Neuraxial Labor Analgesia and Offspring Neurodevelopment

Labor Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04964206
• Other study ID #: 2021-026
• Status: Recruiting
• Start date: October 14, 2022
• Est. completion date: May 2026

Study information

• Verified date: April 2023
• Source: Peking University First Hospital
• Contact: Dong-Xin Wang, MD,PHD
• Phone: 86-13910731903
• Email: wangdongxin[@]hotmail.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5580
• Est. completion date: May 2026
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression, Postpartum
• Labor Pain
• Neurodevelopmental Delay
• Offspring, Adult
• Postpartum Depression

Intervention

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 labor analgesia
Neuraxial analgesia will not be performed. Analgesics will be prescribed by the obstetricians according to routine practice.

Locations

Country	Name	City	State
China	Beijing Gynecological and obstetrical hospital	Beijing	Beijing
China	Beijing University First Hospital	Beijing	Beijing
China	Taiyuan Central Hospital	Taiyuan	Shanxi
China	Ningxia Women and Children's Hospital	Yinchuan	Ningxia

Sponsors (4)

Lead Sponsor	Collaborator
Dong-Xin Wang	Beijing Obstetrics and Gynecology Hospital, Ningxia Women and Children's Hospital, Taiyuan central hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Wong CA. Advances in labor analgesia. Int J Womens Health. 2010 Aug 9;1:139-54. doi: 10.2147/ijwh.s4553. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Use of oxytocin	Use of oxytocin during the intrapartum period.	Up to the end of childbirth (stage 3)
Other	Maternal use of antibiotics	Maternal use of antibiotics	Up to hospital discharge
Other	Neonatal admission to the neonatal intensive care unit	Neonatal admission to the neonatal intensive care unit	Up to hospital discharge
Other	Neonatal use of antibiotics	Neonatal use of antibiotics	Up to hospital discharge
Other	Persistent pain	Persistent or recurrent pain that lasted for more than 1 months after childbirth.	At 42 days postpartum
Other	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
Primary	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	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
Secondary	Maternal intrapartum fever	Defined as the highest maternal temperature =38.0? during any stage of labor.	Up to the end of childbirth (stage 3)
Secondary	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
Secondary	Histologic chorioamnionitis	According to pathological examination of placenta	Up to hospital discharge
Secondary	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
Secondary	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