The clinical performance of the M4 decision support model to triage women with a pregnancy of unknown location as at low or high risk of complications

Abstract

Study question: What are the adverse outcomes associated with using the M4 model in everyday clinical practice for women with pregnancy of unknown location (PUL)?

Summary answer: There were 17/835 (2.0%) adverse events and no serious adverse events associated with the performance of the M4 model in clinical practice.

What is known already: The M4 model has previously been shown to stratify women classified as a PUL as at low or high risk of complications with a good level of test performance. The triage performance of the M4 model is better than single measurements of serum progesterone or the hCG ratio (serum hCG at 48 h/hCG at presentation).

Study design, size, duration: A prospective multi-centre cohort study of 1022 women with a PUL carried out between August 2012 and December 2013 across 2 university teaching hospitals and 1 district general hospital.

Participants/materials, setting, methods: All women presenting with a PUL to the early pregnancy units of the three hospitals were recruited. The final outcome for PUL was either a failed PUL (FPUL), intrauterine pregnancy (IUP) or ectopic pregnancy (EP) (including persistent PUL (PPUL)), with EP and PPUL considered high-risk PUL. Their hCG results at 0 and 48 h were entered into the M4 model algorithm. If the risk of EP was ≥5%, the PUL was predicted to be high-risk and the participant was asked to re-attend 48 h later for a repeat hCG and transvaginal ultrasound scan by a senior clinician. If the PUL was classified as 'low risk, likely failed PUL', the participant was asked to perform a urinary pregnancy test 2 weeks later. If the PUL was classified as 'low risk, likely intrauterine', the participant was scheduled for a repeat scan in 1 week. Deviations from the management protocol were recorded as either an 'unscheduled visit (participant reason)', 'unscheduled visit (clinician reason)' or 'differences in timing (blood test/ultrasound)'. Adverse events were assessed using definitions outlined in the UK Good Clinical Practice Guidelines' document.

Main results and the role of chance: A total of 835 (82%) women classified as a PUL were managed according to the M4 model (9 met the exclusion criteria, 69 were lost to follow-up, 109 had no hCG result at 48 h). Of these, 443 (53%) had a final outcome of FPUL, 298 (36%) an IUP and 94 (11%) an EP. The M4 model predicted 70% (585/835) PUL as low risk, of which 568 (97%) were confirmed as FPUL or IUP. Of the 17 EP and PPUL misclassified as low risk, 5 had expectant management, 7 medical management with methotrexate and 5 surgical intervention.Nineteen PUL had an unscheduled visit (participant reason), 38 PUL had an unscheduled visit (clinician reason) and 68 PUL had deviations from protocol due to a difference in timing (blood test/ultrasound).Adverse events were reported in 26 PUL and 1 participant had a serious adverse event. A total of 17/26 (65%) adverse events were misclassifications of a high risk PUL as low risk by the M4 model, while 5/26 (19%) adverse events were related to incorrect clinical decisions. Four of the 26 adverse events (15%) were secondary to unscheduled admissions for pain/bleeding. The serious adverse event was due to an incorrect clinical decision.

Limitations, reasons for caution: A limitation of the study was that 69/1022 (7%) of PUL were lost to follow-up. A 48 h hCG level was missing for 109/1022 (11%) participants.

Wider implications of the findings: The low number of adverse events (2.0%) suggests that expectant management of PUL using the M4 prediction model is safe. The model is an effective way of triaging women with a PUL as being at high- and low-risk of complications and rationalizing follow-up. The multi-centre design of the study is more likely to make the performance of the M4 model generalizable in other populations.

Study funding/competing interests: None.

Trial registration number: Not applicable.

Keywords: adverse events; decision support techniques; ectopic pregnancy; miscarriage; pregnancy of unknown location; triage; ultrasonography.

Figure 1

The three possible predictions and management plans as recommended by the M4 model after inputting the initial (0 h) and 48 h serum hCG results. PUL, pregnancy of unknown location; EP, ectopic pregnancy; FPUL, failed pregnancy of unknown location; IUP, intrauterine pregnancy; US, ultrasound; UPT, urine pregnancy test.

Figure 2

Flowchart of patient recruitment and protocol deviations.

Figure 3

Flowchart of final outcome data and correct versus incorrect risk stratification according to the M4 model.

Figure 4

Breakdown of adverse and serious adverse events in the study cohort. AE, adverse event; SAE, serious adverse event; PPUL, persistent pregnancy of unknown location; PVB, per vaginal bleeding.