TABLE 2.

GRADE Working Group grades of evidence for included studies

Certainty assessment							No. of patients		Effect
No. of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	History-indicated cerclage alone	History-indicated cerclage plus adjuvant 17-OHPC	Relative (95% CI)	Absolute (95% CI)	Quality of evidence (GRADE)	Importance
Preterm birth <23.2 wk of gestation (follow up: mean 24 wk)
4	Observational studies	Not serious	Not serious	Not serious	Not serious	None	26/317 (8.2%)	15/150 (10.0%)	RR .86 (.45-1.65)	14 fewer per 1000 (from 55 fewer to 65 more)	⊕⊕⊕엯 MODERATE	CRITICAL
Preterm birth <28 wk of gestation (follow up: mean 26.5 wk)
4	Observational studies	Not serious	Not serious	Not serious	Not serious	None	42/297 (14.1%)	28/150 (18.7%)	RR .85 (.54-1.32)	28 fewer per 1000 (from 60 more to 86 fewer)	⊕⊕엯엯 LOW	IMPORTANT
Preterm birth <32 wk of gestation (follow up: mean 30.2 wk)
2	Observational studies	Not serious	Not serious	Not serious	Not serious	None	21/139 (15.1%)	14/57 (24.6%)	RR .74 (.40-1.38)	64 fewer per 1000 (from 93 more to 147 fewer)	⊕⊕엯엯 LOW	IMPORTANT
Preterm birth <37 wk of gestation (follow up: mean 36.2 wk)
5	Observational studies	Not serious	Not serious	Not serious	Not serious	None	146/354 (41.2%)	84/181 (46.4%)	RR .90 (.70-1.17)	46 fewer per 1000 (from 79 more to 139 fewer)	⊕⊕⊕엯 MODERATE	IMPORTANT
Respiratory distress syndrome
4	Observational studies	Not serious	Not serious	Not serious	Not serious	None	35/255 (13.7%)	23/141 (16.3%)	RR .81 (.50-1.32)	31 fewer per 1000 (from 52 more to 82 fewer)	⊕⊕엯엯 LOW	CRITICAL
Necrotizing enterocolitis
3	Observational studies	Not serious	Not serious	Not serious	Not serious	None	4/237 (1.7%)	4/136 (2.9%)	RR .60 (.16-2.34)	12 fewer per 1000 (from 25 fewer to 39 more)	⊕⊕엯엯 LOW	IMPORTANT
Birthweight
5	Observational studies	Not serious	Not serious	Not serious	Not serious	None	368	198	-	MD 51.47 lower (244.04 lower to 141.11 higher)	⊕⊕⊕엯 MODERATE	IMPORTANT
Neonatal intensive care unit (NICU) stay (follow up: mean 5.3 wk)
3	Observational studies	Not serious	Not serious	Not serious	Not serious	None	68/237 (28.7%)	38/136 (27.9%)	RR .99 (.71-1.38)	3 fewer per 1000 (from 81 fewer to 106 more)	⊕⊕엯엯 LOW	CRITICAL
Gestational age at delivery (follow up: mean 35.4 wk)
4	Observational studies	Not serious	Not serious	Not serious	Not serious	None	234	129	-	MD .48 higher (.51 lower to 1.47 higher)	⊕⊕⊕엯 MODERATE	IMPORTANT
Fetal and neonatal loss
3	Observational studies	Not serious	Not serious	Not serious	Not serious	None	6/154 (3.9%)	5/114 (4.4%)	RR .78 (.23-2.57)	10 fewer per 1000 (from 34 fewer to 69 more)	⊕⊕엯엯 LOW	IMPORTANT
Neurological morbidity (intraventricular hemorrhage plus periventricular leukomalacia)
3	Observational studies	Not serious	Not serious	Not serious	Not serious	None	5/215 (2.3%)	4/158 (2.5%)	RR .94 (.26-3.42)	2 fewer per 1000 (from 19 fewer to 61 more)	⊕⊕엯엯 LOW	CRITICAL
Neonatal sepsis
2	Observational studies	Not serious	Not serious	Not serious	Not serious	None	4/73 (5.5%)	4/48 (8.3%)	RR .57 (.14-2.20)	36 fewer per 1000 (from 72 fewer to 100 more)	⊕⊕엯엯 LOW	IMPORTANT

GRADE Working Group grades of evidence

High quality: Further research is very unlikely to change our confidence in the estimate of effect.

Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

Effects of interventions (history-indicated cerclage alone vs history-indicated cerclage plus adjuvant 17-OHPC (Relative and Absolute effects) (in bold).

CI, confidence interval; MD, mean difference; RR, relative risk.

The overall GRADE evidence of this review is low-moderate.