Syphilis in Pregnant Women and Congenital Syphilis in Japan, 2022 to 2023: A Warning for Other Countries

Amid surging heterosexual syphilis transmission in Japan, based on national surveillance, notifications of syphilis-infected pregnant women and congenital syphilis doubled for 2 years, hitting record levels in 2023.

Abstract

After a brief decline, syphilis case counts among pregnant women reported through Japan's national surveillance doubled from 2021 to 2023; congenital syphilis case counts/100,000 live births also doubled to >5. The unprecedented trends in Japan highlight the current heterosexual syphilis epidemic's relentlessness, with important implications for other countries.

Syphilis has reemerged as a serious global public health concern. In the United States, cases among heterosexual men and women have surged, with congenital syphilis (CS) reaching alarming levels in 2022—more than 10 times the number reported in 2012. ^1,2 Japan has been no exception. ³ Although men who have sex with men were previously disproportionately affected, since 2011, syphilis cases from heterosexual transmission have shown a marked increase. ⁴ In recent years, however, this rise has been unprecedented. After a brief decline in 2019 to 2020, the number of cases reported through Japan's National Epidemiological Surveillance of Infectious Diseases (NESID) reached the highest level in decades by 2022, ⁵ and provisional 2023 data indicate that notifications are even higher. ⁶ Reported cases among women aged 15 to 44 years increased from 1656 in 2020 to 4546 in 2023, a 174.5% increase.

The increase in syphilis among women of reproductive age raises concerns about a potential increase in CS from transplacental transmission. ^7–9 Fortunately, since systematic reporting of syphilis in pregnancy began in 2019, no substantial rise in cases among pregnant women or in CS was observed through 2021. ¹⁰ However, the recent resurgence underscores the urgent need for enhanced monitoring and reassessment to quickly detect changes in epidemiological patterns, along with strengthened public health communication for timely interventions. Here, we present the recent trends and changes in cases of syphilis in pregnant women and CS in Japan; as the rise in heterosexual syphilis began in 2011, ⁴ this report serves as a warning to other countries regarding the persistent nature of the current epidemic. ³

MATERIALS AND METHODS

In Japan, syphilis is notifiable under the Infectious Diseases Control Law via NESID, requiring laboratory confirmation for non-CS cases and specified clinical or laboratory criteria for CS cases. ^4,11 Syphilis cases in pregnant women were defined by reported pregnancy status on the notification form. ¹⁰ We analyzed NESID data from 2019 to 2023, using finalized data for 2019 to 2022 and provisional data for 2023 (as of January 5, 2024). Data on live births and maternal age at delivery were obtained from vital statistics based on birth notification forms. ¹²

For each diagnosis year, we described the number of syphilis cases among pregnant women and their reported epidemiological characteristics, including syphilis stage, reporting prefecture, age group, history of providing commercial sex within the previous 6 months, and trimester, as well as the ratio of CS case counts to 100,000 live births. For the ratio of syphilis-infected pregnant case counts to 100,000 live births, we mapped the difference in this ratio, comparing the 2019 to 2022 average to the 2022 to 2023 average; this difference represents the absolute change in the burden of syphilis in pregnant women for every 100,000 live births. Similarly, we compared this ratio by age group. In addition, although NESID does not require reporting on perinatal outcomes or circumstances leading to diagnosis, we summarized relevant information from the free-text fields in the 2022 to 2023 notifications. Because these fields are optional, only cases with explicitly documented information were counted.

Ethical approval was not required, as this analysis involved legally collected, nonidentifiable NESID data for public health purposes.

RESULTS

The annual number of syphilis cases reported among pregnant women rose sharply from approximately 200 during 2019–2021 to 267 in 2022 and 383 in 2023, doubling since 2021 (N = 187) (Fig. 1A; Fig. S1, http://links.lww.com/OLQ/B199). CS cases also doubled, from 2.5 to 5.1 for every 100,000 live births (N = 20 in 2021 to N = 37 in 2023), reaching the highest level since NESID began in 1999. The increase in CS cases experienced a slight lag relative to the increase in syphilis cases among pregnant women, remaining at 2.5 for every 100,000 live births in 2022. Among pregnant women, the proportion of primary and secondary (P&S) syphilis, indicative of recent infection, increased from 23.0% in 2021 to 27.3% in 2022 but decreased slightly to 24.8% in 2023 (Fig. 1A). The trend was similar for the absolute number of P&S syphilis cases in pregnant women; the year-to-year increase from 2021 (N = 43) to 2022 (N = 73) was 1.7-fold but declined to 1.3-fold in 2023 (N = 95). Although the yearly increase for total syphilis-infected pregnant case counts was 1.4-fold in both 2022 and 2023, P&S syphilis cases increased proportionally more in 2022 and less in 2023.

Figure 1.

Syphilis cases among pregnant women and congenital syphilis cases in the National Epidemiological Surveillance of Infectious Diseases, 2019 to 2023. A, Number of syphilis cases among pregnant women and the ratio of congenital syphilis case counts to 100,000 live births. B, Difference in the ratio of syphilis-infected pregnant case counts to 100,000 live births, 2022 to 2023 versus 2019 to 2021. Note: Tertiary syphilis cases among pregnant women were not reported. The 2023 data are provisional and subject to updates as additional reports are received and verified. Test for trend based on Poisson regression for the number of syphilis-infected pregnant women from 2021 to 2023.

During 2022–2023, the average ratios of syphilis-infected pregnant case counts to 100,000 live births exceeded the previous 3-year average in 40 of 47 prefectures, showing a nationwide increase (Fig. 1B). The greatest increases were observed in Miyazaki (63.3), Hokkaido (59.1), and Nagasaki (53.1) prefectures; Osaka recorded the highest ratio in both 2022 (89.3) and 2023 (57.1).

Consistent with previous years, the 20- to 24-year age group accounted for the majority of cases among pregnant women (44.9% [N = 120] in 2022 and 44.4% [N = 170] in 2023). The 15- to 19-year age group, however, showed a considerably higher ratio of case counts to 100,000 live births in 2022 to 2023 (463.5 in 2022, 832.4 in 2023), compared with those aged 20 to 24 years (227.1 in 2022, 360.2 in 2023). Notably, this ratio for those aged 15 to 19 years in 2023 was 2.4 times higher than that of 2021 (344.8; Fig. S2, http://links.lww.com/OLQ/B199). The proportion of pregnant cases with a history of providing commercial sex rose continuously, from 12.8% (N = 24) in 2021 to 18.0% (N = 69) in 2023. Similarly, the ratio of cases with this history to those without rose slightly from 0.3 (24 of 84) in 2021 to 0.4 (69 of 162) in 2023 (Fig. S3, http://links.lww.com/OLQ/B199). The proportion of diagnoses in the second trimester or later (≥14 weeks) and the ratio of these to first-trimester diagnoses both declined steadily from 2021 (47.6%, 1.0) to 2023 (37.9%, 0.6; Fig. S4, http://links.lww.com/OLQ/B199).

Information from the free-text fields revealed instances of potential infection during pregnancy and severe perinatal outcomes. Specifically, several cases of seroconversion were documented, where syphilis initially tested negative but later converted to positive (N = 1 in 2022, N = 4 in 2023). Reported complications included miscarriage (N = 3 in 2022, N = 2 in 2023), stillbirth (N = 11 in 2022, N = 9 in 2023), and induced abortion (N = 43 in 2022, N = 28 in 2023), although a causal link to syphilis cannot be confirmed.

DISCUSSION

In recent years, syphilis case counts among pregnant women have surged in Japan. As universal antenatal syphilis screening has long been in existence per national guidelines, increased screening is unlikely to be a factor.⁴ Moreover, the proportion of P&S syphilis, representing recent and symptomatic infection, rose in 2022, which would usually not be expected from expanded screening efforts that are independent of clinical suspicion.^5,10 In addition, CS cases—less biased by health care–seeking behaviors and expected a priori to rise with an increase in pregnant women with syphilis—also increased. Consistent with these findings, a nationwide questionnaire survey involving physicians at obstetrical facilities in 2022, compared with a similar 2016 survey, found a 3-fold increase in syphilis cases among pregnant women. ¹³ Taken together, there has likely been a true increase in incident syphilis infections among pregnant women.

Our findings reveal a high burden of syphilis among young pregnant women, particularly 15- to 19-year-olds, and an increasing number of cases with a recent history of commercial sex work. Similar characteristics have been observed among mothers of CS cases in Japan, where social vulnerabilities contribute to gaps in syphilis prevention knowledge and infection risk awareness, ^14,15 with similar challenges reported in the United States. ¹⁶ These findings highlight the need not only for targeted education but also for improving access to testing and social support for young women and high-risk groups to strengthen prevention efforts. In addition, consistent with prior trends, ¹⁰ approximately 40% of diagnoses continue to occur in the second trimester or later, and cases of seroconversion suggest that delays in accessing antenatal care or infections during the early stages of pregnancy are occurring to some extent. In the United States, these missed opportunities similarly contribute to the prevention challenges for CS. ^1,2

Meanwhile, in 2023, signs of slowing in the increase of new infections were observed, marked by a proportionate decrease in P&S syphilis cases. At the same time, increases in asymptomatic cases and first-trimester diagnoses may reflect improved detection of latent syphilis. These trends may reflect the effects of intensified efforts in more recent years aimed at reducing new infections and promoting earlier diagnosis during pregnancy; the national government intensified social media campaigns, and local governments expanded opportunities for free syphilis testing. Osaka Prefecture, for example, has introduced a regular nighttime testing service, staffed by women specifically for women, to provide same-day results. ¹⁷ In addition, to address the lack of guidance for physicians on syphilis testing beyond the first trimester, ¹⁴ a Japanese medical society has updated guidelines to suggest considering additional testing in later stages of pregnancy if symptoms appear or recent exposure is suspected. ¹⁸

This recommendation aligns with recent treatment guidelines in the United States, which advise repeat testing at the third trimester and at delivery in high-risk communities. ^19,20 Furthermore, new guidelines for CS management were issued in 2023 to encourage early diagnosis and appropriate response by health care providers in Japan. ^21,22 Together with awareness-raising activities, these initiatives may have helped slow the increase in syphilis infections among pregnant women, marking an important step toward CS prevention, while possibly leading to increased detection of latent syphilis. Continued monitoring will be essential to determine whether the rate of new infections is truly declining. Our experience underscores the persistent challenge of controlling syphilis transmission, serving as a cautionary example for other countries to maintain vigilant surveillance and sustained prevention efforts.