A Screening Strategy for Q Fever Among Pregnant Women
A Screening Strategy for Q Fever Among Pregnant Women
Q fever in the Netherlands is becoming more common. A Q fever infection is a serious threat
 to certain risk groups,including pregnant women. Pregnant women are more often than the
 general population asymptomatic. Studies from France show that an infection with Coxiella
 burnetii may cause obstetric complications including spontaneous abortion, intrauterine fetal
 death, intrauterine growth retardation and oligohydramnios.

 The aim of this study is to assess the effectiveness and cost effectiveness of a
 multidisciplinary screening program, whereby pregnant women in first line healthcare in
 high-risk areas for Q fever are screened with a single blood sample during pregnancy. If
 found positive for Q fever, advise for antibiotic treatment will follow as part of regular
 healthcare. Treatment is therefore not part of the study protocol.

 The results of this study will give more insights in the risks of asymptomatic Q fever in
 pregnancy and the benefits and harms of a screening strategy during pregnancy. This study
 will be used to give an evidence based advice to the Dutch minister of health on screening
 for Q fever in pregnancy.
We will conduct a clustered randomized controlled trial among pregnant women within an area
 of high transmission. The study participants will be recruited by the midwives in high risk
 areas, defined by postal code from the RIVM. To inform the public in this area about the
 study we will publish an article in local newspapers. The midwife centers will be randomized
 to recruit pregnant women for either the control group or the intervention group. The
 pregnant women will receive study information by mail using the midwives patients file. It is
 estimated that approximately 10,000 eligible women live in the areas of transmission. After
 written informed consent, they will start with the strategy for which the midwife center is
 randomized.

 Participants will be asked for a blood sample in their second trimester of pregnancy,
 possibly combined with the routine structural ultrasound around 20 weeks of pregnancy to
 minimize hospital visit. If participants are enrolled in their third trimester, they will
 have their blood sampling as soon as possible after inclusion.

 When taking part in the intervention group the sample will be tested immediately for Q fever.
 If found positive for acute or chronic Q fever, patients have to be referred, according to
 local protocol, to a hospital for further pregnancy monitoring and long-term bacteriostatic
 treatment. Follow-up blood samples are required at 14 days, 3, 6 and 12 months after the
 first blood sampling as part of the standardized control of Q fever disease to diagnose
 possible chronicity of infection. Furthermore, current routine for pregnant women being
 treated with antibiotics against Q fever is to perform monthly blood analyses to monitor
 treatment, and if the serological parameters descend, these controls are brought back to once
 every two months. According to local protocol patients with Q fever have to deliver in
 hospital. After pregnancy serology should be continued with check-ups at 3, 6 and 12 months
 following the current protocol. Furthermore, after delivery a bacteriocide treatment with
 doxycycline or an alternative will be started by the specialist as part of regular health
 care.

 In the control arm the blood samples will be stored, and analyzed for Q fever after delivery.
 If tested positive for Q fever after pregnancy antibiotics could be started if needed as part
 of regular health care.

 At baseline, a questionnaire will be administered to all participants asking about the
 current pregnancy , pregnancy outcome of any previous pregnancies and demographics. Further
 risk factors for pregnancy outcome will also be obtained such as smoking and drinking
 behavior, risk-elevating comorbidities and medication use.

 After delivery all relevant outcome data will be collected by questionnaires filled out by
 the midwife, GP or specialist after delivery, notably the presence of obstetric
 complications. One month after delivery or end of pregnancy, a last questionnaire will be
 administered to the participant to verify potential long-term consequences of Q fever,
 potential loss of income, health-related quality-of-life, fatigue and depressive symptoms.
 Furthermore questions will be asked about the condition of the newborn and risk-accessing
 questions for Q fever infection will be asked.

 In the context of the secondary research questions an extra blood sample will be required,
 and placentas as well as amniotic fluid will be collected after delivery. The latter will
 only take place in a limited number of women and only if they gave birth in a hospital.

 All participants will receive usual care and will be asked to visit the general practitioner
 if symptoms of Q fever occur. He/she will start diagnostic research and treatment or will
 refer the patient to the hospital. Furthermore, both arms have access to an expert team for
 support.
Inclusion Criteria:

 -  being pregnant under first line healthcare

 -  being eighteen years or older

 -  having signed an informed consent form

 -  having a estimated date of delivery between June 1th 2010 en December 31th 2010

 Exclusion Criteria:

 -  unable to fulfill study procedures

 -  absence of informed consent

 -  have been tested positive for Q fever prior to pregnancy

 -  unable to understand Dutch