Coxsackie Virus in Pregnancy and Congenital Heart Disease

Coxsackievirus Group B (CVB) Infection in Early Pregnancy

Investigators would like to find out if a woman's exposure to Coxsackievirus has an effect or increase in incidence of babies being born with congenital heart disease(CHD)

Study Overview

• Status: Completed
• Conditions: Congenital Heart Disease in Pregnancy

Detailed Description

The investigator proposes that Coxsackievirus group B (CVB) infection in early pregnancy induces pathological changes in congenital heart defects. To test the hypothesis, it will be determined if the incidence of CVB infection in women with babies that are congenital heart defect-(CHD) affected pregnancies are higher than in control subjects.

After informed consent participants will provide the following samples during one study visit: 10 mL (about 2 teaspoons) blood draw, a nose swab, provide a stool specimen (or have a rectal swab) and complete a study questionnaire Our 3 study groups are the following-Group 1 is Hypoplastic Left Heart Syndrome or HLHS effected pregnancies. Group 2 is OCHD- Other Congenital Heart Defects and Group 3 is Unaffected Controls (UC) also known as healthy controls.

After informed consent participants will provide the following samples: 10 mL (about 2 teaspoons) blood draw, a nose swab, provide a stool specimen (or have a rectal swab).

A health history review and questionnaire will also be obtained.

Analysis of these samples(blood, stool and nose secretions), a medical history review and questionnaire data will help to determine if there is a link or increased risk of those who may be exposed to virus.

Note- Prior to April 2016- the protocol and the healthy control (HC)subjects group were enrolled to come in for three study visits at varying times in their pregnancy. Blood, nose and stool samples were obtained at all three visits.

• Study Type: Observational
• Enrollment (Actual): 122

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St Louis Childrens Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Pregnant Woman whose babies have been diagnosed with CHD ( a congenital heart defect) and controls (pregnant women babies without CHD).

Description

Inclusion Criteria

• Fetal echocardiogram demonstrating one of the following: Hypoplastic Left Heart Syndrome (HLHS) or variant, other congenital heart disease (OCHD), or unaffected control (UC)
• Gestation is ≥20 wks-fetal group (HLHS, OCHD)
• Subject is able and willing to give informed consent.

Exclusion Criteria

• Subject is < 18 years of age.
• Subject is pregnant with twins or multiple gestations.
• Subject's pregnancy is affected by 3 or more congenital anomalies (in addition to the heart defect).
• Subject's pregnancy is affected by chromosomal anomalies (OCHD & UC groups)
• Maternal history of chromosomal anomaly (OCHD & UC groups)
• Infertility treatment for current/index pregnancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
1-(HLHS) effected pregnancies; Consent,blood draw, nose swab, stool collection,questionnaire and review of medical records.
2-Other Congenital Heart Defect (OCHD); Consent, blood draw, nose swab, stool collection, questionnaire and review of medical records.
3-Healthy Controls (UC); Consent, blood draw, nose swab, stool collection, questionnaire and review of medical records.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal prenatal and newborn Cox B viral strand identification	Virus identification: Comparison to VP1 sequences available in GenBank will be used to identify the strain of CVB in the isolates.	3 - 5years
Maternal prenatal and newborn Cox B antibody levels	Serum CVB antibody titers: Past or current CVB infection will be determined from titers (>/= 1:80) collected from stool, serum and a nasal swab.	3 - 5years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variables and trends influencing Congenital Heart Disease	Questionnaires and medical records: To account for potential confounders of CVB serology results through exploratory regression type analysis. Preliminary data is needed to investigate the relationship between variables and measured endpoints.	3-5 years

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Pirooz Eghtesady, MD, Washington University School of Medicine

Publications and helpful links

General Publications

• Tchervenkov CI, Jacobs JP, Weinberg PM, Aiello VD, Beland MJ, Colan SD, Elliott MJ, Franklin RC, Gaynor JW, Krogmann ON, Kurosawa H, Maruszewski B, Stellin G. The nomenclature, definition and classification of hypoplastic left heart syndrome. Cardiol Young. 2006 Aug;16(4):339-68. doi: 10.1017/S1047951106000291.
• Hickey EJ, Caldarone CA, McCrindle BW. Left ventricular hypoplasia: a spectrum of disease involving the left ventricular outflow tract, aortic valve, and aorta. J Am Coll Cardiol. 2012 Jan 3;59(1 Suppl):S43-54. doi: 10.1016/j.jacc.2011.04.046.
• Kallewaard NL, Zhang L, Chen JW, Guttenberg M, Sanchez MD, Bergelson JM. Tissue-specific deletion of the coxsackievirus and adenovirus receptor protects mice from virus-induced pancreatitis and myocarditis. Cell Host Microbe. 2009 Jul 23;6(1):91-8. doi: 10.1016/j.chom.2009.05.018.
• Shi Y, Chen C, Lisewski U, Wrackmeyer U, Radke M, Westermann D, Sauter M, Tschope C, Poller W, Klingel K, Gotthardt M. Cardiac deletion of the Coxsackievirus-adenovirus receptor abolishes Coxsackievirus B3 infection and prevents myocarditis in vivo. J Am Coll Cardiol. 2009 Apr 7;53(14):1219-26. doi: 10.1016/j.jacc.2008.10.064.
• Bergelson JM, Cunningham JA, Droguett G, Kurt-Jones EA, Krithivas A, Hong JS, Horwitz MS, Crowell RL, Finberg RW. Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science. 1997 Feb 28;275(5304):1320-3. doi: 10.1126/science.275.5304.1320.
• McBride KL, Marengo L, Canfield M, Langlois P, Fixler D, Belmont JW. Epidemiology of noncomplex left ventricular outflow tract obstruction malformations (aortic valve stenosis, coarctation of the aorta, hypoplastic left heart syndrome) in Texas, 1999-2001. Birth Defects Res A Clin Mol Teratol. 2005 Aug;73(8):555-61. doi: 10.1002/bdra.20169.
• Delorme-Axford E, Donker RB, Mouillet JF, Chu T, Bayer A, Ouyang Y, Wang T, Stolz DB, Sarkar SN, Morelli AE, Sadovsky Y, Coyne CB. Human placental trophoblasts confer viral resistance to recipient cells. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):12048-53. doi: 10.1073/pnas.1304718110. Epub 2013 Jul 1.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: April 11, 2017
• First Submitted That Met QC Criteria: November 7, 2018
• First Posted (Actual): November 9, 2018

Study Record Updates

• Last Update Posted (Actual): August 4, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital
• Other Study ID Numbers: 201602122

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No