28 June 2017

Second Trimester Fevers Increase Autism Risks 40%

A new study finds that fevers in pregnant women during the second trimester increase the risk of a child with autism by 40%. The magnitude of this effect closely matches estimates from previous independent studies. The sample size is 95,000 (which is just barely big enough to measure these effects), while most other fevers are not as definitvely associated with autism risk.
The link is strongest in the second trimester, when a single fever is associated with a 40 percent increase in autism risk. Three or more fevers after the first trimester triples the risk of having a child with autism, according to the study, which appeared 13 June in Molecular Psychiatry. 
The findings support the idea that a pregnant woman’s immune response, which often includes fever, can disrupt brain development in the fetus, says lead researcher Mady Hornig, associate professor epidemiology at the Columbia University. 
The study is inconclusive on whether drugs that lower fever mitigate the risk, but the results hint that they might, says Sarkis Mazmanian, professor of biology at the 
California Institute of Technology. . . .

15,701 of the mothers reported on a health questionnaire that they’d had one or more fevers while pregnant. The team followed all of the participants’ children until they reached age 9, on average, and found that 583 received an autism diagnosis.

The timing of the fever matters for autism risk, the researchers found. Compared with the 40 percent increase in the second trimester, having a fever in the first trimester carries a 34 percent increase in the risk of autism, but that result is not statistically significant. Having a fever in the third semester has no effect on autism risk.

The researchers also found a dose-response relationship for fever: The increase in risk ranges from 30 percent throughout pregnancy for one or two episodes of fever, to more than threefold for three or more episodes in the second trimester and beyond.

Still, the vast majority of women who have a fever during pregnancy do not have a child with autism and the absolute increase in risk is small. Even among mothers who had three or more fevers, only 5 out of 308 children (about 1.6 percent) have autism, compared with 376 of 65,502 children (about 0.6 percent) whose mothers reported no fevers. . . .
Hornig’s team examined whether medications that lower body temperature would reduce the risk. More than 5,600 women took acetaminophen for fever during their second trimester. The team found an association between acetaminophen use and a decrease in autism risk, but it was not statistically significant. Only 161 women took ibuprofen during the second trimester, and none of them have a child with autism. (About half of pregnant women use acetaminophen at least once, but doctors generally advise against ibuprofen use during pregnancy.) . . .
A 2013 study led by Hertz-Picciotto found that drugs that lower fever mitigate the increase in autism risk associated with fever. 
The mechanism for fevers to cause autism in a fetus might include autoimmune responses and/or inflammation (which aren't mutually exclusive - inflammation is one type of autoimmune response).

Autism has a strong genetic component, although it appears that a lot of the risk comes from de novo mutations that were not present in either of the parents when they were born. It also appears that women have protective genes that are absent in men that mitigate autism symptoms or prevent them from arising.

Baseline autism spectrum disorder risk is on the order of 1% of all births (comprising a large share of symptoms previously classified as cognitive developmental disorders not otherwise classified), so it is closer to 1.4% percent for pregnant women who have fevers in the second trimester (a scenario consistent with the notion that the anatomical systems that develop in this time period during gestation are the ones that are associated with autism).

But, if the 40% figure is to be applied on a case by case basis, rather than across the board (which isn't clear from the media report that I link) the concern may be much more of a concern in pregnancies where this is a high risk of autism (e.g. in cases where the father is middle aged or older, where there is a family history of sub-clinical autism-like personality traits, and where the fetus is male), than in pregnancies where no autism risk factors are present. 

On the other hand, if this is an across the board increase in risk, that does not interact with other risk factors, then second trimester fevers may be the main source of risk in otherwise low autism risk pregnancies, while it is a minor consideration relative to other risk factors in high autism risk pregnancies.

This is one of only a handful of well documented environmental causes of autism, which has a strong genetic component. Another is exposure of the parents to agricultural chemicals (before conception in the case of fathers and during gestation in the case of mothers).

27 June 2017

Yet More SCOTUS Rulings

There were five new merits decisions from the U.S. Supreme Court on Monday which combined with orders entered today, wraps up the year (the October 2016 session) for the court.

* CALPERS v. ANZ Securities. The three year statute of repose for a suit alleging false statements in a registration statement is not tolled for individual claims while a class action lawsuit is pending. The decision is 5-4 involving the usual suspects. The dissent argues that individual claims of people who opt out of a class action are effectively part of the same civil action and hence are not untimely. But, the court takes an anti-class action stance once again.

* Davila v. Davis. A trial lawyer for a defendant convicted and sentenced to death preserved an arguably valid legal objection at trial, but the appellate lawyer for the defendant failed to raise the issue on appeal in conduct that arguably constituted ineffective assistance of counsel. The habeas corpus lawyer then failed to timely raise the issue of the appellate lawyer's ineffective assistance of counsel, which was arguably a second distinct instance of ineffective assistance of counsel. But, SCOTUS holds that ineffective assistance of habeas counsel in failing to point out ineffectively assistance of counsel by appellate counsel, is not sufficient to overcome the usual deadline for complaining about ineffective assistance of counsel by the appellate counsel. If the mistake had been made by trial counsel and habeas counsel, rather than appellate counsel and habeas counsel, review would have been available. The decision is 5-4 involving the usual suspects. Justice Thomas emphasizes the fact that there is no constitutional right to a criminal appeal (which is true, but generally irrelevant when there is a statutory right to a criminal appeal as there is in every state).

Trinity Lutheran Church of Columbia, Inc. v. Comer. A state constitutional provision barring any public assistance for religious schools is held unconstitutional as applied to a religious school seeking a grant for rubberized surface material upgrades in a playground. The Court distinguishes between being denied benefits because one is a religious institution and being denied benefits because it would use the benefits for religious purposes (which the Court has previously held is permissible). The decision is 7-2 with Thomas and Gorsuch providing one concurring opinion and Breyer concurring in judgment only.  Thomas and Gorsuch would overturn Locke which held that denying funds that could be used for religious purposes is permissible. Breyer focuses on a narrow ruling limited to "a general program designed to secure or to improve the health and safety of children.", that has no religious content. Sotomayor and Ginsburg, in dissent emphasize that the Court is "holding, for the first time, that the Constitution requires the government to provide public funds directly to a church." This is contrary to state constitutions in more than 30 states including Colorado. It isn't clear if the conservatives have the votes to extend this to voucher cases like the one arising in Douglas County, Colorado's schools that would have allowed high school vouchers to be used for private religious schools at the K-12 level whose instruction would be explicitly religious, which were remanded for reconsideration by the Colorado Supreme Court in light of this opinion. A New Mexico case involving closer facts was also remanded to be reconsidered in light of this opinion. This case could portend a major change in establishment clause jurisprudence, or could involve only a narrow exception to existing law with little material impact.

Hernandez v. Mesa, per curiam. The case is a Bivens action against a border guard is shot and killed a 15 year old Mexican boy on the other side of the border from the U.S. for no justifiable reason. The legal standard to determine if a Bivens action is available was clarified in a recently decided SCOTUS case (which is generally favorable to the government and was decided with a four justice plurality that might not have had the same result if all justices participated) and the high court disagreed with one aspect of the Court of Appeals' analysis of the facts (which is generally favorable to the Mexican boy's estate). The Court remanded to the Court of Appeals to reconsider the case in light of the new law and a differently applied factual issue before SCOTUS addresses the merits of the case, with procedural issues to be decided first in order to avoid the substantive law question if possible. It is quite likely that the Court of Appeals, on remand, will deny the boy's estate a right to bring a Bivens action and that the case may return to the U.S. Supreme Court for further review, either way.

Trump v. International Refugee Assistance Project, per curiam. The Court grants cert with regard to the Trump administration's Muslim ban on an expedited briefing schedule, sustaining the stay of the ban as to some people affected by it, while terminating the stay as applied to people with "no connection to the United States at all", pending resolution of the case by SCOTUS. This effectively reinstates the ban as to many refugees who had been fully vetted and has visas in place in a manner that will probably render their case moot by the time that the Court can hear it on the merits (since the ban was proposed to be for 90 days). But, since the stay was in place for a significant period of time pending this order, many such people will have already entered the United States at this point.