Across the initial and updated searches, we returned 3401 studies (3041 from the initial search and 360 from the updated search). Following title and abstract screening, a total of 93 studies were selected for full-text review. Of these, 36 studies were included in our review. In total, 22 economic evaluations were included [21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40]; fifteen had the outcome framed in DALYs [21,22,23,24,25,26,27,28,29,30,31,32,33,34, 41], and seven had the outcome framed in QALYs [35,36,37,38,39,40, 42]. Two primary studies were identified after hand-searching reference lists [40, 43]. Note that one primary study was also an economic evaluation [40]. Thirteen burden of disease studies were included as part of the review: seven studies as part of the GBD series published by the Institute of Health Metrics and Evaluation [4, 44,45,46,47,48,49], four country-related landmark burden of disease studies [50,51,52,53], and two other separate burden of disease studies [54, 55]. Fig. 1 displays the PRISMA flowchart.

PRISMA flowchart of the search strategy. *one economic evaluation using QALYs was also a primary study and thus should only be counted once toward the total

Supplementary Table S11 summarises the key characteristics of the 36 studies reviewed. For the 22 economic evaluations, two studies were from low-income countries [21, 27], three from lower-middle-income countries [32, 33, 41], three from upper-middle-income countries [22, 29, 31], eight from high-income countries [23, 35,36,37,38,39,40, 42], and six from a mixture of countries [24,25,26, 28, 30, 34]. Fifteen studies (68%) reported the cost-effectiveness of antenatal screening for syphilis [21, 22, 24,25,26,27,28,29,30,31,32,33,34, 36, 37]. In addition to studies reporting weights for mothers and their newborns, other common populations included blood donors and patients receiving blood transfusions [23, 41, 42], and people living with HIV [35, 39].

Table 1 summarises the characteristics of the 22 economic evaluations. Of these, the primary outcome was the cost-per-DALY-averted in 15 studies and the cost-per-QALY-gained in seven studies. Health states reported in the text below and Tables 1, 2, 3, 4 and 5 reflect the choice of wording within the respective study (e.g. “mild early syphilis” or “stage one”), however with ambiguous terms we have standardised them to reflect the more widely accepted medical terminology.

Table 2summarises the disability weights and associated durations used in the 15 economic evaluations in which the primary outcome was framed in DALYs [21,22,23,24,25,26,27,28,29,30,31,32,33,34, 41]. The commonly used health states for newborns were congenital syphilis (n=13) with disability weight ranges from 0·315 to 0·316, low birth weight (n=9) with ranges from 0·106 to 0·291, and miscarriage (n=3), stillbirth (n=13), and neonatal death (n=12) all with values of 0 or 1. Health states for adult syphilis included early syphilis (n=4), tertiary syphilis (n=4), and HIV and syphilis coinfection (n=1), with disability weight ranges from 0·006 to 0·38. Eleven economic evaluations sourced their disability weights directly from a Global Burden of Diseases study [21,22,23,24,25,26, 28, 29, 31,32,33]. Of these eleven studies, only one used weights from after the 2010 update [23]. Three studies referenced other economic evaluations in our review for their disability weights [27, 30, 34]. The only economic evaluation that did not use GBD weights assumed the health state utility value, giving a disability weight of 0·12 for syphilis [41].

Eleven studies used a disability weight of 0·315 for clinical congenital syphilis [21,22,23,