| Objective:1. To perform reported estimates of adverse pregnancy outcomes(APOs) among women with and without syphilis through a systematic review of published literatures.2. To investigate the maternal and paternal factors associated with congenital syphilis(CS) and APOs in pregnant women with syphilis by using a prospective nested case-control study.3. To introduce the program for prevention of mother-to-child transmission(MTCT) of syphilis from2002to2012in Shenzhen, South China and assess its effectiveness, and finally to develop a synthesized prevention and control model for MTCT of Syphilis.Methods:1. According to PRISMA guidelines, Pubmed, Cochrane Central, Google Scholar and databases from China were searched for literatures assessing APOs among women with syphilis and without syphilis. The pooled estimates of APOs were calculated using either fixed-effects models or, in the presence of heterogeneity, random-effects models. Subgroup analysis was performed to explore the heterogeneity. Begg rank correlation test was used to assess publication bias.2. Pregnant women attending antenatal services were offered serologic tests, and those diagnosed as having syphilis were recruited from2007to2012in Shenzhen, South China. In a nested case-control study for the pregnancy outcomes of syphilis-infected women, we assessed risk factors comparing infants born with CS (group II) and with any APOs (group III) to infants without CS or APOs (group I). Categorical variables were described using frequencies and percentages, and the continuous variables were described using means and SDs. Proportions and means were compared using χ2, Fisher exact test, and Student t tests, as appropriate. Rates and95%confidence intervals (CIs) were calculated for each measure. Odd ratios (ORs) and their95%CI were used to demonstrate the level of association. The unadjusted ORs (UnaOR) and adjusted ORs (aOR) were calculated by logistic regression. All factors that were associated with CS and APOs at the> level of5%in the univariate analysis were included in the multivariable logistic regression.3. The program for prevention of MTCT of syphilis from2002to2012in Shenzhen, South China was introduced, and its effectiveness was also assessed. Our evaluation indicators of interest were syphilis testing coverage and positivity rates among pregnant women along with years, treatment, continuing pregnancies and follow-up rates among syphilis-infected women, spouse notification, testing, positivity and treatment rates, and prevalence of CS and APOs among offspring. Statistical tables and figures were used to describe the distribution of evaluation indicators. The trend χ2was used to assess the association between years and evaluation indicators.Results:1. Fifty-five literatures involving11498syphilitic women and43575non-syphilitic women were included from4187records initially found. Among untreated mothers with syphilis, pooled estimates were76.8%(95%CI:68.8-83.2) for all APOs,36.0%(95%CI:28.0-44.9) for CS,23.2%(95%CI:18.1-29.3) for preterm,23.4%(95%CI:12.8-38.6) for low birth weight,26.4%(95%CI:21.9-31.4) for stillbirth or fetal loss,14.9%(95%CI:11.4-19.4) for miscarriage and16.2%(95%CI:10.1-25.1) for neonatal deaths. Among syphilitic mother receiving treatment only in the late trimester, pooled estimates were64.4%(95%CI:45.2-79.8) for APOs,40.6%(95%CI:31.3-50.7) for CS,17.6%(95%CI:11.4-26.5) for preterm,12.4%(95%CI:5.9-24.2) for low birth weight, and21.3%(95%CI:17.2-26.0) for stillbirth or fetal loss. Among syphilitic mothers with high titers, pooled estimates were42.8%(95%CI:26.2-61.2) for all APOs,25.8%(95%CI:15.4-40.1) for CS,15.1%(95%CI:5.2-36.9) for preterm,9.4%(95%CI:2.7-27.5) for low birth weight,14.6%(95%CI:6.5-29.7) for stillbirth or fetal loss and16.0%(95%CI:12.0-21.1) for neonatal deaths. Among non-syphilitic mothers, the pooled estimates were13.7%(95%CI:12.0-15.6) for all APOs,7.2%(95%CI:5.6-9.3) for preterm birth,4.5%(95%CI:2.0-10.0) for low birth weight,3.7%(95%CI:2.6-5.1) for stillbirth or fetal loss,2.3%(95%CI:1.8-3.0) for miscarriage and2.0%(95%CI:1.2-3.3) for neonatal death. Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (I2=93.9%; P<0.0001) and women without syphilis (I2=94.8%; P<0.0001).2. From2007to2012,1771050pregnant women were screened. Overall,5369(300/100000;95%CI:290-310/100000) positive cases were tested. At the end of follow-up,96infants were diagnosed as having CS (group Ⅱ),438women who had at least1of APOs were categorized as group Ⅲ, and2195women with syphilis who had normal delivery were categorized as group Ⅰ. Maternal education(ORcs=0.65;ORAPOs=0.79) and history of syphilis(ORCS=0.28;ORAPOs=0.61) as well as paternal age(ORCS=0.62;ORAPOs=0.86) and education(ORCS=0.66;ORAPOs=0.86) were negatively associated with CS and APOs, but maternal unmaORied status(ORCS=1.95;ORAPOs=2.61), inadequate antenatal care(ANC)(ORCS=3.61;ORAPOs=1.79), more sexual partners(ORcs=1.51; ORApOs=1.39), every week of delay in treatment(ORCS=2.82; shorter length of time between the end of the first treatment to childbirth(ORCS=16.67;ORAPOs=3.41), incomplete treatment(ORcS=14.68;ORAPOs=3.20), higher titers(ORcs=5.65; ORAPOs=1.47), early stage of infection(ORcs=23.24; ORAPOs=26.95), and non-penicillin treatment (ORCS=3.00;ORAPOs=2.16) as well as paternal history of cocaine use(ORCS=2.70;ORAPOs=2.44) and positive(ORCS=4.14; ORAPOs=1.50) or unknown(ORCS=2.37; ORAPOs=2.06) status of syphilis increased the risk of CS and APOs. Maternal age(OR=0.65), experience of amativeness(OR=0.78) and condom use in the amativeness process(OR=0.70) also decreased risk of CS, but history of cocaine use increased risk of APOs(OR=1.81).3. Overall, of the2441237pregnant women screened,8455(350/100000) positive cases were detected from2002to2012. Screening coverage increased from89.8%in2002to97.2%in2012(χ2trend=11146.951, P=0.000). All positive rate of syphilis lifted from320to520cases per100000pregnant women from2002to2005, but decreased to220cases per100000pregnant women in2012(χ2tredn=488.690, P=0.000). More and more syphilitic women were tested before28weeks in their pregnancy, and the proportion of positive number increased from49.4%in2003to64.4%in2012(χ2trend=47.746, P=0.000). The proportions increased from44.5%to83.5%from2002to2012for syphilis-infected women who decided to continue their pregnancies after they were given their risk evaluation(χ2trend=49.734, P=0.000). The proportion of pregnant women with syphilis who were lost during the following-up progress also declined from18.9%in2002to2.1%in2012(χ2tredn=53.329,p=0.000).Syphilis testing rate was only21.3%among spouses in2003, but up to86.3%in2012(χ2trend=42.942, P=0.000). Overall, more than25%of spouses were infected with syphilis during the10-year study period. Positive syphilis rate among spouses decreased from36.4%in2003to20.8%in2012(χ2trebd=34.567, P=0.000). During the10-year study period, the prevalence rate declined from42.7%to19.2%for all APOs(χ2trend=44.897, P=0.000), from19.1%to3.5%for CS, from15.8%to2.6%for miscarriage, and from19.0%to3.3%for stillbirth or fetal loss. Yet, the prevalence rate of preterm was almost unchanged. The incidence of CS evidently decreased from109.3to9.9cases per100000live births from2002to2012in Shenzhen(χ2trebd=198.941, P=0.000), while distinctly increased from5.9to97.4cases per100000live births from2002to2012in China(χ2trebd=218.436, P=0.000).Conclusion:1. Syphilis continues to be an important cause of substantial numbers of perinatal deaths and disabilities that could be prevented by early testing and treatment, and also reminds policy-makers charged with resource allocation that the elimination of MTCT of syphilis is a public health priority. Most adverse outcomes occurred among women who were not treated for syphilis or who receiving treatment only in the late trimester or who had high baseline titers.2. Maternal high level of education, history of syphilis as well as paternal old age, high level of education will reduce the risk of CS and APOs. In addition, maternal old age, experience of amativeness, condom use in sexual intercourse will also decrease the risk of CS. However, maternal unmarried status, history of cocaine use, more sexual partners, inadequate antenatal care, every week of delay in treatment or shorter length of time between the end of the first treatment to childbirth or incomplete treatment, high baseline titers, early stage of infection and non-penicillin treatment as well as paternal history of cocaine use,and positive or unknown status of syphilis will increase the risk of CS and APOs.3. Ten-year program consisting of screening of target population and treatment of infected cases, early ANC, health education, sexual partners tracking, detection and treatment, follow-up visits and information management of medical records is the only effective means to block MTCT of syphilis.The medical model of prevention-treatment-management based on medical integration may be a good method to block MTCT of syphilis in the future in China. |
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