Prenatal exposure to paracetamol and the risk of urogenital system disorders or neurodevelopmental disorders in offspring: a systematic review of observational studies

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Systematic review and meta-analysis

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  PARACETAMOL
• Medical condition to be studied:
  Cryptorchism

  Hypospadias

  Attention deficit hyperactivity disorder

  Autism spectrum disorder
• Additional medical condition(s):
  Urogenital system disorders: cryptorchidism, late descent, anogenital distance (AGD) and other genital development outcomes such as penile length, penile width, testicular descent distance and hypospadia.Neurodevelopmental disorders: due to the different rating scales used, the outcomes of interest were broadly grouped into motor problems, behavioural problems, temperament problems, ADHD, ASD

Population studied

• Short description of the study population:
  Pregnant women who had paracetamol exposure during pregnancy.
• Age groups:
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 years)
  • Adults (65 to < 75 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  700000

Study design details

• Main study objective:
  The aim of this systematic review is to provide an overview of the available observational studies looking at the association between maternal paracetamol exposure during pregnancy and the risk of neurodevelopment disorders and urogenital system disorders in offspring.
• Outcomes:
  Urogenital system disorders: cryptorchidism, late descent, anogenital distance (AGD) and other genital development outcomes such as penile length, penile width, testicular descent distance and hypospadia.Neurodevelopmental disorders: due to the different rating scales used, the outcomes of interest were broadly grouped into motor problems, behavioural problems, temperament problems, ADHD, ASD
• Data analysis plan:
  The interpretation of studies was based upon distinguishing between different comparisons and reference groups reported for the included observational studies. The rationale for this approach is that, for associations where a potential confounding by indication might affect the evaluation, assessment of causality may be better informed by assessing associations from different comparison/reference groups and study designs.