Perspectives of Pitocin administration on behavioral outcomes in the pediatric population: recent insights and future implications

Torres, Germán; Mourad, Mervat; Leheste, Joerg R.

doi:10.1016/j.heliyon.2020.e04047

Cited by 6 publications

(5 citation statements)

References 80 publications

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“…These studies are relevant in the context of human neurodevelopmental disorders, as there are growing numbers of human studies investigating the efficacy of OXT infusions for ameliorating symptoms in individuals with ASD [23,41,42]. Perinatal administration of synthetic OXT (pitocin) is a common obstetric practice to accelerate childbirth, and OXTR antagonists are often administered in order to prevent premature labour [43]. Interestingly, OXT administration during labour has been associated with higher odds of C-section [44] with consequences that remain be fullyexplored.…”

Section: Introductionmentioning

confidence: 99%

Early-life oxytocin attenuates the social deficits induced by caesarean-section delivery in the mouse

Morais

Golubeva

Casey

et al. 2021

Neuropsychopharmacol.

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The oxytocin (OXT) system has been strongly implicated in the regulation of social behaviour and anxiety, potentially contributing to the aetiology of a wide range of neuropathologies. Birth by Caesarean-section (C-section) results in alterations in microbiota diversity in early-life, alterations in brain development and has recently been associated with long-term social and anxiety-like behaviour deficits. In this study, we assessed whether OXT intervention in the early postnatal period could reverse C-section-mediated effects on behaviour, and physiology in early life and adulthood. Following C-section or per vaginum birth, pups were administered with OXT (0.2 or 2 μg/20 μl; s.c.) or saline daily from postnatal days 1–5. We demonstrate that early postnatal OXT treatment has long-lasting effects reversing many of the effects of C-section on mouse behaviour and physiology. In early-life, high-dose OXT administration attenuated C-section-mediated maternal attachment impairments. In adulthood, low-dose OXT restored social memory deficits, some aspects of anxiety-like behaviour, and improved gastrointestinal transit. Furthermore, as a consequence of OXT intervention in early life, OXT plasma levels were increased in adulthood, and dysregulation of the immune response in C-section animals was attenuated by both doses of OXT treatment. These findings indicate that there is an early developmental window sensitive to manipulations of the OXT system that can prevent lifelong behavioural and physiological impairments associated with mode of birth.

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Section: Introductionmentioning

confidence: 99%

Early-life oxytocin attenuates the social deficits induced by caesarean-section delivery in the mouse

Morais

Golubeva

Casey

et al. 2021

Neuropsychopharmacol.

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“…Our finding that intrapartum sOT exposure was not associated with adverse neurodevelopmental outcomes in the offspring is consistent with findings from several prior studies [ 12 , 20 – 28 ]. In contrast to some of these prior studies and current results, preclinical studies suggest that sOT exposure might disrupt fetal neurodevelopment [ 61 , 62 ] via cellular mechanisms such as epigenetic triggering [ 2 , 63 – 65 ], oxytocin receptor alterations [ 6 ], DNA damage and cellular death [ 66 , 67 ], complex signaling pathways [ 19 ], and transgenerational hormonal imprinting [ 68 , 69 ]. Biologically plausible mechanisms that could link fetal exposure to intrapartum sOT with ADHD or ASD include excessive uterine contractility leading to decreased uteroplacental perfusion and fetal hypoxemia [ 18 , 70 – 76 ], and especially at high cumulative doses [ 17 ] and transplacental transfer of sOT [ 77 , 78 ] resulting in sOT-induced oxytocinergic signaling in the developing brain, the importance of which is suggested by the role that oxytocinergic signaling plays in the development of social behaviors that are characteristically impaired in ASD [ 79 ].…”

Section: Discussionmentioning

confidence: 80%

“…Child neurodevelopmental outcomes following intrapartum sOT exposure have not been studied in large samples of children born in the United States (US) [ 13 , 14 ], where obstetric medical practices may differ from those of other countries [ 15 ]. Among existing studies, some report associations between sOT exposure and ADHD and/or ASD [ 13 , 14 , 16 – 19 ], some report mixed results [ 20 – 25 ], and some report no associations [ 12 , 26 – 29 ]. Preclinical models provide evidence of potential neuroprotective effects of endogenous oxytocin; however, if pulsatile uterine contractions are excessively prolonged by treatment with exogenous sOT, uteroplacental perfusion can be reduced to an extent sufficient to alter brain development [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

Intrapartum exposure to synthetic oxytocin, maternal BMI, and neurodevelopmental outcomes in children within the ECHO consortium

Kurth,

O’Shea,

Burd

et al. 2024

J Neurodevelop Disord

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Background Synthetic oxytocin (sOT) is frequently administered during parturition. Studies have raised concerns that fetal exposure to sOT may be associated with altered brain development and risk of neurodevelopmental disorders. In a large and diverse sample of children with data about intrapartum sOT exposure and subsequent diagnoses of two prevalent neurodevelopmental disorders, i.e., attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), we tested the following hypotheses: (1) Intrapartum sOT exposure is associated with increased odds of child ADHD or ASD; (2) associations differ across sex; (3) associations between intrapartum sOT exposure and ADHD or ASD are accentuated in offspring of mothers with pre-pregnancy obesity. Methods The study sample comprised 12,503 participants from 44 cohort sites included in the Environmental Influences on Child Health Outcomes (ECHO) consortium. Mixed-effects logistic regression analyses were used to estimate the association between intrapartum sOT exposure and offspring ADHD or ASD (in separate models). Maternal obesity (pre-pregnancy BMI ≥ 30 kg/m2) and child sex were evaluated for effect modification. Results Intrapartum sOT exposure was present in 48% of participants. sOT exposure was not associated with increased odds of ASD (adjusted odds ratio [aOR] 0.86; 95% confidence interval [CI], 0.71–1.03) or ADHD (aOR 0.89; 95% CI, 0.76–1.04). Associations did not differ by child sex. Among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of offspring ADHD (aOR 0.72; 95% CI, 0.55–0.96). No association was found among mothers without obesity (aOR 0.97; 95% CI, 0.80–1.18). Conclusions In a large, diverse sample, we found no evidence of an association between intrapartum exposure to sOT and odds of ADHD or ASD in either male or female offspring. Contrary to our hypothesis, among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of child ADHD diagnosis.

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“…OT insufficiency may cause stillbirth, increased risk of cesarean section [173]. Postpartum hemorrhage often occurs following cesarean section, stillbirth, preterm birth, and macrosomia, particularly in women with uterine atony and retained placenta; pitocin, a synthetic preparation of OT, is widely used in the obstetric management of labor and postpartum hemorrhage [174, 175]. Decrease in OT pulsatility during lactation and failure in the milk-ejection reflex may increase oxidative stress in the mammary gland and facilitate the occurrence of precancerous lesions [107].…”

Section: Discussionmentioning

confidence: 99%

Dual Oxytocin Receptor-G Protein Signaling in the Autoregulation of Activities of Oxytocin Neurons

Liu,

Ling,

Liu

et al. 2023

Neuroendocrinology

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Oxytocin (OT), a hypothalamic nonaneuropeptide, can extensively modulate mental and physical activities; however, the regulation of its secretion from hypothalamic OT neurons remains poorly understood. OT neuronal activity is generally modulated by neurochemical environment, synaptic inputs, astrocytic plasticity, and interneuronal interactions. By changing intracellular signals and ion channel activity, these extracellular factors dynamically regulate OT neuronal activity and OT release in a microdomain-specific manner. In this process, OT receptor (OTR) and OTR-coupled G proteins are pivotal, typically observed during lactation. Suckling-elicited somatodendritic release of OT causes sequential activation of Gq and Gs proteins to increase the firing rate gradually and trigger burst firing transiently, and then of Gi/o protein to cause post-burst inhibition, as a result of potential bolus somatodendritic release of OT during burst. Under chronic social stress like mother-baby separation and cesarean section, excessive somatodendritic secretion of OT and over-excitation of OT neurons cause post-excitation inhibition of OT neuronal activity and reduction of OT secretion. In this process, dominance of G protein that couples to OTR is switched from Gq to OTR-Gi/o type, because of inhibition of OTR-Gq signaling following negative feedback of downstream Gq signaling or crosstalk of Gq with Gs and Gi signals. This review summarizes our current understandings of OT/OTR signaling in the autoregulation of OT neuronal activity under physiological and pathological conditions.

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Perspectives of Pitocin administration on behavioral outcomes in the pediatric population: recent insights and future implications

Cited by 6 publications

References 80 publications

Early-life oxytocin attenuates the social deficits induced by caesarean-section delivery in the mouse

Early-life oxytocin attenuates the social deficits induced by caesarean-section delivery in the mouse

Intrapartum exposure to synthetic oxytocin, maternal BMI, and neurodevelopmental outcomes in children within the ECHO consortium

Dual Oxytocin Receptor-G Protein Signaling in the Autoregulation of Activities of Oxytocin Neurons

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