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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Anxiety; Major Depression; Pregnancy Loss, Early; Stress (Psychology)
• Intervention / Treatment: Other: COPL participation

• Study Type: Interventional
• Enrollment (Estimated): 30000
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Hvidovre, Denmark
    • Department of Gynecology-and-Obstetrics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: COPL participant; Women with pregnancy loss participating in the COPL Cohort	Other: COPL participation; Participation in the COPL cohort
No Intervention: Controls; Women not included in the COPL cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sick leave	Total number of sick-leave days	First 12 months after PL
Health care utilization	Total GP use, referral to psychologist/psychiatrist	12 months after PL
Time to pregnancy	Time from time zero to next pregnancy	Up to 12 months
Post-natal mood disorder	In case of subsequent delivery, prevalence of post-natal mood disorder	Up to 12 months after time zero

Collaborators and Investigators

• Sponsor: Amager Hospital
• Investigators: Principal Investigator: Henriette Svarre Nielsen, Professor, Copenhagen University Hospital, Hvidovre

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2020
• Primary Completion (Actual): April 11, 2025
• Study Completion (Estimated): April 11, 2027

Study Registration Dates

• First Submitted: June 29, 2026
• First Submitted That Met QC Criteria: June 29, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: June 29, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Mental Disorders; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Mood Disorders; Depressive Disorder; Anxiety Disorders; Abortion, Spontaneous; Depressive Disorder, Major
• Other Study ID Numbers: 10.46540/4308-00131B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: It is not permitted

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No