Neonatal Deaths Clinical Trial
Official title:
Using Ongoing Newborn Intervention Trials to Obtain Additional Data Critical to Maternal, Fetal and Newborn Health in a Harmonized Way: The AMANHI* Study *Alliance for Maternal and Newborn Health Improvement (AMANHI)
The goal of this study is to generate unique information to guide improvements on
interventions to reduce maternal and newborn mortality as well as prevent stillbirths.
The objective of this study is to determine the burden, timing, and causes of maternal
deaths, stillbirths and neonatal deaths.
This will be an observational study where data will be collected retrospectively in the
context of the ongoing study in Haryana, India.
Women of reproductive age living in the study area have already been enumerated for the
parent studies. Active surveillance is being conducted for identifying pregnancies and
deaths among women of reproductive age in the population through 3 monthly home visitations.
Verbal autopsies will be conducted for all deaths of women in the reproductive age,
including those who died in pregnancy, childbirth and up to 42-60 days after childbirth.
Verbal autopsy interviews will also be conducted for all stillbirths.
RATIONAL & BACKGROUND INFORMATION
Among the Millennium Development Goals, those that aim to reach significant reductions in
maternal and child mortality have been proving the hardest to achieve.
Most maternal and neonatal deaths are caused by a few conditions, and majority of them are
preventable with currently available, effective interventions. About a third of stillbirths
occur in the intrapartum period, integrally related to the availability and quality of
essential and emergency childbirth services. Effective interventions to reduce maternal
deaths, stillbirths and newborn and child deaths reach less than half the pregnant women,
mothers, newborns and children who need them. Information on mortality and morbidity as well
as health care delivery is largely available only from surveys, which have inherent
methodological issues that limit validity. Vital registration information and reliable
information from the health system is missing in the same countries where the burden of
mortality is the highest and health care is least accessible. This leads to underestimates
of the magnitude of the problem with negative implications for the prioritization of
interventions to scale-up.
The BMGF and WHO are supporting a set of large intervention trials that will follow cohorts
of pregnant women and newborns to document the impact of the interventions. These trials
provide a unique opportunity to address additional questions relevant for improving
maternal, newborn and child health (MNCH) programs and for addressing the above-mentioned
gaps in data.
STUDY GOALS AND OBJECTIVES Goal
The study will be conducted as a part of the large ongoing parent study on newborn health
research in Haryana, India titled "Efficacy of neonatal vitamin A supplementation in
improving child survival in Haryana, India: generation of evidence necessary for informing
global policy" to better understand the epidemiology of maternal mortality, stillbirths and
neonatal deaths.
Objective
The current study is collecting information on the burden, timing and causes of neonatal
deaths and an estimate of maternal deaths and still births. The proposed additional study
presents a unique opportunity to estimate population-based burden, timing, and causes of
maternal deaths and stillbirths.
Study Design
This will be an observational study where data will be collected retrospectively.
Study Population
This study will be conducted in the same study areas and population as the parent study. The
participants in this study will be pregnant women identified through surveillance among all
women of reproductive age in the population where the parent study is being conducted, and
their newborn infants. Some women not eligible for enrollment into the parent study due to
loss of their babies or live babies with exclusion criteria or those who do not give consent
for the parent study or women who died during pregnancy or child birth may still be included
in the AMANHI study. Information on women refusing to take part in the parent studies is
being documented. This information will be used for analysis exploring whether this group
has a different risk of maternal or newborn mortality. Only the control group in the parent
study will be considered for analysis of neonatal deaths in this observational study.
Maternal mortality, pregnancy outcomes and consequent neonatal mortality will be measured
among women identified as pregnant during surveillance and followed-up until 42-60 days
after delivery.
The period of data collection for this objective will be 12-24 months.
Sample Size Estimates
Maternal mortality, stillbirth rates and neonatal mortality will be estimated for all
pregnant women, mothers and newborns from the time that the site meets the minimum criteria
for inclusion.
The verbal autopsies will be filled retrospectively for a window period of 1 year for deaths
in women and for still births.
Verbal autopsies for neonatal deaths are already being filled in parent study.
METHODOLOGY
Description of study site:
The parent study, Neonatal Vitamin A supplementation trial, is being conducted in 16
clusters, of which 13 are catchment areas of Primary Health Centres in Faridabad and Palwal
districts in the state of Haryana and 3 are urban slum clusters in Faridabad district.
Study Procedures
Active surveillance is being conducted for identifying pregnancies and deaths among women of
reproductive age in the population through 3 monthly home visitations.
At the time of identification of pregnancy, information is recorded on the details of the
pregnancy including last menstrual period. For women whose infants are enrolled into the
study, information on vital status of the mother is obtained from the 3 monthly follow up
visit and the pregnancy surveillance register retrospectively as well as prospectively for
those infants whose 3 month follow up visits are still due.
For women whose infants are not enrolled due to exclusion criteria or women who had still
births or abortions, visits are made at 42 to 60 days to record information on vital status
of the women.
Miscarriages/abortions, stillbirths, live births, neonatal deaths and maternal deaths are
recorded. Verbal autopsies will be conducted for all deaths of women in the reproductive
age, including those who died in pregnancy, childbirth and up to 42-60 days after childbirth
for still births and neonatla death. Sites will use a standardized verbal autopsy
questionnaire. Specially trained workers will conduct verbal autopsies within 3 months of
reporting of a death. For deaths that have already been reported since the initiation of the
parent studies, verbal autopsies can be done within 12 months of death (WHO verbal autopsy
standards, 2007).
The verbal autopsy instruments have been pre-tested and used extensively in many settings.
Nevertheless, the site will translate the questionnaire and pretest it to ensure that the
translated questions capture the intended information. Any changes based on pre-tests will
be made prior to implementation.
Safety Considerations
This is an observational study in which pregnant women are being identified and followed up
until the end of the postnatal period to identify stillbirths and maternal and neonatal
deaths as part of the parent studies. A verbal autopsy interview will be conducted for all
of these deaths. There are no direct safety concerns.
Ethical Considerations
Ethical approval has been obtained from WHO and SAS ERC.
Informed Consent
Informed consent is already being requested from each household to conduct reproductive
surveillance in order to identify pregnant women and periodic follow up. This consent is
verbal and the informed consent form is signed by the member of the research team obtaining
consent to confirm that he/she has accurately read the consent form to the potential
participant/head of household, the individual has had the opportunity to ask questions and
has consented freely. The informed consent forms for verbal autopsies will be confirmed with
a signature or thumbprint by the participant. In the absence of a signature, a witness
(other than the member of the research team obtaining consent) will be asked to sign and
counter signed by the member of the research team obtaining consent.
Confidentiality
All identifier information will be delinked and identifier information will be stored under
lock and key after the analysis is complete.
Data Management
Information on a core set of variables will be collected with standard definitions used
across all sites. The WHO will provide a set of range and consistency checks that must be
applied to these variables, although the exact procedures used to carry out these checks
will be left to the individual sites.
Electronic data capture or double data entry by separate data entry specialists will be
performed onsite. Alternatively, scanning of forms using special TeleForms software will be
performed. The site will be responsible for initial cleaning of the data, including running
range and consistency checks as well as periodic reviews of distributions and identification
of outliers. The study site will resolve any inconsistencies within their database in
consultation with their field data collection team and with field verification if needed.
Data on the core set of variables from the study site will be sent every 3 months to a
central data repository established for the project at the WHO. The WHO team will run
another set of range and consistency checks including checking of consistency of data
quality across sites. Any inconsistencies or queries will be provided to the study site,
which will be expected to check and address the list of queries and resubmit data. Cleaned
data from all sites will be pooled and stored in a SQL database at the WHO.
Statistical Analysis
All verbal autopsies will be analyzed using reliable and valid computer-based methods
including the Random Forests, Inter-VA and Tariff methods. The site will conduct the
analysis of their verbal autopsy data in order to determine the causes of deaths for
stillbirths and neonatal and maternal deaths. A data analysis workshop will be held at the
WHO in Geneva in the second quarter of 2014 to conduct a pooled analysis of the data.
Quality Assurance
Principal investigators will provide monthly progress reports during the entire study period
and will participate in regular telephone conferences with WHO staff.
Field supervisors will check all forms completed by field workers before data entry. Field
supervisors will observe 5% of randomly selected field worker verbal autopsies. Data
cleaning quality assurance will be performed using consistency and range checks both at the
study sites and at the WHO data coordination centre as described above in the data
management section.
The WHO Department of Maternal, Newborn, Child and Adolescent Health will be responsible for
monitoring the study in collaboration with selected site investigators. WHO staff and/or
site investigators will perform site monitoring visits to each site at least every 6 months
to assess the quality of study implementation and data collection using a standardized site
monitoring checklist. The site visit will lead to the provision of recommendations for study
improvement. More intensive visits are planned for the first six months of study
implementation to ensure prompt problem identification and resolution.
;
Time Perspective: Retrospective
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00270530 -
Intermittent Preventive Treatment of Malaria in HIV-Seropositive Pregnant Women in Zambia
|
Phase 4 | |
| Completed |
NCT02412293 -
Community-based Perinatal and Newborn Care in Gilgit District, Northern Areas, Pakistan: an AKU-AKHSP Collaboration
|
N/A |