Effect of Participating in a Study of Causes of Pregnancy Loss on Mental Health Outcomes: A Target Trial Emulation Using the COPL Cohort and Danish National Registries

NCT07684677 | Active Not Recruiting

• 1 other identifier: 10.46540/4308-00131B
• Study Type: interventional
• Target: 30,000
• Locations: 1 country
• Sites: 1

Brief Summary

Pregnancy loss is the most common severe pregnancy complication and is associated with significant mental health sequelae, including depression and anxiety. Standard care in Denmark does not include systematic follow-up or aetiological investigation after pregnancy loss. The Copenhagen Odense Pregnancy Loss (COPL) Cohort offered extensive aetiological investigations, and a dedicated clinical follow-up visit 4-10 weeks post-loss. This is a target trial emulation (TTE) designed to estimate the causal effect of COPL participation on women's mental health outcomes one year after pregnancy loss. We will emulate a target trial comparing (1) enrolment into COPL versus (2) standard pregnancy loss care. The study population comprises women aged ≥18 years with a confirmed intrauterine pregnancy loss (ICD-10: DO020, DO021, DO030-DO034) before 22 weeks' gestation treated at Danish public hospitals between November 2020 and April 2025. The primary outcome is new-onset affective disorder (ICD-10: F32\*-F39\*), neurotic/stress-related disorder (F41\*, F43\*, F48\*), or dispensing of antidepressant (N06A\*), anxiolytic (N05B\*), or sedating (N05C\*) medication within 12 months of pregnancy loss diagnosis. All data will be sourced from Danish National Registries. The difference-in-differences estimator will serve as the primary analytical approach, complemented by instrumental variable analysis (hospital of treatment as instrument) and regression discontinuity design. Inverse probability of treatment weighting will be used to control for measured confounders. Results will be reported as risk ratios and risk differences with 95% confidence intervals. Sensitivity analyses will include per-protocol estimation and exclusion of women with treatable findings identified in COPL.

Conditions

Pregnancy Loss, Early; Major Depression; Anxiety; Stress (Psychology)

Outcome Measures

Primary Outcomes (1)

• New onset affective or stress-related disorder

  Either ICD-10 F32\*-F39\*, F41\*, F43\*, F48\* registered or prescription of antidepressant, anxiolytic or sedating medication after PL

  12 months after PL

Secondary Outcomes (4)

• Sick leave

  First 12 months after PL

• Health care utilization

  12 months after PL

• Time to pregnancy

  Up to 12 months

• Post-natal mood disorder

  Up to 12 months after time zero

Study Arms (2)

COPL participant

EXPERIMENTAL

Women with pregnancy loss participating in the COPL Cohort

Other: COPL participation

Controls

NO INTERVENTION

Women not included in the COPL cohort

Interventions

COPL participation OTHER

Participation in the COPL cohort

COPL participant

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age above 18 years
• Born in Denmark
• Verified intrauterine PL before 22 weeks' gestation treated at a public hospital in Denmark

You may not qualify if:

• Non-visualized PL, ectopic PL
• Gestational age \>22 weeks at loss

Sponsors & Collaborators

• Amager Hospital: lead

Study Sites (1)

Department of Gynecology-and-Obstetrics

Hvidovre, Denmark

Location

MeSH Terms

Conditions

Abortion, Spontaneous; Depressive Disorder, Major; Anxiety Disorders

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Henriette Svarre Nielsen, Professor

  Copenhagen University Hospital, Hvidovre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor, Associate professor

Model Details: Target trial emulation

Study Record Dates

• First Submitted: June 29, 2026
• First Posted: July 6, 2026
• Study Start: November 1, 2020
• Primary Completion: April 11, 2025
• Study Completion (Estimated): April 11, 2027
• Last Updated: July 6, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)