Maternal labor epidural analgesia associated with ASD risk

Maternal labor epidural analgesia associated with ASD risk | Image Credit: © tolikoffphotography - © tolikoffphotography - stock.adobe.com.

According to a recent study published in JAMA Network Open, maternal labor epidural analgesia (LEA) is associated with autism spectrum disorders (ASD) risk in children, with this risk worsened by oxytocin use.

LEA is one of the most common methods of pain management used during delivery in a clinical setting, with short-term safety and efficacy proven by randomized clinical trials. However, there is little data on the long-term safety of LEA in offspring.

A large, population-based study found an association between LEA and ASD risk in children, but following studies displayed inconsistent results. Also, many drugs can be given alongside LEA, making it difficult to isolate risks associated with LEA. Oxytocin use alongside LEA is also common, which may augment ASD risk in children.

Investigators conducted a study to determine the impacts of LEA and oxytocin use on ASD risk in offspring. Participants included singleton offspring born in Kaiser Permanente Southern California (KPSC) hospitals through vaginal delivery at 28 to 44 weeks of gestation from 2008 to 2017.

KPSC is a large health care system with over 4.5 million members containing comprehensive electronic health records (EHRs). Guidelines established by KPSC require screening for ASD in children aged 18 to 24 months during standard well-child visits.

EHRs were consulted for data on maternal demographic characteristics, health conditions, and pregnancy history, perinatal outcomes, and child ASD diagnosis. Follow-up occurred when children were aged 1 year, ending at clinical ASD diagnosis, last date of KPSC membership, child death, or study end date on December 31, 2021. Data was gathered from 160,437 mothers.

LEA and oxytocin administration were the primary exposures of the study, measured from intrapartum admission to delivery. ASD diagnosis during follow-up and age of diagnosis were the primary outcomes of the study, with ASD diagnosis determined using International Classification of Diseases, 9th Revision (ICD-9-CM) or ICD-10-CM codes.

Covariates included birth year, race and ethnicity, maternal age at delivery, household income, education level, comorbidity history, parity, gestational weight gain, prepregnancy body mass index, preeclampsia or eclampsia, diabetes, smoking during pregnancy, and child sex, birth weight, preterm birth status, and medical center of delivery.

There were 205,994 children included in the final analysis, 74.7% of which were exposed to LEA and 57.2% of which were exposed to oxytocin. Mothers not exposed to LEA were aged a median 30.8 years, while those exposed to LEA were aged a median 30 years, those exposed to oxytocin a median 30 years, and those not exposed to oxytocin a median 30.4 years. An induction or augmentation was seen in 64.3% of women, with 88.9% of these women using oxytocin. 

Significant variations in sociodemographic characteristics were seen between women exposed and not exposed to LEA, along with significant social and health variations in women exposed and not exposed to oxytocin. This included higher rates of induction, augmentation, labor dystocia, antepartum hemorrhage, fever during labor, and fetal distress in women exposed to LEA or oxytocin.

An ASD diagnosis during follow-up was seen in 2.5% of children, 2.7% of those exposed to LEA, and 1.9% of those not exposed to LEA. The hazard ratios of ASD were 1.30 for LEA exposure and 1.12 for oxytocin exposure. 

These results indicated a significant association between ASD risk and LEA and oxytocin exposure. Investigators recommended further studies to replicate or refute these results.

Reference

Qiu C, Carter SA, Lin JC, et al. Association of labor epidural analgesia, oxytocin exposure, and risk of autism spectrum disorders in children. JAMA Netw Open. 2023;6(7):e2324630. doi:10.1001/jamanetworkopen.2023.24630