Clinical trial NCT03930017: Pregnancy, Arsenic and Immune Response
Official title: Arsenic and Immune Response to Influenza Vaccination in Pregnant Women and Newborns
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Arsenic--Toxicology
Immunologic Disorders Complicating Pregnancy
Vaccine Response Impaired
Micronutrient Deficiency
Influenza
Keywords: Observational
Influenza
Vaccine immunogenicity
Arsenic
Immunology
Lead sponsor: Johns Hopkins Bloomberg School of Public Health
Sponsor class: OTHER
Collaborators: name: Sanofi Pasteur, a Sanofi Company
name: Institute of Epidemiology, Disease Control and Research
name: Johns Hopkins Bangladesh - The JiVitA Project Site
name: University of Graz
name: Columbia University
name: UNC Gillings School of Global Public Health
First posted: 2019-04-29
Enrollment: 784
Sex: FEMALE
Minimum age (years): 13
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will be conducted at the Johns Hopkins JiVitA project site, in the rural Gaibandha district, Bangladesh, one of the largest project sites in South Asia, covering more than 650,000 people in an area of more than 500 sq. km. Over 150,000 married women of reproductive age have been enlisted through thirteen years of previous studies in the area with approximately 12% of registered women becoming pregnant each year.

Brief summary: As the global availability of vaccines increases, and reaches areas disproportionately affected by arsenic and malnutrition, resolving questions about potential environmental and biologic barriers to maternal immunization has become increasingly urgent. It is not known whether arsenic, a known developmental toxicant, can alter maternal immune responses to vaccination and whether exposure to arsenic during pregnancy can impair the transfer of maternal vaccine-induced antibody to the newborn. Moreover, factors known to affect arsenic metabolism and toxicity outcomes, particularly micronutrients critical in one-carbon metabolism, have not been evaluated in studies of arsenic immunotoxicity and vaccine-induced protection in mothers and their newborns.

The objective in this study is to investigate whether maternal arsenic exposure and one-carbon metabolism micronutrient deficiencies alter maternal and newborn measures of vaccine-induced protection, respiratory morbidity, and systemic immune function following influenza vaccination during pregnancy.

Detailed description: The objective in this study is to investigate whether maternal arsenic exposure and one-carbon metabolism micronutrient deficiencies alter maternal and newborn measures of vaccine-induced protection, respiratory morbidity, and systemic immune function following influenza vaccination during pregnancy. The hypothesis is that maternal arsenic exposure and one-carbon metabolism micronutrient deficiencies alter maternal and newborn influenza antibody titer and avidity, respiratory infection morbidity, and markers of systemic immune function following maternal influenza vaccination during pregnancy. This study leverages a comprehensive pregnancy surveillance system at the JiVitA Maternal and Child Health and Nutrition Research Project site in Bangladesh (hereafter JiVitA) to pursue the following three aims:

Aim 1. Establish whether arsenic exposure during pregnancy alters maternal and newborn influenza antibody titer and avidity following maternal influenza vaccination.

Aim 2. Determine whether markers of systemic immune function mediate the association between arsenic exposure and respiratory illness in pregnant women and their newborns.

Aim 3. Assess whether arsenic exposure and one-carbon metabolism micronutrient deficiencies during pregnancy have a joint effect on markers of systemic immune function and respiratory illness in mothers and their newborns.

This study will yield three expected outcomes. First, it will fill critical knowledge gaps about whether arsenic exposure and one-carbon metabolism micronutrient deficiencies alter immune responses to a vaccination with known benefits for mothers and their newborns. Second, it will increase understanding of arsenic-associated respiratory morbidity and specific immune function pathways between arsenic exposure and respiratory morbidity in mothers and their newborns. Finally, as the global availability of vaccines increases, improving knowledge of potential environmental and biologic barriers to maternal and newborn vaccine-induced protection could lead to improved vaccine regimens (targeted vaccination campaigns, higher vaccine doses, and/or additional booster immunizations) to restore vaccine-induced protection in arsenic-exposed and malnutrition-affected populations of pregnant women and newborns worldwide.

Eligibility criteria: Inclusion Criteria:

Women who:

* are within 13-16 weeks of gestational age (GA) of pregnancy;
* are between 13 and 45 years of age;
* are married;
* provide informed consent for herself and assent for her unborn child;
* agree to receive the seasonal influenza vaccine (VAXIGRIP® TETRA seasonal quadrivalent inactivated influenza vaccine, Sanofi Pasteur) upon study enrollment.

Exclusion Criteria:

Women who:

* have pre-existing immune-related health condition (e.g., immunodeficiency, lupus, chronic infection, or cancer);
* previous or current use of immune-altering drug/therapy (e.g., steroids);
* have already received influenza vaccination for the current season.

Primary outcomes:
measure: Change in influenza hemagglutination-inhibition (HI) antibody titer
timeFrame: Comparing baseline to 28 days post vaccination, birth, and 3 months post-partum
measure: Mean percent influenza virus antibody avidity
timeFrame: Measured at baseline, 28 days post vaccination, birth, and 3 months post-partum
measure: Seroconversion rate
timeFrame: Defined as a post-vaccination HI titer of ≥40 given a pre-vaccination titer ≤10 or, alternatively, a ≥4-fold increase in HI titer between pre-vaccination and post-vaccination sera if the pre-vaccination titer was >10.
measure: Change in geometric mean HI antibody titer (GMT)
timeFrame: Comparing baseline to 28 days post vaccination, birth, and 3 months post-partum
measure: Geometric mean ratio of infant:mother HI titer
timeFrame: Birth and 3 months post-partum
measure: Change in influenza virus neutralizing antibody titer
timeFrame: Comparing baseline to 28 days post vaccination, birth, and 3 months post-partum
measure: Change in anti-influenza virus total immunoglobulin G (IgG) enzyme immunoassay
timeFrame: Comparing baseline to 28 days post vaccination, birth, and 3 months post-partum
Secondary outcomes:
measure: Maternal influenza-like illness (ILI)
timeFrame: From date of enrollment visit until date of 3 months postpartum visit, assessed at weekly intervals
measure: Infant influenza-like illness (ILI)
timeFrame: From date of birth visit until date of 3 months postpartum visit, assessed at weekly intervals
measure: Laboratory-confirmed influenza (LCI)
timeFrame: From date of enrollment visit until date of 3 months postpartum visit, assessed at weekly intervals
measure: Acute respiratory illness (ARI)
timeFrame: From date of enrollment visit until date of 3 months postpartum visit, assessed at weekly intervals
Other outcomes:
measure: Gestational age (GA) at birth
timeFrame: Within 72 hours of birth
measure: Newborn anthropometry weight
timeFrame: Within 72 hours of birth
measure: Newborn anthropometry length
timeFrame: Within 72 hours of birth
measure: Newborn anthropometry head, chest, middle-upper arm circumference
timeFrame: Within 72 hours of birth
measure: Change in micronutrient deficiency status
timeFrame: Comparing baseline to 28 days post vaccination, birth, and 3 months post-partum
measure: Change in cytokines
timeFrame: Comparing baseline to 28 days post vaccination, birth, and 3 months post-partum
measure: Change in peripheral blood lymphocyte numbers
timeFrame: Comparing baseline to 28 days post vaccination, birth, and 3 months post-partum
measure: Change in peripheral blood lymphocyte function
timeFrame: Comparing baseline to 28 days post vaccination, birth, and 3 months post-partum
measure: Change in total circulating immunoglobulin (Ig) levels, including IgG (IgG 1-4 subclasses), IgA, IgM, IgE
timeFrame: Comparing baseline to 28 days post vaccination, birth, and 3 months post-partum
measure: Occurrence of WHO Definition of Diarrhea
timeFrame: From date of enrollment visit until date of 3 months postpartum visit, assessed at weekly intervals
Locations:
city: Gaibandha
country: Bangladesh
facility: JiVitA Maternal and Child Health and Nutrition Research Program
Study officials:
affiliation: Johns Hopkins Bloomberg School of Public Health
name: Christopher D Heaney, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Attreed SE, Navas-Acien A, Heaney CD. Arsenic and Immune Response to Infection During Pregnancy and Early Life. Curr Environ Health Rep. 2017 Jun;4(2):229-243. doi: 10.1007/s40572-017-0141-4.
citation: Heaney CD, Kmush B, Navas-Acien A, Francesconi K, Gossler W, Schulze K, Fairweather D, Mehra S, Nelson KE, Klein SL, Li W, Ali H, Shaikh S, Merrill RD, Wu L, West KP Jr, Christian P, Labrique AB. Arsenic exposure and hepatitis E virus infection during pregnancy. Environ Res. 2015 Oct;142:273-80. doi: 10.1016/j.envres.2015.07.004. Epub 2015 Jul 15.