Clinical trial NCT04964206: Neuraxial Labor Analgesia and Offspring Neurodevelopment
Official title: Impact of Maternal Neuraxial Labor Analgesia on Offspring Neurodevelopment. A Multicenter, Prospective, Longitudinal Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Offspring, Adult
Labor Pain
Maternal Anesthesia and Analgesia Affecting Fetus or Newborn
Neurodevelopmental Delay
Postpartum Depression
Keywords: Neuraxial labour analgesia
Neurodevelopmental delay
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Obstetrics and Gynecology Hospital
name: Ningxia Women and Children's Hospital
name: Taiyuan central hospital
First posted: 2021-07-16
Enrollment: 5580
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of developmental delay in offspring at 24 months of age
timeFrame: At 24 months of age
Secondary outcomes:
measure: Incidence of developmental delay in offspring at 6 and 12 months of age
timeFrame: At 6 and 12 months of age
measure: Maternal intrapartum fever
timeFrame: Up to the end of childbirth (stage 3)
measure: Neonatal Apgar score <8 at 1 and 5 minutes after delivery
timeFrame: At 1 and 5 minutes after delivery
measure: Histologic chorioamnionitis
timeFrame: Up to hospital discharge
measure: Neonatal infection
timeFrame: Within 3 days after birth
measure: Depression score of mothers
timeFrame: At 42 days, 6 months, 12 months, and 24 months after childbirth
Other outcomes:
measure: Use of oxytocin
timeFrame: Up to the end of childbirth (stage 3)
measure: Maternal use of antibiotics
timeFrame: Up to hospital discharge
measure: Neonatal admission to the neonatal intensive care unit
timeFrame: Up to hospital discharge
measure: Neonatal use of antibiotics
timeFrame: Up to hospital discharge
measure: Persistent pain
timeFrame: At 42 days postpartum
measure: Covid-19 infection
timeFrame: During pregnancy
Locations:
city: Beijing
country: China
facility: Beijing University First Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Gynecological and obstetrical hospital
state: Beijing
city: Yinchuan
country: China
facility: Ningxia Women and Children's Hospital
state: Ningxia
city: Taiyuan
country: China
facility: Taiyuan Central Hospital
state: Shanxi
Study officials:
affiliation: Peking University First Hospital
name: Dong-Xin Wang, MD,PHD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Wong CA. Advances in labor analgesia. Int J Womens Health. 2010 Aug 9;1:139-54. doi: 10.2147/ijwh.s4553.
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.
citation: 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.
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.
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.