Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00970866 |
| Other study ID # |
223623 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 2009 |
| Est. completion date |
December 15, 2017 |
Study information
| Verified date |
February 2022 |
| Source |
University of California, Davis |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In Ghana, low micronutrient intakes among pregnant women are a major problem. The standard
nutritional intervention during pregnancy is iron-folic acid tablets, but adherence is low.
The investigators have pioneered the use of multiple micronutrient-fortified semi-solid
pastes called Lipid-based Nutrient Supplements (LNS) (made using vegetable oil, groundnut,
milk, sugar, and micronutrients), and the investigators' previous studies show that the
approach could have great potential for use by pregnant and lactating women.
This study aims to evaluate the effects of LNS-P&L designed for pregnant and lactating women
and LNS-20gM designed for infants. Pregnant women (n=864) randomly selected from ante-natal
clinics in Yilo and Manya Krobo districts of Ghana will be randomized to receive daily (a)
Group 1: Iron/ Folic Acid tablets during pregnancy, and a tablet containing calcium (Ca) only
(akin to a placebo) during lactation (6 mo), (b) Group 2: Multiple Micronutrient tablets
during pregnancy and the first six months of lactation, or (c) Group 3: LNS-P&L during
pregnancy and lactation, whilst their infants receive LNS-20gM daily from 6 to 18 months.
There are two primary outcomes namely:
1. Maternal primary outcome: Birth length
2. Child primary outcome: Child length-for-age z-score at 18 mo.
The investigators hypothesize that a) mean birth length and length-for-age at 18 mo will be
greater in children whose mothers are in Group 2 than those whose mothers are in Group 1, and
b) children whose mothers are in Group 3 will have greater birth length and length-for-age at
18 mo than the children in either of the other two groups.
Description:
Introduction:
Inadequate nutrient intakes during pregnancy remain a major problem worldwide. The standard
nutritional intervention during pregnancy is iron-folic acid tablets, but adherence is
generally quite low. We have pioneered the use of lipid-based nutrient supplements (LNS),
which are multiple micronutrient-fortified semi-solid pastes made using vegetable oil,
groundnut paste, milk, sugar, and micronutrients, for home fortification of complementary
foods for infants. Given results of previous studies with Nutributter in Ghana (1, 2) and
similar LNS in Malawi (3, 4) we believe that the food-based approach using LNS has the
potential to improve the nutritional status of these women, and thereby also enhance their
children's growth and micronutrient status.
Our consortium has formulated LNS-P&L for pregnant and lactating women, and modified the
Nutributter for children, which has been called LNS-20gM in this trial. The LNS-20gM provides
generally the Recommended Nutrient Intakes (RNI) for 18 vitamins and minerals for infants
from 6 to 18 mo of age. The LNS-P&L is modeled on the UNICEF/WHO/UNU international multiple
micronutrient preparation (UNIMMAP) for pregnant and lactating women and similar products
used in Guinea Bissau (5). Each supplement (20 g/day) will provide 118 kcal/day. Both LNS
products (LNS-P&L and LNS-20gM) will, in addition to the multiple micronutrients provided in
the MMN, supply energy (118 kcal/d), fat (11 g/d), protein (2.6 g/d), the essential fatty
acids linoleic acid (=1.29 g/d) and a-linolenic acid (0.29 to >0.6 g/d), as well as calcium,
phosphorus, potassium and magnesium.
Objectives
The study has two objectives, which are:
1. To evaluate the effect of LNS-P&L on the nutritional status of Ghanaian pregnant and
lactating women.
2. To assess the effect of LNS-P&L given to pregnant and lactating women and LNS-20gM
provided to children from 6 to 18 mo of age on child growth and micronutrient status.
Procedures
1. Recruitment:
This study will be a community-based, randomized controlled trial with three
intervention groups. Potential subjects will be Ghanaian pregnant women attending usual
ante-natal clinics at the Government Hospitals at Atua and Akuse, and the St Martins de
Porres Catholic Hospital at Agormanya (Manya Krobo District of Ghana), and the Somanya
Polyclinic at Somanya (Yilo Krobo District of Ghana).
Enrolment into the study will be done in two steps. First, pregnant women who meet an
initial set of criteria will be asked their consent (sign a Screening Consent Form) to
participate in a pre-enrolment screening using a Screening Questionnaire. During this
screening, which will be conducted at the clinics, results of the routine ante-natal
examination already entered in the Ante-natal Cards will be inspected. The screening
questionnaire will also collect additional information, such as description of place of
residence, not recorded in the Ante-natal cards.
Second, women who pass the screening will be contacted in their homes, where we will
provide them with additional details of the study and seek their consent for
recruitment. If they agree, they will sign a recruitment consent form, and enrolment
will be said to be completed. Immediately, we will collect background demographic and
socioeconomic information in the home using a Baseline Questionnaire, and schedule the
women to come to the laboratory to complete a baseline anthropometric and laboratory
assessment (blood and urine sampling, hemoglobin, blood pressure and Ultrasound for
gestational age).
Pregnant women (n = 864) who have completed the baseline assessments and remain eligible
for the study will be randomly assigned (using opaque envelopes with group designations)
to one of three groups: (1) Group 1: Iron and Folic Acid, (2) Group 2: Multiple
Micronutrient (MMN), and (3) Group 3: Lipid-based Nutrient Supplements (LNS).
2. Follow up:
Pregnant women will be followed-up through delivery, up to 6 mo postpartum (i.e.
remaining part of pregnancy from time of recruitment + 6 mo of lactation), the infants
born to the women will be followed-up from birth to 18 mo of age. Field Workers will
visit subjects in their homes biweekly during pregnancy and weekly from birth to 18 mo
to provide supplements and collect data on morbidity and adherence. In the case of
multiple births by a woman, (e.g. twins or triplets), one baby will be randomly selected
immediately after delivery to be the index child from whom infant data and blood samples
will be collected. Anthropometric data will be collected from the unselected twin or
triplets, and those in Group 3 will receive LNS-20gM (because of the cultural belief
that twins and triplets, etc., must be treated the same), but blood samples will not be
collected from the unselected child. In case of loss of child/children during or after
delivery, the mother will be followed-up until 6 mo postpartum. In case of loss of
mother during or after delivery, the baby will be followed-up until 18 mo of age.
If any woman in the study is recommended to take additional vitamins and/ or minerals by
her physician, we will work with the physician to ensure that any supplement given does
not lead to excess intakes.
3. Outcome measures:
The study will have two primary outcomes namely:
1. Maternal primary outcome: Birth length, and
2. Child primary outcome: Child length-for-age z-score at 18 mo.
Secondary outcomes include:
i. Maternal:
- Anthropometric status (weight, BMI, mid upper arm circumference and sub- scapular
skin-fold thickness) at ~ 36 wk gestation and at 6, 12, and 18 mo postpartum.
- Pregnancy outcomes (birth weight, gestational age).
- Anemia, micronutrient (iron, vitamin A, B-vitamins, zinc) and EFA status, and
malarial antigen at ~ 36 wk gestation and 6 mo postpartum.
- Total plasma cholesterol at ~ 36 wk gestation.
- Blood pressure and urinary iodine, isoprostane (marker of oxidative stress) and
8-hydroxy-2'deoxyguanosine (8-OHdG) (marker of DNA damage) at 36 wk gestation.
- Breast milk composition (EFA, vitamin A, B-vitamins, iodine) at 6 mo postpartum.
- Depressive symptoms (which may be related to EFA status) at 6 mo postpartum.
ii. Child:
- Anthropometric status (weight, length, head circumference and mid upper arm
circumference) at birth and 3, 6, 12 and 18 mo.
- Anemia, micronutrient (iron, vitamin A, B-vitamins, iodine) and EFA status, and
malarial antigen at 6 and 18 mo.
- Morbidity between 6 and 18 mo.
- Child feeding practices and maternal report of child sleep patterns at 6, 12 and 18
mo.
- Energy intake from complementary foods at 9 and 15 mo.
- Antibody response to measles vaccination at 12 mo.
- Achievement of five motor milestones (sitting without support, standing alone,
walking with assistance, walking alone and running) and four other developmental
milestones (pronouncing single words like mama / dada, waving goodbye, eating by
self, drinking from a cup) from 0 to 18 mo.
- Neuro-behavioral development at 18 mo of age.
First Post-intervention Follow-up Study: Detailed description
Introduction:
Previous research has suggested that nutrition during pregnancy and early childhood can
have long term effects on growth, health, and cognition. Only a few studies conducted
back in the 1970's, including those in Guatemala (7) and Colombia (8, 9), have followed
a cohort that was provided nutrition supplementation during both pregnancy and early
childhood. The International Lipid-Based Nutrient Supplements (iLiNS)-DYAD Trial in
Ghana examined the effects of a lipid-based nutrient supplement (LNS) provided to women
during pregnancy and the first 6 months postpartum, and to their infants from 6 until 18
months of age. Re-assessing the children from that trial at 4-6 years of age is
important because this is a critical time for certain longer-term outcomes, such as
cognitive development (e.g. school readiness) and body composition prior to puberty.
Main objective The main objective of this first follow-up study is to evaluate the
impact of the iLiNS DYAD-Ghana intervention among participants (women and their
children) and their families at 2-4 years post-intervention.
Primary objectives
To determine the effects of LNS-P&L given to women during pregnancy and the first 6 mo
post-partum, and LNS-20gM given to their children from 6 to 18 months of age on the
following outcomes at 4-6 years of age:
1. Child growth
2. Child neurobehavioral development
Secondary objectives:
To determine the effects of LNS-P&L given to women during pregnancy and the first 6
mo post-partum, and LNS-20gM given to their children from 6 to 18 months of age on
the following outcomes at 4-6 years of age:
a) Health status and stress response of the children b) Sweet taste preferences and food
and drink preferences of the children. c) Mental and physical health status of the women
after receiving LNS-P&L. d) Caregiver investments in the index child and close siblings.
e) Growth of the next younger sibling of the index child. f) Epigenetic DNA
modifications of the index child g) Child activity levels
Study design The study is designed as a follow-up study of a randomized controlled
trial. Eligible women and mothers or caregivers of eligible children who took part in
the iLiNS DYAD-Ghana intervention trial from 2009 to 2014 will be contacted for
enrollment. Fathers and/or younger siblings of eligible children, if available, will
also be enrolled.Ethical approval for the study will be obtained from the institutional
review boards of the University of California in Davis, the University of Ghana College
of Basic and Applied Sciences, and the Ghana Health Service.
Inclusion criteria
1. Mothers and children: Participated in the iLiNS DYAD-Ghana trial.
2. Fathers: Both child and wife (child's mother) participated in the iLiNS DYAD-Ghana
trial.
Exclusion criteria
Potential participants will be excluded if any of the following is present:
a) Severe illness or injury which may interfere with data collection, eg. malignancy,
etc.
b) Unwillingness to participate in or cooperate with the study procedures.
Procedures
1. Recruitment Eligible mothers and fathers will be contacted in their homes,
whereupon their informed consent will be sought for their own participation in the
study, and the participation of their children. Where an eligible child lives in
the care of a caregiver (instead of a parent or parents), informed consent for the
child's participation will be sought from the caregiver and at least one parent, if
possible.
2. Data collection
Data will be collected at the following contact points:
i. Four (4) visits by study workers to the homes of participants:
- Home visit #1: This will occur at or shortly after enrolment. Field workers will
collect background socio-economic and demographic information. Enrollment and
anthropometric measurement of fathers, as well as anthropometric measurements of
younger siblings, may occur at this or any of the subsequent home visits.
- Home visit #2: Will normally occur within the 7 days after Home visit #1. Study
workers will collect children's morbidity data, and arrange with mothers/caregivers
to complete the first visit to the central data collection location.
- Home visit #3: Normally, this will occur within 2 weeks after the Home visit #1.
Study worker will: (a) collect mothers'/caregivers' report of their children's
taste preference; (b) collect information on the mother's perception of the iLiNS
intervention (c) collect saliva samples (sub-set of mothers/index children) to
determine cortisol; and, (d) arrange with women (sub-set) to have their children
complete the second visit to the central data collection location.
- Home visit #4: Normally, this will occur within 5 weeks after enrolment. Study
workers will administer questionnaires (motor and neurocognitive development
questionnaires) and arrange for mother and child to visit the hospital laboratory
for more data/sample collection.
ii. Two (2) visits by mothers and/or children to a central data collection location:
• Data collection location visit #1: Normally, this will occur between the first and the
second week after enrolment. Tasks will include: (a) Anthropometric measurements; (b)
Developmental assessments; (c) Deuterium dosing and saliva samples collection for
assessment of children's body composition; and (d) Distribution of accelerometers to a
sub-sample of children for assessment of physical activity.
• Data collection location visit #2: Will occur for a sub-set of children normally after
2 weeks following enrollment. These children will complete a sweet taste preference test
and a photo game to examine food and drink preference.
iii. Visit by mothers and children to the Hospital laboratory: Data/sample collection
will include: (a) saliva samples (second time for cortisol analysis); (b) mothers'
reproductive history; (c) children's clinical examination (Otoscope data); (d) blood
pressure; (e) cheek swab; (f) hair sample collection; and (g) blood hemoglobin
measurements.
c. Outcome measures
Outcome measures will include the following 8 major domains:
1) Growth and body composition of the index child 2) Neurobehavioral development of the index
child 3) Health status and stress response of the index child 4) Sweet taste and food/drink
preferences of the index child 5) Maternal mental health and stress response 6) Retrospective
perceptions of the LNS intervention, and investments" in the index child and close siblings
7) Growth status of the next younger sibling of the index child 8) Activity level of index
child 9) Epigenetic effects of the intervention on the index child
Second Post-intervention Follow-up Study: Detailed description
Introduction:
At birth, infants depend completely on their caregivers to regulate their emotional and
behavioral states. As the central and autonomic nervous systems develop rapidly during the
first two years of life, infants progressively develop self-regulatory skills. These skills
lay the foundation for social-emotional skills during childhood and adulthood, which are
critical for mental health, success in school and the workplace, and healthy peer and family
relationships. Very few studies have examined factors that influence the development of
social-emotional regulation in low- and middle-income countries, where an estimated 250
million children are at risk for not fulfilling their developmental potential, partly due to
undernutrition. Adequate nutrient intake is essential during pregnancy and infancy, providing
the building blocks for nervous system development. In the first follow-up study of the
iLiNS-DYAD-G trial in Ghana, receiving LNS predicted fewer social-emotional difficulties at
age 4-6 years, and LNS buffered children from the negative effects of materially and socially
disadvantaged home environments on social-emotional well-being. Despite these protective
effects, overall a high percentage of children had social-emotional difficulty scores in the
abnormally high range at age 4-6 years (25% compared to 4-10% in other published studies),
suggesting that children in the study area in Ghana are at high risk for the early
development of social-emotional difficulties.
Main objective of the second follow-up study:
The main objective of the second follow-up study is to examine the long-term effects of
SQ-LNS during pregnancy and infancy on autonomic nervous system regulation and white matter
microstructure properties at age 8-12 years, and to determine whether neural effects account
for protective effects of LNS on social-emotional functioning at this age, as youths
transition into early adolescence, which is a period of high susceptibility to the onset of
depressed mood and depressive disorder.
Specific objectives of the second follow-up study:
To determine the effects of LNS-P&L given to women during pregnancy and the first 6 mo
post-partum, and LNS-20gM given to their children from 6 to 18 months of age on the following
outcomes at 8-12 years of age:
1. Child and adolescent social-emotional development (e.g., SDQ, SCARED, MFQ)
2. Child and adolescent self-regulation (e.g., executive function, risk taking)
3. Child and adolescent autonomic nervous system function
4. Characteristics of child and adolescent brain structure (e.g., white matter
microstructure, cortical volume and thickness)
5. Child and adolescent neurobehavioral development (e.g., cognition, literacy and
arithmetic)
6. Child and adolescent health and anthropometric status
7. Child and adolescent pubertal development
8. Child and adolescent school performance
9. Maternal cognition and mental health
Study design:
The study is designed as a follow-up study of a randomized controlled trial. Eligible women
and mothers or caregivers of eligible children who took part in the iLiNS DYAD-Ghana
intervention trial from 2009 to 2014 will be contacted for enrollment. Ethical approval for
the study will be obtained from the institutional review boards of the University of
California Davis and the Ghana Health Service.
Inclusion criteria:
Mothers and children: Participated in the iLiNS DYAD-Ghana trial.
Exclusion criteria:
Potential participants will be excluded if any of the following is present:
Severe illness or injury which may interfere with data collection, eg. malignancy, etc.
Unwillingness to participate in or cooperate with the study procedures.
Procedures
1. Recruitment Eligible mothers and children will be contacted in their homes, whereupon
their informed consent will be sought for their own participation in the study, and the
participation of their children. Where an eligible child lives in the care of a
caregiver (instead of a parent or parents), informed consent for the child's
participation will be sought from the caregiver and at least one parent, if possible.
2. Data collection
Data will be collected at the following contact points:
i. Home visit by study workers to the homes of participants. Field staff will explain the
study and obtain informed consent. Consenting participants will be administered a survey to
collect demographic and school information (name and location of the child's school and
teacher), other caregiver report questionnaires, and assessment of the home environment.
ii. Project office visit. Normally, this will occur between the first and the second week
after enrolment. Tasks will include: (a) Autonomic nervous system assessments, (b)
Social-emotional and self-regulation assessments, (c) Other neurobehavioral assessments; (d)
Anthropometric measurements, (e) Pubertal assessment, (f) blood pressure; (g) hair sample
collection; and (h) blood hemoglobin measurements and blood spot collection.
iii. School visit. Field staff will visit the child's school to administer teacher-report
questionnaires of the child's behavior.
iv. Visit to hospital for MRI scan (subsample). A subsample of 240 children will be invited
to the hospital to participate in a structural MRI scan with a diffusion MRI acquisition.
c. Outcome measures
Outcome measures will include the following major domains:
1. Child and adolescent social-emotional development (e.g., SDQ, SCARED, MFQ)
2. Child and adolescent self-regulation (e.g., executive function, risk taking)
3. Child and adolescent autonomic nervous system function
4. Characteristics of child and adolescent brain structure (e.g., white matter
microstructure, cortical volume and thickness)
5. Child and adolescent neurobehavioral development (e.g., cognition, literacy and
arithmetic)
6. Child and adolescent health and anthropometric status
7. Child and adolescent pubertal development
8. Child and adolescent school performance
9. Maternal cognition and mental health
