Methods

This was a retrospective review from September 1981 to December 2011 of all women diagnosed with syphilis at ≥18 weeks of gestation who received an ultrasound scanning before treatment to evaluate for evidence of fetal syphilis. Women not treated before delivery and those with serofast syphilis were excluded. Subjects were identified with the use of an established database of patients who were diagnosed with syphilis during pregnancy. A secondary search of our departmental ultrasound database was then performed by searching for syphilis in the indication field.

At our institution, women are tested for syphilis at 3 points during pregnancy: at entry into prenatal care, at 28-32 weeks of gestation, and again at delivery. A nontreponemal antibody test (rapid plasma reagin or venereal disease research laboratory) is used as the initial screening test, and a positive result is confirmed with the use of a treponemal serologic test (fluorescent treponemal antibody absorption) or the microhemagglutination assay for antibodies to Treponema pallidum . After a woman is identified as having syphilis, she is referred to our Infectious Disease Obstetrics Complications Clinic where a thorough medical history and a clinical examination are performed. If the patient reports previous treatment for syphilis, the Dallas County Health Department is contacted for confirmation. Based on the history and physical examination, the patient is assigned a stage of syphilis to direct appropriate therapy. Maternal stage of syphilis is diagnosed according to the CDC guidelines. If the patient is ≥18 weeks of gestation, a targeted ultrasound scan is performed that specifically looks for the presence of hepatomegaly, placentomegaly, polyhydramnios, ascites, and elevated middle cerebral artery (MCA) velocimetry before maternal treatment is undertaken. If the patient is ≥24 weeks of gestation and there is sonographic evidence of fetal infection, the patient is monitored in our labor and delivery suite while receiving treatment because of a concern for a Jarisch-Herxheimer reaction. If the ultrasound scan is without evidence of fetal syphilis, the patient is treated during the same visit and discharged home with a scheduled follow-up visit the next week.

Ultrasound reports and available images from the targeted examination were reviewed. Hepatomegaly was defined as a liver length >95th percentile for gestational age. Placentomegaly was defined as a placental thickness that exceeded the mean plus 2 standard deviations for gestational age as established by Hoddick et al. Ultrasound reports from examinations that were performed before 1985 were reviewed for stigmata of fetal syphilis that was diagnosed by an experienced faculty radiologist or maternal fetal medicine specialist. Polyhydramnios was defined as an amniotic fluid index >250 mm. MCA peak systolic velocity >1.5 multiples of the median was considered abnormal. After the year 2000, this parameter consistently became part of our ultrasound protocol for fetal syphilis to evaluate indirectly for fetal anemia.

After the initial ultrasound scan, all women were treated with benzathine penicillin G intramuscularly according to the stage of syphilis, as per CDC treatment guidelines. In August 1992, we began to treat women with early-stage syphilis using 2 injections of 2.4 million units of benzathine penicillin G 1 week apart to maintain treponemocidal levels. Women with an abnormal result from the pretreatment ultrasound scan were given serial follow-up ultrasound scans until resolution of the sonographic abnormalities or delivery, whichever occurred first. Delivery and infant outcomes were recorded if available. Neonatal physical examination and laboratory findings were recorded as was placental disease. Hepatomegaly was defined as a palpable liver ≥2 cm below the costal margin. Congenital syphilis was diagnosed with CDC diagnostic criteria.

Standard life-table methods were calculated to estimate time to resolution of ultrasound scan abnormalities that were found after adequate maternal syphilotherapy. Kaplan-Meier estimates were constructed for each ultrasound scan abnormality that was found. The Student t test was used to evaluate coninuous variables, and a χ ² test was used for frequencies. A probability value of < .05 was considered significant. This study was approved by the Institutional Review Board at the University of Texas Southwestern Medical Center.

Results

During the study period, 235 women were diagnosed with syphilis ≥18 weeks of gestation and received an ultrasound scan before treatment. Seventy-three women (31%) had ≥1 abnormality that was identified by the ultrasound scan. The most common abnormality that was identified by ultrasound scanning was hepatomegaly (79%), followed by placentomegaly (27%), polyhydramnios (12%), and ascites (10%). Of the 52 women who had MCA peak systolic velocimetry performed, 17 women (33%) had elevated levels ( Table 1 ).

Women with an abnormal finding on the pretreatment ultrasound scan were compared with those with a normal finding. Patient characteristics of the 2 groups are described in Table 2 . There were no differences in age, race, or parity between the 2 groups. There was also no difference in stage of maternal disease ( P = .9). Although most women were diagnosed with early-stage disease, this did not correlate with an abnormal pretreatment ultrasound scan result (58% vs 57%, respectively; P = .9). Consistent with known risk factors for vertical transmission, women with an abnormal pretreatment ultrasound scan result were diagnosed later in pregnancy (27.3 ± 5.3 vs 25.4 ± 6.5 weeks of gestation; P = .03), had fewer prenatal visits (7.1 ± 3.7 vs 8.4 ± 4.2 weeks of gestation; P = .03), and were treated later in pregnancy, although this last comparison did not reach statistical significance. Only 1 patient in each group tested HIV positive.

Delivery outcomes were available for 194 pregnancies. Of the 41 women who were lost to follow-up evaluation, no significant differences were noted in maternal stage of syphilis, gestational age at diagnosis and treatment, or ultrasound abnormalities when compared with women who were not lost to follow-up evaluation. Women with an abnormal pretreatment ultrasound scan delivered significantly earlier than those with a normal pretreatment ultrasound scan (37.3 ± 3.7 vs 38.5 ± 2.4 weeks of gestation; P = .01); in particular, there were significantly more women who had an abnormal pretreatment ultrasound scan who delivered earlier than 32 weeks of gestation (7% vs 1% respectively; P = .01). In women who delivered at <37 weeks of gestation, indications for delivery were analyzed and were not significantly different between the 2 groups. Time from treatment to delivery was shorter in women with an abnormal pretreatment ultrasound scan results (7.1 ± 4.7 vs 9.8 ± 5.3 weeks of gestation; P < .001), and these women tended to deliver within the 30 days after treatment (29% vs 14%, respectively; P = .02).

Infant outcomes were available for 173 pregnancies. Women with an abnormal result on pretreatment ultrasound scan were significantly more likely to have an infant who required treatment for congenital syphilis (39% vs 12%, respectively; P = .001). Clinically significant growth restriction that was defined as ≤3rd percentile was not significantly different in the 2 groups (4% vs 0%, respectively; P = .09). Table 3 describes the examination findings at delivery of the 32 infants who required treatment for congenital syphilis. There were no statistical differences on initial infant examinations between those women with and without abnormal findings on pretreatment ultrasound scanning ( Table 3 ). Interestingly, most infants had hepatomegaly on the initial infant examination, regardless of antenatal ultrasound findings.

After the initial ultrasound scan was performed, all women were treated according to their stage of syphilis per contemporary CDC treatment guidelines. Those women with an abnormal finding on the pretreatment ultrasound scan had serial sonographic follow-up evaluations until resolution or delivery, whichever occurred first. Serial ultrasound scans and/or delivery data were available for 85% of these women. From this, we were able to construct a survival analysis for each ultrasound abnormality ( Figure 1 ). Using the distribution of each curve, we hypothesized that MCA Doppler abnormalities, ascites, and polyhydramnios are the first sonographic abnormalities to resolve, followed by placentomegaly and finally hepatomegaly. Although we can comment only on those abnormalities that were seen with ultrasound scanning, hepatomegaly persisted the longest after maternal syphilotherapy.

Timeline to resolution of abnormal ultrasound findings

Rac. Ultrasound findings of congenital syphilis. Am J Obstet Gynecol 2014 .

Results

During the study period, 235 women were diagnosed with syphilis ≥18 weeks of gestation and received an ultrasound scan before treatment. Seventy-three women (31%) had ≥1 abnormality that was identified by the ultrasound scan. The most common abnormality that was identified by ultrasound scanning was hepatomegaly (79%), followed by placentomegaly (27%), polyhydramnios (12%), and ascites (10%). Of the 52 women who had MCA peak systolic velocimetry performed, 17 women (33%) had elevated levels ( Table 1 ).

Table 1

Frequency of abnormalities in 73 women with an abnormal ultrasound

Variable	Abnormality found on ultrasound scan, a n (%)
Hepatomegaly	58 (79)
Placentomegaly	20 (27)
Polyhydramnios	9 (12)
Ascites	7 (10)
Elevated middle cerebral artery peak systolic velocity	17/52 (33)

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