Placebo Controlled Trial of Docosahexaenoic Acid (DHA) Supplementation in High Risk Pregnancies
试验速览
- 阶段
- 不适用
- 入组人数
- 210
- 试验地点
- 2
- 主要终点
- Measure synaptamide
研究概览
简要总结
Purpose: Determine the effects of maternal docosahexaenoic acid (DHA) supplementation during pregnancy on levels of DHA, synaptamide (novel anti-inflammatory metabolite), and inflammatory biomarkers during pregnancy and at delivery
Research Design: Double blind randomized placebo-controlled study of maternal DHA supplementation during pregnancy.
Methodology /Technical Approach: Investigators plan to enroll 100 pregnant women with a high risk pregnancy related to (1) a pre-pregnancy Body Mass Index (BMI) of ≥30.0 kg/m2 and/or (2) a history of prior preterm delivery at ≤35+6 weeks gestation. Women will be enrolled between the 8th and 14th week of pregnancy and randomized to receive a once daily DHA supplement (DSM Nutritional Products, Columbia Maryland, DHA capsule 441mg/cap) or a placebo (DSM Nutritional Products, Columbia Maryland, Corn Oil/Soybean oil 50/50 mix) for the duration of the pregnancy. DHA is an omega-3 long chain polyunsaturated fatty acid (LCPUFA) and placebo composed of omega-6 LCPUFA's. Investigators will measure maternal levels of plasma DHA, Synaptamide and inflammatory biomarkers at enrollment, at 26-30 weeks of pregnancy, and from cord blood at delivery. Sociodemographic and clinical characteristics will be collected for each mother from pregnancy onset until discharge following delivery. The infant health record and parental report will be reviewed to record clinical data from birth to 12 months corrected age for short term health outcomes potentially related to inflammation-related morbidities, including growth and development, acute infection requiring hospital admission, and any allergic disorder. All plasma samples will be processed at Dr. Kim's NIAAA/NIH laboratories using high-performance liquid chromatography with tandem mass spectrometry
详细描述
All pregnant women meeting the inclusion/exclusion criteria will be identified at the time of their regular OB appointments between the 8th and the 14th week of pregnancy (+/- 3 days) Research team members will approach potential subjects to explain the study and obtain consent for their participation Patients who give their consent for enrollment will be asked to complete a dietary survey at the time of enrollment Patients will be given a paper script for study drug to be taken to the Walter Reed Military Medical Center pharmacy to obtain study drug The Investigational Pharmacy will randomize the patients in double blinded fashion to the intervention group or placebo group.
Patients in the intervention group will recieve a ~1000mg capsule containing ~400mg of DHA. This is not standard of care and is being done for research purposes only Patients in the Placebo group will recieve a ~1000mg capusle containing no DHA and filled with 50:50 mix of corn and soybean oils. This oil is ubiquitous in the american diet and only a very small amount of additional oil will be ingested for study purposes. Giving pregnant women this oil is not standard of care and is being done for research purposes only The placebo and intervention drugs will be packaged in the same capsule membrane and will be indistinguishable by color, shape, or taste.
Patients will be instructed to take 1 capule PO daily until their child is delivered Patients will be issued a 3 month supply of study drug at enrollment and will get refills from the investigational pharmacy
≤5ml of whole blood will be obtained from each subject at enrollment and at 26-30 weeks gestation (+/- 3 days), as part of a routine blood sampling. It is standard of care to collect blood at this point in pregnancy for lab evaluation. The additional tube of blood collected for this study is for research purposes only and not part of the standard of care. This sample will be centrifuged, and the separated plasma will be labeled and frozen at -80° C pending transport to Dr. Kim's lab at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) for bulk analyses.
At delivery, ≤5ml of umbilical cord blood will be obtained from an umbilical artery and from the umbilical vein. These samples will be processed and stored in a similar fashion as the earlier samples. Cord blood is a medical waste product, and collection will therefore have no adverse effect for either mother or newborn. It is standard of care to collect cord blood by OB request for lab evaluation. Collecting additional cord blood for this study anaylsis is for research purposes only All enrollees will complete a dietary survey upon enrollment at 8-14 weeks (+/- 3 days), at 26-30th week of pregnancy (+/- 3 days), and during the delivery admission. This survey will also include the subject's self-report on compliance with taking the study supplement All plasma samples collected will be processed at Dr. Kim's National Institute on Alcohol Abuse and Alcoholism/ National Insititute of Health (NIAAA/NIH) laboratories The Cytokine Assays for IL-6, Il-10, TNF- alpha will be run in Dr Kim's lab using Ensyme Linked Immunosorbent Assay (ELISA) testing The DHA and Synaptamide levels will be analyzed in Dr. Kim's lab using High performance liquid chromatrography with tandem mass spectrometry All babies from multiple birth pregnancies will be enrolled in this study The offspring of enrolled women will be followed through 12 months corrected age to assess the longer term outcomes of study intervention Information will be collected from the maternal medical record at time of enrollment, infant delivery and postpartum discharge.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double blinded, randomized, placebo controlled
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •regnant female military health care beneficiaries ≥18 years of age
- •Between the 8th and 14th week of pregnancy at enrollment
- •BMI of ≥30.0 kg/m2 and/or history of previous preterm delivery at <36 weeks gestation
- •Planning to deliver at WRNMMC
- •DEERS-eligible
- •All infants born to mothers enrolled in this study who do not meet any exclusion criteria
排除标准
- •Routine use of DHA supplement (including DHA containing prenatal vitamins) and/or fish consumption greater than twice per week
- •Women with a fish allergy
- •Known major fetal anomaly believed to be lethal
- •Maternal treatment for clotting disorder
- •Allergy to corn or soybean oils
结局指标
主要结局
Measure synaptamide
时间窗: Sample obtained from cord blood at time of infant delivery
Measurement of fetal plasma synaptamide using tandem mass spec
Measure inflammatory biomarkers
时间窗: Sample obtained from cord blood at time of infant delivery
Measurement of plasma cytokine levels using ELISA human cytokine panel
Measure DHA
时间窗: Sample obtained from cord blood at time of infant delivery
Measurement of fetal plasma DHA using tandem mass spec
次要结局
- Placental pathology(at time of delivery)
- Length at birth(At time of infant birth)
- Maternal Gestational weight gain at end of pregnancy in placebo vs. DHA supplement groups(At time of infant delivery)
- Infant delivery method(At time of infant delivery)
- Maternal death(From enrollment in study at 8-14 weeks of pregnancy until 6 months after infant delivery)
- chorioamionitis(From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first)
- Gestational Diabetes Melitus(From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first)
- Delivery complications(at time of infant delivery)
- Pre-eclampsia(From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first)
- Days of antibiotic exposure during birth hospitalization(During birth admission up to 8 months of chronologic age or discharge from hospital whichever happens sooner)
- non-gestational Diabetes mellitus(From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first)
- Preterm Premature Rupture of Membranes(From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first)
- going past due dates(during last month of pregnancy)
- Head circumference at birth(At time of infant birth)
- Gestational age at birth(At time of infant birth)
- weight at birth(At time of infant birth)
- APGAR score at 1 min(At time of infant birth)
- APGAR score at 5 min(At time of infant birth)
- Resuscitation beyond warm/dry stimulate at birth(At time of infant birth)
- Presence or absence or requirement for respiratory assistance within the first 24 hours after birth(From NICU admission to 24 hours after birth)
- NICU admission(Within the first 5 days of infant's life)
- Duration of birth admission(Birth through 12 months of age or infant discharge, whichever occurs sooner)
- Requirement for phototherapy during birth admission(Birth through 14 days of infant life)
- Culture proven sepsis(From birth through 12 months or until infant discharge whichever occurs sooner)
- Infant Death(From birth through 12 months or until infant discharge whichever occurs sooner)
- Weight at infant hospital discharge(At time of infant's first discharge from hospital or at 12 months corrected, whichever comes first)
- head circumference at infant hospital discharge(At time of infant's first discharge from hospital or at 12 months corrected, whichever comes first)
- Length at infant hospital discharge(At time of infant's first discharge from hospital or at 12 months corrected, whichever comes first)
- Feeding plan at infant discharge(At 12 months chronological if still admitted or at infant discharge, whichever occurs sooner)
- Infant diagnosis in medical record(at 12 months corrected)
- infant weight at 6 months corrected age(at 6 months corrected)
- head circumferene weight at 6 months corrected age(at 6 months corrected)
- head circumference weight at 12 months corrected age(at 12 months corrected)
- Indication of infant developmental delay in medical record from birth through 12 months corrected(birth through 12 months corrected)
- Number of antibiotic prescriptions for infant through first 12 months corrected(birth through 12 months corrected)
- number of inpatient days for infant through 12 months corrected(birth through 12 months corrected)
- infant weight at 12 months corrected age(at 12 months corrected)
- Length weight at 12 months corrected age(at 12 months corrected)
- Number of outpatient visits for infant during first 12 months corrected(birth through12 months corrected)
- Failure to thrive in for infant(birth through 12 months corrected)
- Length weight at 6 months corrected age(at 6 months corrected)
- Documented infant feeding plan through first year(birth through 12 months corrected)