Malnutrition in Pregnancy, Preterm Birth, Child Development, Postpartum Depression, Antepartum Depression
Conditions
Brief summary
The goal of this clinical trial is to test (1) a novel maternal ready-to-use supplementary food and (2) a novel cognitive behavioral therapy intervention in undernourished Sierra Leonean women. The main questions it aims to answer are: * Will the addition of omega-3 long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), as well as choline, to a maternal ready-to-use supplementary food (M-RUSF+) prolong gestation when compared with a similar supplementary food except that it lacks DHA, EPA, and choline (M-RUSF)? * Will M-RUSF+ improve infant cognitive development at 9 months of age when compared with M-RUSF? * Will the novel CBT program improve ante- and post-partum depression?
Detailed description
Undernutrition in pregnancy is common, affecting nearly 10% of women worldwide and 25% of women in Sub-Saharan Africa, and increases risks for both mothers and their offspring, including bleeding, preterm birth, neonatal mortality, and impaired infant cognitive development. Available treatments have limited impact on these outcomes, which affect millions annually. A recent trial in Sierra Leone showed that pairing high-quality supplementary nutrition with anti-infective measures led to greater maternal weight gain, longer and heavier newborns, and reduced neonatal mortality. In addition, ante- and postpartum depression are underrecognized and undertreated in rural Sub-Saharan Africa. The goal of this clinical trial is to test (1) a novel maternal ready-to-use supplementary food (M-RUSF+) and (2) a novel cognitive behavioral therapy (CBT) program developed for illiterate users, in undernourished pregnant women in Sierra Leone. The main questions it aims to answer are: * Will the addition of omega-3 long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), as well as choline, to a maternal ready-to-use supplementary food (M-RUSF+) prolong gestation when compared with a similar supplementary food except that it lacks DHA, EPA, and choline (M-RUSF)? * Will M-RUSF+ improve infant cognitive development at 9 months of age when compared with M-RUSF? * Will the novel CBT program improve ante- and post-partum depression? Participants will present to government-run antenatal clinics for screening. If they quality for enrollment and consent to participate, they will undergo: ANTENATALLY * randomization to intervention vs. control group * bi-weekly anthropometric measurements * ultrasound gestational age estimation * demographic, socioeconomic, and health history questionnaires * bi-weekly blood pressure measurement * bi-weekly screening for ante- and post-partum depression * two blood spot collections POSTNATALLY * birth measurements of mother and offspring * cord blood and placental sampling for a subset * 5 clinic visits for mother and offspring anthropometric measurements, health history, breastfeeding practice, maternal mental health questions * offspring developmental assessments All participants will receive: ANTENATALLY * 100g/day of M-RUSF+ or M-RUSF, containing 530 Kcal, 19g protein, United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) equivalent * insecticide-treated bed nets * a single dose of albendazole de-worming medicine * monthly malaria chemoprophylaxis * single doses of azithromycin in the second and third trimesters * safe birth kits If participants develop ante- or postpartum depression and are randomized to CBT, they will receive 6 sessions of CBT.
Interventions
DIETARY_SUPPLEMENTM-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline)
Balanced energy protein supplement with added DHA/EPA/choline, micronutrients
DIETARY_SUPPLEMENTM-RUSF (Maternal Ready-to-Use Supplementary Food)
Balanced energy protein supplement with added micronutrients
DRUGAzithromycin
1g dose
DRUGAlbendazole
400mg dose
Monthly, 1,500/75mg dose
BEHAVIORALCognitive behavioral therapy
Novel program developed for illiterate end-users
Bed net to prevent malaria
Sponsors
Washington University School of Medicine
Project Peanut Butter
Open Philanthropy
United States Department of Agriculture (USDA)
Ministry of Health and Sanitation, Sierra Leone
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Masking description
In the food comparison, while the 2 study foods taste similar, full masking cannot be guaranteed. In the CBT comparison, participants and therapists will not be masked. In all cases, outcomes assessors will be masked.
Intervention model description
2x2 factorial design
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
In order to be eligible to participate in the M-RUSF+ vs. M-RUSF element of the study, an individual must meet all of the following criteria: 1. Provision of signed (or thumb-printed) and dated informed consent form 1a. Women who are ≥ 18 years of age or married will be allowed to consent for themselves 1b. Women who are \< 18 years of age and unmarried must provide assent and a parent or guardian must provide consent 2. Stated willingness to comply with all study procedures and availability for the duration of the study, including no plan to move from the catchment area of a participating clinic 3. ≥ 13 years of age 4. Pregnant 5. Mid-upper arm circumference ≤ 23 cm or body-mass index \< 18.5 In order to be eligible to participate in the CBT vs. no CBT element of the study (factorial design with the above), an individual must be enrolled in the M-RUSF+ vs. M-RUSF study and meet the following criteria: 1. Provision of signed (or thumb-printed) and dated informed consent form 1a. Women who are ≥ 18 years of age or married will be allowed to consent for themselves 1b. Women who are \< 18 years of age and unmarried must assent and a parent or guardian consent must provide consent 2. Stated willingness to comply with all study procedures and availability for the duration of the study, including no plan to move from the catchment area of a participating clinic 3. Patient Health Questionnaire-9 score ≥ 9
Exclusion criteria
1. Participation in a concomitant supplementary feeding program 2. Known allergy to components of intervention or control study food or medications 3. Known gestational diabetes 4. Hypertension 5. Severe anemia, or other condition requiring immediate hospitalization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Malawi Developmental Assessment Tool (MDAT) global z-score | 9 months post-birth | Infant global age-adjusted z-score on MDAT |
| Adapted Patient Health Questionnaire-9 (PHQ-9) score | 8 weeks after diagnosis with ante- or post-partum depression | Among participants who develop ante- or post-partum depression, adapted Patient Health Questionnaire-9 score, (range 0-27, higher scores are worse) |
| Gestational duration | Enrollment to birth (range 2 to 26 weeks) | Enrollment ultrasound estimated gestational age plus time between enrollment and delivery. For the primary outcome, this will only be assessed among participants enrolled \<= 30 weeks gestational age and with singleton live births |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Birth length | Birth | Infant length at birth |
| Low birth weight | Birth | Birth weight \< 2.5 kg |
| Malawi Developmental Assessment Test sub-domain z-scores | 9 months after birth | Gross motor, fine motor, language, and social domain z-scores (expected range -4 to 2, higher scores are better) |
| Preterm birth | Enrollment to 37 weeks' gestation | Birth \< 37 weeks gestational age |
| Neonatal mortality | Birth to 28 days of age | Infant death within the first 28 days of life |
| Depressive symptoms | Through study completion, an average of 1.25 years | Adapted Patient Health Questionnaire-9 score (range 0-27, higher scores are worse) |
| Maternal and infant DHA status | From Enrollment to delivery, an average of 15 weeks | Maternal plasma, cord blood DHA status |
| Maternal and infant choline status | From Enrollment to delivery, an average of 15 weeks | Blood choline concentration |
| Maternal weight gain | From Enrollment to delivery, an average of 15 weeks | Average weekly weight gain |
| Post-term delivery | From Enrollment to delivery, an average of 15 weeks | Delivery \> 42 weeks' gestation |
| Depression incidence | 8 weeks from time of depression diagnosis | Adapted PHQ-9 \>= 9 |
| Birth chest circumference | Birth | Infant chest circumference |
| Birth thigh circumference | Birth | Infant thigh circumference |
| Birth head circumference | Birth | Infant head circumference |
| Infant weight at 6 weeks, 3 months, 6 months, 9 months | Birth to 9 months | Infant weight |
| Infant length at 6 weeks, 3 months, 6 months, 9 months | Birth to 9 months | Infant length |
| Infant length-for-age z-score at 6 weeks, 3 months, 6 months, 9 months | Birth to 9 months | Infant length-for-age z-score |
| Gestational duration | From Enrollment to birth, an average of 15 weeks | Enrollment ultrasound estimated gestational age plus time between enrollment and delivery. For this secondary outcome, all enrolled women will be included in analysis. |
| Placental weight | Birth | Weight of placenta in grams |
| Infant mortality | Birth to end of follow-up (9 months) | Infant death |
| Small for gestational age (SGA) | Birth | Under 10th percentile in birth weight for gestational age |
| Early preterm birth | Enrollment to 34 weeks' gestation | Birth \< 34 weeks gestational age |
| Birth weight | Birth | Infant weight at birth |
Countries
Sierra Leone
Contacts
PRINCIPAL_INVESTIGATORMark J Manary, MD
Washington University School of Medicine
Outcome results
None listed