Neuraxial Labor Analgesia and Offspring Neurodevelopment

Impact of Maternal Neuraxial Labor Analgesia on Offspring Neurodevelopment. A Multicenter, Prospective, Longitudinal Cohort Study

How perinatal factors affect the long-term development of children has always been an issue of much concern. This study is designed to explore the potential impact of maternal neuraxial labor analgesia exposure on offspring neurodevelopment.

Study Overview

• Status: Recruiting
• Conditions: Postpartum Depression; Labor Pain; Offspring, Adult; Maternal Anesthesia and Analgesia Affecting Fetus or Newborn; Neurodevelopmental Delay
• Intervention / Treatment: Procedure: Neuraxial labor analgesia; Procedure: No neuraxial labor analgesia

Detailed Description

Neuraxial labor analgesia, including epidural analgesia and combined spinal-epidural analgesia, is a well-established technique to alleviate labor pain. It can help to reduce the maternal stress response during labor and might be associated with a lower risk of maternal postpartum depression; which may be beneficial to the long-term neurodevelopment in offspring.

On the other hand, neuraxial labor analgesia is associated with increased risks of intrapartum maternal fever and instrumental delivery, which may produce potentially harmful effects. In addition, it has been reported that the anesthetic exposure during neuraxial analgesia may lead to fetal-neonatal depression and even neurotoxic effects of less mature neonatal brain. Taking all these into account, the potential long-term effects of neuraxial analgesia on offspring neurodevelopment is still controversial and deserves further study.

The objective of study is to investigate if there is any association between maternal neuraxial analgesia exposure during labor and risk of offspring neurodevelopment delay at age 24 months.

• Study Type: Observational
• Enrollment (Estimated): 5580

Contacts and Locations

• Study Contact: Name: Dong-Xin Wang, MD,PHD; Phone Number: 86-13910731903; Email: wangdongxin@hotmail.com
• Study Contact Backup: Name: Ting Ding, MD; Phone Number: 86-13718803529; Email: athenading01@hotmail.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Recruiting
      • Peking University First Hospital
      • Contact: Ting Ding, MD; Phone Number: 13718803529; Email: athena_d@sina.com
      • Contact: Dong-Xin Wang, MD, PHD; Phone Number: +8610-83572784; Email: wangdongxin@hotmail.com
  • Guangdong
    • Shenzhen, Guangdong, China, 518100
      • Recruiting
      • Shenzhen Maternity and Child Healthcare Hospital
      • Contact: Yuantao Li, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Primiparae between 18 and 35 years of age with term single cephalic pregnancy who undergo regular prenatal examination in the study centers and are preparing to deliver vaginally.

Description

Inclusion Criteria:

1. Primiparae between 18 and 35 years of age with term single cephalic pregnancy;
2. Undergo regular prenatal examination in the study centers;
3. Preparing to deliver vaginally.

Exclusion Criteria:

1. History of psychiatric diseases (indicate those that are diagnosed before or during pregnancy by psychiatrists);
2. History of diseases involving the hypothalamic-pituitary-adrenal axis;
3. Presence of contraindications to epidural analgesia, which includes: (1) History of infectious disease of the central nervous system (poliomyelitis, cerebrospinal meningitis, encephalitis, etc.); (2) History of spinal or intra-spinal disease (trauma or surgery of spinal column, intra-spinal canal mass, etc.); (3) Systemic infection (sepsis); (4) Skin or soft tissue infection at the site of epidural puncture; (5) Coagulopathy.
4. Presence of contraindications to vaginal delivery;
5. Other reasons that are considered unsuitable for study participation.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Neuraxial analgesia exposure; For mothers who accept neuraxial labor analgesia, epidural analgesia or combined spinal-epidural analgesia will be provided according to routine practice of each study center.	Procedure: Neuraxial labor analgesia; Epidural or combined spinal-epidural labor analgesia will be performed according to the routine practice of each study center.
No neuraxial analgesia exposure; For patients who do not accept neuraxial labor analgesia, analgesics will be prescribed by obstetricians according to routine practice.	Procedure: No neuraxial labor analgesia; Neuraxial analgesia will not be performed. Analgesics will be prescribed by the obstetricians according to routine practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of developmental delay in offspring at 24 months of age	The Ages & Stages Questionnaires® in Chinese, 3rd edition (ASQ®-3 Chinese) will be used to detect developmental delays among children from 1 month to 60 months of age. The ASQ®-3 Chinese contains 30 items representing five developmental domains: communication, gross motor, fine motor, problem solving, and personal-social behavior. For each domain, a score that is more than 2 standard deviations below the mean indicates suspected developmental delay. A score below the threshold in any of the 5 domains indicates suspected developmental delay.	At 24 months of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of developmental delay in offspring at 6 and 12 months of age	The Ages & Stages Questionnaires® in Chinese, 3rd edition (ASQ®-3 Chinese) will be used to detect developmental delays among children from 1 month to 60 months of age. The ASQ®-3 Chinese contains 30 items representing five developmental domains: communication, gross motor, fine motor, problem solving, and personal-social behavior. For each domain, a score that is more than 2 standard deviations below the mean indicates suspected developmental delay. A score below the threshold in any of the 5 domains indicates suspected developmental delay.	At 6 and 12 months of age
Maternal intrapartum fever	Defined as the highest maternal temperature ≥38.0℃ during any stage of labor.	Up to the end of childbirth (stage 3)
Neonatal Apgar score <8 at 1 and 5 minutes after delivery	Neonatal Apgar score is assessed and recorded by gynecologists or midwives at 1 and 5 minutes after delivery.	At 1 and 5 minutes after delivery
Histologic chorioamnionitis	According to pathological examination of placenta	Up to hospital discharge
Neonatal infection	Neonatal infection is defined by the occurrence of 1 or more of the following: neonatal sepsis, neonatal uncharacterized infection, neonatal pneumonia, or neonatal necrotizing enterocolitis diagnosed according to the Chinese Classification of Disease and Codes (Version 2.0, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10]) established by the Chinese government.	Within 3 days after birth
Depression score of mothers	Maternal depression is assessed with the Edinburgh Postnatal Depression Scale. A score of 10 or higher is defined the presence of depressive symptoms.	At 42 days, 6 months, 12 months, and 24 months after childbirth

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Use of oxytocin	Use of oxytocin during the intrapartum period.	Up to the end of childbirth (stage 3)
Maternal use of antibiotics	Maternal use of antibiotics	Up to hospital discharge
Neonatal admission to the neonatal intensive care unit	Neonatal admission to the neonatal intensive care unit	Up to hospital discharge
Neonatal use of antibiotics	Neonatal use of antibiotics	Up to hospital discharge
Persistent pain	Persistent or recurrent pain that lasted for more than 1 months after childbirth.	At 42 days postpartum
Covid-19 infection	Covid-19 related information was collect before delivery, including whether participants were infected, during pregnancy, what covid-19 related symptoms they had, whether participants received covid-19 vaccine. Performed in part of enrolled patients.	During pregnancy

Collaborators and Investigators

• Sponsor: Dong-Xin Wang
• Collaborators: Shenzhen Maternity and Child Healthcare Hospital
• Investigators: Principal Investigator: Dong-Xin Wang, MD,PhD, Peking University First Hospital

Publications and helpful links

General Publications

• Liu ZH, He ST, Deng CM, Ding T, Xu MJ, Wang L, Li XY, Wang DX. Neuraxial labour analgesia is associated with a reduced risk of maternal depression at 2 years after childbirth: A multicentre, prospective, longitudinal study. Eur J Anaesthesiol. 2019 Oct;36(10):745-754. doi: 10.1097/EJA.0000000000001058.
• Wong CA. Advances in labor analgesia. Int J Womens Health. 2010 Aug 9;1:139-54. doi: 10.2147/ijwh.s4553.
• Morton S, Kua J, Mullington CJ. Epidural analgesia, intrapartum hyperthermia, and neonatal brain injury: a systematic review and meta-analysis. Br J Anaesth. 2021 Feb;126(2):500-515. doi: 10.1016/j.bja.2020.09.046. Epub 2020 Nov 18.
• Flick RP, Lee K, Hofer RE, Beinborn CW, Hambel EM, Klein MK, Gunn PW, Wilder RT, Katusic SK, Schroeder DR, Warner DO, Sprung J. Neuraxial labor analgesia for vaginal delivery and its effects on childhood learning disabilities. Anesth Analg. 2011 Jun;112(6):1424-31. doi: 10.1213/ANE.0b013e3181f2ecdd. Epub 2010 Aug 24.
• Wall-Wieler E, Bateman BT, Hanlon-Dearman A, Roos LL, Butwick AJ. Association of Epidural Labor Analgesia With Offspring Risk of Autism Spectrum Disorders. JAMA Pediatr. 2021 Jul 1;175(7):698-705. doi: 10.1001/jamapediatrics.2021.0376.
• Wei M, Bian X, Squires J, Yao G, Wang X, Xie H, Song W, Lu J, Zhu C, Yue H, Zhu G, Wang Q, Xu R, Wan C, Sun S, Chen J. [Studies of the norm and psychometrical properties of the ages and stages questionnaires, third edition, with a Chinese national sample]. Zhonghua Er Ke Za Zhi. 2015 Dec;53(12):913-8. Chinese.

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 6, 2021
• First Submitted That Met QC Criteria: July 6, 2021
• First Posted (Actual): July 16, 2021

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 29, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Neuraxial labour analgesia; Neurodevelopmental delay
• Additional Relevant MeSH Terms: Urogenital Diseases; Pain; Neurologic Manifestations; Mental Disorders; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Mood Disorders; Puerperal Disorders; Depressive Disorder; Labor Pain; Depression, Postpartum
• Other Study ID Numbers: 2021-026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No