Maternal mid-pregnancy C-reactive protein and risk of autism spectrum disorders: the early markers for autism study
Open accessAbstract
Maternal pregnancy levels of the inflammatory marker C-reactive protein (CRP) has been previously associated with autism spectrum disorder (ASD) in the offspring. We conducted a population-based nested case–control study with 500 children with ASD, 235 with developmental delay (DD) and 580 general population (GP) controls to further investigate whether elevated CRP during pregnancy increases the risk of ASD. Maternal CRP concentration was measured in archived serum collected during 15–19 weeks of pregnancy and genome-wide single-nucleotide polymorphism (SNP) data were generated. The levels of CRP were compared between ASD vs GP and DD vs GP. The genetic associations with CRP were assessed via linear regression. Maternal CRP levels in mid-pregnancy were lower in mothers of ASD compared with controls. The maternal CRP levels in the upper third and fourth quartiles were associated with a 45 and 44% decreased risk of ASD, respectively. Two SNPs at the CRP locus showed strong association with CRP levels but they were not associated with ASD. No difference was found between maternal CRP levels of DD and controls. The reasons for the lower levels of CRP in mothers of ASD are not known with certainty but may be related to alterations in the immune response to infectious agents. The biological mechanisms underlying this association remain to be clarified.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Zerbo et al. found maternal blood C-reactive protein levels lower in weeks 15-19 of pregnancies of a child with ASD than in the general population, and the results appeared not to be genetic.
“A 2016 study found maternal blood C-reactive protein levels to be lower in weeks 15-19 of pregnancies of a child with ASD than the general population, and although the results appear not to be genetic”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Zerbo et al, 2016
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
GCTA: a tool for genome-wide complex trait analysis
Yang, J., Lee, S. H., Goddard, M. E., & Visscher, P. M. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.11.011 · Cited by 8,279 · see citing works
A map of human genome variation from population-scale sequencing.
The 1000 Genomes Project Consortium (2010) · Nature · doi:10.1038/nature09534 · Cited by 7,877 · see citing works
Acute-Phase Proteins and Other Systemic Responses to Inflammation
Gabay, C., & Kushner, I. (1999) · New England Journal of Medicine · doi:10.1056/nejm199902113400607 · Cited by 6,734 · see citing works
LocusZoom: regional visualization of genome-wide association scan results
Pruim, R. J., Welch, R. P., Sanna, S., Teslovich, T. M., Chines, P. S., Gliedt, T. P., Boehnke, M., Abecasis, G. R., & Willer, C. J. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq419 · Cited by 2,707 · see citing works
Autism as a strongly genetic disorder: evidence from a British twin study
Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E., & Rutter, M. (1995) · Psychological Medicine · doi:10.1017/s0033291700028099 · Cited by 2,461 · see citing works
Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism
Hallmayer, J. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.76 · Cited by 1,970 · see citing works
Maternal Immune Activation Alters Fetal Brain Development through Interleukin-6
Smith, S. E. P., Li, J., Garbett, K., Mirnics, K., & Patterson, P. H. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2178-07.2007 · Cited by 1,605 · see citing works
INFANTILE AUTISM: A GENETIC STUDY OF 21 TWIN PAIRS
Folstein, S., & Rutter, M. (1977) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.1977.tb00443.x · Cited by 1,361 · see citing works
Prevalence of Autism in a US Metropolitan Area
Yeargin-Allsopp, M., Rice, C., Karapurkar, T., Doernberg, N., Boyle, C., & Murphy, C. (2003) · JAMA · doi:10.1001/jama.289.1.49 · Cited by 1,248 · see citing works
Most genetic risk for autism resides with common variation
Gaugler, T., Klei, L., Sanders, S. J., Bodea, C. A., Goldberg, A. P., Lee, A. B., Mahajan, M., Manaa, D., Pawitan, Y., Reichert, J., et al. (2014) · Nature Genetics · doi:10.1038/ng.3039 · Cited by 1,239 · see citing works
Maternal Infection Requiring Hospitalization During Pregnancy and Autism Spectrum Disorders
Atladóttir, H. Ó., Thorsen, P., Østergaard, L., Schendel, D. E., Lemcke, S., Abdallah, M., & Parner, E. T. (2010) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-010-1006-y · Cited by 916 · see citing works
A Twin Study of Autism in Denmark, Finland, Iceland, Norway and Sweden
Steffenburg, S., Gillberg, C., Hellgren, L., Andersson, L., Gillberg, I. C., Jakobsson, G., & Bohman, M. (1989) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.1989.tb00254.x · Cited by 780 · see citing works
C Reactive Protein Coronary Heart Disease Genetics Collaboration (CCGC) (2011) · BMJ · doi:10.1136/bmj.d548 · Cited by 642 · see citing works
Heritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample
Colvert, E., Tick, B., McEwen, F., Stewart, C., Curran, S. R., Woodhouse, E., Gillan, N., Hallett, V., Lietz, S., Garnett, T., et al. (2015) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.3028 · Cited by 560 · see citing works
Dehghan, A., Dupuis, J., Barbalić, M., Bis, J. C., Eiríksdóttir, G., Lu, C., Pellikka, N., Wallaschofski, H., Kettunen, J., Henneman, P., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.948570 · Cited by 512 · see citing works
Autism in children with congenital rubella
Chess, S. (1971) · Journal of Autism and Childhood Schizophrenia · doi:10.1007/bf01537741 · Cited by 457 · see citing works
Hertz‐Picciotto, I., Croen, L., Hansen, R. L., Jones, C. R., de Water, J. V., & Pessah, I. N. (2006) · Environmental Health Perspectives · doi:10.1289/ehp.8483 · Cited by 420 · see citing works
Self-citationAutism After Infection, Febrile Episodes, and Antibiotic Use During Pregnancy: An Exploratory Study
Atladóttir, H. Ó., Henriksen, T. B., Schendel, D. E., & Parner, E. T. (2012) · Pediatrics · doi:10.1542/peds.2012-1107 · Cited by 369 · see citing works
Goines, P. E., Croen, L. A., Braunschweig, D., Yoshida, C. K., Grether, J., Hansen, R., Kharrazi, M., Ashwood, P., & Van de Water, J. (2011) · Molecular Autism · doi:10.1186/2040-2392-2-13 · Cited by 351 · see citing works
Self-citationElevated maternal C-reactive protein and autism in a national birth cohort
Brown, A. S., Sourander, A., Hinkka-Yli-Salomäki, S., McKeague, I. W., Sundvall, J., & Surcel, H.-M. (2014) · Molecular Psychiatry · doi:10.1038/mp.2012.197 · Cited by 343 · see citing works
Ridker, P. M., Paré, G., Parker, A. N., Zee, R. Y. L., Danik, J. S., Buring, J. E., Kwiatkowski, D. J., Cook, N. R., Miletich, J. P., & Chasman, D. I. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.03.015 · Cited by 342 · see citing works
Maternal hospitalization with infection during pregnancy and risk of autism spectrum disorders
Lee, B. K., Magnusson, C., Gardner, R. M., Blomström, Å., Newschaffer, C. J., Burstyn, I., Karlsson, H., & Dalman, C. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2014.09.001 · Cited by 337 · see citing works
Autism: Many Genes, Common Pathways?
Geschwind, D. H. (2008) · Cell · doi:10.1016/j.cell.2008.10.016 · Cited by 328 · see citing works
Maternal Infection During Pregnancy and Autism Spectrum Disorders
Zerbo, O., Qian, Y., Yoshida, C., Grether, J. K., Van de Water, J., & Croen, L. A. (2015) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-013-2016-3 · Cited by 298 · see citing works
Self-citationBauman, M. D., Iosif, A.-M., Smith, S. E. P., Bregere, C., Amaral, D. G., & Patterson, P. H. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.06.025 · Cited by 294 · see citing works
Zerbo, O., Iosif, A.-M., Walker, C., Ozonoff, S., Hansen, R. L., & Hertz-Picciotto, I. (2013) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-012-1540-x · Cited by 277 · see citing works
Self-citationThe meta-analysis of genome-wide association studies
Thompson, J. R., Attia, J., & Minelli, C. (2011) · Briefings in Bioinformatics · doi:10.1093/bib/bbr020 · Cited by 250 · see citing works
Hage, F. G., & Szalai, A. J. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.06.012 · Cited by 241 · see citing works
Tjoa, M. L., van Vugt, J. M. G., Go, A. T. J. J., et al. (2003) · Journal of Reproductive Immunology · doi:10.1016/s0165-0378(02)00085-2 · Cited by 218 · see citing works
Hoffmann, T. J., Kvale, M. N., Hesselson, S., Zhan, Y., Aquino, C., Cao, Y., Cawley, S. E., Chung, E. H., Connell, S., Eshragh, J. L., et al. (2011) · Genomics · doi:10.1016/j.ygeno.2011.04.005 · Cited by 210 · see citing works
Belo, L., Santos‐Silva, A., Rocha, S., CASLAKE, M. J., Cooney, J., Pereira‐Leite, L., Quintanilha, A. T., & Rebelo, I. (2005) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2005.02.022 · Cited by 170 · see citing works
Maternal C-reactive protein levels are raised at 4 weeks gestation
Sacks, G. P. (2004) · Human Reproduction · doi:10.1093/humrep/deh179 · Cited by 165 · see citing works
Autism Spectrum Disorder: Interaction of Air Pollution with the MET Receptor Tyrosine Kinase Gene
Volk, H. E., Kerin, T., Lurmann, F., Hertz-Picciotto, I., McConnell, R., & Campbell, D. B. (2014) · Epidemiology · doi:10.1097/ede.0000000000000030 · Cited by 163 · see citing works
C-Reactive Protein in Normal Pregnancy
Watts, D. H., Krohn, M. A., WENER, M. H., & Eschenbach, D. A. (1991) · Obstetrics and Gynecology · doi:10.1097/00006250-199102000-00002 · Cited by 140 · see citing works
Ernst, G. D. S., de Jonge, L. L., Albert Hofman, D., Lindemans, J. W., Russcher, H., Steegers, E. A. P., & Jaddoe, V. W. V. (2011) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2011.03.049 · Cited by 139 · see citing works
Elevated C-reactive protein and cognitive deficits in individuals with bipolar disorder
Dickerson, F., Stallings, C. R., Origoni, A. E., Vaughan, C., Khushalani, S., & Yolken, R. H. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2013.04.039 · Cited by 114 · see citing works
Self-citationLohsoonthorn, V., Qiu, C., & Williams, M. A. (2007) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2006.11.017 · Cited by 96 · see citing works
Okada, Y., Takahashi, A., Ohmiya, H., Kumasaka, N., Kamatani, Y., Hosono, N., Tsunoda, T., Matsuda, K., Tanaka, T., Kubo, M., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq551 · Cited by 93 · see citing works
Maternal serum highly sensitive C‐reactive protein in normal pregnancy and pre‐eclampsia
Hwang, H. S., Kwon, J., Kim, M. A., et al. (2007) · International Journal of Gynecology & Obstetrics · doi:10.1016/j.ijgo.2007.03.050 · Cited by 75 · see citing works
Patterson, P. H. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.09.008 · Cited by 62 · see citing works
Abdallah, M. W., Larsen, N., Grove, J., Bonefeld‐Jørgensen, E. C., Nørgaard‐Pedersen, B., HOUGAARD, D. M., & Mortensen, E. L. (2012) · Cytokine · doi:10.1016/j.cyto.2012.11.015 · Cited by 61 · see citing works
A Genome-Wide Survey of Transgenerational Genetic Effects in Autism
Tsang, K. M., Croen, L., Torres, A., Kharrazi, M., DeLorenze, G. N., Windham, G. C., Yoshida, C. K., Zerbo, O., & Weiss, L. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076978 · Cited by 51 · see citing works
Self-citationNeonatally measured immunoglobulins and risk of autism
Grether, J. K., Croen, L., Anderson, M., Nelson, K. B., & Yolken, R. H. (2010) · Autism Research · doi:10.1002/aur.160 · Cited by 37 · see citing works
Self-citationGenetic Loci Associated With C-Reactive Protein Levels and Risk of Coronary Heart Disease
Elliott, P. (2009) · JAMA · doi:10.1001/jama.2009.954 · Cited by 35 · see citing works
C-reactive protein as a biochemical marker of idiopathic preterm delivery.
Grgić, G., Skokić, F., & Bogdanovic, G. (2010) · PubMed · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Role of the Immune System in Autism Spectrum Disorder
Meltzer, A., & Van de Water, J. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.158 · Cited by 533 · see citing works
Maternal immune activation and autism spectrum disorder: From rodents to nonhuman and human primates
Careaga, M., Murai, T., & Bauman, M. D. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.10.020 · Cited by 348 · see citing works
Gut microbiota changes in patients with autism spectrum disorders
Ding, X., Xu, Y., Zhang, X., Zhang, L., Duan, G., Song, C., Li, Z., Yang, Y., Wang, Y., Wang, X., et al. (2020) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2020.06.032 · Cited by 166 · see citing works
Mendelian randomisation approaches to the study of prenatal exposures: A systematic review
Diemer, E. W., Labrecque, J. A., Neumann, A., Tiemeier, H., & Swanson, S. A. (2021) · Paediatric and Perinatal Epidemiology · doi:10.1111/ppe.12691 · Cited by 21 · see citing works
- Authors
- Zerbo, O., Traglia, M., Yoshida, C., Heuer, L. S., Ashwood, P., Delorenze, G. N., Hansen, R. L., Kharrazi, M., Van de Water, J., Yolken, R. H., Weiss, L. A., & Croen, L. A.
- Affiliations
- Kaiser Permanente (US)
- University of California, San Francisco (US)
- University of California, Davis (US)
- California Department of Public Health (US)
- Johns Hopkins University (US)
- Corresponding author
- Zerbo, O
- Venue
- Translational Psychiatry
- Published
- 2016-04-19
- Volume
- 6
- Issue
- 4
- Pages
- e783-e783
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC4872404
- OpenAlex
- W2338014412
- Cited by
- 67
- References
- 46
- Citations by year
- 2026: 4 · 2024: 7 · 2023: 5 · 2022: 9 · 2021: 5 · 2020: 12 · 2019: 9 · 2018: 11 · 2017: 2 · 2016: 3
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Environmental Health Sciences (R01ES016669)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- C-reactive protein, autism spectrum disorder, maternal inflammation, second trimester, developmental delay, genetic association, single nucleotide polymorphisms, maternal immune response, infectious agents, offspring risk
- MeSH terms
- Autism Spectrum Disorder, Adult, C-Reactive Protein, California, Female, Humans, Infant, Male, Mothers, Pregnancy, Pregnancy Trimester, Second, Risk, Case-Control Studies, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
