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Am J Perinatol 2017; 34(03): 223-228
DOI: 10.1055/s-0036-1585411
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Does Infection During Pregnancy Outside of the Time of Delivery Increase the Risk of Cerebral Palsy?

Kathleen F. Brookfield
1   Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon
,
Sarah S. Osmundson
2   Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, Tennessee
,
Aaron B. Caughey
1   Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon
,
Jonathan M. Snowden
1   Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon
3   School of Public Health, Oregon Health and Science University/Portland State University, Portland, Oregon
› Author Affiliations
Further Information

Publication History

26 February 2016

05 June 2016

Publication Date:
11 July 2016 (online)

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Abstract

Objective We sought to evaluate whether maternal antepartum infection (excluding chorioamnionitis) is associated with cerebral palsy (CP).

Study Design This is a secondary analysis from a multicenter trial in women at risk of preterm delivery who received antenatal magnesium sulfate versus placebo. We compared the risk of CP in the children of women who had evidence of antepartum infection over the course of pregnancy to those women who had no evidence of antepartum infection during pregnancy.

Results Within a cohort of 2,251 women who met our inclusion criteria, 1,350 women had no history of infection in pregnancy and 801 women had a history of some type of antepartum infection during pregnancy. The incidence of CP was similar between the two groups (4.9 vs 5.0%; p = 0.917). After adjustment for maternal and obstetric confounders, we observed no significantly increased risk of CP among infants born to women with evidence of antepartum infection; (adjusted relative risk [aRR], 1.09 (0.72, 1.66); p = 0.68).

Conclusion Compared with women with no evidence of antepartum infection during pregnancy, those women with infections excluding chorioamnionitis may not be at an increased risk of delivering an infant with CP.

Keywords

infection - cerebral palsy - prematurity - pregnancy
 

  • References

  • 1 Goines PE, Croen LA, Braunschweig D , et al. Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: a case-control study. Mol Autism 2011; 2: 13 DOI: 10.1186/2040-2392-2-13.
    CrossrefPubMedGoogle Scholar
  • 2 Palmer CG, Turunen JA, Sinsheimer JS , et al. RHD maternal-fetal genotype incompatibility increases schizophrenia susceptibility. Am J Hum Genet 2002; 71 (6) 1312-1319
    CrossrefPubMedGoogle Scholar
  • 3 Meyer U, Feldon J, Schedlowski M, Yee BK. Immunological stress at the maternal-foetal interface: a link between neurodevelopment and adult psychopathology. Brain Behav Immun 2006; 20 (4) 378-388
    CrossrefPubMedGoogle Scholar
  • 4 Mousa A, Seiger A, Kjaeldgaard A, Bakhiet M. Human first trimester forebrain cells express genes for inflammatory and anti-inflammatory cytokines. Cytokine 1999; 11 (1) 55-60
    CrossrefPubMedGoogle Scholar
  • 5 Yoon BH, Romero R, Park JS , et al. Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years. Am J Obstet Gynecol 2000; 182 (3) 675-681
    CrossrefPubMedGoogle Scholar
  • 6 Meyer U, Nyffeler M, Engler A , et al. The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology. J Neurosci 2006; 26 (18) 4752-4762
    CrossrefPubMedGoogle Scholar
  • 7 Wu YW. Systematic review of chorioamnionitis and cerebral palsy. Ment Retard Dev Disabil Res Rev 2002; 8 (1) 25-29
    CrossrefPubMedGoogle Scholar
  • 8 Patterson PH. Immune involvement in schizophrenia and autism: etiology, pathology and animal models. Behav Brain Res 2009; 204 (2) 313-321
    CrossrefPubMedGoogle Scholar
  • 9 Brown AS, Susser ES. In utero infection and adult schizophrenia. Ment Retard Dev Disabil Res Rev 2002; 8 (1) 51-57
    CrossrefPubMedGoogle Scholar
  • 10 Brown AS, Patterson PH. Maternal infection and schizophrenia: implications for prevention. Schizophr Bull 2011; 37 (2) 284-290
    CrossrefPubMedGoogle Scholar
  • 11 Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 2005; 57 (1) 67-81
    CrossrefPubMedGoogle Scholar
  • 12 Burd I, Balakrishnan B, Kannan S. Models of fetal brain injury, intrauterine inflammation, and preterm birth. Am J Reprod Immunol 2012; 67 (4) 287-294
    CrossrefPubMedGoogle Scholar
  • 13 Stanley F, Blair E, Alberman E. Cerebral Palsies: Epidemiology and Causal Pathways, Vol 151. London, UK: MacKeith Press; 2000
    Google Scholar
  • 14 MacLennan AH, Thompson SC, Gecz J. Cerebral palsy: causes, pathways, and the role of genetic variants. Am J Obstet Gynecol 2015; 213 (6) 779-788
    CrossrefPubMedGoogle Scholar
  • 15 Locatelli A, Incerti M, Paterlini G , et al. Antepartum and intrapartum risk factors for neonatal encephalopathy at term. Am J Perinatol 2010; 27 (8) 649-654
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Cowan F, Rutherford M, Groenendaal F , et al. Origin and timing of brain lesions in term infants with neonatal encephalopathy. Lancet 2003; 361 (9359) 736-742
    Google Scholar
  • 17 Wu YW, Colford Jr JM. Chorioamnionitis as a risk factor for cerebral palsy: A meta-analysis. JAMA 2000; 284 (11) 1417-1424
    CrossrefPubMedGoogle Scholar
  • 18 Bear JJ, Wu YW. Maternal infections during pregnancy and cerebral palsy in the child. Pediatr Neurol 2016; 57: 74-79
    CrossrefPubMedGoogle Scholar
  • 19 Rouse DJ, Hirtz DG, Thom E , et al; Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med 2008; 359 (9) 895-905
    CrossrefPubMedGoogle Scholar
  • 20 VanderWeele TJ, Hernández-Diaz S. Is there a direct effect of pre-eclampsia on cerebral palsy not through preterm birth?. Paediatr Perinat Epidemiol 2011; 25 (2) 115-115
    PubMedGoogle Scholar
  • 21 Cole SR, Hernán MA. Fallibility in estimating direct effects. Int J Epidemiol 2002; 31 (1) 163-165
    CrossrefPubMedGoogle Scholar
  • 22 Hernández-Díaz S, Schisterman EF, Hernán MA. The birth weight “paradox” uncovered?. Am J Epidemiol 2006; 164 (11) 1115-1120
    CrossrefPubMedGoogle Scholar
  • 23 Wilcox AJ, Weinberg CR, Basso O. On the pitfalls of adjusting for gestational age at birth. Am J Epidemiol 2011; 174 (9) 1062-1068
    CrossrefPubMedGoogle Scholar
  • 24 Klebanoff MA, Schoendorf KC. Invited commentary: what's so bad about curves crossing anyway?. Am J Epidemiol 2004; 160 (3) 211-212
    CrossrefPubMedGoogle Scholar
  • 25 Murphy DJ, Sellers S, MacKenzie IZ, Yudkin PL, Johnson AM. Case-control study of antenatal and intrapartum risk factors for cerebral palsy in very preterm singleton babies. Lancet 1995; 346 (8988) 1449-1454
    CrossrefPubMedGoogle Scholar
  • 26 O'Callaghan ME, MacLennan AH, Gibson CS , et al; Australian Collaborative Cerebral Palsy Research Group. Epidemiologic associations with cerebral palsy. Obstet Gynecol 2011; 118 (3) 576-582
    CrossrefPubMedGoogle Scholar
  • 27 McMichael G, MacLennan A, Gibson C , et al; Australian Collaborative Cerebral Palsy Research Group. Cytomegalovirus and Epstein-Barr virus may be associated with some cases of cerebral palsy. J Matern Fetal Neonatal Med 2012; 25 (10) 2078-2081
    CrossrefPubMedGoogle Scholar