Stillbirth is a serious medical issue during childbirth. While, the overall stillbirths worldwide have decreased markedly, from 4 million in 1990 to 2.1 million in 2015 [
Syphilis remains the most common congenital infection worldwide with tremendous consequences for both the mother and her developing fetus if it is left untreated. This infection can occur at any stage of pregnancy and during any trimester [
In China, both stillbirth and syphilis place a large burden on maternal and infant health. The latest data showed that the average stillbirth rate in China was 8.8 per 1000 births from 2012 to 2014, and China ranked in the top five countries of the world in 2015 in the total number of stillbirths [
In this retrospective study, all pregnant women who were infected with syphilis and delivered babies from 2010 to 2016 were included, regardless of their birth outcomes. Stillbirth was defined as fetal death occurring at 28 weeks of gestation or more or death at delivery. Cases where the birthweight was equal or greater than 1000 g were included when the information on gestational weeks was missing. A questionnaire was used to collect all the information, including maternal sociodemographic characteristics, utilization of PMTCT and antenatal care services, pregnancy outcomes, and other factors such as previous pregnancy and birth history and marital status. We also extracted data from medical registries in hospitals and records in the antenatal care systems. Multiple births were excluded because they involve a higher risk of adverse pregnancy outcomes. All data were collected via the network reporting system. The medical staff in hospitals were responsible for data collection. Quality control was performed by researchers from a women’s hospital at Zhejiang University that serves as a center for the PMTCT program. The study was approved by the ethics committee of this women’s hospital (number: 2016–0005). All patient information was kept confidential in Women’s Hospital, School of Medicine, Zhejiang University. Ethical approval was obtained from the Women’s Hospital, School of Medicine, Zhejiang University (2016–0005).
In the Zhejiang province, syphilis testing and counseling was routinely offered to all pregnant women at their first antenatal care visit during the period in which data have been collected. Positive results in both the toluidine red unheated serum test (TRUST)/syphilis rapid plasma reagin (RPR) and the
Data were analyzed using SPSS software v.16.0 for Windows. Categorical variables were presented as numbers and frequencies. The demographic characteristics of the women infected with syphilis were noted. The chi-square test was used to compare the prevalence of specific characteristics in women who did or did not suffer from stillbirths. The odds ratios (OR) and their 95% confidence intervals (CI) of the factors associated with stillbirth were estimated using univariate and multiple logistic regression models.
During the study period, 8,724 women were diagnosed with syphilis at some point in their pregnancy. The stillbirth percentage among pregnant women infected with syphilis was 17.4% (152/8,724). Some stillborn babies did not undergo congenital syphilis screening. The percentage of maternal age, marital status, gravidity, previous syphilis, syphilis stage, maternal serum titer for syphilis testing, adequate treatment, and the time of the first antenatal care visit differed significantly between women who had stillbirths and women who had live births (Table
Comparison of maternal sociodemographic characteristics and syphilis condition between women who had stillbirths and women who had live births.
Variables | Category | Stillbirth ( | Without stillbirth ( | ||||
---|---|---|---|---|---|---|---|
% | % | ||||||
Maternal age (years) | <20 | 17 | 11.18 | 294 | 3.43 | 36.94 | |
20–24 | 46 | 30.26 | 1959 | 22.85 | |||
25–29 | 45 | 29.61 | 3047 | 35.55 | |||
30–34 | 19 | 12.50 | 1925 | 22.46 | |||
≥35 | 25 | 16.45 | 1347 | 15.71 | |||
Employment | Farmer | 49 | 32.24 | 2891 | 33.73 | 1.28 | 0.735 |
Business | 12 | 7.89 | 598 | 6.98 | |||
Unemployed | 63 | 41.45 | 3753 | 43.78 | |||
Unknown | 28 | 18.42 | 1330 | 15.52 | |||
Education | Primary | 29 | 19.08 | 1288 | 15.03 | 5.65 | 0.130 |
Middle | 116 | 76.32 | 6461 | 75.37 | |||
College | 6 | 3.95 | 745 | 8.69 | |||
Unclear | 1 | 0.66 | 78 | 0.91 | |||
Married | 117 | 76.97 | 7845 | 91.52 | 39.64 | ||
Unmarried | 35 | 23.03 | 727 | 8.48 | |||
Gravidity | 1 | 43 | 28.29 | 1594 | 18.60 | 9.21 | |
≥2 | 109 | 71.71 | 6978 | 81.40 | |||
Parity | 0 | 70 | 46.05 | 3827 | 44.65 | 0.12 | 0.729 |
≥1 | 82 | 53.95 | 4745 | 55.35 | |||
Minority | 10 | 6.58 | 541 | 6.31 | 0.02 | 0.893 | |
Previous syphilis | 25 | 16.45 | 3264 | 38.08 | 29.75 | ||
Previous fetal loss | 11 | 7.24 | 822 | 9.59 | 0.96 | 0.328 | |
Syphilis stage | Latent | 118 | 77.63 | 7068 | 82.45 | 21.57 | |
Primary | 16 | 10.53 | 326 | 3.80 | |||
Secondary | 3 | 1.97 | 67 | 0.78 | |||
Tertiary | 0 | 0 | 17 | 0.20 | |||
Unclear | 15 | 9.87 | 1094 | 12.76 | |||
Titer for TRUST/RPR >1 : 4 before delivery | 59 | 38.82 | 1820 | 21.23 | 27.33 | ||
Treated | 76 | 50.00 | 7296 | 85.11 | 140.62 | ||
Adequately treated | 26 | 17.11 | 5310 | 61.95 | 126.423 | ||
First antenatal care visit | ≤12 | 42 | 27.63 | 4087 | 47.68 | 69.92 | |
13–27 | 47 | 30.92 | 3082 | 35.95 | |||
≥28 | 51 | 33.55 | 1111 | 12.96 | |||
Unclear | 12 | 7.89 | 292 | 3.41 |
Using a multiple logistic regression analysis, we found that primary or secondary syphilis (adjusted OR (AOR) = 2.03; 95% CI = 1.17, 3.53) and maternal titers over 1 : 4 (AOR = 1.78; 95% CI = 1.25, 2.53) were significant risk factors for stillbirth, after controlling for the influence of maternal age, marriage, gravidity, previous syphilis, syphilis treatment, and first ANC (antenatal care visit, ANC). In addition, adequate treatment was the only protective factor for stillbirth (AOR = 0.16; 95% CI = 0.10, 0.25) (Table
Multiple logistic regression analysis on associations between gestational syphilis and stillbirth.
Variable | Crude OR (95% CI) | Adjusted OR (95% CI) | ||
---|---|---|---|---|
Syphilis stage | Latent | Ref | Ref | |
Primary or secondary | 2.94 (1.72, 5.01) | 2.03 (1.17, 3.53) | ||
Maternal titer >1 : 4 | 2.35 (1.69, 3.28) | 1.78 (1.25, 2.53) | ||
Completely treated | 0.13 (0.08, 0.19) | 0.16 (0.10, 0.25) |
In order to achieve the World Health Organization’s goal of eliminating HIV infection and congenital syphilis in children by 2015, China faces many national challenges. In the second half of 2010, the Chinese government incorporated the national PMTCT plan for HIV, syphilis, and hepatitis B into the existing maternal and child healthcare system. In this study, data on stillbirth and gestational syphilis from 2010 to 2016 were extracted from this database. The rate of stillbirth among pregnant women infected with syphilis was 17.4 per 1000 births. Our estimate was not only slightly higher than the global average level (14.9 per 1000 live births) in 2015 but also double than China’s national average (8.8 per 1000 births) from 2012 to 2014 [
Stillbirth is closely related to syphilis particularly in low-income and middle-income countries, one of the reasons for it being the low detection rate of syphilis during pregnancy [
In our study, higher maternal serum titers, primary or secondary syphilis stage, and lack of adequate therapy during pregnancy were independent risk factors for stillbirth. These results were consistent with other reports looking at stillbirths in pregnant women with syphilis in many countries including the United States [
The pregnancy outcomes could be greatly improved with adequate treatment. A large-scale meta-analysis indicated that the percentage of stillbirths and fetal loss is 26% for untreated maternal syphilis and 21% for maternal syphilis that was treated by the third trimester, whereas it dropped to 4% for nonsyphilitic mothers [
Screening and diagnosis are the first steps to prevent the transmission of syphilis from pregnant women to the developing fetus [
This study has three main limitations that need to be taken into account. First, only pregnant women infected with syphilis and the ones who delivered babies between 2010 and 2016 were eligible for inclusion. Control group information of women that tested negative for gestational syphilis was not collected. Hence, we could not compare the incidence of stillbirth in women infected with syphilis and women without syphilis infection. Second, data for causes of stillbirth, which could be fetal, placental, external, or undetermined, were not collected. Many potential risk factors associated with stillbirths are modifiable and usually coexist, such as maternal demographic factors, maternal age, environment, nutrition, noncommunicable diseases, antenatal care, obstetric complications, and birth information. These issues were not discussed in our study and should be addressed and followed by adequate interventions. Finally, some stillbirth babies did not undergo syphilis screening. Even with these limitations, this study is important, as it was a large-scale multicenter study in a high-prevalence area. As stillbirth attributed to maternal syphilis has been poorly tracked and investigated in China, our results are valuable for further prevention efforts.
Maternal syphilis is strongly associated with adverse pregnancy outcomes. Mother-to-child transmission of syphilis is a public health issue due to high incidence of gestational syphilis and the negative influence it has on pregnancy outcomes. Early identification of syphilis is needed to improve pregnancy outcomes. Nonlatent syphilis and maternal titers over 1 : 4 were risk factors for stillbirth, and adequate treatment was the only protective factor for stillbirth.
The datasets analyzed during the current study are not publicly available and are available from the corresponding author upon request.
The authors declare that they have no conflicts of interest.