Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04114305 |
| Other study ID # |
IRB 6298 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 18, 2016 |
| Est. completion date |
April 27, 2018 |
Study information
| Verified date |
April 2020 |
| Source |
Johns Hopkins Bloomberg School of Public Health |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
With increased use of effective strategies to prevent HIV transmission from women to their
infants, the number of HIV infected children has dramatically decreased. This has led to an
increased number of children who have been exposed to HIV, but who are not themselves
infected. There is concern that exposure to HIV can lead to poorer health outcomes, including
less optimal neurodevelopment. Because of this possibility in a growing population of
HIV-exposed, but uninfected (HEU) children, there is a need to identify interventions to
optimize their growth and development. This study was undertaken to evaluate the impact of a
two-generation intervention, jointly targeting child neurodevelopment and maternal
psychosocial wellbeing, integrated into antenatal care/prevention of maternal to child
transmission (ANC/PMTCT) clinics.
The intervention was implemented by mothers2mothers (m2m), an organization based in South
Africa with a long-standing program using peer mentors (Mentor Mothers) to support
HIV-infected women and their families. The m2m ECD intervention provided by specially trained
Mentor Mothers included home- and community based activities meant to assist mothers and
other caregivers in building resilience and gaining skills to support their children's
development. The primary intervention was an intensive program of home visits beginning
during pregnancy and continuing until the child reached two years of age, with up to 46 home
visits. At each visit, the ECD Mentor Mothers helped parents/caregivers to learn about ages
and stages of growth (including pre-birth), and to facilitate responsive parenting and early
learning opportunities for their children. Mentor Mothers also conducted parenting
information play groups (PIPs) in each community for ECD clients and ECD information was
integrated into the existing facility support groups provided at each health clinic. The
intervention covered general areas of maternal and child health, nutrition, social services,
support for primary caregivers and stimulation for early learning.
Since the intervention was targeted at two generations, the primary aims were two-fold: to
assess the impact on pediatric neurodevelopment and on maternal psychosocial function.
Secondary aims included assessment of maternal and child retention in care, maternal HIV
outcomes and child mortality, health, growth and nutrition. Children were enrolled into one
of two study arms: 1) the intervention arm included children from clinics where the m2m ECD
program was being implemented, and 2) the comparison arm included children from government
clinics that offered standard of care services but no m2m or ECD program.
Mothers were enrolled during antenatal care, in the third trimester of pregnancy. Children
and their mothers were followed though 18 months of age and their evaluation included an
assessment of development (Mullen Scale of Early Learning) at 9 and 18 months, as well as
assessments of child growth, maternal psychosocial well-being, parenting practices and
retention in care.
Description:
Intervention Methods
ECD Intervention. Mothers2mothers (m2m) was selected to pilot-test a parenting intervention
integrated within the Eswatini standard integrated antenatal care and PMTCT program developed
according to the World Health Organization (WHO) Option B+ recommendations. Each clinic
selected for the pilot test had already implemented a m2m mentor mother (MM) peer support
program at the facility, as well as defaulter follow-up in the community.
The parenting intervention strategy, known as "uMntfwana Wami, uMntfwana Wetfu"( "My Child,
Our Child") was focused on peer support for pregnant women and parents/caregivers of young
children to assist them in building resilience and gaining skills to support their children's
development.
M2m's facility-based Mentor Mothers (MMs) recruited pregnant women at the ANC/PMTCT clinics.
Both HIV-positive and HIV-negative women were eligible to participate in the m2m
intervention. Community-based ECD MMs, who received five weeks of program-specific training,
provided the parental training intervention.
Evaluation Methods
Evaluation Design. The independent evaluation was designed as a quasi-experimental comparison
between clinic sites (and their surrounding communities) implementing the intervention and
similar clinic sites not implementing the intervention.
Sample size calculations. A sample size of 416 participants (213 intervention arm, 203
comparison arm) was estimated to be sufficient to detect a clinically meaningful difference
of 0.5 standard deviation (SD) on an age-normed Mullen scale, after allowing for potential
10% child mortality and 20% loss to follow-up, and accounting for clustering at the clinic
level.
Enrollment of participants. At intervention arm clinics, m2m facility MMs referred ANC
clients in the third trimester of pregnancy, residing in the clinic catchment area, and
interested in participating in both intervention and study to the study team. At comparison
arm clinics, nurses referred interested third trimester pregnant women to the study. A study
research assistant based at each clinic conducted eligibility screening and obtained informed
consent. Although women could participate in the parental training intervention irrespective
of HIV status, the evaluation was designed to assess its effect only on the HIV-positive
subgroup of mothers. Participant inclusion criteria were: a woman, aged at least 18, with
confirmed HIV-positive status recorded on a clinic chart or register, visiting the PMTCT
clinic in the 3rd trimester of pregnancy, and verified resident within the clinic-defined
catchment area. Participants who planned to move outside the catchment area or switch HIV
care to another site, did not provide written consent to participate in the study or did not
complete the enrollment questionnaire were excluded.
Data collection and follow up. Study participants were interviewed at enrollment to collect
demographic and contact information, abstract patient-held HIV and maternal health cards, and
carry out baseline assessments. Follow-up interviews and abstraction of the patient-held HIV,
maternal health and well child care cards were targeted for two weeks after the baby's birth
and when the baby reached three, six, nine and 18 months of age. A home visit and observation
were conducted when the baby was between 12-15 months of age. If the mother was not
reachable, the baby's primary caregiver was interviewed.
Primary outcomes assessment.
The primary pediatric outcome of cognitive development at nine and 18 months of age was
assessed using the Mullen Scales of Early Learning, administered by two assessors. The items
were translated into siSwati as needed and adapted for and tested on emaSwati children in the
relevant age groups. At the 18-month time point, inter-rater reliability was assessed by
independently scoring a sample of 40 children.
The primary maternal outcome of psychosocial well-being was assessed using the Edinburgh
Postnatal Depression Scale (EPDS), categorized dichotomously as depressive symptoms present
(EPDS score >13) or absent (EPDS score ≤13). The cutoff was selected based on work in
neighboring South Africa by Tomlinson et al (2017). Parenting self-confidence was also
assessed, using the Maternal Self-Report Inventory (Short Form) (MSRI). These instruments
were administered to women at enrollment and at nine and 18 months postpartum.
Secondary outcomes assessment. Length, weight, head circumference and mid-upper arm
circumference were measured at the child's 9- and 18-month visits and compared to norms
established by the WHO Multicentre Growth Reference Study..[ref 49]. Three separate
anthropometric measurements were taken and the median value used. Retention in care and
pediatric HIV testing was assessed based on health care visits and outcomes abstracted from
multiple sources including: participant-held maternal health/ANC and HIV cards and child
health and HIV cards, postnatal care and child welfare registers at the clinics, and the
client management information system (CMIS) in some clinics, as well as self-report.
Compliance with feeding recommendations was obtained by maternal or caregiver report.
Mortality information was obtained by report from families.
Potential mediators. Information on routine caregiving practices and household
characteristics was obtained by observation using the Home Observation for Measurement of the
Environment (HOME) Inventory [refs2 3] during a home visit at 12-15 months of age. Households
were instructed to carry out everyday household activities during this observation visit.
Study Research Assistants (RAs) completed classroom training on this instrument and then
pilot-tested it in the field using non-participating households. Inter-rater reliability was
assessed by having multiple observers score the pilot and then discuss discrepancies in
scoring. Key, non-routine child stimulation practices were assessed by interview using the
Family Care Indicator, a series of standardized questions developed as part of the UNICEF
Multiple Indicator Cluster Surveys (MICS) version 3 (2006), which was administered at
baseline to all participating mothers who at the time had children under age five, and to all
mothers and caregivers at the 9-month and 18-month assessments.
Potential confounding factors. Eswatini was affected by a drought during 2016-2017 and its
impact was assessed at home visits (age 12-15 months), and at the 18-month interview using
the Household Food Insecurity Access Scale (HFIAS).
Contamination assessment. Participants in both arms were interviewed about their contact with
m2m at each visit and at the 18-month assessment.
Statistical methods.
Mullen scores:
Scores from each domain (Visual Reception, Fine Motor skills, Receptive Language, Expressive
Language and Gross Motor skills) were analyzed separately. For each domain, the within-sample
means and standard deviations of the raw scores by arm were calculated. To facilitate
understanding of the effect sizes, the Mullen scores in each domain were then transformed
into within-study sample standardized scores (Z-scores), for which effect sizes represent
unit changes in the distribution SD. Multivariable linear mixed effects regression models
with a random effect for enrollment site were applied to test the difference in the
standardized mean scores between the two study arms at each time point. Adjusters selected
based on the literature included the child's actual age at the assessment date, the child's
gender, and an indicator for stunting (length-for-age Z-score < 2) as a proxy for chronic
malnutrition. Additional adjusters were included in the multivariate model based on their
strong (p<=0.2) effects in bivariate analyses: the size of the mother's household at
enrollment, the length of residence of the mother at her current location at enrollment,
household asset-based socio-economic status of the mother at enrollment, the mother's number
of other living children at enrollment, her number of previous miscarriages, and her years of
education.
Other measures. Growth: Percentages of children with Z-scores of the WHO-standardized
anthropometric measurements < -2 at the 9 month and 18 month assessments were reported.
Maternal retention in HIV care: Time in care was calculated as days from the date of
enrollment in the study to the last documented visit as found in the patient-held HIV cards,
the chronic care file of the HIV clinic at the clinic where they enrolled, the CMIS and from
self-report. A log-rank test for equality of mean retention between the two arms was
conducted.
Socio-economic status: Principal components analysis was used to develop a composite score of
socio-economic status based on reported household assets, which was divided into quintiles
for analysis. Family Care Indicator. Performance on individual items was assessed and as well
as through a combined score (possible range: 0-6) of activities that someone in the household
was reported to have performed with the child: (1) "Read books or look at picture books" (2)
"Sing songs" (3) "Tell stories" (4) "Play with" (5) "Take [the child] outside the home,
compound, yard or enclosure" and (6) spend time naming, counting and/or drawing things."
Mediation analysis. The multivariable linear regression model used in the primary analysis of
the 18-month timepoint was extended into a generalized structural equation model to evaluate
a potential mediating effect of book-sharing with the child on the relationships between
study arm and expressive language scores, and between study arm and visual reception scores.
Robust variance estimation was used to adjust for site clustering The presence of book
sharing was defined as a positive response to item (1) on the Family Care Indicator at the 18
month timepoint.
