Coxsackie Virus in Pregnancy and Congenital Heart Disease

Congenital Heart Disease in Pregnancy Clinical Trial

Official title:

Coxsackievirus Group B (CVB) Infection in Early Pregnancy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03737006
• Other study ID #: 201602122
• Status: Completed
• Start date: March 1, 2016
• Est. completion date: December 1, 2018

Study information

• Verified date: August 2022
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 122
• Est. completion date: December 1, 2018
• Est. primary completion date: December 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Congenital Heart Disease in Pregnancy
• Heart Defects, Congenital
• Heart Diseases

Locations

Country	Name	City	State
United States	St Louis Childrens Hospital	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

Shi Y, Chen C, Lisewski U, Wrackmeyer U, Radke M, Westermann D, Sauter M, Tschöpe 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. — View Citation

Tchervenkov CI, Jacobs JP, Weinberg PM, Aiello VD, Béland 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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