Using Ongoing Newborn Intervention Trials to Obtain Additional Data Critical to Maternal, Fetal and Newborn Health in a Harmonized Way
Condition: Maternal Deaths; Neonatal Deaths; Still Births
MeSH terms: Perinatal Death; Maternal Death; Stillbirth; Death
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): This is an observational study being conducted as a substudy of antoher trial.
Intervention type(s): Other
Time perspective: Retrospective
Sampling method: Non-Probability Sample
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. The parent study is not conducting an intervention related to
        maternal health or stillbirths. Therefore, the results of the AMANHI study related to
        maternal and stillbirth outcomes are not likely to be influenced by what happens in the
        parent study. However, only the control group in the parent study will be considered for
        analysis of neonatal deaths in this observational study.
      
Keywords: Verbal autopsies; Maternal deaths; Still births