Two Australian case reports highlight infant management following infection in pregnancy, an area severely lacking evidence-based guidance.
Many believe the potential risk of bacterial transmission from mother to infant warrants the recommendation to avoid breastfeeding their newborn.
While Coxiella burnetii, the causative bacteria for Q fever, has previously been found in human breastmilk, no definitive cases of infant Q fever have ever been reported.
With the theoretical evidence base and the lack of definitive guidance around whether or not an infected mother should breastfeed, optimal management of infants has never been established, and no consensus guidelines exist.
While best practice is mostly guided by the occasional case reports of Q fever in pregnancy, authors of a recent case report series published in Emerging Infectious Diseases said that there was minimal discussion of infant management in prior case studies, leaving a large knowledge gap and a lack of published evidence.
C. burnetii, which is found globally except in New Zealand and Antarctica, has a tropism for the placenta in humans and other mammals.
At least half of Q fever infections are asymptomatic, and infection during pregnancy can result in fetal death. Chronic Q fever is rare, but more common in pregnancy due to bacterial replication in the placenta.
The series presented two women with Q fever in pregnancy; one infected in the first trimester and one likely infected several months before conception.
Both women received appropriate antimicrobial therapy (doxycycline in the first trimester, cotrimoxazole until 32-34 weeks’ gestation) and gave birth to healthy infants at term. Both infants were breastfed for at least the first six months without transmission of Q fever.
As C. burnetii is aerosolised and the placenta carries a high bacterial load, additional infection control precautions were prioritised in both births.
“Although transmission precautions at the time of delivery remain key, our experience, as well as review of the literature, provides reassurance for women who wish to breastfeed after Q fever infection during pregnancy,” the authors wrote.
“Given the rarity and paucity of strong scientific evidence, we would advocate that all pregnant persons with Q fever infection be referred to an expert group.”
Case one
A 28-year-old woman was admitted to hospital with fever and headaches at 10 weeks’ gestation. This was her second pregnancy and she was otherwise healthy.
She lived in Brisbane and had not travelled overseas or had contact with cattle or sheep farms. A few months prior to conception, she started working at a pet food cannery, which carried the risk of livestock exposure through the food. She was not immunised, despite Q fever vaccination being recommended for known occupational risk.
At the hospital, her blood serologic testing was nonreactive, and she was prescribed two weeks of empiric doxycycline. However, seroconversion was observed at 24 weeks’ gestation, and PCR performed on the sample from her initial presentation showed C. burnetii DNA.
Retrospective diagnosis of Q fever was made, and cotrimoxazole was prescribed for the period of 25–32 weeks’ gestation.
Routine fetal ultrasound at 20 weeks’ gestation showed no morphologic abnormalities. A third trimester scan found mild shortening of fetal femurs, but was otherwise unremarkable, and blood tests confirmed seroconversion to Q fever.
At 39 weeks’ and six days’ gestation, the woman delivered a healthy baby boy by spontaneous vaginal delivery. He was 2.56kg (3rd percentile) at birth and required a 24-hour admission to the special care nursery for hypoglycaemia.
Phase 2 results of IgM serologic testing on the infant were nonreactive at birth and remained nonreactive when tested on four occasions in his first year. He had high IgG titers at six weeks, but this waned over time, indicating transplacental transfer of maternal IgG rather than infection.
He was exclusively breastfed for the first six months, and continued breastfeeding into the second year of life. His growth parameters tracked into the 80th percentile and he has shown no clinical signs of Q fever infection.
C. burnetii was still detected in the mother’s blood at the time of delivery, and serologic titers in the postpartum period increased. The bacteria werealso detected in the placenta, but not in the cord blood or breastmilk.
Placental histopathology showed acute chorionitis and chorionic vasculitis. The inflammatory infiltrate contained multinucleated giant cells and areas of focal but marked necrosis beneath the chorionic plate. There were also focal features of chronic villitis.
Importantly, there was no necrotising villitis or placental abscess formation, findings that differ from previously reported cases of Q fever–associated placentitis in Queensland.
Serologic testing of the mother remained strongly positive with a chronic infection profile, but she elected not to undertake doxycycline therapy postpartum.
Her echocardiogram at three months postpartum was normal and further imaging evaluations (e.g., fludeoxyglucose-18 positron emission tomography or computer tomography) were not conducted. She was informed of the risks of repeat placental infections and advised to contact her infectious disease physician before future pregnancies.
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Case two
This involved a 30-year-old woman living on a dairy farm who had four previous viable births.
She tested positive for C. burnetii DNA at eight weeks’ gestation as part of a public health investigation, and known exposure had occurred two months earlier when she aided in the delivery of a calf.
At the time of positive PCR, serological testing showed reactive phase 2 and phase 1 IgG and IgM – similar to blood test results from four months prior. Notably, retrospective PCR also found C. burnetii DNA in this previous sample. Q fever serology from 10 years earlier was negative.
Given this, the exact timing of infection was unclear, but the patient was diagnosed with chronic/persistent focalisd Q fever infection in pregnancy and began doxycycline until 13 weeks’ gestation, followed by cotrimoxazole with folic acid supplementation up to 34 weeks’ gestation.
There were no morphologic abnormalities detected and the pregnancy was otherwise uncomplicated. Serologic tests for Q fever remained positive throughout.
A healthy baby boy was born by induced vaginal delivery at 37 weeks’ gestation with a birth weight of 2.51kg (2nd percentile). He was breastfed for the first eight months and remained well. His growth parameters tracked on the 10th to 25th percentile and showed no serological evidence of acquiring Q fever. IgM nonreactive and IgG were nonreactive by six months of age.
C. burnetii DNA was not detected in the placenta or breastmilk (tested on four occasions throughout the first six months) and placental histology showed no signs of acute or chronic infection.
The mother’s phase IgG remained elevated in the nine months postpartum that were documented (1:320 at most recent testing).
There are maternal and neonatal toxicity considerations in antimicrobial treatment in women with Q fever infection in pregnancy.
Doxycycline is considered safe in pregnancy until 18 weeks’ gestation, and the US Centers for Disease Control and Prevention guidelines recommend ceasing cotrimoxazole at 32 weeks.
“Many physicians, including ourselves, recommend continuing to 36 weeks or until delivery,” the authors wrote.
“Of note, the cessation of cotrimoxazole at 32 weeks in case one might have contributed to blood PCR positivity at the time of birth and subsequent higher maternal serologic titers.
“Although doxycycline has been shown to have superior anti-Coxiella activity than cotrimoxazole, until further safety data are available on doxycycline’s use during the second and third trimesters, we recommend doxycycline until week 16 followed by cotrimoxazole until delivery.”
The researchers also noted that published case reports have selection bias, as asymptomatic infections in uncomplicated pregnancies were unlikely to be assessed for Q fever. Acknowledging this limitation, they concluded that there was no evidence of congenital Q fever syndrome.
While there have been two documented cases of placental transmission, where C. burnetii was detected in aborted fetuses, babies born to infected mothers have shown no signs or sequelae of in utero infection.
“After the birth of an infant to a parent with Q fever in pregnancy, we recommend histologic examination and PCR testing of the placenta; clinical, serologic, and PCR monitoring of mother and infant for a period of six months to one year; and, if feasible, serial PCR testing of breastmilk,” the authors wrote.
“Our second case also demonstrates the potential for Q fever to develop chronicity or recrudescence after preconception acute infection, likely reflecting Coxiella burnetii’s tropism for uterine tissue.
“As such, close observation for Q fever in pregnancy should also be recommended for any cases of acute Q fever in the period three–six months before conception. Reactivation of Q fever in subsequent pregnancies has also been described.”
