Keywords
fetal syphilis - maternal syphilis - hydrops fetalis - penicillin - early testing
Syphilis remains the most common congenital infection in the world.[1]
[2] In pregnancy, syphilis is associated with numerous findings, including placentomegaly,
hepatomegaly, polyhydramnios, fetal anemia, and hydrops fetalis. Typically, hepatomegaly
and placentomegaly precede signs of hydrops fetalis on ultrasound.[2] Abnormal ultrasound findings are associated with poor outcomes and higher risk of
neonatal treatment failure.[2] In severe cases, syphilis infection in pregnancy leads to prematurity, low birth
weight, and stillbirth.[2]
[3]
Nonimmune fetal hydrops (NIFH) is defined as two or more abnormal fetal fluid collections
without red blood cell alloimmunization.[4] These include generalized skin edema (thickness > 5 mm), pleural effusions, pericardial
effusion, or ascites. Concomitant sonographic findings include polyhydramnios and
placental thickening of at least 4 or 6 cm in diameter at the second and third trimesters,
respectively. This condition is an uncommon but serious sequelae of various infectious
processes, including advanced stages of neonatal syphilis.[5]
[6] NIFH accounts for up to 90% of all fetal hydrops cases and presents a poor prognosis.[7] Rarely, NIFH may resolve after delivery, including one instance of syphilis-induced
NIFH.[8]
[9]
[10]
[11] The signs of neonatal syphilis, including hepatic and bone dysfunction, improved
with penicillin.[10]
To our knowledge, there is no prior documentation of in utero resolution of syphilis-related
NIFH during pregnancy. Herein, this report presents one such case following treatment
with penicillin.
Case
Our patient, a 38-year-old gravida 5 para 3, presented at 285/7 weeks' gestation as a transfer from an outside hospital for newly diagnosed maternal
syphilis and concern for fetal hydrops. Her pregnancy was otherwise complicated by
chronic hypertension, history of preeclampsia, history of gestational diabetes mellitus,
four prior cesarean sections, and an elevated second trimester α-fetoprotein in the
setting of a normal anatomy scan and reassuring noninvasive prenatal testing (declined
amniocentesis).
The patient was diagnosed with syphilis following a rapid plasma regain (RPR) titer
result of 1:16 at a routine prenatal care visit at 275/7 weeks and confirmed with a treponemal test. First trimester syphilis screening results
were ultimately never found. However, the patient reported normal syphilis screens
with her prior four pregnancies, the last of which was 10 years prior. She denied
symptoms concerning for syphilis infection, including genital chancre or rash on her
hands and feet. She returned for initiation of penicillin and follow-up ultrasound
at 285/7 weeks (3 weeks after her last ultrasound which had revealed normal growth and anatomy)
which then demonstrated fetal ascites, mild ventriculomegaly, and an elevated middle
cerebral artery (MCA) Doppler at 1.41 multiple of the median (MoM). She was admitted
to an outside hospital for further monitoring and administration of betamethasone
and penicillin. A few hours following the first dose of penicillin, her unremarkable
fetal monitoring changed to minimal variability and intermittent late decelerations.
She was transferred to our center for higher level of care.
On arrival, fetal monitoring redemonstrated intermittent late decelerations every
60 minutes, without active concern for fetal acidemia. Standard maternal resuscitation
measures were initiated. When the fetal status was reassuring, an ultrasound was performed
revealing a singleton intrauterine pregnancy in cephalic presentation, fetal pleural
effusions, ascites, and ventriculomegaly ([Fig. 1]). MCA Dopplers were 1.49 MoM. Estimated fetal weight was in the 86th percentile
by Hadlock, and the placental diameter was 4.84 cm.
Fig. 1 Initial presentation on hospital day (HD)1 with pleural effusion (A, arrow), ventriculomegaly (B, arrow), enlarging fetal ascites (C), and elevated middle cerebral artery (MCA) Dopplers (D), compared with resolution of pleural effusion (A), ventriculomegaly (B), fetal ascites (C), and normalized MCA (D) Dopplers on HD8.
Over the next 4 days, continuous fetal monitoring remained reactive without further
decelerations and was de-escalated to twice daily 1-hour nonstress tests. A repeat
ultrasound on hospital day (HD) 6 showed resolution of the pleural effusion, ascites,
and ventriculomegaly. A third ultrasound on HD 8 again redemonstrated the above and
normalized MCA Dopplers at 1.23 to 1.34 MoM. A complete NIFH workup, including other
infectious etiologies of parvovirus and cytomegalovirus serologies, was negative.
Amniocentesis was declined in favor of formal testing for a possible fetal syphilis
infection for the following reasons: normal anatomic survey at 253/7 weeks' gestation, no alternate sources for NIFH and resolution of the NIFH following
treatment, and high suspicion for a successful treatment of a fetal syphilis infection.
The patient received three total doses of intramuscular penicillin and was discharged
home in stable condition on HD 9.
Twice weekly outpatient nonstress tests were reassuring. Weekly “hydrops check” ultrasounds
were performed and never again demonstrated any signs of fetal hydrops. A follow-up
fetal growth scan revealed appropriate growth. Genetic workup of the resolved ventriculomegaly
was declined, and no evidence of structural anomalies including aqueductal stenosis,
neural tube defects, agenesis of the corpus callosum, or a Dandy-Walker malformation
was observed. At 364/7 weeks, she ultimately was diagnosed with preeclampsia with severe features and underwent
a repeat cesarean section. She delivered a healthy male neonate with Apgar scores
of 8 and 8 at 1 and 5 minutes, respectively.
There were no signs of congenital syphilis, neonatal anemia, or anatomic abnormalities
following a thorough evaluation from our neonatology team. Laboratory testing was
notable for hemoglobin 18.2 g/dL and a platelet count of 241,000. The syphilis screen
for the neonate was notable for a reactive treponema pallidum antibody with an RPR
screen positive and an RPR titer of 1:8. Prior to discharge, the neonate received
a single dose of benzathine penicillin.[12] The neonate had continued close outpatient follow-up with no further laboratory
testing performed.
Discussion
NIFH can present a severe risk to overall fetal well-being and has multiple infectious
etiologies.[9]
[10]
[13] In the setting of confirmed syphilis infection and negative workup for hydrops fetalis,
the patient's course was likely secondary to fetal syphilis infection. Infections
such as syphilis can cause fetal anemia. When untreated, this leads to fetal heart
failure, an increase in central venous pressure, and fluid accumulation in the interstitium,
leading to NIFH.[13] Although hepatomegaly and placentomegaly are the first and most common signs of
fetal syphilis infection, our patient's presentation indicated that these findings
do not necessarily precede NIFH and fetal anemia in cases of fetal syphilis.[2] Percutaneous umbilical blood sampling for fetal anemia was considered, but not performed
as MCA Dopplers remained less than 1.5 and improved. Given hydropic findings, including
pleural effusion and fetal ascites, a robust response to penicillin was not expected.[3]
Decreased fetal movement, uterine contractions, and transient late decelerations were
initially observed after the first dose of penicillin but not the second. These findings
may represent a fetal Jarisch–Herxheimer reaction (JHR). In the adult patient, JHR
presents after receipt of penicillin with patients experiencing shaking chills, a
rise in temperature, and intensified skin rash.[14] JHR also occurs in up to 40% of pregnant patients being treated for syphilis. Transient
late fetal heart rate decelerations, decreased fetal movement, and uterine contractions
following penicillin administration have been previously reported in a fetus with
hydrops.[15]
[16] The authors suggest these findings indicate a fetal JHR, which is consistent with
this case.[15]
[16]
Although the patient developed preeclampsia, no significant relationship has been
described between maternal syphilis infection and preeclampsia.[17] Given the patient's history of chronic hypertension and preeclampsia in a prior
pregnancy, this instance likely represents a disease process independent of maternal
syphilis infection.
Conclusion
This case underscores the importance of routine maternal syphilis screening as per
Centers for Disease Control and Prevention recommendation is imperative.[1]
[2]
[3] Repeat third trimester syphilis screening may have saved the life of this fetus
because the first trimester screen had not resulted when the decision to send this
follow-up screen was made.[18] Furthermore, this case supports the idea of a fetal JHR in the setting of fetal
heart rate tracing abnormalities after penicillin administration. Additionally, this
case lends support to the idea that complete in utero recovery from fetal syphilis
infection and prevention of congenital syphilis are possible with penicillin treatment.
