Abstract Background Perinatal Depression and anxiety (PDA) is prevalent in new and expectant mothers affecting millions of women worldwide. Those with a history of mood and anxiety disorders are at the greatest risk of experiencing PDA at a subsequent pregnancy. Current safety concerns with pharmacological treatments have led to a greater need for adjunctive treatment options for PDA. Changes in the composition of the microbiome have been associated with various diseases during pregnancy and these changes are thought to be at least partially at play in perinatal mood disorders. While the relation between PDA and the microbiome has not been explored, evidence suggests that nutritional interventions, with fiber, fish oils, and probiotics, may play a favorable role in neuropsychiatric outcomes during and after pregnancy. The primary objective of the present study is to assess the feasibility and acceptability of a combination of non-pharmacological interventions in currently stable and pregnant women with a history of anxiety and/or depression. This study will also aim to understand ease of recruitment, treatment compliance, and protocol adherence in this cohort. Methods This a single centered, partially randomized-placebo controlled-double blind feasibility trial. 100 pregnant women, with a history of depression and/or anxiety/PDA will be recruited and randomized into one of four arms which could include: receiving a daily dose of both investigational products and dietary counselling on increasing dietary fiber, receiving a daily dose of both investigational drugs only, receiving fish oil investigational product and placebo, and a control arm with no intervention. The study involves six study visits, all of which can be conducted virtually every 3 months from the time of enrollment. At all study visits, information on diet, mental health, physical activity, and sleep quality will be collected. Additionally, all participants will provide a stool sample at each visit. Discussion It is anticipated that pregnant women with a history of depression and anxiety will be particularly interested in partaking in this trial, resulting in favourable recruitment rates. Given the positive findings of O3FA and probiotic supplements on mental health symptoms in non-pregnant adults, we expect a similar trend in PDA symptoms, with a low likelihood of adverse events. This study will build the foundation for larger powered studied to further contribute evidence for the efficacy of this potential treatment option. Trial Registration This trial was registered at ClinicalTrials/gov on October 6, 2023; NCT06074250. Trial Sponsor: The Canadian College of Naturopathic Medicine, 1255 Sheppard Ave E, Toronto, ON M2K 1E2, 416-498-1255. Steering committee: [ The committee meets monthly to oversee the trial. Keywords Mental health, Maternal health, Nutrition, Omega-3 fatty acids, Probiotics, Fiber

The authors have declared no competing interest.

NCT06074250

This study was funded by the Lotte & John Hecht Memorial Foundation

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study has been reviewed by the Research Ethics Board of the Canadian College of Naturopathic Medicine and the Research Ethics Board of Sunnybrook Health Sciences Centre. These Research Ethics Boards gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors