(12)(13)(14).…”