Assessing risk of neurodevelopmental disorders after birth with oxytocin: a systematic review and meta-analysis

Abstract

Experts have raised concerns that oxytocin for labor induction and augmentation may have detrimental effects on the neurodevelopment of children. To investigate whether there is the reason for concern, we reviewed and evaluated the available evidence by searching databases with no language or date restrictions up to 9 September 2018. We included English-language studies reporting results on the association between perinatal oxytocin exposure and any cognitive impairment, psychiatric symptoms or disorders in childhood. We assessed the quality of studies using the Newcastle–Ottawa Quality Assessment Scales. Independent risk estimates were pooled using random-effects meta-analyses when at least two independent datasets provided data on the same symptom or disorder. Otherwise, we provided narrative summaries. Two studies examined cognitive impairment, one examined problem behavior, three examined attention-deficit/hyperactivity disorder (ADHD) and seven focused on autism spectrum disorders (ASD). We provided narrative summaries of the studies on cognitive impairment. For ADHD, the pooled risk estimate was 1.17; 95% confidence interval (CI) 0.77–1.78, based on a pooled sample size of 5 47 278 offspring. For ASD, the pooled risk estimate was 1.10; 95% CI 1.04–1.17, based on 8 87 470 offspring. Conclusions that perinatal oxytocin increases the risks of neurodevelopmental problems are premature. Observational studies of low to high quality comprise the evidence-base, and confounding, especially by the genetic or environmental vulnerability, remains an issue. Current evidence is insufficient to justify modifying obstetric guidelines for the use of oxytocin, which state that it should only be used when clinically indicated.

Is there an association between labor induction and attention-deficit/hyperactivity disorder among children?

“…A meta-analysis study was performed by Lønfeldt et al [ 11 ] in 2019. The authors reported a significant association between labor induction and the risk of ADHD (RR, 1.17; 95% CI, 0.77–1.78).…”

“…To date, only Lønfeldt et al [ 11 ] performed a meta-analysis of the association between labor induction and the risk of ADHD. The authors did not report a significant association between labor induction and the risk of ADHD (relative risk [RR], 1.17; 95% confidence interval [CI], 0.77–1.78).…”

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

“…with Pitocin to stimulate contractions and to control postpartum hemorrhage (Arrowsmith and Wray, 2014;Page et al, 2017). As early exposure to drugs is thought to affect the developing fetus, it is reasonable to suspect that exposure to Pitocin might impact cellular pathways that determine the wellbeing of the perinatal child (Figure 3; Kenkel et al, 2014;Lønfeldt et al, 2019). This particular reasoning is important because there is limited information regarding the physical embodiment and health consequences of synthetic oxytocin in the obstetric population.…”

“…There are also reports suggesting that perinatal Pitocin use may increase the risk of infants developing Attention Deficit/Hyperactivity Disorder, Autistic Disorder and increasing the rates of neonatal morbidity (Kurth and Haussmann, 2011;Buchanan et al, 2012;Weisman et al, 2015). However, there is also a number of mostly retrospective studies showing no significant side-effects or adverse events in the studied populations, with most studies referring to administration of Pitocin around the time of labor being well tolerated by the infant (Henriksen et al, 2015;Gottlieb, 2016;Stokholm et al, 2018;Lønfeldt et al, 2019). Finally, as far as the authors are aware, no studies have evaluated single-nucleotide polymorphisms within the oxytocin receptor genes in an attempt to correlate Pitocin exposure with infant behavioral outcome.…”

New Perspectives in Attention Deficit Hyperactivity Disorder: Possible Link to Oxytocin

“…Although the exact underlying pathophysiology of ADHD remains unknown, multiple genetic and environmental factors including prenatal alcohol or tobacco exposure, structural brain disorders, mutations at dopaminergic and serotonergic pathways, Turner syndrome, Tuberous Sclerosis Complex, Neurofibromatosis I and Fragile X syndrome have been implicated [2]. Obstetrical use of oxytocin has been proposed as potential risk factor in ADHD in few studies recently, however, a recent meta-analysis study demonstrated no statistically significant association [3]. Nevertheless, all studies conducted in this field are observational studies with low-to-middle scientific study quality and multiple interventional studies continue to be conducted.…”