Avian Flu Diary: Of Pregnancy, Flu & Autism

Photo Credit – CDC

# 6711

We’ve known for a long time that influenza during pregnancy can endanger the mother, and unborn child’s life. Furthermore, it appears that pregnant women are more susceptible to influenza than are non-pregnant women.

Why is not exactly known, although it is theorized that the normal protections of a woman's immune system are temporarily altered to allow her to carry what is essentially a foreign body - a fetus - without rejection.

During the 2009 H1N1 pandemic pregnant women were six times more likely to be hospitalized than non-pregnant women (see Pregnancy & Flu: A Bad Combination).

And in 2011, in BMJ: Perinatal Outcomes After Maternal 2009/H1N1 Infection we saw a study where pregnant women who were admitted to the hospital with an H1N1 infection experienced a 3 to 4 times higher rate of preterm birth, 4 to 5 times greater risk of stillbirth, and a 4 to 6 times higher rate of neonatal death.

Over the past decade we’ve also seen a handful of studies tentatively linking prenatal exposure to influenza (or an influenza-like-illness) with a variety of child and adolescent development disorders.

A few examples include:

In a 2004 study (Serologic evidence of prenatal influenza in the etiology of schizophrenia Brown et al.) found a 7-fold increase in the risk of developing schizophrenia when exposed to influenza during the first trimester. No increased risk was found for exposure during the second and third trimester.

Another study from 2008 (Structural brain alterations in schizophrenia following fetal exposure to the inflammatory cytokine interleukin-8 Ellman et al.) suggested that it was prenatal exposure to a type of protein - (proinflammatory cytokines, specifically interleukin-8) – produced by the body during viral infections, that can lead (in rare cases) to brain abnormalities.

And earlier this year, research by a team at UC Davis found that fever (from any cause) during pregnancy more than doubled the odds of having a child with autism or developmental delays (see Is Maternal Influenza or Fever During Pregnancy Associated with Autism or Developmental Delays? Results from the CHARGE (CHildhood Autism Risks from Genetics and Environment) Study Zerbo et al.)
- Flu, specifically, during pregnancy was not associated with greater developmental risks only fever by `any cause’.
- Children of mothers who took antipyretics for fever did not show any increase in developmental disorders.

These studies are admittedly small and less than conclusive.

And while they suggest an increase in relative risk over pregnancies without fever or viral infection – in terms of absolute risk – the odds that a mother’s fever or viral infection during pregnancy would result in a developmentally challenged child remains low.

Today, we’ve a new study appearing in the journal Pediatrics that adds, incrementally, to earlier suspicions regarding prenatal exposure to influenza and the risks of developmental disorders.

Researchers followed up on more than 96,000 Danish children born between 1997 and 2003. They compiled a (self reported) history of the mother’s pregnancy (including infections, fevers, and antibiotic use), and compared that to diagnoses of ASD and infantile autism among the children.

Autism After Infection, Febrile Episodes, and Antibiotic Use During Pregnancy: An Exploratory Study

Hjördis Ósk Atladóttir, MD, PhD, Tine Brink Henriksen, MD, PhD, Diana E. Schendel, PhD, and Erik T. Parner, PhD^d

RESULTS: Overall, we found little evidence that various types of mild common infectious diseases or febrile episodes during pregnancy were associated with ASD/infantile autism. However, our data suggest that maternal influenza infection was associated with a twofold increased risk of infantile autism, prolonged episodes of fever caused a threefold increased risk of infantile autism, and use of various antibiotics during pregnancy were potential risk factors for ASD/infantile autism.

The two major findings were:

A twofold increase in autism among children with prenatal influenza exposure
A threefold increase in autism among children with prolonged prenatal fever exposure

It should be noted that these are relative risk increases, and once again, the absolute risk of having an autistic or developmentally challenged child after experiencing an influenza infection or fever during pregnancy is still quite low.

Nor does this study point to influenza (or fever) during pregnancy as being a major cause of autism. For now, this study only suggests that these could be two of many possible causes for the disorder.

And this caveat: This just one study, based on a limited cohort of subjects, that relied heavily on (potentially unreliable) self-reporting of illness/fever during pregnancy.

Meaning that we need to approach these findings cautiously.

Maggie Fox of NBC News has more on this story.

Flu, fever linked with autism in pregnancy study

By Maggie Fox, NBC News

Doctors trying to find some of the causes of autism put another piece into the puzzle on Monday: They found women who had flu while they were pregnant were twice as likely to have a child later diagnosed with autism. Those who had a fever lasting a week or longer -- perhaps caused by flu or maybe by something else -- were three times as likely to have an autistic child.

(Continue . . .)

Even without this latest study, the preponderance of evidence continues to show that pregnant women – and their unborn children – are at greater risk from influenza than most people appreciate.

Which is why the the CDC and other public health entities continue to stress the importance of seasonal flu vaccination for pregnant women.

In October of 2011, in IDSA: Flu Vaccines In Pregnancy, we saw several studies presented at the 49th Annual Meeting of the Infectious Diseases Society of America (IDSA) reaffirming the benefits and safety of maternal vaccination.

The CDC has synopsized these studies in: