Acetaminophen_Exposure/effect relationship (metaPreg)

Exposed non-exposed, cohort studies

Study Country
Study period
Study design		 Data source Exposure definition Non-exposure definition Exposition period Sample size
(exposed/unexposed) Or (case / control)		 Remarks Risk of bias
Ahlqvist_High exposure
2024 		Sweden
1995 - 2019
population based cohort retrospective 		The Swedish Medical Birth Register, the Prescribed Drug Register and the National Patient Register. Children exposed to acetaminophen (ATC: N02BE) during pregnancy (ever-use). unexposed (general population or NOS)
Children not exposed to acetaminophen (ATC: N02BE) during pregnancy. 		during pregnancy (anytime or not specified) 185909 / 2294888
1995-2019: Prospective collection during the first antenatal visit (typically at 8-10 weeks’ gestation), during which midwives conducted structured interviews (including OTC), and later in pregnancy by the midwife and physician. From 2005: supplemented with Prescribed Drug Register.
Ahlqvist_Low exposure
2024 		Sweden
1995 - 2019
population based cohort retrospective 		The Swedish Medical Birth Register, the Prescribed Drug Register and the National Patient Register. Children exposed to acetaminophen (ATC: N02BE) during pregnancy (ever-use). unexposed (general population or NOS)
Children not exposed to acetaminophen (ATC: N02BE) during pregnancy. 		during pregnancy (anytime or not specified) 185909 / 2294888
1995-2019: Prospective collection during the first antenatal visit (typically at 8-10 weeks’ gestation), during which midwives conducted structured interviews (including OTC), and later in pregnancy by the midwife and physician. From 2005: supplemented with Prescribed Drug Register.
Ahlqvist_Medium exposure
2024 		Sweden
1995 - 2019
population based cohort retrospective 		The Swedish Medical Birth Register, the Prescribed Drug Register and the National Patient Register. Children exposed to acetaminophen (ATC: N02BE) during pregnancy (ever-use). unexposed (general population or NOS)
Children not exposed to acetaminophen (ATC: N02BE) during pregnancy. 		during pregnancy (anytime or not specified) 185909 / 2294888
1995-2019: Prospective collection during the first antenatal visit (typically at 8-10 weeks’ gestation), during which midwives conducted structured interviews (including OTC), and later in pregnancy by the midwife and physician. From 2005: supplemented with Prescribed Drug Register.
Liew_High exposure
2014 		Denmark
1996 - 2002
prospective cohort 		The Lifestyle During Pregnancy Study (LDPS), a sub-cohort nested within the Danish National Birth Cohort (DNBC), combined with the Danish National Hospital Registry, the Danish Psychiatric Central Registry and the Danish Prescription Registry. Children born to mothers who reported use of acetaminophen during the entire pregnancy or during the first (1-12 weeks), second (13-24 weeks), or third (25th-delivery) trimester. unexposed (general population or NOS)
Children born to mothers who never used acetaminophen during pregnancy or the reported period of exposure. 		during pregnancy (anytime or not specified) 36187 / 28135 Methods completed with Liew 2016. Overlapping: For ADHD: Liew 2016a studied Attention and Liew 2014 studies ADHD medication or hyperkinetic disorder (with same dataset) => only 1 result reported: the most global and robust: i.e Liew 2014 (ICD-10).
Paracetamol use was collected in three computer-assisted telephone interviews conducted at gestational weeks 12 and 30 and 6 months postpartum. At each interview, mothers were asked if they had taken acetaminophen as a singular or combination drug available over the counter or via prescription.
Liew_Low exposure
2014 		Denmark
1996 - 2002
prospective cohort 		The Lifestyle During Pregnancy Study (LDPS), a sub-cohort nested within the Danish National Birth Cohort (DNBC), combined with the Danish National Hospital Registry, the Danish Psychiatric Central Registry and the Danish Prescription Registry. Children born to mothers who reported use of acetaminophen during the entire pregnancy or during the first (1-12 weeks), second (13-24 weeks), or third (25th-delivery) trimester. unexposed (general population or NOS)
Children born to mothers who never used acetaminophen during pregnancy or the reported period of exposure. 		during pregnancy (anytime or not specified) 36187 / 28135 Methods completed with Liew 2016. Overlapping: For ADHD: Liew 2016a studied Attention and Liew 2014 studies ADHD medication or hyperkinetic disorder (with same dataset) => only 1 result reported: the most global and robust: i.e Liew 2014 (ICD-10).
Paracetamol use was collected in three computer-assisted telephone interviews conducted at gestational weeks 12 and 30 and 6 months postpartum. At each interview, mothers were asked if they had taken acetaminophen as a singular or combination drug available over the counter or via prescription.
Liew_Medium exposure
2014 		Denmark
1996 - 2002
prospective cohort 		The Lifestyle During Pregnancy Study (LDPS), a sub-cohort nested within the Danish National Birth Cohort (DNBC), combined with the Danish National Hospital Registry, the Danish Psychiatric Central Registry and the Danish Prescription Registry. Children born to mothers who reported use of acetaminophen during the entire pregnancy or during the first (1-12 weeks), second (13-24 weeks), or third (25th-delivery) trimester. unexposed (general population or NOS)
Children born to mothers who never used acetaminophen during pregnancy or the reported period of exposure. 		during pregnancy (anytime or not specified) 36187 / 28135 Methods completed with Liew 2016. Overlapping: For ADHD: Liew 2016a studied Attention and Liew 2014 studies ADHD medication or hyperkinetic disorder (with same dataset) => only 1 result reported: the most global and robust: i.e Liew 2014 (ICD-10).
Paracetamol use was collected in three computer-assisted telephone interviews conducted at gestational weeks 12 and 30 and 6 months postpartum. At each interview, mothers were asked if they had taken acetaminophen as a singular or combination drug available over the counter or via prescription.
Ystrom_High dose
2017 		Norway
1999 - 2009
prospective cohort 		The Norwegian Mother and Child Cohort Study (MoBa), linked with the Norwegian Patient Registry. Pregnant women that reported use of acetaminophen during pregnancy. unexposed (general population or NOS)
Pregnant women that reported never use of acetaminophen during pregnancy. 		during pregnancy (anytime or not specified) 52707 / 60266 Overlapping: Gustavson 2019 and Stoltenberg 2020 => 2 ad hoc studies (dedicated to fever indication and methodological one, respectively) essentially based on the same dataset than Ystrom 2017 (prenatal acetaminophen and ADHD) => use of Ystrom 2017.
Information on acetaminophen use was obtained through MoBa questionnaires, at week 18, week 30, and 6 months postpartum. The mother could name the medication taken in an open textbox and specify the exposure windows (total calculated across all exposure windows).
Ystrom_Low dose
2017 		Norway
1999 - 2009
prospective cohort 		The Norwegian Mother and Child Cohort Study (MoBa), linked with the Norwegian Patient Registry. Pregnant women that reported use of acetaminophen during pregnancy. unexposed (general population or NOS)
Pregnant women that reported never use of acetaminophen during pregnancy. 		during pregnancy (anytime or not specified) 52707 / 60266 Overlapping: Gustavson 2019 and Stoltenberg 2020 => 2 ad hoc studies (dedicated to fever indication and methodological one, respectively) essentially based on the same dataset than Ystrom 2017 (prenatal acetaminophen and ADHD) => use of Ystrom 2017.
Information on acetaminophen use was obtained through MoBa questionnaires, at week 18, week 30, and 6 months postpartum. The mother could name the medication taken in an open textbox and specify the exposure windows (total calculated across all exposure windows).
Ystrom_Medium dose
2017 		Norway
1999 - 2009
prospective cohort 		The Norwegian Mother and Child Cohort Study (MoBa), linked with the Norwegian Patient Registry. Pregnant women that reported use of acetaminophen during pregnancy. unexposed (general population or NOS)
Pregnant women that reported never use of acetaminophen during pregnancy. 		during pregnancy (anytime or not specified) 52707 / 60266 Overlapping: Gustavson 2019 and Stoltenberg 2020 => 2 ad hoc studies (dedicated to fever indication and methodological one, respectively) essentially based on the same dataset than Ystrom 2017 (prenatal acetaminophen and ADHD) => use of Ystrom 2017.
Information on acetaminophen use was obtained through MoBa questionnaires, at week 18, week 30, and 6 months postpartum. The mother could name the medication taken in an open textbox and specify the exposure windows (total calculated across all exposure windows).

Case-control studies

Study Country
Study period
Study design		 Data source Case Control Exposition Exposition period Sample size
(exposed/unexposed) Or (case / control)		 Remarks Risk of bias

Risk of bias: : NA;   : low;   : moderate;   : serious;   : critical;   : unclear;  

Empty. There are no case-control studies available for this drug.

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