The ROOT Study: Scaling the 'Standard of Care Plus' Obstetric Nutrition Model to Optimize Maternal and Infant Health

Overview

The 'Standard of Care Plus' ('PLUS') model in the ROOT Study consists of analyzing select micronutrient and gene variants of pregnant females to construct trimester-specific and personalized nutrition and lifestyle recommendations in collaboration with in-person standard obstetric care (SOC). In 2014, the investigators demonstrated statistically significant reductions in adverse maternal and infant outcomes using the 'PLUS' model compared to SOC alone. Further study in a 50% Medicaid Oregon 'PLUS' cohort (N=387) demonstrated association with highly significant risk reductions in all primary outcomes (p-value \<0.001): preterm birth: relative risk (RR) = 0.238 (4.2x less likely), hypertensive disorders of pregnancy: RR = 0.229 (4.4x less likely), gestational diabetes: RR = 0.071 (14x less likely), small for gestational age: RR = 0.252 (4x less likely), and large for gestational age: RR = 0.357 (2.8x less likely). A 100% Medicaid and ethnically diverse Nevada 'PLUS' cohort showed similar trends in all outcomes that were not statistically significant because of small sample size. Structured as a prospective interventional study, the study evaluates whether the 'PLUS' model can achieve similar outcome improvements within the Novant Health (NH) system in North Carolina. The study will assess both clinical outcomes and digital nutrition platform performance within the existing healthcare infrastructure. The primary hypothesis of the ROOT study is that collaborative implementation of the 'PLUS' nutritional care model at NH Triad Obstetrics/Gynecology (OB/GYN) Clinic will be associated with reduced maternal and infant adverse outcome rates when compared to historical regional and NH system outcomes in those who received SOC alone. The secondary hypothesis of the ROOT Study is that the 'PLUS' model applied during pregnancy will be associated with reduced pediatric adverse outcomes. The 'PLUS' offspring that remain in the NH system will be observed longitudinally over 5 years with chart review at birth through 2 weeks of age, and at 1, 3, and 5 years of life. The outcomes assessed include neonatal intensive care unit (NICU) admission in the first two weeks of life, atopic dermatitis, eczema, asthma, allergies, otitis media, obesity, and autism. The 'PLUS' adverse outcome rates will be compared to adverse outcome rates in children born regionally and nationally under SOC alone. Participant compliance with the 'PLUS' model, and participant and nutritionist access to the digital health platform will be studied during each trimester of use, as well as in the postpartum time period. The exploratory hypothesis is that the digital platform will not affect access, compliance, and rates of maternal and neonatal adverse outcomes.

Over a consecutive 2-year period, all pregnant females \>17 years old presenting to Novant Health (NH) Triad Obstetrics/Gynecology (OB/GYN) at \<20 weeks' gestation will be offered the cost-free virtual digital nutrition platform standard of care 'Plus' ('PLUS') model in addition to the in-person standard of care (SOC) routinely provided at the clinic. The 'PLUS' model will be offered to all eligible females regardless of payor source. After instruction and consent by 'PLUS'-trained clinic personnel, each participant will be on-boarded via a digital nutrition and health intake. Based on health information disclosed by the participant, body weight and height collected by the clinic, and select micronutrient and genomic evaluation, customized nutrition and lifestyle education and recommendations will be created through the digital nutrition platform with direct oversight by a 'PLUS'-trained board-certified nutrition professional. Virtual contact time allotment for the participant with the nutritionist is 60 minutes per trimester for customization of the nutrition and lifestyle plan, with unlimited text or digital follow-up. The 'PLUS' diet is based on a pregnancy-adapted Mediterranean Diet modified by a low glycemic index with a 40% carbohydrate / 30% fat / 30% protein ratio that is seasonally, geographically, and socio-economically sensitive. Macronutrients will be calculated, and adjustments to the core food plan will be made each trimester based on nationally accepted pregnancy-specific Mifflin St. Jeor standards, with further refinement based on pre-pregnancy body mass index (BMI), gestational weight gain, activity, and dietary preferences. Nutrition education will be personalized by trimester-specific physiologic demand, and by select gene variant analysis and micronutrient analysis. Gene variant analysis will include 42 gene variants used in the prior study associated with adverse maternal and neonatal outcomes, and non-communicable disease risk in the offspring. Micronutrient analysis will occur at intake, at each subsequent trimester, and at postpartum. It will include a complete blood count, serum zinc, carnitine (total and free), vitamin D (25(OH)D), ferritin, homocysteine, ionized calcium, vitamin B12, folate, glycosylated hemoglobin, and a lipid panel (total cholesterol, low density lipoprotein, high density lipoprotein, triglycerides). Sleep quality, movement, exogenous stress and mood will be assessed at intake, at 24-28 weeks gestation, and at 6-8 weeks postpartum. Other common pregnancy-related concerns will be addressed at each visit. 'PLUS' participants will receive a multi-nutrient prenatal supplement and iron separate from the multivitamin, a probiotic, and an Omega 3 fatty acid supplement or its vegan algal oil alternative. Because protein intake commonly remains insufficient, a protein supplement will be added. Collagen is selected because of its tolerability and ease of intake. Vitamin D3, acetyl l-carnitine, choline, and myo-inositol supplementation will occur if identified needs cannot be met with diet/lifestyle modification and base nutrient support alone. Other identified micronutrient insufficiencies will be managed with nutrient-rich food incorporation in the diet. All participant-facing materials are created at 8th grade reading level and will be translated into Spanish, as needed. Nutrition and lifestyle communication will be transferred through the digital health platform which is Health Insurance Portability and Accountability Act (HIPAA) \& Systems and Organization Controls 2 (SOC2) compliant. Clinic staff will receive a 30-minute virtual training and an in-clinic logistical visit. Further OB provider communication regarding intervention changes, clinical condition, or persistent nutrient insufficiencies obtained through real-time chart review by the board-certified MD investigator will occur via secure e-mail to the OB provider or designee. Consent for pediatric longitudinal follow-up of neonatal participants under the 'PLUS' model will occur at maternal participant intake. All neonatal participants remaining in the Novant Health system will be followed by chart review at 2 weeks for neonatal intensive care admission, and at 1, 3, and 5 years of life for occurrence of atopic dermatitis and eczema, asthma and allergy, otitis media, obesity, and autism spectrum disorder. The investigators will examine the usability of the digital nutrition and lifestyle health platform that interfaces with NH Triad OB/GYN's electronic medical record to accomplish collaborative virtual personalized nutrition and lifestyle evaluation, education, and recommendations. The outcomes assessed will include participant and nutritionist access, compliance, and user experience during each trimester of use, and during the postpartum time period. Additionally, the investigators will evaluate the cost-efficiency of the 'PLUS' model compared to standard of care alone within the NH system by comparing frequency of and assigned reimbursement for the adverse maternal, neonatal, and childhood diagnoses and ICD-10 codes under study.