Clinical trial NCT03312049: Aflatoxin Birth Cohort Study Nepal (AflaCohort)
Official title: Relationship Between Maternal Exposure to Mycotoxins, Birth Outcomes and Stunting in Infants: A Birth Cohort Study in Nepal
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Stunting
Birth Weight
Birth Length
Height for Age
Linear Growth Failure
Keywords: Aflatoxin B1
Aflatoxin M1
Aflatoxin
Mycotoxin
Stunting
Linear growth
Pregnancy
Birth outcomes
Nepal
Lead sponsor: Tufts University
Sponsor class: OTHER
Collaborators: name: Helen Keller International
name: Patan Academy of Health Sciences
name: Purdue University
name: Government of Nepal
name: Nepalgunj Medical College
First posted: 2017-10-17
Enrollment: 1675
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All pregnant women and adolescent girls aged 16-49 years and living in the study areas will be invited to join the study. Women who are less than 30 weeks into their gestation will be eligible to participate if their expected delivery date falls within the enrollment period.

Brief summary: The study focuses on the causal relationship between mycotoxin exposure (particularly aflatoxin B1), birth outcomes, and height for age among young children in Nepal. Previous studies have shown a strong association of stunting with mycotoxin exposure yet causality has not been proven. Thus, this study will provide a better understanding of the association between maternal and/or early life mycotoxin exposure (rates in the blood and breast milk) and infant and young child growth. This information is essential if we are to more fully understand and effectively address the high rates of stunting in Asia.

Detailed description: In 2012, a research prioritization meeting organized by IFPRI and the Bill and Melinda Gates Foundation on food-borne toxins concluded, "While there is solid association of stunting with exposure to mycotoxins, the causality has not been proven and the percentage of stunting attributable to mycotoxins in general or to specific mycotoxins is not known." (IFPRI/BMGF 2012) In other words, the extent of the problem, although widely suspected, has been poorly documented and the biological mechanisms thought to be involved remain poorly understood.

To contribute to a better understanding of the mycotoxin-stunting relationship, the Feed the Future Feed the Future Nutrition Innovation Lab-Asia proposes to explore the impact of mycotoxins, with a focus on mycotoxins on child nutrition in Nepal. Through its PoSHAN study, the Nutrition Innovation Lab-Asia is currently undertaking research in Nepal in collaboration with the Child Health Division of the Ministry of Health and Population and multiple local partners on how investments in agriculture can achieve significant impacts on maternal and child nutrition, and on demonstrating how large-scale programs best incorporate such evidence into cost-effective multi-sectoral interventions. Adding a study component on food safety (mycotoxin contamination of the food supply) will significantly enhance our understanding of nutrition outcomes linked to investments in agriculture. As noted by participants of the IFPRI/BMGF (2012) meeting, "only 35% of stunting of children can be attributed to known factors". This leaves room for research to uncover other suspected contributors to the world's huge nutrition problems, which could then lead testable recommendations for innovative interventions to address newly identified factors. The team will assess current mycotoxin risk so that potential mitigation strategies can be developed.

Given the significant statistical associations shown between mycotoxin exposure in children and height gain in infants and young children, the Nutrition Innovation Lab-Asia will undertake an mycotoxin birth cohort study to further the understanding of the causal relationship between past and current mycotoxin exposure (maternal and infant), birth outcomes and length-for-age in Nepali infants and young children. The study will also seek to validate the use of low cost data collection methods (e.g. dried blood spots versus venous blood samples) for mycotoxin analysis.

The specific aims of this study are:

1. To examine the relationship of maternal mycotoxin exposure in pregnancy and birth outcomes, including infant birth weight.
2. To examine the relationship of exposure to mycotoxin of infants through breast milk and their linear growth.
3. To examine the relationship of exposure to mycotoxin through complementary feeding and linear growth.
4. To enumerate the relative contributions of maternal and infant mycotoxin exposures in impairing linear growth, controlling for other potential explanatory factors.

Controlling for factors such as diet, maternal education, maternal height and BMI, household socio-economic status, infections and inflammation, and other elements such as storage patterns, knowledge of food contaminants and mitigation practices, the specific hypotheses of this study are:

1. There is an incremental effect of in utero, lactation and complementary feeding mycotoxin exposures on rate of length gain and stunting outcomes for age Z-scores in children at 2 year of age.
2. Maternal exposure to mycotoxins will be significant predictor of birth weight in infants, thereby being a significant contributor to the burden of stunting at 2 years of age.
3. Exposure to mycotoxins through breast milk before 6 months of age along with continued exposure through both breast milk and complementary foods (after 6 months of age) is a significant contributor to the burden of stunting at 2 years of age.
4. Improper farm management, food processing and storage practices are significantly related to higher levels of serum mycotoxins in the blood of mothers and their children.
5. Knowledge of the problem of food-borne contaminants is associated with improved food processing and storage practices.

Eligibility criteria: Inclusion Criteria:

* Pregnant women and adolescent girls (less than 30 weeks gestation)
* Aged 16-49 years
* Living in the study area
* Intends to reside in the study area through the study period
* Intends to deliver in the study area
* Provides informed consent herself or through a legal guardian
* Live Birth
* Single Birth

Exclusion Criteria:

* Severely malnourished mother \<17.5 cm
* Severely anemic mother hemoglobin\<7 g/dL
* Pregnancy induced hypertension
* Congenital anomalies
* Very low birth weight \<1500 g
* Sepsis
* Respiratory distress syndrome
* Severe malnutrition infant ≤-3 WFH z-score (3 months), \<11.5 cm MUAC or edema
* Severe anemia infant (hemoglobin\<7 g/dL)
* Fetal loss
* Early termination of pregnancy
* Still births
* Infant death
* Relocation of household

Primary outcomes:
measure: Change in Height for Age Z-scores (HAZ)
timeFrame: Measured at birth and when infant turns 3, 6, 9, 12, 18 and 24 months of age
Secondary outcomes:
measure: Aflatoxin M1 (breast milk)
timeFrame: Measured when infant is 3 months of age
measure: Low birth weight
timeFrame: Measured at birth
measure: Aflatoxin B1 (serum)
timeFrame: Measured during pregnancy
measure: Change in infant aflatoxin B1
timeFrame: Measured when infant turns 3, 6, 12 and 18 months of age
measure: Fumonisin B, Deoxynivalenol (DON) (urine)
timeFrame: Measured when infant turns 18 months of age
measure: Ochratoxin A (serum)
timeFrame: Measured when infant turns 18 months of age
Other outcomes:
Locations:
Study officials:
affiliation: Tufts University
name: Patrick Webb, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Patan Academy of Health Sciences
name: Kedar P Baral, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tufts University
name: Shibani Ghosh, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lamichhane A, Webb P, Andrews-Trevino J, Pokharel A, Acharya S, Shrestha R, Davis D, Baral K, Wang JS, Xue K, Paudel K, Ghosh S. Dietary determinants of aflatoxin B1-lysine adduct among infants in Nepal. Eur J Clin Nutr. 2022 Nov;76(11):1557-1565. doi: 10.1038/s41430-022-01142-1. Epub 2022 Apr 20.
citation: Andrews-Trevino JY, Webb P, Shively G, Kablan A, Baral K, Davis D, Paudel K, Shrestha R, Pokharel A, Acharya S, Wang JS, Xue KS, Ghosh S. Aflatoxin exposure and child nutrition: measuring anthropometric and long-bone growth over time in Nepal. Am J Clin Nutr. 2021 Apr 6;113(4):874-883. doi: 10.1093/ajcn/nqaa397.
citation: Andrews-Trevino JY, Webb P, Shively G, Rogers BL, Baral K, Davis D, Paudel K, Pokharel A, Shrestha R, Wang JS, Ghosh S. Relatively Low Maternal Aflatoxin Exposure Is Associated with Small-for-Gestational-Age but Not with Other Birth Outcomes in a Prospective Birth Cohort Study of Nepalese Infants. J Nutr. 2019 Oct 1;149(10):1818-1825. doi: 10.1093/jn/nxz122.