B3225 - Acetaminophen Exposure in Utero and Subsequent Impact on Female Reproductive Function - 12/12/2018

B number: 
B3225
Principal applicant name: 
Katherine Cameron | University of Pennsylvania (USA)
Co-applicants: 
Abigail Fraser PhD
Title of project: 
Acetaminophen Exposure in Utero and Subsequent Impact on Female Reproductive Function
Proposal summary: 

The number of eggs in a woman’s ovaries is determined by a) how many eggs she was born with, and b) how quickly they diminish during her lifespan. Because the total number of eggs she will ever have is established while forming in her mother’s womb, it is important to know if there are any factors in that prenatal environment that may affect the development of the eggs within the ovaries. Women with fewer eggs may suffer later in life from infertility or early menopause. Several studies have shown through experiments with animals that paracetamol taken by the mother while pregnant may have harmful effects on the reproductive function of the resulting female offspring. However, no studies have examined this in humans. In animal models, there are three proposed mechanisms for the effects seen in the female offspring: 1) disruption of the chemical signaling from the brain to the ovaries to induce puberty, resulting in earlier age of the onset of periods (which in human studies may be associated with earlier onset of menopause), 2) disruption of the natural menstrual cycle, resulting in shorter menstrual periods (which in human studies may be associated with earlier onset of menopause), and 3) formation of fewer follicles (eggs) in the ovaries, which can be approximated by measurement of anti-mullerian hormone (AMH) in the blood. Given that paracetamol is used worldwide as the analgesic of choice during pregnancy it is of critical importance that large-scale studies of humans be performed to investigate this association. This study will look at children of mothers who did and did not use paracetamol during their pregnancies and compare 1) the age of their first period, 2) how regular their periods are, and 3) their AMH levels.

Impact of research: 
This will be the first epidemiologic investigation of in utero paracetamol exposure on female reproductive dysfunction. While there have been several animal studies demonstrating deleterious effects of paracetamol in therapeutic doses to female offspring reproductive function, this has not been demonstrated in humans. If this study does show an association of paracetamol exposure with earlier onset if menarche, increased incidence of menstrual irregularity, or lower AMH levels this will suggest that there may be an effect in humans and may indicate a possible mechanism. This would have major public health implications as paracetamol is currently the analgesic of choice for women in pregnancy. If there are no findings from this investigation associating paracetamol use with reproductive outcomes then this is reassuring for the population of pregnant women who rely on paracetamol to treat pain in pregnancy.
Date proposal received: 
Monday, 10 December, 2018
Date proposal approved: 
Wednesday, 12 December, 2018
Keywords: 
Epidemiology, Fertility/infertility, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Endocrine - endocrine disrupters, Environment - enviromental exposure, pollution, Puberty