Evidence table: Outcomes associated with syphilis during pregnancy Study ref Design LoE N Aim, setting, methods Results Comments (Arnesen et al 2015) SLR IV 8 studies Aim: To perform a systematic review and of reported estimates of the association between gestational syphilis (GS) and stillbirth. Setting: the Americas Methods: Cochrane Library, Embase, LILACS, MEDLINE/PubMed, PLOS, and ScienceDirect were searched for original research studies quantifying the relationship between GS and stillbirth in the region. A cumulative meta-analysis plus four subgroup meta-analyses of study data on the association between maternal syphilis during pregnancy and stillbirth were conducted. The four meta-analyses were based on 1) definition of cases and the control; 2) syphilis treatment (presence or absence, effective or ineffective); 3) definition of stillbirth as “showing no signs of life at birth”; and 4) definition of stillbirth based on low birth weight and gestational age. Random-effects meta-analyses were used to calculate pooled estimates of stillbirth with exposure to GS, and each subgroup analysis was tested for heterogeneity. Women with GS had increased odds of stillbirth (pooled OR 6.87; 95%CI 2.93 to 16.08). There was considerable heterogeneity across the studies (I2= 95). The funnel plot was not statistically significant, pointing to a lack of publication bias. Increased odds of stillbirth among pregnant women with syphilis were also seen in all four subgroup meta-analyses. Review includes observational studies and is of low to moderate methodological quality (see Section 3.1.6)
(Gomez et al 2013) SLR IV 6 studies Aim: To perform a systematic review and of reported estimates of adverse pregnancy outcomes among untreated women with syphilis and women without syphilis. Settings: Malawi, Tanzania, United Kingdom, United States, Zambia Methods: PubMed, EMBASE and Cochrane Libraries were searched for literature assessing adverse pregnancy outcomes among untreated women with seroreactivity for Treponema pallidum infection and non-seroreactive women. Adverse pregnancy outcomes were fetal loss or stillbirth, neonatal death, prematurity or low birth weight, clinical evidence of syphilis and infant death. meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses. Pooled estimates showed that among untreated pregnant women with syphilis, fetal loss and stillbirth were 21% more frequent, neonatal deaths were 9.3% more frequent and prematurity or low birth weight were 5.8% more frequent than among women without syphilis. Of the infants of mothers with untreated syphilis, 15% had clinical evidence of congenital syphilis. The single study that estimated infant death showed a 10% higher frequency among infants of mothers with syphilis. Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (66.5%; 95%CI 58.0 to 74.1; I2 = 91.8%; P<0.001) and women without syphilis (14.3%; 95%CI 11.8 to 17.2]; I2 = 95.9%; P<0.001). Review includes observational studies and is of low to moderate methodological quality (see Section 3.1.6) effects
(Shiber & Todia 2014) Cohort III-2 58,569 Aim: to determine the clinical utility and cost of repeating syphilis testing in the third trimester of pregnancy in a high-risk urban population. Setting: United States Methods: A retrospective cohort analysis was performed for patients delivering from January 1993 through December 2009 with at least 1 venereal disease research laboratory (VDRL) test sent during pregnancy. Chart review was performed for patients with confirmed syphilis to determine the temporal relationship of syphilis diagnosis to the pregnancy. For patients who seroconverted during pregnancy (no antecedent history or treatment for syphilis), newborn charts were reviewed. The costs of treating seropositive neonates and the costs of implementing additional third-trimester syphilis screening were then compared. In all, 113 new cases of syphilis occurred (192.9/100,000 deliveries). There were 17 detected seroconversions; 10 were not rescreened in the third trimester and tested positive at delivery. These 10 patients may have benefitted from implementing uniform VDRL testing at weeks’ gestation. All newborns were asymptomatic with a negative workup and received empiric penicillin therapy. Based on 2011 hospital charges, the cost of evaluating and treating a neonate for syphilis is $11,079. Implementing an additional VDRL screen at 28-32 weeks’ gestation for each pregnant patient during the 17 years studied would cost $1,991,346. An 18-fold increase in syphilis prevalence (3500/100,000 [3.5%] deliveries) would be required for the cost of implementation of universal early third-trimester screening to be equal to the potential health care charges saved by detecting maternal seroconversion and obviating the need for neonatal therapy.