Virus during pregnancy autism

Stratifying on a variable that can be a marker for exposure would lead to biased results. Hernan et al. Among controls, mothers with any infection during pregnancy were more likely than those without diagnosed infections to be younger and be white, non-Hispanic or black. Maternal education and plurality did not affect the measure of association between ASD and maternal infection in multivariable analyses, and therefore were not included in the final adjusted models.

The frequency of maternal infection anytime during the pregnancy period, for the preconception period, and for each trimester was similar for cases and controls Table 3. Genitourinary GU infections were among the more commonly diagnosed infections during pregnancy among both case and control mothers Table 4.

During the entire pregnancy period and during the 2nd and 3rd trimesters, GU infections were diagnosed somewhat more often in case than control mothers but risk estimates were of borderline significance Table 4. Skin infections diagnosed in the preconception period and infections of unknown organ system diagnosed anytime during pregnancy and the 2nd trimester were also more common in case mothers compared with controls Table 4.

The vast majority of bacterial infections occurred during the third trimester. Mothers of children with ASD were diagnosed with viral infections no more often than mothers of control children at any time during pregnancy, or during any trimester Table 5. There were no diagnoses of cytomegalovirus or measles in this study population, and other specific viral infections previously reported to be associated with risk of ASD were diagnosed infrequently Herpes Simples: 3 cases, 21 controls; Influenza: 3 cases, 19 controls; Rubella: 0 cases, 1 control; Varicella: 0 cases, 4 controls.

Mycosal infections during pregnancy were marginally associated with increased risk of ASD Table 5. Parasitic infections were rare and only observed in control mothers. Although not very common, inpatient infections diagnosed during the second trimester were associated with the highest risk of ASD Table 6. Bacterial infections accounted for the majority of infections diagnosed during a hospital admission, and were associated with increased risk of ASD Table 6.

The majority of bacterial infections were diagnosed in the third trimester. Mothers of ASD children were more likely than mothers of controls to have two or more infections during pregnancy Two or more infections diagnosed in the third trimester of pregnancy was associated with even higher increased risk of ASD Treatment of infection in an outpatient setting did not change the association between maternal infection during pregnancy and risk of ASD.

We did not find an overall association between diagnoses of any maternal infection during pregnancy and ASD in the child. However, women with any infections diagnosed during a hospital admission, particularly bacterial infections, were at increased risk of delivering a child who was diagnosed with ASD. The most commonly- diagnosed bacterial infections in our study were urinary tract infections. A previous study that found an association between bacterial infection diagnosed during a hospitalization and ASD also reported urinary tract infections as the most common bacterial infection.

Atladottir et al. Our findings that mothers with 2 or more diagnosed infections were at higher risk of having a child with autism also supports the suggestion that more severe infections during pregnancy may increase the risk of ASD. Abdallah et al. We did not observe an association between maternal viral infections during pregnancy and ASD risk. This is in contrast to previous case reports and small studies indicating that rubella, cytomegalovirus, and influenza increased risk of ASD.

Chess, ; Deykin and MacMahon, ; Yamashita, et al. Our results are also inconsistent with those of two recent Danish studies. The first reported an association between maternal viral infection in the first trimester and ASD in the offspring Atladottir, et al. Self-reported data on infection may suffer from over-counting or under-counting, depending on severity and characteristics of the mothers related to access to health care and care-seeking behavior.

It is also possible that medical records may undercount viral infections, since physicians discourage seeking their services for viruses. Women who had an infection 30 days before conception had a non-statistically elevated risk of having a child diagnosed with autism. This suggests that maternal immune activation around the time of conception may adversely impact fetal neurodevelopment. Our study had several strengths, including large numbers of subjects, population-based identification of cases and controls from the same birth cohort, the use of prospectively-collected information on diagnoses documented in medical records, and an appropriately matched internal comparison group with no documented ASD diagnoses.

We were also able to examine the risk for specific periods during pregnancy and to adjust for several important covariates. Despite these strengths, our findings must be considered in the context of several study limitations. ASD status was determined by diagnoses recorded in medical records, and not validated by a standardized clinical assessment for all cases.

Croen, et al. Infections included in our study were restricted to those documented in medical records, and based on ICD9 diagnostic codes, rather than serologic evidence. Subclinical infections or illnesses for which women did not seek medical attention were not counted. Information on treatment was limited to prescription medications picked up at a KPNC pharmacy, and may not accurately reflect actual exposure to all medication use during pregnancy.

Our analysis may have missed over-the-counter medications such as fever reducers or anti-inflammatory drugs, and undercounted medication given to women during their hospitalization. We did not have information on possible confounding factors, such as alcohol intake or vitamin supplementation. Our analysis was also hampered by small numbers in some cells, which is reflected in the wide confidence intervals around some of the point estimates.

Moreover, because of the relatively small sample size, we had limited power to distinguish the effect of treatment from that of infection on risk of ASD. Finally, because we were interested in identifying all possible associations, we did not correct the results for multiple comparisons. Due to the number of analyses we conducted, our findings could be due to chance, and require follow-up in larger studies.

The mechanism by which maternal infection during pregnancy might lead to neurodevelopmental disorders such as autism is unclear. The fact that both severe infection and urinary tract infection conferred the same level of risk "highlights that there's something very subtle that can be very profound in brain development, and it probably has to do with sensitive periods in brain development that we don't understand yet," she said. One in 7 babies prenatally exposed to Zika has health problems, CDC says.

In her own research on sex differences and brain development, she found that a lot of immune system signaling "sculpts" the male brain during development. How fever in early pregnancy can cause birth defects. Alan S. Brown , a professor of psychiatry and epidemiology at the Columbia University Medical Center, said in an email that "overall, the investigators have done a commendable job.

A previous study from Taiwan showed that treatment for infection in the third trimester was related to autism risk, explained Brown, who was not involved in the new study. Get CNN Health's weekly newsletter. This trend did not achieve statistical significance. The study is the first to assess the risk for ASD based on laboratory-verified maternal influenza infection, not just survey data or medical records.

Results appear in the journal mSphere. The researchers analyzed questionnaires and blood samples from mothers of children with ASD and matched controls, as part of the Autism Birth Cohort Study, a prospective birth cohort in Norway. Blood samples were collected from mothers at mid-pregnancy and after delivery. Recent epidemiological studies reported significant differences in maternal cytokine and chemokine levels during pregnancy between autism cases and controls.

Goines et al. Abdallah et al. Previous researchers on maternal infections and risk of neurodevelopmental disorders have postulated that maternal reaction to infections rather than the direct effects of the infectious agents may be the mechanism by which infections in mothers were associated with disorders like schizophrenia and autism Shi et al. In the present study, the majority of the reported fever is associated with infections, despite the null association of influenza infection with autism spectrum disorders.

We did not have measurements of maternal cytokines during pregnancy, but fever represents a clinical manifestation of pro-inflammatory cytokines due to either infections or other unknown causes. Elevated levels of cytokines like Il-6 have also been observed in pregnant women with fever during labor in the absence of infections Goetzl et al. This type of fever has been found to be associated with early unexplained seizure in some infants Lieberman et al.

In addition to the cytokine hypothesis, maternal antibodies raised against fetal brain tissue have been proposed as a possible mechanism of maternal immune activation that can lead to neurodevelopment abnormalities Grether et al.

In conclusion, we did not find an association between maternal influenza infection during pregnancy and either ASD or developmental delay. However, mothers whose children had autism spectrum disorders at ages 2—5 years were more likely to report fever from any cause during pregnancy compared to those of similarly aged children with typical development.

This was also true of mothers whose child had developmental delay. Our results additionally suggest that anti-fever medication used to control fever during pregnancy can reduce or eliminate the association we observed between maternal fever and autism. Electronic supplementary material The online version of this article doi Conflict of interest The authors declare that they have no conflict of interest. Robin L. National Center for Biotechnology Information , U. J Autism Dev Disord. Author manuscript; available in PMC Jan 1.

Hansen , and Irva Hertz-Picciotto. Author information Copyright and License information Disclaimer. Corresponding author. Ousseny Zerbo: ude. Present Address: O. Copyright notice. The publisher's final edited version of this article is available at J Autism Dev Disord. See other articles in PMC that cite the published article.

Abstract We analyzed data from case groups of children with autism spectrum disorders ASD and with developmental delays DD , and from typically developing controls to assess associations with maternal influenza or fever during pregnancy.

Keywords: Maternal influenza, Fever, Autism, Anti-fever medication. Exposure Data A telephone interview was conducted by trained bilingual English and Spanish interviewers with the mother regarding preconceptional, prenatal, and early childhood exposures and experiences of the index child. Statistical Analysis We performed univariate descriptive analysis to check for data completeness, outliers, and distributional assumptions of the variables.

Table 1 List of medications that women reported they took for influenza and fever symptoms, and list of medications that we determined were antipyretic. Open in a separate window. Table 5 Weighted multivariate analysis of the association between self-reported fever during pregnancy and developmental outcome.

The reference group was mothers with no fever; none took medications for fever. Discussion In this case—control study, odds ratios were elevated but not significantly for maternal influenza and either autism spectrum disorders ASD or developmental delays, but fever during pregnancy was associated with both sets of conditions. Footnotes Electronic supplementary material The online version of this article doi Amniotic fluid inflammatory cytokines: Potential markers of immunologic dysfunction in autism spectrum disorders.

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Archives of General Psychiatry. Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring. American Journal of Psychiatry. Autism in children with congenital rubella. Journal of autism and childhood schizophrenia. Cytokines and fever. Frontiers in Bioscience. No association between prenatal exposure to influenza and autism.