The estimated screening rate was very good in the outbreak Soest, although the visitors to the farmers market came from various locations in Germany. Conversely, the screening rate in Jena was only 27%. It is important to point out, however, that the screening rate in Soest was calculated using an estimated number of pregnant women exposed. The low screening rate in Jena was probably due to the fact that the information letter did not contain sufficient details regarding the expected benefits of screening and treatment. A recent study on determinants for refusing participation on Q fever screening in pregnancy found a response rate of 56%. Approximately one quarter refused to participate because they had doubts about the side effects of the antibiotic treatment or were afraid of the consequences of participation
. Another reason for the low screening rate in Jena could have been the misconception that C. burnetii infection contracted during pregnancy would always be symptomatic. This, and the frequent request to screen all pregnant women with complications, could have led to a selection of pregnancies with complications or concomitant diseases. Our rate of 27% (3/11) of symptomatic women compared to 10% (1/10) in a previous study corresponds to preselection
However, we found no obvious association between C. burnetii infection and negative pregnancy outcome, although 73% (8/11) of the women did not receive the recommended cotrimoxazole therapy of at least five weeks
. The woman that was treated with clarithromycin for the entire pregnancy gave birth to a newborn with syndactyly. Syndactyly is a common fetal malformation (approximately 1 of 200 births) and several genetic disorders can cause this disease
. Given the high incidence of the disorder and the consequent treatment of the mother, Q fever as causative agent appears to be unlikely but cannot be ruled out.
The woman treated for Q fever pneumonia with erythromycin/clarithromycin for three weeks, prematurely delivered although all relevant tests were negative for C. burnetii. Given Germany’s premature birth rate of 7% this prematurity could be coincidental. All other women delivered full term without complications.
In contrast to our findings a study, of 53 pregnant women diagnosed with Q fever at the French National Reference Centre for Rickettsioses revealed obstetric complications in 81% of the 37 women without long-term cotrimoxazole therapy
. But the study had a high probability of a bias towards complicated cases.
Published evidence on the association between Q fever and negative pregnancy outcomes is low. A systematic review in 1990 identified only articles with level IV and V evidence
. Of the 84 cases reported in the literature to date, 53 were part of the large case series noted above
A recent large population based study in the Netherlands investigated 1174 serum samples collected by an existing national prenatal screening programme (at the 12th week of pregnancy) and data from the Netherlands Perinatal Registry on diagnosis and outcome. Out of these serum samples, 56 cases with acute C. burnetii infection during pregnancy were identified and no association between C. burnetii infection and preterm delivery, low birth weight or perinatal mortality was observed
. In another comprehensive study with 4588 participants, including 200 seropositive women, they found an association between phase II antibody titre ≥ 1:32 and gestational age ≤ 36 weeks, current or previous neonatal death, and higher parity. C. burnetii was not identified by PCR or culture in the placentas investigated
The agent has been isolated in intact as well as necrotic placentas with immaturity, abortion, maternofetal death and stillbirth
[4, 14, 16, 19–23], but also from normal placentas in undisturbed pregnancies
[21, 24–26]. This suggests evidence against C. burnetii infection posing a high risk to pregnancies. In our study all examined placentas were negative for C. burnetii.
We found C. burnetii in the milk of one woman with serological antibody pattern compatible to chronic infection but no clinical signs. Breastfeeding was stopped and the child had an uneventful follow up. In other reports C. burnetii was found repeatedly in human milk with unclear implications for the breastfed child
[24, 27, 28].
Whether pregnant women have an increased risk of developing clinically apparent chronic Q fever remains unresolved. In the largest case series published, 28 of 53 pregnant women developed a serological profile of chronic Q fever. Three out of these 28 women developed an endocarditis, corresponding to 7% of all included pregnant women
. A follow up study on 1569 acute Q fever cases revealed a development of endocarditis in 12 (0.76%) cases
. This suggests a higher risk for women infected during pregnancy compared with the general population. In our study two patients developed a serological profile of chronic Q fever but none developed clinically apparent chronic Q fever. Altogether our limited data cannot yet give conclusive answers to this question.
Several antibiotics such as cotrimoxazole, ciprofloxacine, azithromycin, rifampicin, clarithromycin, doxycycline, erythromycin and tifomycin have been given to treat Q fever in pregnancy. The only study investigating antibiotic treatment of Q fever in pregnancy found that long-term cotrimoxazole therapy prevented obstetric complications (p=0.009). However, patients (n=16) who presented with obstetric complications at the time of diagnoses did not receive the long-term cotrimoxazole therapy. Investigating only the 37 women with no complications at the time of diagnoses, the efficacy of long-term cotrimoxazole therapy to prevent IUFD was less significant (0.047). Nevertheless, administration for all pregnant women with proven Q fever was recommended
. Even under cotrimoxazole therapy C. burnetii was detected in the placenta in some cases
[4, 16, 25]. Cotrimoxazole is a folic acid antagonist that inhibits deoxyribonucleic acid synthesis by interfering with the production of folic acid. Exposure to it during pregnancy appears to be associated with an increased risk of small-for-gestational-age newborns, preterm births, cardiovascular and neural tube defects
[30–33]. Additional folinic acid supplementation has a strong effect in the reduction of preterm birth and defects of the neural tube