A multi-nutrient intervention for pregnant women experiencing symptoms of depression and anxiety.

INTERVENTION: Micronutrient formula Adherence to the intervention will be assessed fortnightly throughout the study period. Participants are required to report the number of capsules missed over a two week period and return any unused capsules to the study investigators every fourth week. CONDITION: Anxiety Depression PRIMARY OUTCOME: Edinburgh Postnatal Depression Scale (EPDS; Cox et al, 1987) assesses the presence of depression and anxiety. The Clinical Global Impressions Improvement (CGI‐I) Scale (Guy, 1976) produces a score based on how much the clinician thinks the participant has improved since baseline ranging from 1 (very much improved) to 7 (very much worse). SECONDARY OUTCOME: Depression, Anxiety, Stress Scale ‐ 21 ‐ assesses the severity of depression, anxiety and stress. Difficulties in Emotion Regulation Scale ‐ Short Form (DERS‐SF; Kaufman et al, 2015) assesses emotion disregulation. Electroencephalography (EEG) will be measured at rest and in response to simple audio/visual cues will be used to index anxiety‐related endophenotypes, neurophysiological markers of anxiety and related psychophysiological processes. ; Generalized Anxiety Disorder – 7 item (GAD‐7; Spitzer, Kroenke, Williams and Lowe, 2006) a self report questionnaire measuring the severity of anxiety. Inflammatory biomarkers: interleukin – 6 (IL‐6), tumor necrosis factor alpha (TNF‐a), interleukin‐4 (IL‐4) and interleukin‐10 (IL‐10), C‐reactive protein (CRP) assessed in plasma from blood samples taken at baseline and at 12 weeks RCT. A complete blood count from the blood samples will also be assessed to assist in the interpretation of the biomarkers. Microbiome assessed from stool samples taken at baseline and at week 12 RCT. Nutrient levels: vitamin C, vitamin B12, vitamin D, folate, zinc, selenium, iron and homocysteine ‐ assessed in plasma from blood samples taken at baseline and at 12 weeks RCT. Short Form Health Survey ‐ 12 (SF‐12; Ware, Kosinski & Keller, 1996) assesses quality of life. The Antidepressant Side‐Effect Checklist (ASEC; Uher et al, 2009) and a review of medical records will assess side effects, safety & adverse events of the intervention. The ASEC has been adapted for the purposes of this study. The Montgomery and Asberg Depresion Rating Scale (MADRS; Montgomery & Asberg, 1979) will replace the HAM‐D to assess the frequency, severity and duration of depressive symptoms. The Pittsburgh Sleep Quality Index (PSQI; Buysse, Reynolds, Monk, Verman & Kupfer, 1989) assesses sleep quality, latency, duration, disturbance, efficiency and daytime dysfunction. INCLUSION CRITERIA: 1) women aged 19 years and over; 2) 12‐24 weeks gestation; 3) low risk singleton pregnancy; 4) free from psychiatric medication for four weeks; 5) score of 13 or more on the Edinburgh Postnatal Depression Scale (EPDS); 6) deemed reliable and compliant with the protocol. Control group INCLUSION CRITERIA: 1) pregnant women aged 19 years and over Participants will be randomly assigned to receive either a micronutrient formula or a placebo for twelve weeks. After twelve weeks, all participants will enter into an open‐label phase whereby all mothers can choose to take the micronutrient formula for another 12 weeks or until the birth of their child. Both the micronutrient formula and the placebo are in capsule form and are to be taken orally at a dose of 12 capsules per day; four capsules taken three times per day with food and water. The micronutrient formula and placebo adhere to the New Zealand Ministry of Health recommendation for the daily intake of iodine for pregnant and lactating women. The micronutrient intervention is a blend of vitamins, minerals, antioxidants and amino acids. The formula, Daily Essential Nutrients, is being manufactured and donated by Hardy Nutritionals (Registered Trademark), Canada and consists of the following ingredients. The following doses are for 12 capsules (full dose per day): Vitamin A (as retinyl palmitate), 5,760 IU; Vitamin C (as ascorbic acid), 600 mg; Vitamin D (as cholecalciferol), 3,000 IU; Vitamin E (as d‐alpha tocopheryl succinate), 360 IU; Vitamin K (75% as phylloquinone; 25% as menaquinone‐7), 120 mcg; Thiamin (as thiamin mononitrate), 60 mg; Riboflavin, 18 mg; Niacin (as niacinamide), 90 mg; Vitamin B6 (as pyridoxine hydrochloride), 69.9 mg; Folate (as L‐methylfolate calcium), 801 mcg; Vitamin B12 (as methylcobalamin), 900 mcg; Biotin, 1080 mcg; Pantothenic acid (as d‐calcium pantothenate), 30 mg; Calcium (as chelate), 1,320 mg; Iron (as chelate), 13.8 mg; Phosphorus (as chelate), 840 mg; Iodine (as chelate), 204 mcg; Magnesium (as chelate), 600 mg; Zinc (as chelate), 48 mg; Selenium (as chelate), 204 mcg; Copper (as chelate), 7.2 mg; Manganese (as chelate), 9.6 mg; Chromium (as chelate), 624 mcg; Molybdenum (as chelate), 144 mcg; Potassium (as chelate), 240 mg. Proprietary blend: Choline bitartrate, Alpha‐lipoic acid, Mineral wax, Inositol, Acetyl‐L‐carnitine, Grape seed extract, Ginkgo biloba leaf extract, L‐methionine, N‐acetyl‐L‐cysteine, Boron, Vanadium, Lithium orotate, Nickel. Other ingredients: Vegetarian capsule (hypromellose), microcrystalline cellulose, magnesium stearate, silicon dioxide, titanium dioxide.