Behavioral effects of pain medications

Increased risk of adverse neurodevelopmental outcomes following prenatal non-prescription paracetamol exposure

2018 Study Highlights

  • All nine studies suggest prenatal APAP is associated with adverse neurodevelopment.
  • These neurodevelopmental endpoints include ADHD, ASD and lower IQ.
  • Associations were strongest for hyperactivity and attention-related outcomes.
  • Controlling for indication for use, when possible, did not explain associations.
  • Given these findings, pregnant women should be cautioned against indiscriminate APAP use.


The non-prescription medication paracetamol (acetaminophen, APAP) is currently recommended as a safe pain and fever treatment during pregnancy. However, recent studies suggest a possible association between APAP use in pregnancy and offspring neurodevelopment.

To conduct a review of publications reporting associations between prenatal APAP use and offspring neurodevelopmental outcomes.

Relevant sources were identified through a key word search of multiple databases (Medline, CINAHL, OVID and TOXNET) in September 2016. All English language observational studies of pregnancy APAP and three classes of neurodevelopmental outcomes (autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and intelligence quotient (IQ)) were included. One reviewer (AZB) independently screened all titles and abstracts, extracted and analyzed the data.

64 studies were retrieved and 55 were ineligible. Nine prospective cohort studies fulfilled all inclusion criteria. Data pooling was not appropriate due to heterogeneity in outcomes. All included studies suggested an association between prenatal APAP exposure and the neurodevelopmental outcomes; ADHD, ASD, or lower IQ. Longer duration of APAP use was associated with increased risk. Associations were strongest for hyperactivity and attention-related outcomes. Little modification of associations by indication for use was reported.

Together, these nine studies suggest an increased risk of adverse neurodevelopmental outcomes following prenatal APAP exposure. Further studies are urgently needed with; precise indication of use and exposure assessment of use both in utero and in early life. Given the current findings, pregnant women should be cautioned against indiscriminate use of APAP. These results have substantial public health implications.

Behavioral effects of birth control pills

Developmental estrogen exposures and disruptions to maternal behavior and brain: Effects of ethinyl estradiol, a common positive control

2018 Study Highlights

  • Developmental EE2 exposure increases time spent on maternal self-care.
  • Pups born to EE2-treated females were less likely to initiate nursing on LD14.
  • Exposure to EE2 altered ERα expression in the MPOA both early and late in lactation.
  • Developmental EE2 exposure decreased dopaminergic cells in the VTA on LD2.
  • Effects of EDCs on maternal behavior depend on chemical and period of exposure.


Due of its structural similarity to the endogenous estrogen 17β-estradiol (E2), the synthetic estrogen 17α-ethinyl estradiol (EE2) is widely used to study the effects of estrogenic substances on sensitive organs at multiple stages of development.

Here, we investigated the effects of EE2 on maternal behavior and the maternal brain in females exposed during gestation and the perinatal period.

We assessed several components of maternal behavior including nesting behavior and pup retrieval; characterized the expression of estrogen receptor (ER)α in the medial preoptic area (MPOA), a brain region critical for the display of maternal behavior; and measured expression of tyrosine hydroxylase, a marker for dopaminergic cells, in the ventral tegmental area (VTA), a brain region important in maternal motivation.

We found that developmental exposure to EE2 induces subtle effects on several aspects of maternal behavior including time building the nest and time spent engaged in self-care. Developmental exposure to EE2 also altered ERα expression in the central MPOA during both early and late lactation and led to significantly reduced tyrosine hydroxylase immunoreactivity in the VTA.

ur results demonstrate both dose- and postpartum stage-related effects of developmental exposure to EE2 on behavior and brain that manifest later in adulthood, during the maternal period. These findings provide further evidence for effects of exposure to exogenous estrogenic compounds during the critical periods of fetal and perinatal development.

About perimenopausal and postmenopausal women using hormones treatment

Barbara Seaman, New York University, 2003

Barbara Seaman, American author, activist, and journalist, talks.

Should Doctors Consider Body Size When Prescribing Drugs ?

Does a one-size-fits-all strategy works fine for many medications ?

“Children are the special case in which weight-based dosing is always required.

For adults, shouldn’t doctors take into account body size when prescribing drugs?

As a small female, I worry about getting the same dosage of antibiotics as men who weigh 100 pounds more than I do.”

Read the debate on ASK WELL, nytimes, 2018/06/08.