Intelligence and Neurodevelopmental Outcome After Prenatal Exposure to Labour Epidural Analgesia: a Sibling Matched Clinical Ambidirectional Cohort Study

Primary objective:

To compare the intelligence of children prenatally exposed to labour epidural analgesia with that of sibling matched unexposed children.

Secondary objective(s):

To compare parentally reported traits of ASD, ADHD, ODD and CD of children prenatally exposed to labour epidural analgesia with that of sibling matched unexposed children.

Endpoints:

• Primary endpoint: Wechsler full scale intelligence quotient
• Secondary endpoints: multiple indexes assessed by the Wechsler intelligence scale: verbal comprehension index, visual spatial index, working memory index, fluid reasoning index and processing speed index. Total scores and subscores of the parental questionnaires "social responsiveness scale" (SRS) and "vragenlijst voor gedragsproblemen bij kinderen 6-16" (VvGK6-16) are additional secondary endpoints.

Sample size:

At least 64 prenatally exposed children and 64 prenatally unexposed children

Summary of eligibility criteria:

Dutch speaking sibling pairs discordant for prenatal exposure to labour epidural analgesia will be included. Children born from 1st January 2014 until 1st November 2019 will be included. Children prenatally exposed to maternal surgery, foetal surgery/interventions, chemotherapy, radiotherapy, radiology and oncologic pathology will be excluded. Children with a diagnosis of severe disability of genetic origin (e.g., Fragil X, Down syndrome,…), history of head trauma, major congenital birth defects, children born at a gestational age < 37 weeks or > 42 weeks, or with a birth weight < 2.5 kg will be excluded. Children exposed to general anaesthesia after birth, twins/triplets/multiple births will be excluded. Elective and intrapartum caesarean sections will be excluded.

Maximum duration a research subject remains in the study:

Study will be conducted in 2024-2027. The end of the study for each individual participant is determined by the date at which the neuropsychological testing is planned. Neuropsychological testing usually takes no longer than 2 hours.

Inclusion criteria

• Exposed children: Children prenatally exposed to labour epidural analgesia
• Unexposed children: Sibling of an exposed child, Prenatally not exposed to labour epidural analgesia
• Exposed & unexposed children: Children born from 1st January 2014 until 1st November 2019, Parental informed consent

Exclusion criteria

• Children whose mothers underwent maternal surgery or foetal surgery/interventions during the same pregnancy.
• Children exposed to general anaesthesia after birth
• Children prenatally exposed to chemotherapy, radiotherapy, radiology, oncologic pathology
• Children born at a gestational age < 37 weeks or > 42 weeks, or with a birth weight < 2.5 kg
• Twins, triplets, multiple births
• No Dutch-speaking children
• Diagnosis of severe disability of genetic origin (e.g., Fragil X, Down syndrome,…), history of head trauma, major congenital birth defects
• Elective caesarean section and intrapartum caesarean section (the number of caesarean sections will be reported and compared between both groups)
• Foetus died before start of delivery