Malaria
Conditions
Keywords
malaria,Malawi,pregnancy
Brief summary
The purpose of this study is to test prevention strategies for pregnancy-related malaria. Researchers will compare different malaria treatments and treatment schedules which include chloroquine therapy (weekly doses versus being dosed twice during pregnancy for 3 days each time) to the standard practice of preventive treatment intervals in pregnancy (with the drug sulfadoxine-pyrimethamine given twice during pregnancy). Participants will include 900 pregnant women, who will be assigned to one of three treatment groups. Blood samples will be collected at every visit before birth and any time the participant is ill to determine if malaria is present. Pregnant women will be monitored during pregnancy and newborns will be assessed at birth and followed until about 14 weeks. Participant involvement in the study is expected to last about 12 months.
Detailed description
In areas of high malaria endemicity, typical of much of sub-Saharan Africa, despite having achieved semi-immunity to malaria in adulthood, women become vulnerable to malaria infection during pregnancy, especially during their first or second pregnancy. They have increased rates of infection in the peripheral blood and high concentrations of parasites can be found in the placenta. On histological examination, mature asexual parasites, forms that are not usually detected in the peripheral blood, accumulate in the placenta. Pregnancy-specific variant surface antigens are responsible for the increased vulnerability of pregnant women to malaria because they are unrecognized by the immune systems of women who encounter them for the first time in their first pregnancy. In subsequent pregnancies, women develop immunity to these parasite surface antigens and the parasites are cleared by the host response. Plasmodium (P) falciparum infection during pregnancy has important health consequences for both pregnant women and their newborns. Adverse outcomes of pregnancy-associated malaria that have been documented in Malawi include maternal anemia, low birth weight (LBW), and increased infant mortality. The primary objective of the study is to compare weekly chloroquine prophylaxis and chloroquine intermittent preventative therapy (IPT) for malaria in pregnancy (IPTp) to the standard practice \[IPTp with sulfadoxine-pyrimethamine (SP)\] with respect to prevention of placental malaria. The secondary objectives are: to compare weekly chloroquine prophylaxis and chloroquine IPTp to the standard practice (IPTp with SP) with respect to prevention of malaria during pregnancy; to compare weekly chloroquine prophylaxis and chloroquine IPTp to the standard practice (IPTp with SP) with respect to prevention of the adverse maternal and newborn effects of pregnancy-associated malaria. The exploratory objective identify the vulnerable periods during pregnancy when malaria infection is more likely to cause placental infection, maternal anemia, and low infant birth weight. This is a randomized controlled trial to compare chloroquine as IPT or chloroquine as chemoprophylaxis to IPTp with SP. Women will be randomized after Screening and enrollment, and they begin the assigned treatment between Week 20 and Week 28 gestation. Specimens will be collected at every prenatal visit and any time the participant is ill to determine if malaria is present. Pregnant women will be monitored during pregnancy, and newborns will be assessed at birth and followed until they are approximately 14 weeks of age. Participants will be randomized to one of the following regimens: Chloroquine approximately 1,500 mg base over 3 days, twice during pregnancy (2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2); Chloroquine base 600 mg (2 tablets) loading dose followed by 300 mg (1 tablet) orally once per week until delivery; SP 1500 mg/75 mg twice during pregnancy.
Interventions
DRUGChloroquine
Chloroquine tablets contain 300 mg chloroquine base per tablet. Dosages: Chloroquine 1,500 mg base over 3 days twice during pregnancy or Chloroquine 600 mg loading dose followed by 300 mg orally once per week. Intermittant preventative treatment in pregnancy (IPTp) doses will be administered between weeks 20-28 and weeks 28-34 gestation, 4 weeks apart. Participants randomized to IPTp with chloroquine will require their second and third doses of chloroquine after the initial dose given in the clinic and those assigned to chloroquine chemoprophylaxis will require weekly doses.
DRUGSulfadoxine-pyrimethamine
Sulfadoxine-pyrimethamine 3 tablets (1,500 mg sulfadoxine and 75 mg pyrimethamine) twice during pregnancy. Intermittant preventive treatment in pregnancy (IPTp) doses will be administered between weeks 20-28 and weeks 28-34, 4 weeks apart.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
No minimum to 99 Years
Healthy volunteers
No
Inclusion criteria
Women who present to the Ndirande Antenatal Clinic (ANC) and meet the following inclusion criteria will be enrolled in the study: -Before the end of 27th week of gestation -First or second pregnancy -Anticipate remaining in Blantyre until 14 weeks after delivery -Agree to deliver at the Ndirande Health Centre or Queen Elizabeth Central Hospital (QECH) -Provision of informed consent
Exclusion criteria
-Chronic use (\>14 days) of any medication with antimalarial or antifolate activity -Human immunodeficiency virus (HIV) infection -Known high-risk pregnancy requiring regular supervision of an obstetrician -Allergy to any of the study drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Placental Malaria Infection Based on Histology | At delivery: Approximately 12-36 weeks after enrollment | The placenta was collected at the time of delivery for examination by histology to determine malaria infection. Malaria infection was concluded if histology identified parasites or malaria pigment in the placental tissue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Maternal Anemia (Hemoglobin < 10 Grams/Deciliter) | From enrollment until delivery, approximately 12-36 weeks | Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of anemia among maternal participants during pregnancy . Anemia is defined as having a hemoglobin value less than 10 grams/deciliter (gm/dL). |
| Incidence of Maternal Severe Anemia (Hemoglobin < 7gm/dl) | From enrollment until delivery, approximately 12-36 weeks | Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of severe anemia among maternal participants during pregnancy. Severe anemia is defined as having a hemoglobin value less than 7 gm/dl. |
| Incidence of Stillbirth | At delivery: Approximately 12-36 weeks after enrollment | Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of participants' deliveries whose outcome was stillbirth, defined as an infant born without any signs of life at 28 weeks or greater of gestation. |
| Incidence of Miscarriage | At delivery: Approximately 12-36 weeks after enrollment | Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of participants' deliveries whose outcome was miscarriage, defined as an infant delivered without any signs of life at less than 28 weeks of gestation. |
| Incidence of Preterm Delivery | At delivery: Approximately 12-36 weeks after enrollment | Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of participants' deliveries whose outcome was preterm delivery, defined as delivery less than 37 weeks of gestation. The outcome of the delivery was not considered, and could have been live birth, stillbirth, or miscarriage. |
| Infant Mortality Rate to 14 Weeks of Age | For 14 weeks after delivery. | Infants were followed from the time of delivery until 14 weeks of age. This outcome measure provides the incidence of infants who died within 14 weeks of delivery. |
| Incidence of Placental Malaria by Placental Impression Smear | At delivery: Approximately 12-36 weeks after enrollment | Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of malaria infection in the placenta based on diagnosis by positive placental impression smear results. |
| Incidence of Intrauterine Growth Restriction (IUGR) | At delivery: Approximately 12-36 weeks after enrollment | Infants were followed from the time of delivery until 14 weeks of age. This outcome measure provides the incidence of infants with IUGR at delivery. IUGR is defined as weight below the 10th percentile for gestational age based on the World Health Organization (WHO) fetal growth curve. This classification is supported by literature resulting from the INTERGROWTH-21st Project; José Villar. |
| Incidence of Active Placental Malaria Infection | At delivery: Approximately 12-36 weeks after enrollment | Maternal participants were followed to outcome of the pregnancy. This outcome measure provides the number of placental malaria infections in maternal subjects diagnosed by the presence of parasites and/or pigment on histological section or molecular evidence of infection (PCR). |
| Incidence of Malaria Infection, All Species. | Enrollment to delivery (approximately 12-36 weeks) | Maternal participants were followed to outcome of the pregnancy. This outcome measure provides the number of malaria infection episodes measured by positive parasitemia in maternal subjects. |
| Incidence of Clinical Malaria, All Species | Enrollment to delivery (approximately 12-36 weeks) | Maternal participants were followed to outcome of the pregnancy. Clinical malaria is defined as malaria infection at any parasite density with associated symptoms including at least one of the following: objective fever measured at the clinic, history of fever in the past 48 hours or other symptoms in the last 48 hours including: headache, myalgia, vomiting, or weakness. |
| Incidence of Infection in the Fetal Circulation | At delivery: Approximately 12-36 weeks after enrollment | Maternal participants were followed to outcome of the pregnancy. This outcome measure provides the number of positive for malaria cord blood smear and cord PCR results in maternal subjects based on the results of the thick smear and PCR from the cord blood sample. |
| Incidence of Low Birth Weight (LBW) (Birthweight < 2500 Grams) | At delivery: Approximately 12-36 weeks after enrollment | Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of infants whose birthweight was less than 2500 grams. |
Countries
Malawi
Participant flow
Recruitment details
Participants were pregnant women in their first or second pregnancy recruited during presentation at the Ndirande Antenatal Clinic (ANC) at the Ndirande Health Centre, enrolled between 22 February 2012 and 16 May 2014.
Pre-assignment details
The infants born to these participants were also enrolled in the study to be assessed at birth and followed to 14 weeks. The infants are reported here as separate arms of the study, grouped by the study product given to the mother.
Participants by arm
| Arm | Count |
|---|---|
| Maternal Chloroquine Prophylaxis Maternal participants receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week until delivery. | 300 |
| Maternal Chloroquine IPT Maternal participants receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks. | 300 |
| Maternal SP IPT Maternal participants receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks. | 300 |
| Infant Chloroquine Prophylaxis Infants born to maternal participants who received chloroquine prophylaxis. | 270 |
| Infant Chloroquine IPT Infants born to maternal participants who received chloroquine IPT. | 274 |
| Infant SP IPT Infants born to maternal participants who received SP IPT. | 259 |
| Total | 1,703 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 1 | 0 | 7 | 10 | 8 |
| Overall Study | Death of Subject's Infant | 5 | 10 | 11 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 44 | 42 | 50 | 23 | 25 | 21 |
| Overall Study | Protocol Violation | 2 | 1 | 3 | 2 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 15 | 14 | 12 | 7 | 7 | 2 |
Baseline characteristics
| Characteristic | Maternal Chloroquine IPT | Maternal SP IPT | Infant Chloroquine Prophylaxis | Maternal Chloroquine Prophylaxis | Infant Chloroquine IPT | Infant SP IPT | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 81 Participants | 90 Participants | 270 Participants | 99 Participants | 274 Participants | 259 Participants | 1073 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 219 Participants | 210 Participants | 0 Participants | 201 Participants | 0 Participants | 0 Participants | 630 Participants |
| Age, Continuous | 20.67 years STANDARD_DEVIATION 3.24 | 20.44 years STANDARD_DEVIATION 3.14 | 0 years STANDARD_DEVIATION 0 | 20.40 years STANDARD_DEVIATION 3.59 | 0 years STANDARD_DEVIATION 0 | 0 years STANDARD_DEVIATION 0 | 20.50 years STANDARD_DEVIATION 3.33 |
| Gender Female | 300 Participants | 300 Participants | 133 Participants | 300 Participants | 143 Participants | 136 Participants | 1312 Participants |
| Gender Male | 0 Participants | 0 Participants | 137 Participants | 0 Participants | 131 Participants | 123 Participants | 391 Participants |
| Region of Enrollment Malawi | 300 participants | 300 participants | 270 participants | 300 participants | 274 participants | 259 participants | 1703 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 255 / 300 | 251 / 300 | 234 / 300 | 195 / 270 | 186 / 274 | 171 / 259 |
| serious Total, serious adverse events | 23 / 300 | 29 / 300 | 26 / 300 | 46 / 270 | 65 / 274 | 43 / 259 |
Outcome results
Primary
Incidence of Placental Malaria Infection Based on Histology
The placenta was collected at the time of delivery for examination by histology to determine malaria infection. Malaria infection was concluded if histology identified parasites or malaria pigment in the placental tissue.
Time frame: At delivery: Approximately 12-36 weeks after enrollment
Population: All participants from whom the placental histopathology slides collected at the time of delivery were reviewed are included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maternal Chloroquine Prophylaxis | Incidence of Placental Malaria Infection Based on Histology | 11.58 percentage of pregnancies |
| Maternal Chloroquine IPT | Incidence of Placental Malaria Infection Based on Histology | 15.42 percentage of pregnancies |
| Maternal SP IPT | Incidence of Placental Malaria Infection Based on Histology | 15.42 percentage of pregnancies |
Comparison: The null hypothesis is the incidence of placental malaria infection based on histology is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.p-value: 0.2441Fisher Exact
Comparison: The null hypothesis is the incidence of placental malaria infection based on histology is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.p-value: 1Fisher Exact
Secondary
Incidence of Active Placental Malaria Infection
Maternal participants were followed to outcome of the pregnancy. This outcome measure provides the number of placental malaria infections in maternal subjects diagnosed by the presence of parasites and/or pigment on histological section or molecular evidence of infection (PCR).
Time frame: At delivery: Approximately 12-36 weeks after enrollment
Population: This analysis population includes all maternal subjects with placental slides reviewed and PCR results obtained.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maternal Chloroquine Prophylaxis | Incidence of Active Placental Malaria Infection | 3.09 percentage of participants |
| Maternal Chloroquine IPT | Incidence of Active Placental Malaria Infection | 3.16 percentage of participants |
| Maternal SP IPT | Incidence of Active Placental Malaria Infection | 4.74 percentage of participants |
Comparison: The null hypothesis is the incidence of active placental malaria infection is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.p-value: 0.369Fisher Exact
Comparison: The null hypothesis is the incidence of active placental malaria infection is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.p-value: 0.4947Fisher Exact
Secondary
Incidence of Clinical Malaria, All Species
Maternal participants were followed to outcome of the pregnancy. Clinical malaria is defined as malaria infection at any parasite density with associated symptoms including at least one of the following: objective fever measured at the clinic, history of fever in the past 48 hours or other symptoms in the last 48 hours including: headache, myalgia, vomiting, or weakness.
Time frame: Enrollment to delivery (approximately 12-36 weeks)
Population: The analysis population includes all maternal participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maternal Chloroquine Prophylaxis | Incidence of Clinical Malaria, All Species | 0.67 percentage of participants |
| Maternal Chloroquine IPT | Incidence of Clinical Malaria, All Species | 1.33 percentage of participants |
| Maternal SP IPT | Incidence of Clinical Malaria, All Species | 3.00 percentage of participants |
Comparison: The null hypothesis is the incidence of clinical malaria (all species) is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.p-value: 0.0268Cox proportional hazards
Comparison: The null hypothesis is the incidence of clinical malaria (all species) is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.p-value: 0.1646Cox proportional hazards
Secondary
Incidence of Infection in the Fetal Circulation
Maternal participants were followed to outcome of the pregnancy. This outcome measure provides the number of positive for malaria cord blood smear and cord PCR results in maternal subjects based on the results of the thick smear and PCR from the cord blood sample.
Time frame: At delivery: Approximately 12-36 weeks after enrollment
Population: The analysis population includes all maternal participants with cord blood smears and cord PCR results obtained.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maternal Chloroquine Prophylaxis | Incidence of Infection in the Fetal Circulation | 1.95 percentage of participants |
| Maternal Chloroquine IPT | Incidence of Infection in the Fetal Circulation | 2.78 percentage of participants |
| Maternal SP IPT | Incidence of Infection in the Fetal Circulation | 0.80 percentage of participants |
Comparison: The null hypothesis is the incidence of infection in the fetal circulation is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.p-value: 0.4501Fisher Exact
Comparison: The null hypothesis is the incidence of infection in the fetal circulation is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.p-value: 0.1758Fisher Exact
Secondary
Incidence of Intrauterine Growth Restriction (IUGR)
Infants were followed from the time of delivery until 14 weeks of age. This outcome measure provides the incidence of infants with IUGR at delivery. IUGR is defined as weight below the 10th percentile for gestational age based on the World Health Organization (WHO) fetal growth curve. This classification is supported by literature resulting from the INTERGROWTH-21st Project; José Villar.
Time frame: At delivery: Approximately 12-36 weeks after enrollment
Population: This analysis population includes all infants with weight captured at delivery and with mothers having reported gestational age at delivery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maternal Chloroquine Prophylaxis | Incidence of Intrauterine Growth Restriction (IUGR) | 16.54 percentage of participants |
| Maternal Chloroquine IPT | Incidence of Intrauterine Growth Restriction (IUGR) | 18.01 percentage of participants |
| Maternal SP IPT | Incidence of Intrauterine Growth Restriction (IUGR) | 20.80 percentage of participants |
Comparison: The null hypothesis is the incidence of intrauterine growth restriction is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.p-value: 0.2553Fisher Exact
Comparison: The null hypothesis is the incidence of intrauterine growth restriction is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.p-value: 0.4354Fisher Exact
Secondary
Incidence of Low Birth Weight (LBW) (Birthweight < 2500 Grams)
Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of infants whose birthweight was less than 2500 grams.
Time frame: At delivery: Approximately 12-36 weeks after enrollment
Population: The analysis population includes all infants born alive with weight data collected at birth.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maternal Chloroquine Prophylaxis | Incidence of Low Birth Weight (LBW) (Birthweight < 2500 Grams) | 15.59 percentage of infants |
| Maternal Chloroquine IPT | Incidence of Low Birth Weight (LBW) (Birthweight < 2500 Grams) | 10.98 percentage of infants |
| Maternal SP IPT | Incidence of Low Birth Weight (LBW) (Birthweight < 2500 Grams) | 12.11 percentage of infants |
Comparison: The null hypothesis is the incidence of low birth weight is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.p-value: 0.2566Fisher Exact
Comparison: The null hypothesis is the incidence of low birth weight is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.p-value: 0.7839Fisher Exact
Secondary
Incidence of Malaria Infection, All Species.
Maternal participants were followed to outcome of the pregnancy. This outcome measure provides the number of malaria infection episodes measured by positive parasitemia in maternal subjects.
Time frame: Enrollment to delivery (approximately 12-36 weeks)
Population: The analysis population includes all maternal participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maternal Chloroquine Prophylaxis | Incidence of Malaria Infection, All Species. | 0.67 percentage of participants |
| Maternal Chloroquine IPT | Incidence of Malaria Infection, All Species. | 1.67 percentage of participants |
| Maternal SP IPT | Incidence of Malaria Infection, All Species. | 3.00 percentage of participants |
Comparison: The null hypothesis is the incidence of malaria infection (all species) measured by positive parasitemia is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.p-value: 0.063Fisher Exact
Comparison: The null hypothesis is the incidence of malaria infection (all species) measured by positive parasitemia is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.p-value: 0.4184Fisher Exact
Secondary
Incidence of Maternal Anemia (Hemoglobin < 10 Grams/Deciliter)
Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of anemia among maternal participants during pregnancy . Anemia is defined as having a hemoglobin value less than 10 grams/deciliter (gm/dL).
Time frame: From enrollment until delivery, approximately 12-36 weeks
Population: The analysis population includes all maternal participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maternal Chloroquine Prophylaxis | Incidence of Maternal Anemia (Hemoglobin < 10 Grams/Deciliter) | 18.3 percentage of maternal participants |
| Maternal Chloroquine IPT | Incidence of Maternal Anemia (Hemoglobin < 10 Grams/Deciliter) | 23.7 percentage of maternal participants |
| Maternal SP IPT | Incidence of Maternal Anemia (Hemoglobin < 10 Grams/Deciliter) | 22.0 percentage of maternal participants |
Comparison: The null hypothesis is the incidence of maternal anemia is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.p-value: 0.3089Fisher Exact
Comparison: The null hypothesis is the incidence of maternal anemia is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.p-value: 0.6973Fisher Exact
Secondary
Incidence of Maternal Severe Anemia (Hemoglobin < 7gm/dl)
Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of severe anemia among maternal participants during pregnancy. Severe anemia is defined as having a hemoglobin value less than 7 gm/dl.
Time frame: From enrollment until delivery, approximately 12-36 weeks
Population: The analysis population includes all maternal participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maternal Chloroquine Prophylaxis | Incidence of Maternal Severe Anemia (Hemoglobin < 7gm/dl) | 0.0 percentage of maternal participants |
| Maternal Chloroquine IPT | Incidence of Maternal Severe Anemia (Hemoglobin < 7gm/dl) | 0.3 percentage of maternal participants |
| Maternal SP IPT | Incidence of Maternal Severe Anemia (Hemoglobin < 7gm/dl) | 0.3 percentage of maternal participants |
Comparison: The null hypothesis is the incidence of maternal severe anemia is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.p-value: 1Fisher Exact
Comparison: The null hypothesis is the incidence of maternal severe anemia is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.p-value: 1Fisher Exact
Secondary
Incidence of Miscarriage
Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of participants' deliveries whose outcome was miscarriage, defined as an infant delivered without any signs of life at less than 28 weeks of gestation.
Time frame: At delivery: Approximately 12-36 weeks after enrollment
Population: The analysis population includes all maternal participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maternal Chloroquine Prophylaxis | Incidence of Miscarriage | 0.33 percentage of pregnancies |
| Maternal Chloroquine IPT | Incidence of Miscarriage | 0.67 percentage of pregnancies |
| Maternal SP IPT | Incidence of Miscarriage | 1.00 percentage of pregnancies |
Comparison: The null hypothesis is the incidence of miscarriage is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.p-value: 0.6237Fisher Exact
Comparison: The null hypothesis is the incidence of miscarriage is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.p-value: 1Fisher Exact
Secondary
Incidence of Placental Malaria by Placental Impression Smear
Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of malaria infection in the placenta based on diagnosis by positive placental impression smear results.
Time frame: At delivery: Approximately 12-36 weeks after enrollment
Population: The analysis population includes all maternal participants whose pregnancies were followed to delivery and from whom a placenta was collected and an impression smear performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maternal Chloroquine Prophylaxis | Incidence of Placental Malaria by Placental Impression Smear | 0 percentage of placentas |
| Maternal Chloroquine IPT | Incidence of Placental Malaria by Placental Impression Smear | 0 percentage of placentas |
| Maternal SP IPT | Incidence of Placental Malaria by Placental Impression Smear | 0.40 percentage of placentas |
Comparison: The null hypothesis is the incidence of malaria by placental impression smear is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.p-value: 0.4941Fisher Exact
Comparison: The null hypothesis is the incidence of malaria by placental impression smear is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.p-value: 0.499Fisher Exact
Secondary
Incidence of Preterm Delivery
Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of participants' deliveries whose outcome was preterm delivery, defined as delivery less than 37 weeks of gestation. The outcome of the delivery was not considered, and could have been live birth, stillbirth, or miscarriage.
Time frame: At delivery: Approximately 12-36 weeks after enrollment
Population: The analysis population includes all participants whose pregnancies were followed to delivery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maternal Chloroquine Prophylaxis | Incidence of Preterm Delivery | 8.46 percentage of deliveries |
| Maternal Chloroquine IPT | Incidence of Preterm Delivery | 9.89 percentage of deliveries |
| Maternal SP IPT | Incidence of Preterm Delivery | 6.84 percentage of deliveries |
Comparison: The null hypothesis is the incidence of preterm delivery is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.p-value: 0.5187Fisher Exact
Comparison: The null hypothesis is the incidence of preterm delivery is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.p-value: 0.2163Fisher Exact
Secondary
Incidence of Stillbirth
Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of participants' deliveries whose outcome was stillbirth, defined as an infant born without any signs of life at 28 weeks or greater of gestation.
Time frame: At delivery: Approximately 12-36 weeks after enrollment
Population: The analysis population includes all participants whose pregnancies were followed to delivery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maternal Chloroquine Prophylaxis | Incidence of Stillbirth | 1.10 percentage of deliveries |
| Maternal Chloroquine IPT | Incidence of Stillbirth | 0.37 percentage of deliveries |
| Maternal SP IPT | Incidence of Stillbirth | 1.90 percentage of deliveries |
Comparison: The null hypothesis is the incidence of stillbirth is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.p-value: 0.4979Fisher Exact
Comparison: The null hypothesis is the incidence of stillbirth is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.p-value: 0.1166Fisher Exact
Secondary
Infant Mortality Rate to 14 Weeks of Age
Infants were followed from the time of delivery until 14 weeks of age. This outcome measure provides the incidence of infants who died within 14 weeks of delivery.
Time frame: For 14 weeks after delivery.
Population: The analysis population includes all enrolled infants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maternal Chloroquine Prophylaxis | Infant Mortality Rate to 14 Weeks of Age | 2.22 percentage of infants |
| Maternal Chloroquine IPT | Infant Mortality Rate to 14 Weeks of Age | 3.65 percentage of infants |
| Maternal SP IPT | Infant Mortality Rate to 14 Weeks of Age | 3.09 percentage of infants |
Comparison: The null hypothesis is the incidence of infant mortality within 14 weeks of delivery is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.p-value: 0.5959Fisher Exact
Comparison: The null hypothesis is the incidence of infant mortality within 14 weeks of delivery is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.p-value: 0.8127Fisher Exact