Hydrops fetalis caused by congenital syphilis: An ancient disease?

Background

Treponema pallidum can be transmitted sexually or from mother-to-child in utero. Although most women with maternal syphilis are asymptomatic, more than 50% of untreated cases have poor pregnancy outcomes, including early fetal death, stillbirth, preterm birth, low birth weight, neonatal death, and congenital infection.^1,2

In 2007, the World Health Organization (WHO) launched a global initiative for the control of mother-to-child syphilis transmission. In 2008, it was estimated that 1.36 million maternal syphilis infections caused 520,095 adverse pregnancy outcomes. In 2012, four years after the global initiative, a decrease of the global burden of maternal syphilis and congenital infection was observed: 930,000 maternal syphilis infections caused 350,000 adverse pregnancy outcomes. Nevertheless, in developed countries, the number of cases is rising.^1,3–5

Data from the National Statistics Institute of Spain shows that the cases per 100,000 inhabitants have tripled in the last 20 years, while in 2003 the case rate was 0.25:100,000 live births, in 2007 it was 2.23:100,000 live births. ⁴

European and American guidelines recommend testing T. pallidum serology between 12 and 14 weeks of pregnancy.^6–8 Only women with risk factors (drug addiction, multiple sexual partners, HIV infection, history of fetal death greater than 20 weeks), or those who develop symptoms suggestive of syphilis (non-immune fetal hydrops) should undergo repeated serology in second and/or third trimesters of gestation.

We report a case of severe congenital syphilis in order to emphasize that, currently, fetal infection still occurs, and that current prenatal care screening may not be accurate enough.

Case presentation

The present case was the fourth gestation of a Hispanic woman aged 23 years old, with a background of two previous miscarriages of unknown cause and a healthy son. The current pregnancy was managed in a primary care center, and first-trimester serology blood tests, including nontreponemal (NTTs) rapid plasma reagin (RPR) tests for syphilis, were negative. At 31 weeks and 4 days of gestation the routine ultrasound showed hydrothorax, ascites, and short long bones; therefore the patient was referred to our hospital.

An amniocentesis was performed in order to rule out intrauterine infections (cytomegalovirus, Toxoplasma, parvovirus, enterovirus and syphilis), and QF-PCR and array-CGH to rule out achondroplasia and hypochondroplasia. After the amniocentesis, preterm rupture of membranes was observed. For that reason, steroids (in order to promote lung maturity) and antibiotic prophylaxis with ampicillin, gentamicin and azithromycin were started. In the subsequent hours, the patient developed a rash and uterine contractions, which was thought to be an allergic reaction. An urgent caesarean section was performed at 32 weeks of gestation due to an altered cardiotocographic record.

A male of 2510 g of birth weight was born with severe hydrops and bloody nasal secretions that required advanced resuscitation. Apgar test score was 2/3/6. He presented with umbilical cord artery pH of 6.98. At the neonatal intensive care unit, high-frequency oscillatory ventilation was started. Lymphocytic liquid was obtained from the drainage of a left pleural effusion. Empirical antibiotic therapy with ampicillin and cefotaxime was started from the first hour of life. The infant presented high pulmonary hypertension that required maximum inotropic drugs and nitric oxide. He also presented acute kidney failure, disseminated intravascular coagulation and massive hepatocellular necrosis. At 48 h of life, the multiorgan failure triggered an intraventricular hemorrhage with a massive hemorrhagic stroke in the left cerebral lobes (Figure 1). In agreement with the family, withdrawal of cardio-respiratory support was decided.

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Figure 1.

Postmortem MRI. Intraventricular hemorrhage grade IV is observed.

In order to elucidate the hydrops etiology, many studies were performed: serologies and PCR of infectious agents (parvovirus, enterovirus, cytomegalovirus, and Trypanosoma cruzi), hemoglobinopathies, first line of inborn metabolic disorders and skeletal dysplasia. After neonatal death, syphilis maternal seroconversion was reported (nontreponemal, Venereal Disease Research Laboratory [VDRL] 1:64, IgG and IgM anti-T. pallidum positives). Congenital syphilis was confirmed by a positive VDRL test in cerebrospinal fluid obtained postmortem.

A postmortem skeletal X-ray revealed specific signs of syphilis with radiolucent central areas and sclerotic rims (Figure 2). Treponemas were not found in the necropsy, probably due to the effect of ampicillin treatment. Later on, the father disclosed he had genital lesions compatible with syphilis.

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Figure 2.

Postmortem X-ray. Radiolucent lines in bone epiphysis and sclerotic rims are observed.

Conclusion

Congenital syphilis should be a long forgotten disease since it is preventable with an early detection together with penicillin treatment of infected women. ⁹ In the present case, the negative of maternal first trimester serology, the apparent absence of risk factors for sexually transmitted infections, and the critical status of the newborn made it difficult to properly interpret the classical signs of congenital syphilis such as the fetal hydrops, premature delivery, the Jarisch–Herxheimer reaction and the hemorrhagic rhinitis.

The negative RPR test in the first trimester was most likely due to acquisition of infection during late pregnancy. We did not find causes of a possible false negative RPR test in the mother. It is important to remember that negative screening does not exclude the diagnosis. Bone signs were not detected in initial X-rays, since they were focused on the thorax and abdomen. On postmortem X-ray, bone lesions in the typical areas were observed clearly (Figure 2). Despite the delay in neonatal diagnosis, treatment with ampicillin was started promptly, and the infant outcome would probably not have changed. The misdiagnosis and undertreatment of pregnant women can lead to serious adverse outcomes. Clinicians should be prepared to obtain a thorough history and explore symptoms of early syphilis in women and their sexual partners and consider re-screening later in pregnancy. Standards of prenatal care in developed countries should be reconsidered in order to enable early diagnosis and treatment of women with syphilis seroconversion during pregnancy. Sometimes cases can be missed with only one nontreponemal (RPR) test in the first trimester. For this reason, we suggest repeating the screening in areas with high prevalence of this infection and in cases where there is a suspicion of infection during the pregnancy after the negative initial screening, especially if the mother and/or their sexual partner report risk behaviors or develop clinical symptoms. On the other hand, obstetricians should raise awareness to enable rapid diagnosis when a pregnant woman presents with classical fetal syphilis signs.