Compliance to prenatal iron and folic acid supplement use in relation to low birth weight in lilongwe, Malawi

Prenatal iron and folic acid (IFA) supplements are offered free to all pregnant women in Malawi to reduce maternal anemia and improve birth outcomes. We investigated the association between self-reported compliance to IFA intake and risk of low birth weight (LBW). Pregnant women who attended Bwaila Maternity Wing of Lilongwe District Hospital for delivery were recruited (n = 220). We used a questionnaire to collect self-reported information on IFA use and maternal sociodemographic data. Before delivery, blood samples for maternal hemoglobin (Hb) and folate status, and upon delivery, birth weight, and other newborn anthropometrics were measured. We used multivariable logistic regression to determine risk of LBW by prenatal IFA intake. The self-reported number of IFA pills taken during pregnancy was positively associated with Hb, but not serum and RBC folate concentration: <45, 45–89 and ≥90 pills taken corresponded with mean (SD) Hb 10.7 (1.6), 11.3 (1.8), and 11.7 (1.6) g/dL, respectively (p = 0.006). The prevalence of LBW was 20.1%, 13.5% and 5.6% for those who reported taking IFA pills <45, 45–89, and ≥90 pills, respectively (p = 0.027). Taking >60 IFA pills reduced risk of LBW delivery (OR (95% CI) = 0.15 (0.03–0.70), p = 0.033) than taking ≤30 pills. Self-reported compliance to IFA use is valid for assessing prenatal supplement program in Malawi, especially Hb status, and can reduce the rate of LBW. The retrospective cross-sectional study design was not pre-specified and was considered exploratory. All pregnant women reporting for delivery at the Bwaila Maternity Wing of Lilongwe District Hospital were asked to participate in the study. Recruitment of subjects followed convenience sampling and included women of all age groups with viable singleton pregnancy or twin gestation delivering at 28 weeks or more. The women resided in Lilongwe district (rural, peri-urban or urban), which is the catchment area for this hospital. We recruited women with pregnancies of various gestation ages (28 weeks and upwards). The study excluded dyads where the mother had severe anemia (requiring a blood transfusion), the presence of placenta previa (or history of bleeding during pregnancy due to early partial separation of placenta), delivery involved instrumentation, and those where an infant had brain trauma. Additionally, participants must not have had a severe medical condition known to severely affect maternal nutrition status, placenta health, or newborn health. In summary, we excluded all obstetrical and medical emergencies. Babies and mothers that were in intensive care unit (ICU), high dependence unit (HDU), or required constant medical support and monitoring were excluded, so that their medical care was not interrupted. Of the 220 pregnant women who consented to participating in the study, seven who delivered twins were excluded from the final analysis. The final analytic sample size included 213 pregnant women. Ethical clearance or institutional review board approval was obtained from Michigan State University and the National Health Sciences Research Committee (NHSRC) in Malawi. At the hospital level, the Lilongwe District Health Officer (DHO), the overseer of all health services in the district, was contacted for approval to use the facility and their patients, and a letter of support for this research was issued. The nurse/midwife in-charge of the maternity unit was contacted for support. She informed the members of the staff in the unit about the study and urged them to offer daily support to the data collection. We obtained consent from the pregnant women or their mother/husband. If a woman was unable to write, we obtained a fingerprint of her thumb of non-dominant hand as a proof of her consent to voluntarily participate in the research study. Data and blood sample collection only commenced after the women gave voluntary consent to participate in the study. The Malawian government uses prenatal supplements as a short-term solution to fight micronutrient malnutrition (particularly iron deficiency anemia) in pregnant women and improve the health status of mothers and newborns. All pregnant women, regardless of hematological status or the trimester of pregnancy, receive prenatal supplements of pills of combined iron and folic acid from the first antenatal care visit to delivery. Each tablet contains 60 mg iron (ferrous) and 0.25 mg folic acid, taken once a day. Every month, the woman gets a new supply without a check if she actually utilized the prescription given the previous month. The program is run on the assumption that women understand the need to take the supplements, despite documented evidence of poor compliance due to side effects and women forgetting to take the pills [18,19]. Monitoring prenatal supplementation intake has been continued because it is the most feasible way to fight micronutrient malnutrition and improve health outcomes at least in the short term, compared to diet, considering the current social economic status of Malawians. Using a short questionnaire, the basic characteristics of the pregnant woman were collected: age of the mother, gestation age, gravidity (number of pregnancies), parity (number of deliveries), education level of the mother, and area of residence. The questionnaire also contained questions on antenatal care that the pregnant woman was able to access during pregnancy. This included information on IFA supplement use, which was obtained from self-reports and confirmed by checking medical records (health passport book, a little handbook that contains all medical information and previous treatments; the women carry the book everywhere). We used the same questions as those used in the Malawi demographic and health survey [6]. The questions ask if the participant received or bought IFA supplements in pregnancy; if she took any of the IFA pills; how many pills she was able to take during pregnancy. Our questionnaire also included questions on the number of antenatal visits the woman received, at what gestation of the pregnancy (trimester) did she start prenatal care, and reasons for starting prenatal care early or late [19]. Information about vaccinations, malaria prophylaxis, and use of anti-helminthes (anti-worms) during pregnancy was abstracted from the medical record (health passport book). We also obtained medical history about sickness during the current pregnancy, such as anemia (blood transfusions) and if the pregnant woman was on any long-term treatment or chronic diseases such as diabetes, hypertension and asthma/allergies. History of contraceptive use prior to the current pregnancy was obtained [20,21]. Maternal weight was taken on the day of the survey just before delivery of the baby using Seca weighing scale (Seca, Chino, CA, USA). Weight was measured to the nearest 0.1 kg in mothers. The midwives performed the anthropometric measurements on pregnant women who participated in the study. The women’s height was measured using a stadiometer. They had to remove anything that she was wearing on her head and ensure that her braided hair was as flat as possible by loosening her hair and pressing her headpiece. The women also had to remove their shoes and heavy clothing (subjects were dressed in light clothes) during the anthropometric measurement process. Height was recorded to the nearest 0.1 cm. Most of the maternal characteristics are routinely documented on the labor-monitoring chart; therefore, only the parameters that are not available from the chart were asked to avoid duplication. We collected blood samples from women before they gave birth. Upon obtaining consent and explaining the procedure, the women was asked to sit or lie on a bed, as per their preference. A tourniquet was applied around the upper left arm and a 70% alcohol swab was used to clean the skin on the site (cubital). A 10 mL syringe with 21-gauge needle (SkyRun Pharma Co., Ltd., Nanjing, China) was then used to withdraw a venous whole blood sample from the cubital region. Each blood specimen was collected in two different sample tubes of 5 mL each—one for serum and the other for red blood cell (RBC) folate analysis. The third specimen type was taken using a Microcuvette from the same 10 mL to measure iron status (hemoglobin). The blood sample for folate was allowed to flow freely into the specimen bottle by vacuum pressure, after piercing the rubber cover with the needle of the syringe. The sample for RBC folate analysis was put in a 5 mL tube containing an anticoagulant (ethylenediaminetetraacetic acid, EDTA). The EDTA ensured that the sample did not clot, and that there was adequate plasma for analysis of hematocrit (needed for calculation of RBC folate later). The tube was then gently shaken to mix the blood and the anticoagulant. The serum folate sample was put in a tube without an anticoagulant to allow cells to separate from the serum after clotting. This tube had a gel to separate the red cells from the serum after the clotting of cells. The samples were kept at room temperature for 2–6 h, until they were transferred to a laboratory outside the Bwaila maternity wing (research site hospital) at the African Bible College Clinic—Center for Medical Diagnostics (CMED). At CMED, the RBC folate blood sample was centrifuged and frozen, kept at −80 °C until transfer by air to South Africa. The folic acid analysis was done in South Africa by Lancet laboratories (Lancet, Johannesburg, South Africa) using ARCHITECT assay kits (Abbott Ireland, Longford, Ireland) on the ARCHITECT i system. The hemoglobin measurements were taken at bedside using a Hemocue Hb 201+ (HemoCue America, Brea, CA, USA). All data analyses were conducted using SPSS version 24 (SPSS Inc., Armonk, NY, USA) and SAS version 9.4 (SAS Institute, Cary, NC, USA). Descriptive statistics were used to calculate frequencies and mean and standard deviation values of variables. We also determined associations between maternal health and compliance to IFA factors, and hemoglobin and folate status using correlation analyses. Finally, multivariable logistic regression models were used to determine the degree of influence of iron and folic acid supplements on LBW infants as an outcome after controlling for covariates. Covariates were maternal age, education, total number of pregnancies, first prenatal visit trimester, and total number of prenatal visits.