Neuraxial Labor Analgesia and Offspring Neurodevelopment

Study Overview
=================
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.

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

Conditions
-----------------
Offspring, Adult, Labor Pain, Maternal Anesthesia and Analgesia Affecting Fetus or Newborn, Neurodevelopmental Delay, Postpartum Depression

Intervention / Treatment
-----------------
* Procedure: Neuraxial labor analgesia
* Procedure: No neuraxial labor analgesia


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Primiparae between 18 and 35 years of age with term single cephalic pregnancy; Undergo regular prenatal examination in the study centers; Preparing to deliver vaginally. Exclusion Criteria: History of psychiatric diseases (indicate those that are diagnosed before or during pregnancy by psychiatrists); History of diseases involving the hypothalamic-pituitary-adrenal axis; 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. Presence of contraindications to vaginal delivery; Other reasons that are considered unsuitable for study participation.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Neuraxial analgesia exposure<br>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<br>* Epidural or combined spinal-epidural labor analgesia will be performed according to the routine practice of each study center.<br>|
| No neuraxial analgesia exposure<br>For patients who do not accept neuraxial labor analgesia, analgesics will be prescribed by obstetricians according to routine practice. | Procedure: No neuraxial labor analgesia<br>* Neuraxial analgesia will not be performed. Analgesics will be prescribed by the obstetricians according to routine practice.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Neuraxial labour analgesia, Neurodevelopmental delay