Fetal Infection and Teratogens

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Chapter 7

Fetal Infection and Teratogens

Fetal Infection

Case 1 A 24-year-old woman is referred for detailed ultrasonographic examination at 17 weeks’ gestation because biochemical serum screening predicted a 1 in 40 risk for Down syndrome. Ultrasonographic examination reveals two intracranial lesions, which are suspected to be calcifications, and mild fetal hydrops.

Intracranial calcifications with or without fetal hydrops are strongly suggestive of an infectious cause such as toxoplasmosis, cytomegalovirus, herpes simplex virus or varicella. Intracranial calcifications are seen rarely in the setting of an inherited disorder.

Serologic testing of the mother is ordered to look for evidence of parvovirus B19 and TORCH infections (toxoplasma, rubella, cytomegalovirus, herpes simplex virus), and an amniocentesis is performed. The fetal karyotype is normal. The results of serologic tests reveal positive toxoplasma IgG and IgM. Serology for parvovirus B19, rubella, cytomegalovirus, and herpes simplex virus shows evidence of past infections. The woman reports no medical problems during the pregnancy. She has cats at home and changes a litter box. She gardens without gloves.

Primary toxoplasmosis infections are usually asymptomatic in a pregnant woman. The patient has serologic evidence of a toxoplasmosis infection and has associated risk factors. Whether the woman has had a recent toxoplasmosis infection or one in the distant past cannot be determined from the results of her serology. IgM antibodies appear early in acute toxoplasmosis infection but can persist for longer than a year. Besides intracranial calcifications, other features of toxoplasmosis embryopathy that may be evident in utero in the second trimester include hydrocephalus, cataracts, microcephaly, hepatosplenomegaly, hydrops, and intrauterine growth restriction. For cases such as this woman’s where routine serology cannot distinguish between an acute or previously acquired infection, an algorithm for further and more complex serologic testing at a specialized laboratory such as the Palo Alto Medical Foundation Toxoplasma Serology Laboratory is recommended. Establishing the timing of the infection will influence decisions about whether to initiate maternal drug treatment and pursue diagnostic testing of the fetus.

The risk of congenital infection is dependent on gestational age at the time of seroconversion with risks of about 6%, 40%, and 72%, depending on whether seroconversion occurs in the first, second, or third trimester, respectively. However, among fetuses with congenital infection, the probability of developing clinical features of toxoplasmosis embryopathy and the severity of those features before age 3 years is inversely correlated with gestational age at the time of maternal seroconversion with risks of 60%, 25%, and 9% for maternal infections acquired in the first, second, or third trimesters, respectively.

Invasive testing by amniocentesis to test for the toxoplasma organism in amniotic fluid by polymerase chain reaction is recommended when maternal serology suggests a recently acquired infection and when fetal ultrasonographic examination reveals abnormalities suggestive of or consistent with toxoplasmosis embryopathy. Decisions regarding invasive testing for immunosuppressed women who are at risk for reactivation of a latent toxoplasmosis infection must take into account the underlying maternal disease state as HIV infection may be a contraindication to amniocentesis.

The results of maternal serology performed in a reference laboratory confirms the evidence for an acute toxoplasmosis infection in the mother. Polymerase chain reaction testing of amniotic fluid is positive for toxoplasma DNA, confirming a fetal infection. The woman is informed that the fetus has a significant chance of suffering from complications of a congenital toxoplasmosis infection. The woman plans to continue the pregnancy.

Treatment with antibiotics has been shown to be effective in reducing the probability of maternal to fetal transmission and in reducing the severity of abnormalities in affected fetuses. In general, recommendations for treatment of women in whom toxoplasmosis is confirmed or suspected to have been acquired during the pregnancy will be influenced by the gestational age at which the maternal infection was acquired and the results of molecular testing for toxoplasma DNA in amniotic fluid. Because maternal treatment can be associated with both maternal and fetal toxicity, experts in the management of acute toxoplasmosis infections should be consulted. In the United States, two sources are the Palo Alto Medical Foundation Toxoplasma Serology Laboratory and the US National Collaborative Treatment Trial Study in Chicago.

Further Reading

1. Montoya JG, Remington JS (2008) Management of Toxoplasma gondii infection during pregnancy. Clinical Infectious Diseases 47:554–66.

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Jul 31, 2016 | Posted by in OBSTETRICS | Comments Off on Fetal Infection and Teratogens
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