Clinical trial NCT04069195: Docosahexaenoic Acid (DHA) Supplementation in High Risk Pregnancies
Official title: Placebo Controlled Trial of Docosahexaenoic Acid (DHA) Supplementation in High Risk Pregnancies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Inflammation
Pregnancy Related
Keywords: Inflammation
DHA
Pregnancy
preterm
overweight
Lead sponsor: Walter Reed National Military Medical Center
Sponsor class: FED
Collaborators: name: National Institutes of Health (NIH)
name: DSM Nutritional Products, Inc.
name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2019-08-28
Enrollment: 210
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double Blinded, Randomized, Placebo controlled
Primary purpose: PREVENTION

Brief summary: 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

Detailed description: 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.

Information will be collected from the infant medical record at time of birth discharge, and 12 months corrected age.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Measure DHA
timeFrame: Sample obtained between 8-14 weeks of pregnancy
measure: Measure DHA
timeFrame: Sample obtained between 26-30 weeks of pregnancy
measure: Measure DHA
timeFrame: Sample obtained from cord blood at time of infant delivery
measure: Measure synaptamide
timeFrame: Sample obtained between 8-14 weeks of pregnancy
measure: Measure synaptamide
timeFrame: Sample obtained between 26-30 weeks of pregnancy
measure: Measure synaptamide
timeFrame: Sample obtained from cord blood at time of infant delivery
measure: Measure inflammatory biomarkers
timeFrame: Sample obtained between 8-14 weeks of pregnancy
measure: Measure inflammatory biomarkers
timeFrame: Sample obtained between 26-30 weeks of pregnancy
measure: Measure inflammatory biomarkers
timeFrame: Sample obtained from cord blood at time of infant delivery
Secondary outcomes:
measure: Maternal Gestational weight gain at end of pregnancy in placebo vs. DHA supplement groups
timeFrame: At time of infant delivery
measure: Infant delivery method
timeFrame: At time of infant delivery
measure: Delivery complications
timeFrame: at time of infant delivery
measure: Maternal death
timeFrame: From enrollment in study at 8-14 weeks of pregnancy until 6 months after infant delivery
measure: Pre-eclampsia
timeFrame: From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first
measure: chorioamionitis
timeFrame: From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first
measure: Gestational Diabetes Melitus
timeFrame: From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first
measure: non-gestational Diabetes mellitus
timeFrame: From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first
measure: Preterm Premature Rupture of Membranes
timeFrame: From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first
measure: going past due dates
timeFrame: during last month of pregnancy
measure: Placental pathology
timeFrame: at time of delivery
measure: Head circumference at birth
timeFrame: At time of infant birth
measure: Length at birth
timeFrame: At time of infant birth
measure: weight at birth
timeFrame: At time of infant birth
measure: Gestational age at birth
timeFrame: At time of infant birth
measure: APGAR score at 1 min
timeFrame: At time of infant birth
measure: APGAR score at 5 min
timeFrame: At time of infant birth
measure: Resuscitation beyond warm/dry stimulate at birth
timeFrame: At time of infant birth
measure: Presence or absence or requirement for respiratory assistance within the first 24 hours after birth
timeFrame: From NICU admission to 24 hours after birth
measure: Days of antibiotic exposure during birth hospitalization
timeFrame: During birth admission up to 8 months of chronologic age or discharge from hospital whichever happens sooner
measure: NICU admission
timeFrame: Within the first 5 days of infant's life
measure: Duration of birth admission
timeFrame: Birth through 12 months of age or infant discharge, whichever occurs sooner
measure: Requirement for phototherapy during birth admission
timeFrame: Birth through 14 days of infant life
measure: Culture proven sepsis
timeFrame: From birth through 12 months or until infant discharge whichever occurs sooner
measure: Infant Death
timeFrame: From birth through 12 months or until infant discharge whichever occurs sooner
measure: Weight at infant hospital discharge
timeFrame: At time of infant's first discharge from hospital or at 12 months corrected, whichever comes first
measure: head circumference at infant hospital discharge
timeFrame: At time of infant's first discharge from hospital or at 12 months corrected, whichever comes first
measure: Length at infant hospital discharge
timeFrame: At time of infant's first discharge from hospital or at 12 months corrected, whichever comes first
measure: Feeding plan at infant discharge
timeFrame: At 12 months chronological if still admitted or at infant discharge, whichever occurs sooner
measure: Infant diagnosis in medical record
timeFrame: at 12 months corrected
measure: infant weight at 6 months corrected age
timeFrame: at 6 months corrected
measure: infant weight at 12 months corrected age
timeFrame: at 12 months corrected
measure: head circumferene weight at 6 months corrected age
timeFrame: at 6 months corrected
measure: head circumference weight at 12 months corrected age
timeFrame: at 12 months corrected
measure: Length weight at 6 months corrected age
timeFrame: at 6 months corrected
measure: Length weight at 12 months corrected age
timeFrame: at 12 months corrected
measure: Number of outpatient visits for infant during first 12 months corrected
timeFrame: birth through12 months corrected
measure: Failure to thrive in for infant
timeFrame: birth through 12 months corrected
measure: number of inpatient days for infant through 12 months corrected
timeFrame: birth through 12 months corrected
measure: Indication of infant developmental delay in medical record from birth through 12 months corrected
timeFrame: birth through 12 months corrected
measure: Number of antibiotic prescriptions for infant through first 12 months corrected
timeFrame: birth through 12 months corrected
measure: Documented infant feeding plan through first year
timeFrame: birth through 12 months corrected
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Walter Reed National Miltiary medical center
state: Maryland
Study officials:
affiliation: Walter Reed National Miltary Medical Center
name: Peter F Knickerbocker, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: NIH/ NIAAA
name: Kim Hee-Yong, PhD
role: STUDY_DIRECTOR
affiliation: Uniformed Services University of the Health Sciences
name: Carl Hunt, MD
role: STUDY_CHAIR
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