The Prevention of Rh Disease of Newborns in Pakistan
The Prevention of Rh Disease of Newborns in Pakistan
The investigators aim to demonstrate the feasibility of point-of-care identification of
 Rh-negative women in a poor, rural setting in Pakistan. Feasibility will be assessed across 2
 major domains: 1) acceptance by pregnant women to receive the point-of-care test; and, 2)
 ability of health workers to administer the point of care test and interpret results. The
 investigators will also measure whether RhIg prophylaxis can be successfully delivered and is
 accepted by pregnant women in this setting. The socio-demographic correlates of the
 acceptance of point-of-care testing and where applicable, the acceptance of RhIg prophylaxis
 will also be assessed. In addition, the investigators will also explore the baseline
 knowledge of Rh disease among pregnant women and lady health visitors in this study
 population and will investigate socio-demographic correlates of baseline knowledge and the
 uptake of knowledge among pregnant women. Finally, the prevalence of Rh negativity will be
 calculated and stillbirth and neonatal mortality will be tracked among all participants. All
 stillbirths and neonatal deaths in this population will be characterized with respect to
 cause and Rh-negativity.
Rhesus (Rh) disease is a preventable condition caused by an incompatibility between maternal
 and fetal red blood cells (RBCs). If a person's RBCs lacks a certain protein s/he is said to
 be Rh-negative. Similarly, if a person's RBCs have that same protein, s/he is said to be
 Rh-positive. If a pregnant woman's is Rh-negative and her fetus is Rh-positive, the baby is
 at risk of Rh disease. The complications associated with Rh disease include miscarriage,
 stillbirth, and neonatal death. Among surviving newborns, Rh disease can cause anemia (low
 RBCs, which can appear as feeling tired or weak or having a shortness of breath), jaundice
 (yellowing of the skin), and brain damage. If Rh-negative women are identified, there is a
 very high chance that Rh disease of the newborn can be prevented.

 The purpose of this study is to demonstrate the feasibility of point-of-care identification
 of Rh-negative women in Dadu district, Pakistan. Determining the Rh status of pregnant women
 is the first step towards prevention of Rh disease of the newborn. By collecting information
 about a) the Rh status and blood type of pregnant women; b) the acceptability of a point of
 care test blood test of Rh disease; and, c) the acceptability of treatment for Rh negativity
 in pregnant women, the investigators will be able to improve antenatal care and prevent Rh
 disease of the newborn in rural settings. The implementation of a point-of-care Rh test will
 allow us for the identification of Rh-negative women, prompt provision of treatment, and
 prevention of Rh disease of the newborn in rural settings in Pakistan.

 As part of this study, participants will be asked a series of questions to assess
 reproductive history of pregnant women and other demographic characteristics (i.e. questions
 about home environment and lifestyle). The investigators will also ask whether they are
 willing to provide a drop of blood, collected via finger prick, to allow us to determine your
 Rh status by ELDONCARD. If Rh test reveals that the pregnant women are Rh negative, the
 investigators will offer them up to two doses of treatment, first at approximately 28 weeks
 of gestation and again within 72 hours of delivery. The injections will be administered at
 the health facility. They will also be asked to undergo an ultrasound procedure by a trained
 technician at health facility. Moreover, after the newborn is delivered, the investigators
 will also ask a series of question and perform an in-person assessment of newborn to assess
 their health within 72 hours of delivery and then again on their 29th day of life. If they
 are found to be Rh-negative and they have a miscarriage, stillbirth, or baby dies within the
 first month of life, the investigators will ask them if we can collect a sample of their
 blood for further testing.

 The investigators will conduct a prospective cohort study in Tehsil Headquarter Hospital
 (THQ) and District Headquarter Hospital (DHQ) that are situated in Dadu District, Sindh,
 Pakistan. In total, between 3 and 5 Lady Health Visitors (LHVs) will be enrolled at the study
 THQ and DHQ to administer the point-of-care test and if necessary, prophylaxis. Over the
 course of the study period, approximately 2000 pregnant women will be enrolled in total
 (across both study sites); liveborn newborns delivered to enrolled pregnant women will be
 followed for the first month of life. The sample size of 2000 pregnant women in this study is
 driven by the estimated prevalence of Rh negativity in the population (7%) and hence, the
 number of women investigators expect to offer two injections of RhIg (n=140). A sample size
 of 140 participants will enable us to measure the acceptance RhIg by pregnant women.

 This prospective cohort will include two groups of participants: a) between 3 and 5 LHVs who
 are full time employees at THQ Johi and DHQ Dadu and, b) 2000 pregnant women from the
 communities in the catchment area of THQ Johi and DHQ Dadu.

 To address one of our study aims, a single questionnaire will be administered to a cadre of
 approximately 30 health professionals (i.e., physicians, lady health visitors, nurses, etc.)
 who are not otherwise engaged in study activities.
Inclusion criteria for pregnant women

 -  Pregnant women who present to THQ Johi and DHQ Dadu for ANC

 -  At least 13 weeks gestation (assessed using self-reported first day of last menstrual
 period)

 -  Currently resides within one of 5 Union Council's surrounding THQ Johi and in the
 catchment area of DHQ Dadu at a fixed address

 -  Intends to deliver and remain in study catchment area for 1-month after the delivery
 of their newborn(s)

 -  Provides written informed consent

 -  Was not previously enrolled in this study during a different pregnancy

 Exclusion criteria for pregnant women

 -  Previously consented into this study

 -  Reported that they previously had an anaphylactic reaction to an injection of an
 antibody blood product

 -  Has any chronic disease related to the heart, liver, kidney, or lungs

 -  Does not currently reside within the study's catchment area

 -  Intends to deliver outside of the catchment area

 -  Plans to relocate outside of the catchment area within 1-month after the delivery of
 their newborn(s)

 -  Does not provide written consent

 Inclusion criteria for lady health visitors

 -  Working full-time at THQ Johi and DHQ Dadu as a Lady Health Visitor

 -  Verbal consent provided from LHV's direct supervisor

 -  LHV provides verbal consent to complete a test on baseline knowledge of Rh disease and
 jaundice

 -  LHV can attend a 1 day training and orientation session

 -  LHV provides written informed consent to participate in study

 Exclusion criteria for health care workers

 -  Verbal consent not provided from LHV's direct supervisor

 -  Does not consent to completing a test on baseline knowledge of Rh disease and jaundice

 -  Cannot attend a 1 day training and orientation session

 -  Does not provide written informed consent to participate in study

 Non-study health care professional recruitment

 A convenience sample of approximately 30 health care professionals including physicians,
 LHVs, nurses, lady health workers, and midwives, who are not otherwise engaged in study
 activities will be identified and approached at THQ Johi, DHQ Dadu, and other surrounding
 health care facilities. To be eligible for participation, health care professionals must
 not be employed by the study or enrolled in the study as a participant. If health care
 professionals are determined eligible, they will be asked to complete a short questionnaire
 to assess their knowledge of Rh disease, similar to the questionnaire administered to LHVs.
 These health care professionals will not be enrolled into the study or followed
 prospectively and thus, only verbal consent will be obtained.