JMIR Publications

ABSTRACT

Background:

Perinatal mood disorders such as depression and anxiety are common, with subclinical symptomology manifesting as perinatal mood disturbances (PMD) being even more prevalent. These could potentially impact breastfeeding practices and infant development. Pregnant and lactating women usually limit their exposure to medications, including for psychological symptoms. Interestingly, the naturally-occurring probiotic, Bifidobacterium longum (BL) NCC3001, has been shown to reduce anxious behaviour in preclinical models and to reduce feelings of low mood in non-pregnant human adults. With the COVID-19 pandemic, mental health issues have increased and conventionally-conducted clinical trials had been restricted by social-distancing regulations.

Objective:

To use a decentralized clinical trial design to test whether the probiotic BL NCC3001 can reduce symptoms of depression, anxiety and stress over the perinatal period.

Methods:

This protocol for a double-blind, placebo-controlled, randomised, 3-parallel arm study aimed to recruit 180 women to compare the efficacy of the probiotic taken either 1) pre- and post-partum (from 28-32 weeks’ gestation until 12 weeks post-delivery; n=60) or 2) post-partum only (from birth until 12 weeks post-delivery; n=60) with a placebo-control group (n=60). Participants consumed the probiotic or matched placebo in a drink once daily. Mood outcomes were measured using the State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale questionnaires, captured electronically at baseline (28-32 weeks’ gestation) and during e-study sessions over 5 further time-points (36 weeks’ gestation, 9 days postpartum, and 4, 8 and 12 weeks postpartum). Saliva and stool samples were collected longitudinally at home to provide mechanistic insights.

Results:

520 women registered their interest online, of which 184 were eligible and randomised. Five withdrew post-randomisation, leaving 179 participants who completed the study. Recruitment occurred between November 2020 and August 2021. Advertising on social media brought in 46.9% of participants, followed by parenting-specific websites (22.3%), and physical posters on the metro public transport (12.3%). Nation-wide recruitment was achieved. Data processing is on-going and there are no outcomes to report yet.

Conclusions:

Multiple converging factors contributed to speedy recruitment and retention of participants despite COVID-19 restrictions. This entirely decentralized trial design sets a precedent for similar studies in addition to potentially providing novel evidence on the impact of the probiotic BL NCC3001 on symptoms of PMD. This study was ideal for remote conduct because of the high digital literacy and public trust of digital security in Singapore, the intervention could be self-administered without regular clinical monitoring, and the eligibility criteria and outcomes could be measured using electronic questionnaires and self-collected biological samples. Such a design was particularly suited for a vulnerable group, such as pregnant women, during the challenging times of COVID-19 social restrictions. Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04685252