tylenol in pregnancy, and differing interpretations of serious women vs men

the NY Times had a couple of interesting articles recently:

1. they had an opinion piece on the potential adverse effects of acetaminophen in pregnancy (see http://www.nytimes.com/2016/09/25/opinion/sunday/the-trouble-with-tylenol-and-pregnancy.html ), which was prompted by a recent article in JAMA Pediatrics (see acetaminophen and pregnancy jamapedi2016 in dropbox, or doi:10.1001/jamapediatrics.2016.1775 ), but they also make the following points (I added some of the scientific details and provided references to some relevant studies):

--experiments show that acetaminophen impedes our ability to empathize (eg, see Mischkowski D. Soc Cogn Affect Neurosci. 2016; 11: 1345)

--it suppresses the immune response after vaccination, eg with combo of pneumococcal and DTaP vaccines (see Prymula R. Lancer 2009; 374 (9698): 1339). One study found that in patients infected with rhinovirus, acetaminophen suppressed serum neutralizing antibody response and increased symptoms (see Graham NM J Infect Dis 1990; 162(6):1277)

--there has been speculation that by depleting glutathione (an antioxidant), acetaminophen could increase lung inflammation and the incidence of asthma (a Norwegian study found that prenatal acetaminophen increased 7 yo kids’ risk of asthma by 13% and postnatal exposure by 29% --see Magnus MC. Int. J Epidemiol 2016 -- doi: 10.1093/ije/dyv366)

--and, the study below…

--7796 mothers from the prospective birth cohort study ALSPAC (Avon Longitudinal Study of Parents and Children) in Bristol, England,  enrolled in 1991

--maternal age 29, gestational age 39 weeks, birth wt 3.4 kg, maternal prepregnancy BMI 23, 16% low SES/42% intermediate/42% high, 93% no maternal psychiatric illness, 82% never smoked during pregnancy, 45% never drank during pregnancy

--assessed acetaminophen use when 18 and 32 weeks pregnant, and then again postnatally when kid was 61 months; then assessed kid’s development at 7 yo

--results:

            --overall, 5% of the kids had behavioral problems, at mean age of 79 months

            --acetaminophen use at 18 weeks, associated with behavioral issues in kids:

                        --20% increased risk of conduct problems, RR 1.20 (1.06-1.37)

                        --23% increased risk of hyperactivity symptoms, RR 1.23 (1.08-1.39)

            --acetaminophen use at 32 weeks, behavioral issues in kids:

                        --46% increased risk of SDQ difficulties, RR 1.46 (1.21-1.77) [SDQ, Strengths and Difficulties Questionnaire, is validated test of  behavioral issues in kids, including emotional symptoms, conduct problems, hyperactivity symptoms, peer relationships, pro-social behaviors]

                        --29% increased risk of emotional symptoms, RR 1.29 (1.09-1.53)

                        --42% increased risk of conduct problems, RR 1.42 (1.25-1.62)

                        --31% increased risk of hyperactivity symptoms, RR 1.31 (1.16-1.49)

            --postnatal acetaminophen use: NO significant increase in behavioral issues in kids; also none with partner’s use at 61 months postnatal visit (97% of the partners stated they were the biological fathers)

--none of these increases in developmental issues in kids changed when controlling for postnatal acetaminophen use

            --there was no significant relationship between maternal ADHD polygenic risk scores (a composite score of molecular risk factors for ADHD from available genotype data. see paper for details) and maternal prenatal acetaminophen use at 18 or 32 weeks, or postnatally

Commentary:

** >50% of pregnant women in the US use acetaminophen (50-60% in the EU)

**Animal studies suggest that acetaminophen is hardly benign: if given to mice during neonatal brain development, cognitive function is affected as well as change in BNDF (brain-derived neurotrophic factor). Also there are endocrine effects: long-term acetaminophen Is associated with increased risk of cryptorchidism

** Proposed mechanism?? some thoughts: acetaminophen does cross the placenta, and animal studies have found that the fetus can produce toxic metabolites of acetaminophen; acetaminophen reduces serum antioxidants and could thereby increase oxidant stresses.

** A Danish National Birth Cohort study found increased ADHD when acetaminophen is used during pregnancy. Also found in New Zealand study. And a large Norwegian found that kids exposed prenatally to acetaminophen for >28 days had poorer gross motor development, communication, externalizing behavior, and higher activity levels. Those exposed but to <28 days, had poorer gross motor outcomes, though less so than with greater exposure

** This current study tried to control somewhat for confounding (ie, looking at use in mothers when not pregnant, to see if there was an underlying non-pregnancy related condition which led to increased acetaminophen use as well as to neurodevelopmental problems with the kid; assessing partner use as a ??marker of social/familial stressors)

** The association of neurodevelopmental issues in kids was more pronounced when acetaminophen was taken in the 3^rd trimester, in concordance with other studies.

** Unfortunately no data available on why women were taking the acetaminophen, only their usage

** So, this is a tough one. Given the adverse effects of NSAIDs, most women are steered towards acetaminophen for pain relief. Though it is hard to come to definitive conclusions based on the above data, and it is pretty unethical to do a real RCT where some women are randomized to acetaminophen and others to placebo; so we may never know for sure. Based on the above, it certainly makes sense to avoid acetaminophen for minor indications. And, it makes sense to use nonpharmacologic remedies to the extent possible (massage therapy for pain, yoga, etc)

2. a rather striking "gray matter" piece by Lisa Feldman Barrett, a psychology professor at Northeastern University, who has explored the interpretation of similar facial expressions by men and women (see http://www.nytimes.com/2016/09/25/opinion/sunday/hillary-clintons-angry-face.html ​). details:

--the head of the Republican National Committee tweeted after a speech by Hillary Clinton that she was "angry and defensive the entire time -- no smile and uncomfortable", which brought up the issue: are women who are serious viewed differently from men??

--a study by the author (Dr Feldman Barrett) in the journal Emotion in 2009 (see doi.org/10.1037/a0016821 ): participants were shown photos of male and female faces (eg with smiles, frowns, widened eyes) and asked why they thought he face was that way.  The participants viewed the women as being emotional (an internal expression), whereas the men were felt to be reacting to an external situation (the are "just having a bad day")

--a further study used the same computer-generated androgynous faces, but with gender-typical hair. The participants were again more likely to attribute the exact same facial expression as from an internal, emotional cause in those photos with female-looking hair, and an external situational cause in those with male-looking hair

--this discrepancy might be at least partially responsible for some documented issues:

    --women who visit the ER for chest pain and shortness of breath are more likely than men to be dismissed as having anxiety, and perhaps this is part of the reason women end up dying more frequently from heart attacks

    --when a woman "violates her emotion stereotype" she is more likely to be seen as less likable and less trustworthy. One example is in court when women accuse men of rape or domestic violence. If a woman expresses grief on the witness stand, the judge is more likely to give the perpetrator a harsher sentence. If she expresses anger (ie violating the stereotype of being passive, helpless), the perpetrator tends to get a lighter sentence

--and, as the author concludes, though Hillary is generally seen as a more credible candidate, when she acts "presidential", she is interpreted as being harsh and cold. Trump, on the other hand, can make outrageous comments about immigrants and be interpreted that his anger being situational ("he is just upset about terrorism”)……..