CONGENITAL SYPHILIS — Congenital syphilis occurs when the spirochete Treponema

pallidum is transmitted from a pregnant woman to her fetus. Infection can result in
stillbirth, hydrops fetalis, or prematurity and associated long-term morbidity. Because
of this morbidity, great emphasis has been placed on routine syphilis screening of all
pregnant women.

Epidemiology — The incidence of congenital syphilis reflects the rate of syphilis in

women of childbearing age. Many congenital cases develop because the mother
received no prenatal care, no penicillin treatment, or inadequate treatment before or
during pregnancy. Among women with untreated early syphilis, 40 percent of
pregnancies result in spontaneous abortion [37] .

Incidence — The Centers for Disease Control and Prevention (CDC) set a goal for
reducing cases of congenital syphilis in the United States to fewer than 40 per 100,000
live births by the year 2000. The overall number of cases of congenital syphilis declined
51.8 and 7.6 percent comparing 2000 to 1997 and 1999, respectively; only two states,
Arkansas and South Carolina, had more than 40 cases per 100,000 live births [38] . The
number of cases of congenital syphilis decreased in all ethnic groups, but minority
ethnic populations still had the highest rates of this congenital infection.

Transmission — Syphilis is acquired routinely by direct sexual contact with ulcerative

lesions of the skin or mucous membranes of infected persons or by transplacental
transmission. Transplacental transmission can occur at any time during gestation but
typically occurs during the second half of pregnancy. Studies have shown that T.
pallidum can be transferred across the placenta and infect the fetus at as early as six
weeks of gestation. Women with primary or secondary syphilis are more likely to
transmit the disease to their fetuses than are those women with latent (not clinically
apparent) disease [16] .

Clinical manifestations — Two-thirds of live-born neonates with congenital syphilis are

asymptomatic at birth. Overt infection can manifest in the fetus, the newborn, or later
in childhood. Clinical manifestations after birth are divided arbitrarily into early (≤ 2
years of age) and late (>2 years of age) [39] .

Fetal manifestations — Syphilis has many possible fetal manifestations, including

stillbirth, neonatal death, and overt infection at birth, such as hydrops fetalis.
Intrauterine death is estimated to occur in 25 percent of affected infants, with perinatal
mortality in an additional 25 to 30 percent, if untreated [6] .

Early congenital manifestations — Early manifestations can be quite variable and often
appear within the first five weeks of life [40] . Cutaneous lesions, when present,
frequently occur on the palms and soles; if ulcerative in nature, they are highly
contagious. Other early manifestations include hepatosplenomegaly, jaundice, anemia,
and occasionally snuffles. Metaphyseal dystrophy and periostitis often are noted on
radiographs at birth.

Late congenital manifestations — Late manifestations develop from scarring related to

early infection but can be prevented by treatment of the infant within the first three
months of birth [6] . Late findings can include frontal bossing, short maxilla, high
palatal arch, Hutchinson triad (Hutchinson teeth [blunted upper incisors], interstitial
keratitis, and eighth nerve deafness), saddle nose, and perioral fissures [6,41] .

Diagnosis — Because the majority of newborns with congenital syphilis are

asymptomatic at birth, serologic tests most often provide a diagnosis. In patients with
overt manifestations, a definitive diagnosis of syphilis can be made by direct
visualization of the spirochetes using darkfield microscopy or direct fluorescent
antibody tests of lesion exudate or tissue. However, these procedures may not be
available in all centers.

Serologic tests — A presumptive diagnosis can be made using serologic testing. A

nontreponemal test, such as VDRL (Venereal Disease Research Laboratory) or RPR
(rapid plasma reagin), is used for screening because the test is sensitive but not
specific. These tests are inexpensive, are performed rapidly, and provide quantitative
results, which are helpful indicators of disease activity and are used to monitor
response to treatment [42] . If the nontreponemal test is positive, confirmatory testing
is performed with a specific treponemal test, such as the microhemagglutination test
for T. pallidum (MHA-TP) and the fluorescent treponemal antibody absorption (FTA-
ABS). These latter tests are not quantitative and, once positive, will remain so for life,
even after successful treatment.

Serologic testing of the newborn often is problematic because IgG antibody may be a
reflection of maternal rather than infant infection. Unless the nontreponemal titer is
considerably higher in the newborn than in the mother, follow-up serology over the first
six months of life, when maternal IgG is lost, would be required to make a diagnosis,
losing precious time when treatment could be initiated [6] .

Newborn evaluation — Because of the problems with both direct visualization and
serology, a case definition of congenital syphilis was advanced by the CDC [6] . The
evaluation of the newborn for congenital syphilis should include the following elements:
Maternal history of syphilis, including treatment and adequacy of treatment before and
during the pregnancy Physical examination of the newborn Quantitative nontreponemal
and treponemal tests, if indicated Complete blood count (CBC) with platelets, long-
bone radiographs, CSF studies (VDRL, cell count, and protein), and chest radiograph
and/or liver function tests, if clinically indicated Pathologic examination of the placenta
or umbilical cord using specific fluorescent antitreponemal antibody staining

According to the CDC, the diagnosis of syphilis is confirmed if T. pallidum is identified in

skin lesions, placenta, umbilical cord, or autopsy. A presumptive diagnosis, which
results in treatment, is made if the newborn has a positive serologic test for syphilis
and any of the following: Compatible findings on physical examination CSF
abnormalities, including positive VDRL, increased white blood cell count (WBC), or
elevated protein Osteitis on radiography of long bones Placentitis or funisitis
Nontreponemal test fourfold higher than the maternal result on the same test Positive
FTA-ABS-19S IgM antibody

Although CSF findings are a component of the case definition, at least one
retrospective study has called into question their value [43] . Among a group of 329
asymptomatic infants whose mothers had untreated or inadequately treated syphilis,
only two (0.6 percent) had positive CSF VDRL, and neither the WBC nor protein differed
from a control group of newborns undergoing a sepsis evaluation with negative results.
Among the other criteria, the nontreponemal test only occasionally is fourfold higher
than the maternal one, and the 19S IgM test is not readily available. The infant also is
presumed to have syphilis if the mother has a history of contact with an individual with
primary or secondary syphilis within 90 days of delivery and did not receive treatment
[39] .

Another study explored the dilemmas of diagnosing central nervous system

involvement in infants born to mothers with syphilis, using rabbit infectivity of CSF as
the gold standard, and found further complications in the interpretation of the data
[44] . Most, but not all, infants with a positive CSF rabbit infectivity test were diagnosed
by a combination of conventional tests. In addition, 13 patients had a negative rabbit
infectivity test but positive polymerase chain reaction (PCR) or IgM immunoblots; six of
these infants had been exposed to antibiotics prior to obtaining CSF. It is not clear from
the study whether or not prior antibiotics influenced the rabbit infectivity test or
whether the PCR or IgM immunoblot results were false positives.

Treatment — Parenteral penicillin G is the drug of choice for all stages of syphilis.
Infants should be given aqueous crystalline penicillin G (100,000 to 150,000 U/kg per
day IV in 2 divided doses for 7 days and then every 8 hours to complete a 10-day
course) or procaine penicillin G (50,000 U/kg per day IM in a single dose for 10 days)
[45] .

This therapy should be given if the newborn meets any of the criteria noted above or if
the mother was treated less than four weeks before delivery, or with a regimen that did
not contain penicillin, or if maternal titers suggest inadequate response to treatment
before or early in pregnancy. Treatment of the mother during pregnancy is effective; in
one prospective study of 340 pregnant women, the overall success rate for therapy
was 98 percent, with the lowest rate of 95 percent in those with secondary syphilis [46]
.