Managing Infections in Pregnancy

Yves Villel Marianne Leruez-Ville

Disclosures

Curr Opin Infect Dis. 2014;27(3):251-257. 

In This Article

Toxoplasmosis

Nonimmune pregnant women may acquire toxoplasma infection, with a 10–100% risk of transmission to the baby through transplacental transmission of the parasite. Risks of transmission to the baby are higher later in pregnancy, but manifestations in the infant are less severe. However although congenital infection in early pregnancy is rare, it can lead to miscarriages, stillbirths or the birth of children with signs of central nervous system involvement, such as hydrocephalus, meningoencephalitis and retinochoroiditis. However, retinochoroiditis can appear and relapse anytime after birth. Systematic education and serological screening of pregnant women are the most reliable and currently available strategies for the prevention, diagnosis and early treatment of the infection in the offspring because toxoplasmosis in pregnant women most often goes unrecognized. One recent monocentric study has applied homogeneous selection criteria and the same biological techniques to determine the date of maternal contamination. Probabilities of congenital infection were less than 10% for maternal infections before 12 weeks of gestation, rose to 20.0% at 19 weeks, and 52.3% and almost 70% at 28 and 39 weeks, respectively. Overall, the probability of clinical signs at 3 years was 22%, one-third being detected after the age of 1. Long-term follow-up is therefore essential in order to control a somewhat unforeseeable evolution, and the prognosis remains generally good.[24] Treatment of the infection during the first year of life has been demonstrated to significantly improve the clinical outcome.

Seroprevalence and Epidemiological Consequences of Screening Policies

Incidence and prevalence of Toxoplasma infection have markedly decreased during the last 30 years, at least in Europe. This decrease may be explained by a lower exposure to the parasite by changes in food habits and by improved hygiene practices in meat production. In France, when combining data of 42 208 women in three national perinatal surveys (NPS) and choosing the age of 30 for modelling, the incidence decreased from 7.5/1000 susceptible women in 1980 to 3.5/1000 in 2000 and 2.4/1000 in 2010. The observed incidence of seroconversion during pregnancy in NPS in 2010 was estimated at 2.1/1000 susceptible pregnant women (95% CI 1.3–3.1). The predicted incidence and prevalence for 2020 were 1.6/1000 and 27%, respectively.[25] The same trend was reported in the UK. Seroprevalence was significantly higher in non-UK born women and in heavily mixed populations with different toxoplasma prevalence and risk behaviours; individual risk assessment may be favoured and toxoplasma screening could be justified according to risk. Epidemiological surveillance of congenital toxoplasmosis needs to be improved in order to determine the true burden of the disease and to assess the effectiveness of and the need for existing prevention programmes. In Europe, only four countries report the surveillance of congenital toxoplasmosis: Italy, Denmark, France and Germany.[26,27]

There is a lack of evidence regarding knowledge of risk factors for toxoplasmosis and the impact of this knowledge on prevention. A systematic review recently showed that 90% of women seem to know about the risks of infection through consumption of raw beef and unwashed salad and 80% are aware of the risk with handling of cat litter. As far as preventive behaviours were concerned, although 90% report washing vegetables and fruits eaten raw, only 50% know that washing hands after handling raw meat helps prevent infection and only 25% report washing their hands following potential contaminant exposure. Furthermore, there is very little evidence from RCTs that prenatal education is effective in reducing congenital toxoplasmosis, although evidence from observational studies suggests it is.[24,25,28]

From Neonatal Treatment to Prenatal Management

There is consensus that infected infants should be treated with pyrimethamine and sulfadiazine for 6–12 months.

Amniocentesis seems advisable following primary infection because the performance of real-time PCR techniques that target the 529-bp DNA fragment of Toxoplasma gondii is excellent and a negative result is associated with a low likelihood that infection has occurred. A positive PCR result means that pyrimethamine–sulfonamides treatment can be offered and ultrasound monitoring can be intensified. When severe foetal lesions are detected, termination can be contemplated. Another reason for identifying infected foetuses before birth is to enable postnatal treatment to be initiated early after birth.[24]

Although spiramycin and pyrimethamine–sulfonamides are reportedly well tolerated and nonteratogenic, we still do not know whether treating infected mothers with spiramycin, pyrimethamine–sulfonamides or a combination of these antiparasitic drugs is more effective than no treatment at reducing the incidence of foetal infection. Current recommendations are based on clinical experience rather than evidence. Among 1438 pregnant women with primary infection identified as a result of screening, those treated within 3 weeks showed a weak benefit compared with treatment started after 8 or more weeks (OR 0.48, P = 0.05). Among 550 infected infants identified by perinatal screening, prenatal treatment did not significantly reduce the risk of clinical symptoms in infected infants (OR for treated vs. not treated 1.11, 95% CI 0.61–2.02). Only a large randomized controlled clinical trial would provide clinicians and patients with valid evidence of the potential benefit of prenatal treatment.[29] Furthermore, treatment may save the pregnancy without preventing infection in the neonate and lead to an increase in congenital disease.[30] This, however, does not seem to be the case. In one study, there was a significant reduction in risk since 1992 when monthly screening was introduced (59.4 vs. 46.6% at 26 weeks of gestation; P = 0.038) and a better outcome at 3 years of age in infected children while applying prenatal treatment both to prevent vertical transmission and to treat infected foetuses.[24]

Although these fundamental questions are not subjected to any appropriately designed RCT, a randomized phase-3 trial is currently comparing the efficacy and tolerance of prenatal therapy with pyrimethamine and sulfadiazine vs. spiramycine to reduce vertical transmission of T. gondii following primary infection in pregnancy. Prenatal diagnosis with amniocentesis is offered after 18 weeks gestation and 4–6 weeks after the maternal infection (NCT01189448 in clinicaltrials.gov).

Influenza

One systematic review and meta-analysis of 33 observational studies suggests that first trimester maternal exposure to influenza is associated with an increased risk of nonchromosomal congenital abnormalities [adjusted OR (AOR) 2.00, 95% CI 1.62–2.48], broadly distributed and including neural tube defects (3.33, 2.05–5.40), hydrocephalus (5.74, 1.10–30.00), congenital heart defects (1.56, 1.13–2.14), cleft lip (3.12, 2.20–4.42), gastrointestinal tract anomalies (1.72, 1.09–2.68) and limb reduction defects (2.03, 1.27–3.27). The most likely mechanism could be hyperthermia in the embryonic period. However, these pregnancies have also been exposed to influenza-related medication. Furthermore, the observational studies gathered in this review could be subject to limitations such as confounding, retrospective maternal exposure reports and nonresponse of intended participants.[31]

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