Association of epidural analgesia during labor with neurodevelopment of children during the first three years: the Japan Environment and Children’s Study

Abstract

Background: Epidural analgesia relives pain during labor. However, the long-term effects on neurodevelopment in children remain unclear. We explored associations between exposure to epidural analgesia during labor and childhood neurodevelopment during the first 3 years of life, in the Japan Environment and Children's Study (JECS), a large-scale birth cohort study. Methods: Pregnant women were recruited between January 2011 and March 2014, and 100,304 live births of singleton children born at full-term by vaginal delivery, and without congenital diseases were analyzed. Data on mothers and children were collected using a selfadministered questionnaires and medical record transcripts. The children's neurodevelopment was repeatedly assessed for five domains (communication, gross motor, fine motor, problem solving, and personal-social), using the Ages and Stages Questionnaires, Third Edition, at six time points from age 6 to 36 months. After adjusting for potential confounders, the associations between exposure to epidural analgesia during labor and children's neurodevelopment at each time point were assessed. Results: Of the 42,172 children with valid data at all six time points, 938 (2.4%) were born to mothers who received epidural analgesia during labor. Maternal exposure to epidural analgesia was associated with neurodevelopmental delays during the first 3 years after birth. Delay risks in gross and fine motor domains were the greatest at 18 months (adjusted odds ratio (aOR) [95% confidence interval (CI)]: 1.40 [1.06, 1.84] and 1.54 [1.17, 2.03], respectively), subsequently decreasing. Delay risks in communication and problemsolving domains were significantly high at 6 and 24 months, and remained significant at 36 months (aOR [95% CI]: 1.40 [1.04, 1.90] and 1.28 [1.01, 1.61], respectively). Exposure to epidural analgesia was also associated with the incidence of problem solving and personal-social delays from 18 to 24 months old. Neurodevelopmental delay risks, except for communication, were dominant in children born to mothers aged ²30 years at delivery. Conclusions: This study showed that maternal exposure to epidural analgesia during labor was associated with neurodevelopmental delays in children during the first 3 years after birth.

Association between combined spinal‐epidural analgesia and neurodevelopment at 3 years old: The Japan Environment and Children's Study

“…16 The discrepancies in findings between our study and the former study may be due to the differences in sample size, participant populations, or exposure. 16 Perinatal findings in our study indicated that CSEA does not affect the offspring immediately after birth. The labor duration was longer in the exposed group than in the control group, as observed in previous studies, 31,32 and this mechanism is explained by the lower maternal oxytocin levels with NLA administration.…”

“…These results are not consistent with the findings of our study; however, our research analyzed child developmental abnormalities using the ASQ‐3, which is a screening tool for neurodevelopmental abnormalities, whereas the previous studies examined the incidence of specific conditions in children who were already diagnosed or registered, which might have accounted for the discrepancies between our findings and those of other studies. Another study using the same JECS dataset reported an increased risk of neurodevelopmental delays in communication and problem‐solving domains in children born to mothers who received EA 16 . Although maternal characteristics of the control groups between the former study and our own were similar, those of exposed groups somewhat differed 16 .…”

“…16 Although maternal characteristics of the control groups between the former study and our own were similar, those of exposed groups somewhat differed. 16 The discrepancies in findings between our study and the former study may be due to the differences in sample size, participant populations, or exposure. 16 Perinatal findings in our study indicated that CSEA does not affect the offspring immediately after birth.…”

“…Recently, some studies have reported an association between offspring's neurodevelopment and maternal exposure to NLA during vaginal delivery; however, their findings are controversial, and all of them have focused on either maternal EA or NLA. [11][12][13][14][15][16] In addition, few studies have investigated the association between maternal CSEA and child development.…”

“…Several studies have focused on the perinatal outcomes of NLA; in contrast, there are only limited studies evaluating its long‐term effects on child neurodevelopment. Recently, some studies have reported an association between offspring's neurodevelopment and maternal exposure to NLA during vaginal delivery; however, their findings are controversial, and all of them have focused on either maternal EA or NLA 11–16 . In addition, few studies have investigated the association between maternal CSEA and child development.…”