Congenital syphilis (CS) is a serious and potentially fatal condition caused by the transmission of Treponema pallidum from an infected woman to her fetus during pregnancy. Syphilis infection during pregnancy can cause miscarriage, stillbirth, early infant death, or adverse birth outcomes, including premature birth, low birth weight, birth defects, blindness, and hearing loss.1 However, CS can be prevented among syphilis-infected pregnant women if a series of steps are followed, including receiving prenatal care, receiving syphilis testing, and initiating and completing treatment before delivery. The Centers for Disease Control and Prevention (CDC)–recommended treatment of syphilis during pregnancy is benzathine penicillin G at least 30 days before delivery.2 Treatment with benzathine penicillin G during pregnancy is 98% effective in preventing CS.3
Since 2012, the United States has experienced an increase in the incidence of CS. In 2012 to 2014, the CS rate increased 38% from 8.4 to 11.6 cases per 100,000 live births.4 However, during this period in California, there was a 208% increase in CS cases, from 6.6 to 20.3 cases per 100,000 live births.5 This increase in the CS rate coincided with a 167% increase in the primary and secondary syphilis rate among women during this period in California, from 0.6 to 1.6 cases per 100,000 women.5
To understand the increase in CS cases in California and gaps in CS prevention efforts, we examined demographic, clinical care, and risk behavior characteristics associated with delivering an infant with CS. Our objectives were to compare characteristics among syphilis-infected women who delivered an infant with CS (CS mothers) with those of syphilis-infected women who delivered an infant without CS (non-CS mothers), and to identify missed opportunities for prevention among syphilis-infected pregnant women.
MATERIALS AND METHODS
First, we identified syphilis-infected women of reproductive age (15–45 years) by reviewing the California Department of Public Health surveillance records for probable and confirmed syphilis cases diagnosed from March 13, 2012, to December 31, 2014. These records included syphilis cases of any stage reported to all local health departments in California except San Francisco County Department of Public Health because it uses a different surveillance system. We defined syphilis cases and syphilis stages according to the CDC surveillance case definitions.6 March 13, 2012, was selected because it is 42 weeks (the typical maximum gestation period) before January 1, 2013, and our goal was to identify all syphilis-infected women who might have delivered a live-born infant in California in 2013 and 2014.
Next, we linked syphilis case records to records of live births in California in 2013 and 2014 using a deterministic algorithm to identify which women delivered a live infant. Deterministic algorithms match records according to whether records' pairs agree or disagree on a given set of individual identifiers, such as date of birth, last name, and so on.7
We modified an algorithm developed by Martin8 and used different combinations of individual identifiers, such as date of birth, first name, last name, and county of residence, to identify matching records (Appendix, http://links.lww.com/OLQ/A232). This algorithm accounted for misspellings, transpositions, and other data entry errors to increase sensitivity in identifying matching records. We defined a CS mother as a women diagnosed as having syphilis in the surveillance records during pregnancy or at delivery whose infant was reported with probable or confirmed CS according to the CDC surveillance case definitions.6 We defined a non-CS mother as a woman diagnosed as having syphilis in the surveillance records during pregnancy or at delivery whose infant was not reported with probable or confirmed CS. Infants born to infected mothers who did not receive adequate treatment at least 30 days before delivery, as outlined in CDC's STD Treatment Guidelines,2 were included in the probable CS category per the CDC surveillance case definition.6 Probable CS also includes infants born to infected mothers whose treatment was inadequate for their stage of syphilis (treatment begun ≥30 days before delivery, but who missed one required dose for their stage of syphilis).
Treatment documentation of CS and non-CS mothers was reviewed to verify CS classification of infants. Because some treatment dates were missing among non-CS mothers during the study period, adequate treatment was presumed for non-CS mothers having at least 1 dose of benzathine penicillin G documented at least 30 days before delivery.
As part of routine syphilis case investigations, local health department staff obtained testing and treatment data from laboratory reports, medical records, and interviews with health care providers, which were available through surveillance data review. Local health department staff also interviewed women with early syphilis (primary, secondary, or early latent syphilis) to collect additional data on demographics, self-reported risk behaviors during the 12 months before diagnosis, and sexual partners. Women diagnosed as having late latent syphilis or latent syphilis of unknown duration were not routinely interviewed.
Only data that were collected as part of routine syphilis case investigations, regardless of infant case status, were used for analysis. Frequencies of demographic, clinical care, and risk behavior characteristics among CS and non-CS mothers were calculated and compared by using χ2 tests or Fisher exact tests for counts less than 5. Frequencies of risk behavior characteristics were only assessed among interviewed mothers with early syphilis. A CS prevention cascade showing sequential steps necessary to achieve CS prevention was constructed by adapting the HIV care cascade framework.9 We then calculated the proportion of syphilis-infected pregnant women who met the CS prevention criteria indicated in each step of the cascade.
For date of first prenatal care visit, we used the earliest date of first prenatal visit in the California birth records or the date of first syphilis test during pregnancy in the syphilis surveillance records. However, to be counted as prenatal care before delivery, date of first prenatal care visit must have been greater than 2 days before the delivery date. Timing of first syphilis test before delivery was analyzed with at least 40 days as the reference to allow for treatment initiation within 10 days of specimen collection, because treatment initiation of at least 30 days before delivery is required to meet the CDC STD Treatment Guidelines for adequate treatment.2 For risk behavior questions, women who refused to answer or had a missing response were excluded from the analysis. In all analyses, P < 0.05 was considered statistically significant. All analyses were conducted using SAS v. 9.4 (SAS Institute, Inc, Cary, NC). To protect confidentiality, data were stored on a secure network drive only accessible to staff involved in the study. Because this study used routinely collected public health surveillance data for the purpose of guiding public health disease control efforts, it was determined by CDC not to be subject to institutional review board approval for human research protections.
A total of 2498 women aged 15–45 years were reported with probable or confirmed syphilis and diagnosed from March 13, 2012, to December 31, 2014, in the California Department of Public Health surveillance records (Fig. 1). Of these, 427 women (17%) were matched by algorithm to live birth records and were diagnosed as having syphilis during pregnancy or at delivery; 134 (31%) had an infant reported with CS, and 293 (69%) did not have an infant reported with CS. Of the 293 women who did not have an infant reported with CS, 30 (10%) were not adequately treated, indicating unreported infants who met the probable CS case definition. Of these 30 women, 15 (50%) were untreated and 15 (50%) began treatment less than 30 days before delivery. After reviewing CS surveillance records and treatment documentation for the 427 women linked to live births in California birth records and diagnosed as having syphilis during pregnancy or at delivery, 164 (38%) women were defined as CS mothers and 263 (62%) women were defined as non-CS mothers. The 30 women with unreported infants were all defined as CS mothers.
Table 1 shows the demographic and clinical care characteristics of CS and non-CS mothers. No significant differences between CS and non-CS mothers were observed in age at delivery or in race/ethnicity. However, CS mothers were less likely than non-CS mothers to have completed any college. As expected, CS mothers were less likely to receive prenatal care compared with non-CS mothers. Nonetheless, 84% of CS mothers received prenatal care before delivery and 73% received prenatal care at least 40 days before delivery. Mothers with CS were more likely than non-CS mothers to have their first prenatal care visit in the third trimester and less likely to be enrolled in health insurance at delivery.
We found significant differences in syphilis testing between CS and non-CS mothers. Approximately one third (29%) of CS mothers were tested less than 40 days before delivery and an equal proportion were not tested before delivery, whereas all of the non-CS mothers were tested at least 40 days before delivery. Approximately 70% of CS and non-CS mothers were classified as late syphilis cases. Only 6 (4%) of CS mothers received adequate treatment with the recommended regimen per CDC guidelines; 95 (58%) were not treated before delivery, 42 (26%) began treatment less than 30 days before delivery, 20 (12%) began treatment at least 30 days before delivery, but missed at least one of the recommended doses for their stage of syphilis, and 1 (<1%) received nonpenicillin therapy.
We also compared risk behavior characteristics between interviewed CS mothers and non-CS mothers with early syphilis. Of the 45 CS mothers with early syphilis, 35 (78%) were interviewed. Of the 74 non-CS mothers with early syphilis, 63 (85%) were interviewed. We did not find any significant differences between CS and non-CS mothers in risk behaviors (Table 2). The following risk behaviors were common among all mothers: fewer than 1 male sex partner (29%), sex while intoxicated or high (29%), anonymous sex partners (13%), methamphetamine use (21%), and incarceration in the last 12 months (13%).
Lastly, we examined the CS prevention cascade among all CS and non-CS mothers to identify missed opportunities for prevention (Fig. 2). Of the 427 syphilis-infected pregnant women in our study, 382 (89%) received prenatal care at least 40 days before delivery and 331 (78%) were tested for syphilis at least 40 days before delivery. Only 290 women (68%) began treatment at least 30 days before delivery and 269 women (63%) completed recommended treatment before delivery. Assessing gaps between steps in the cascade, we found that 11% of women did not receive prenatal care at least 40 days before delivery, 11% of women were not tested for syphilis at least 40 days before delivery, 10% of women did not begin treatment at least 30 days before delivery, and 5% of women did not complete adequate treatment before delivery. Six women (1%) completed recommended treatment before delivery, but CS was not prevented because these women were reinfected or treatment failed. The final step of the cascade showed that 263 (62%) of 427 potential CS births were prevented overall.
Our findings showed that early prenatal care is critical to prevent CS. Approximately 70% of non-CS mothers in our study had their first prenatal care visit in the first trimester compared with only 43% of CS mothers. Prenatal care beginning in the first trimester creates the opportunity to provide timely prenatal screening and treatment, which can reduce the risk of maternal and infant mortality and pregnancy-related complications.10 Conversely, late prenatal care can lead to delays in prenatal screening and treatment, which were characteristics we found to be associated with delivery of an infant with CS.
Although most pregnant women with syphilis in this study had late syphilis, only women with early syphilis were routinely interviewed during the study period. The exclusion of women with late syphilis might bias our understanding of risk factors and consequently limit the effectiveness of interventions to prevent CS. To better understand risk factors associated with syphilis infection among pregnant women and to target interventions, we recommend that local health departments interview women with both early and late syphilis. In interviews of pregnant women with early syphilis, we found that high proportions reported high-risk sexual behaviors, methamphetamine use, or incarceration. These findings are similar to the proportions noted by Kirkcaldy et al.,11 among pregnant women with early syphilis in Arizona but as a result of nonresponse, the true number of women with high-risk behaviors is likely even higher. We found that methamphetamine was the predominant illegal drug reported. Methamphetamine can increase sexual arousal while reducing inhibitions and has been linked to acquisition of sexually transmitted infections including HIV in some populations.12,13 Overall, these findings indicate that CS prevention efforts should target pregnant women with a history of substance abuse.
Our identification of 30 missed cases of probable CS in 2013 to 2014 indicates that improvements in CS surveillance and case management by state and local health departments in California are necessary to prevent CS. We recommend that local health departments prioritize following up on pregnant women with all stages of syphilis. However, completeness of pregnancy status in reports to public health agencies also needs to be improved to help identify women who might be pregnant. State health departments can consider specifying pregnancy status as a required data element for syphilis reporting.14 The California Department of Public Health is working to capture pregnancy status from electronic laboratory reports by extracting prenatal test and disease diagnosis codes from data transmissions.
We recommend that local health departments follow pregnant women with syphilis through delivery to ensure adequate treatment for the mother and evaluation of the infant at birth. Complete treatment documentation and infant test results, whether positive or negative, are important to effectively monitor successes and challenges in CS prevention. To encourage initiation and completion of adequate treatment, patient support tools, including mobile messages and transportation assistance, might be useful. State and local health departments might consider offering home visits to pregnant women with syphilis that include education and counseling. A statewide maternity support program for Medicaid-enrolled women in Michigan that included home visitation was associated with decreased odds of low birth weight, preterm birth, and infant mortality.15,16 Similar programs could be developed for pregnant women with syphilis to ensure prenatal screening and adequate treatment, which could lead to decreased odds of CS, as well as other congenital and perinatal infections. Finally, to prevent reinfection of mothers, we recommend that local health departments follow up with reported sex partners to provide them with referrals for testing and treatment.
Rather than a large gap in a single step, our CS prevention cascade shows small gaps of 5% to 11% in several steps. Strategies that can address each of these gaps are highlighted in Figure 3. To increase access to prenatal care, a strong system for referrals and linkages to prenatal care is needed. In California, several options exist to allow uninsured pregnant women to obtain health insurance exist through Covered California and Medi-Cal, California's Medicaid health care program.17 These programs are available for persons with household incomes within specified limits of federal poverty levels and include options for non-US citizens and undocumented women. Our findings showed that 10% of syphilis-infected pregnant women were not enrolled in health insurance at the time of delivery. Although other barriers to enrollment cannot be ruled out, it is possible that women were not aware of these programs or their eligibility for these programs. State and local health departments might consider increasing awareness through outreach efforts and referrals, as well as adopting strategies that address barriers to enrollment such as substance abuse and mental health issues. Increasing awareness among health care providers is also important to help address gaps in testing and treatment.
Rapid, or point-of-care, testing, is being evaluated at sites across the United States as a possible strategy to increase syphilis testing among pregnant women18 that might also help to overcome barriers to care. Although more evidence is needed, results from 2 cluster-randomized trials showed promising results in the effectiveness of rapid testing in syphilis detection and treatment, including reduced delay in seeking treatment.19 In areas of high syphilis morbidity, a third trimester screening might be needed in addition to the recommended routine prenatal screening at the first prenatal visit.2 The California Department of Public Health supports this strategy in high-morbidity counties. Like similar studies, incarceration was common among women in our study.11,20 To prevent CS among this population, the California Department of Public Health recommends screening women of reproductive age when they enter jails in high-morbidity counties. Blank et al.20 found that a rapid syphilis testing and treatment program at a women's correctional health clinic in New York City prevented 7 of 8 potential CS births among inmates.
This analysis had a number of limitations. First, we were unable to include women who had stillbirths in our analysis because 2013–2014 California fetal death records were not available. In 2013 to 2014, 11 syphilitic stillbirths were reported in California. Because women who had syphilitic stillbirths might be more likely to have risk behaviors, this exclusion likely underestimates our association of risk behaviors with being a CS mother. Future research should aim to include syphilitic stillbirths in analyses of characteristics of mothers with syphilis and in the CS prevention cascade. We also excluded female syphilis cases from San Francisco County. However, there were only 96 female syphilis cases in San Francisco County in 2013 to 2014 and none delivered an infant with CS. In addition, we used a deterministic algorithm to link surveillance records to birth records. Although this approach is likely to be highly specific, it is less sensitive than a probabilistic algorithm; therefore, it might have missed linkages to mothers. We were unable to assess certain risk factors potentially associated with being a CS mother, such as homelessness, HIV status, and partner risk behaviors, as a result of missing data or because variables were not collected by all local health departments in California. Finally, infant CS case status might have been misclassified. For example, some CS mothers with late syphilis might be non-CS mothers because of missing testing and treatment documentation. However, this potential misclassification is unlikely to change our findings because CS and non-CS mothers had similar demographic and risk behavior characteristics.
Even with these limitations, our results support the use of several strategies to narrow gaps in the CS prevention cascade. The CS prevention cascade should be applied in different states and countries to explore gaps in prevention efforts specific to those contexts. We recommend leveraging partnerships with maternal, adolescent, and child health programs, as well as other programs such as HIV, perinatal hepatitis B, and Zika virus prevention to narrow treatment gaps for all pregnant women. Through collaborative partnerships and effective strategies to reduce gaps in prenatal care, syphilis testing, and treatment during pregnancy, CS can be prevented.
1. Centers for Disease Control and Prevention. Congenital Syphilis—CDC Fact Sheet. Available at: https://www.cdc.gov/std/syphilis/stdfact-congenital-syphilis.htm
. Accessed June 29, 2017.
2. Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64(RR-03):1–137.
3. Alexander JM, Sheffield JS, Sanchez PJ, et al. Efficacy of treatment for syphilis in pregnancy. Obstet Gynecol 1999; 93:5–8.
4. Bowen V, Su J, Torrone E, et al. Increase in incidence of congenital syphilis—United States, 2012–2014. MMWR Morb Mortal Wkly Rep 2015; 64:1241–5.
5. California Department of Public Health. STD Data Tables. Available at: https://www.cdph.ca.gov/Programs/CID/DCDC/CDPH%20Document%20Library/STD-Data-All-STDs-Tables.pdf
. Accessed December 5, 2017.
6. Centers for Disease Control and Prevention. Syphilis (Treponema pallidum
) 2014 case definition. Available at: https://wwwn.cdc.gov/nndss/conditions/syphilis/case-definition/2014/
. Accessed June 23, 2017.
7. Dusetzina SB, Tyree S, Meyer AM, et al. Linking data for health services research: A framework and instructional guide. Available at: https://www.ncbi.nlm.nih.gov/books/NBK253312/
. Accessed December 5, 2017.
8. Martin K. Making fuzzy merges more precise using the COMPARE function in SAS. Available at: http://lexjansen.com/wuss/2012/92.pdf
. Accessed June 29, 2017.
9. Gardner EM, McLees MP, Steiner JF, et al. The spectrum of engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection. Clin Infect Dis 2011; 52:793–800.
10. U.S. Department of Health and Human Services Office of Disease Prevention and Health Promotion. 2020 Topics & Objectives: Maternal, Infant, and Child Health. Available at: https://www.healthypeople.gov/2020/topics-objectives/topic/maternal-infant-and-child-health
. Accessed December 17, 2017.
11. Kirkcaldy RD, Su JR, Taylor MM, et al. Epidemiology of syphilis among Hispanic women and associations with congenital syphilis, Maricopa county, Arizona. Sex Transm Dis 2011; 38(7):598–602.
12. Bazzi AR, Rangel G, Martinez G, et al. Incidence and predictors of HIV and sexually transmitted infections among female sex workers and their intimate male partners in Northern Mexico: A longitudinal, multilevel study. Am J Epidemiol 2015; 181:723–31.
13. Buchacz K, McFarland W, Kellogg TA, et al. Amphetamine use is associated with increased HIV incidence among men who have sex with men in San Francisco. AIDS 2005; 19(13):1423–4.
14. The Revisor of Statutes State of Minnesota. Minnesota Administrative Rules: 4605.7044 Chronic Infections, Perinatally Transmissible. Available at: https://www.revisor.mn.gov/rules/?id=4605.7044
. Accessed June 29, 2017.
15. Meghea CI, You Z, Raffo J, et al. Statewide Medicaid enhanced prenatal care programs and infant mortality. Pediatrics 2015; 136:334–42.
16. Roman L, Raffo JE, Zhu Q, et al. A statewide Medicaid enhanced prenatal care program: Impact on birth outcomes. JAMA Pediatr 2014; 168:220–7.
17. Covered California. Health coverage options for pregnant women. Available at: http://www.coveredca.com/individuals-and-families/getting-covered/pregnant-women/
. Accessed June 28, 2017.
18. Parr N. Identifying optimal uses of the rapid syphilis test: RFA Informational Webinar. Available at: http://essentialelements.naccho.org/wp-content/uploads/2016/10/RST-RFA-Informational-Webinar.pdf
. Accessed June 29, 2017.
19. Shahrook S, Mori R, Ochirbat T, et al. Strategies of testing for syphilis during pregnancy. Cochrane Database Syst Rev 2014; 10:Cd010385.
20. Blank S, McDonnell DD, Rubin SR, et al. New approaches to syphilis control. Finding opportunities for syphilis treatment and congenital syphilis prevention in a women's correctional setting. Sex Transm Dis 1997; 24:218–26.