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From 2005 to 2010 we identified six episodes of bacterial meningitis in pregnant women (Table 1). Four patients were aged over 35 years and all were multigravida. Gestational age at presentation ranged from 5 to 39 weeks, and pregnancies had been without complications up to the development of bacterial meningitis. Predisposing factors for meningitis were present in five patients and consisted of otitis in four. One patient had remote head injury 5 years before the episode of meningitis for which a craniotomy was performed. Five patients had had symptoms for <24 h and all presented with a decreased level of consciousness. One patient had a 2-week history of malaise and otitis, for which she was treated with oral antibiotics. Neurological examination revealed neck stiffness in all but one.
Table 1. Clinical characteristics and laboratory findings for six pregnant patients with bacterial meningitis
|Characteristics||Patient 1||Patient 2||Patient 3||Patient 4||Patient 5||Patient 6|
|Gestational age at presentation (week)||29||36||5||39||36||37|
|Predisposing factor||Otitis||Otitis||None||Otitis||Remote head injury||Otitis|
|Symptoms on admission|
| Temperature (°C)||39.1||38.9||38.2||38.7||39.3||39.6|
| Neck stiffness||Yes||Yes||Yes||Yes||No||Yes|
| Score on Glasgow Coma Scalea||11||11||13||15||11||13|
| Signs of circulatory shockb||No||No||No||No||Yes||No|
|Computed tomography (CT) brain on admission||Diffuse brain swelling||Diffuse brain swelling||Normal||Mastoid pacification, intracranial air||Remote craniotomy||Normal|
|CSF indexes of inflammation|
| White cell count (per mm3)||200||1213||4500||13300||1930||8688|
| Protein (g/L)||4.2||2.6||2.5||3.9||1.1||2.5|
| Glucose (mM)||<0.1||0.2||0.2||0.1||0.5||<0.1|
| Gram stain||Gram-positive cocci||Gram-positive cocci||Gram-positive cocci||Gram-positive cocci||Gram-positive cocci||Gram-positive cocci|
| Culture||S. pneumoniae||S. pneumoniae||S. pneumoniae||S. pneumoniae||S. pneumoniae||S. pneumoniae|
|Initial antibiotic therapy||Ceftriaxone||Penicillin||Amoxicillin, ceftriaxon||Ceftriaxon||Penicillin||Cefotaxime|
|Complications during admission||Sepsis, brain herniation||Sepsis, brain herniation||None||None||Sepsis, herpes stomatitis||Hemiparesis|
|Maternal outcome||Death||Death||Good recovery||Good recovery||Good recovery||Good recovery|
|Foetal outcome||Preterm birth, good||Good||Miscarriage||Good||Good||Good|
|Mode of delivery||Emergency Caesarean section||Emergency Caesarean section||–||Spontaneous vaginal delivery||Emergency Caesarean section||Emergency Caesarean section|
Lumbar puncture was performed in all patients and CSF analyses were indicative of bacterial meningitis in all patients. CSF-Gram stain of all patients showed Gram-positive cocci and CSF cultures grew penicillin-susceptible Streptococcus pneumoniae. Initial therapy consisted of monotherapy with third-generation cephalosporin in three patients and penicillin in two patients. One patient received a combination of amoxicillin and ceftriaxone. Four patients were treated with adjunctive dexamethasone 4 dd 10 mg QID and one patient was treated with betamethasone for foetal lung maturation.
Complications developed during admission in four patients and consisted of septic shock in two patients (patients 1 and 2). These two patients also developed clinical signs of brain herniation (deterioration of consciousness, bradycardia and fixed and dilated pupils) and died shortly after admission. Cranial computed tomography (CT) showed generalized cerebral oedema in both patients. Time from disease onset to death was <6 h in both patients. The patient presenting with septic shock (patient 5) developed a deterioration of consciousness during admission, but finally recovered without sequelae. Patient 6 developed a left-sided hemiparesis without abnormalities on cranial CT and recovered without sequelae.
Emergency Caesarean section was performed in four patients (gestational age 29, 36, 36 and 37 weeks) and all children were in good health. One patient gave birth to a healthy child 2 days after meningitis was diagnosed. The patient in the first trimester of pregnancy had a miscarriage at 9 weeks gestation, 3 weeks after the meningitis episode. Another specific cause of the miscarriage was not identified. In two of four patients with otitis an otolaryngologist was consulted (patient 2 and 6), who performed paracentesis.
Review of the Literature
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PubMed was searched using Entrez for articles published to 20 September 2010 using search terms ‘bacterial meningitis’ and ‘pregnancy’ in the English, French and German language. Additional studies were identified by a search of references listed in those published studies. The search retrieved 136 studies and 18 were relevant to our review. A total of 42 cases of bacterial meningitis during pregnancy were reported. The most common causative microorganisms were S. pneumoniae (25 cases; 60%) and L. monocytogenes (seven cases; 17%) [7–19]. Pathogens in other cases were Neisseria meningitidis (two), Haemophilus influenzae (one), Group A streptococci (two), Group B streptococci (two), Neisseria gonorrhoea (two) and Pasteurella multocida (one) [20–29].
Six of the 25 cases of pneumococcal meningitis during pregnancy were included in a previous review study , and 15 were reported in a Nigerian case series performed from 1958 to 1962 (Table 2) . Combining these patients with those from our case series, we found the average age was 33 years and all 31 patients were multigravida. Otitis and sinusitis were the most common predisposing conditions, present in nine of 15 reported patients (60%). Five patients presented in the first trimester of pregnancy (17%), eight in the second trimester (27%) and 17 episodes occurred in the third trimester (57%). Overall maternal mortality rate was 28% and 11 pregnancies (37%) resulted in miscarriage, stillbirth or neonatal death. No maternal deaths occurred when pneumococcal meningitis occurred in the first trimester.
Table 2. Patients reported in the literature with pneumococcal meningitis during pregnancy
|Author||Lucas ||Landrum ||Bakaya ||Vives ||Felisati ||Iinuma ||Present study||Total|
|Study period||1958–1962||1962–2006||1967||1996||2004||2007||2005–2010|| |
|Study type||Case series||Case report and review||Case report||Case report||Case report||Case report||Case series||1958–2010|
|No. of cases||15||6||1||1||1||1||6||31|
|Mean age (range)||Not reported||30 (21–38)||31||36||39||30||36 (28–43)||33 (21–43)|
|Predisposing factors||Not reported||1 otitis 1 pneumonia 2 sinusitis||Multiple pneumococcal infections||Sinusitis||Mastoiditis, sinusitis and otitis||None||4 otitis 1 remote head injury||9/16 otitis/sinusitis (56%) 1/16 pneumonia (6%) 1/16 remote head injury (6%) 1/16 pneumococal infections (6%)|
|Gestational age at presentation|
| 1st trimester||3||1||0||0||0||0||1||4 (14%)|
| 2nd trimester||5||1||0||1||0||1||0||8 (28%)|
| 3rd trimester||7||4||1||0||1||0||5||17 (59%)|
|Multigravida||Not reported||All||Yes||Yes||Not reported||Yes||All||All reported|
|Maternal outcome|| || || || || || || ||8 deaths (28%)|
| 1st trimester||3 recovered||1 recovered|| || || || ||1 recovered||5 recovered (100%)|
| 2nd trimester||2 deaths 3 recovered||1 recovered|| ||1 death|| ||1 death|| ||4 deaths (50%) 4 recovered (50%)|
| 3rd trimester||7 recovered||2 deaths 2 recovered||1 recovered|| ||1 recovered|| ||2 deaths 3 recovered||4 deaths (22%) 14 recovered (78%)|
|Foetal outcome|| || || || || || || ||11 deaths (38%)|
| 1st trimester||2 miscarriages 1 term birth||1 term birth|| || || || ||1 miscarriage||3 miscarriages (60%) 2 term births (40%)|
| 2nd trimester||2 miscarriages 2 term births 1 patient died undelivered||1 term birth|| ||1 preterm birth|| ||1 miscarriagea|| ||3 miscarriages (38%) 1 preterm birth (13%) 1 patient died undelivered (13%) 3 term births (38%)|
| 3rd trimester||1 stillbirth 1 neonatal death 1 preterm birth 4 term births||2 neonatal deaths 1 preterm birth 1 term birth||1 term birth|| ||1 preterm birth|| ||1 preterm birth 4 term births||1 stillbirth (5%) 3 neonatal deaths (17%) 4 preterm births (22%) 10 term births (56%)|
We identified seven cases of L. monocytogenes meningitis during pregnancy in the literature (Table 3) [18,19]. The average age of pregnant women with L. monocytogenes meningitis was 26 years. All of the reported cases were diagnosed at the end of the second trimester or at the beginning of the third trimester. One patient was diagnosed with tuberculous meningitis and developed a superinfection with L. monocytogenes . No predisposing conditions for L. monocytogenes infection were identified other than pregnancy. There was a high rate of foetal loss: four of seven (56%) pregnancies ended in neonatal death. There were two maternal deaths (29%).
Table 3. Patients reported in the literature with bacterial meningitis during pregnancy due to microorganisms other than S. pneumoniae
|Causative organism||Neisseria meningitidis [20,21]||Haemophilus influenzae ||Group A streptococci [23,24]||Group B streptococci [25,26]||Listeria monocytogenes [18,19]||Neisseria gonorrhoea [27,28]||Pasteurella multocida ||Total|
|No. of cases||2||1||2||2||7||2||1||17|
|Age (year)||19 and 34||22||33 and 30||27 and 28||26 (average)||21 and 14||35||26 (average)|
|Predisposing factors||1 sinusitis, 1 URI||URI||None||None||1 tuberculous meningitis||None||None||4/17 (24%)|
|Gestational age at presentation|
| 1st trimester||0||0||0||1||0||0||0||1/10 (10%)|
| 2nd trimester||1||0||0||0||All 2nd or 3rd trimester||1||1||3/10 (30%)|
| 3rd trimester||1||1||2||1||1||0||6/10 (60%)|
| Death||1|| || || ||2|| || ||3/17 (18%)|
| Neurological sequelae||1|| || ||1|| || || ||2/17 (11%)|
| Complete recovery|| ||1||2||1||5||2||1||12/17 (70%)|
| Foetal death||1a|| || ||1b||4/7 (57%)a|| || ||6/16 (38%)|
| Preterm birth|| || ||1|| || || || ||1/16 (6%)|
| Term birth||1||1||1||1||3||1||1||9/16 (56%)|
Although meningococcal meningitis is the most frequent cause of invasive disease in adolescents , only two cases of meningococcal meningitis were reported during pregnancy [20,21]. The first patient was a 34-year-old primigravida in her second trimester, presenting with Waterhouse-Friderichsen syndrome . Eight days after admission she delivered a stillborn baby and 1 day later she died. The second case report concerned a 19-year-old primigravida in the third trimester, who developed meningococcal meningitis after an episode of sinusitis . The clinical course was complicated by multiple epileptic seizures, and she recovered incompletely with facial palsy. The child was born healthy at term.
Neisseria gonorrhoeae meningitis during pregnancy was reported in two cases [27,28]. Although most cases of gonococcal meningitis were reported before antibiotics were available, the cases in pregnant women were reported recently (2006 and 2008) . In both cases mother and child were well after treatment.
Meningitis due to H. influenzae, group A and B streptococci, has been described in a few case reports only [22–26]. These microorganisms infrequently cause bacterial meningitis in adults and an increased frequency during pregnancy can not be established. None of these patients had specific characteristics predisposing to bacterial meningitis due to these pathogens. One patient with group B streptococcal meningitis was found to have an ectopic pregnancy during admission for which she received surgery.
One case of Pasteurella multocida meningitis in pregnancy is described . This patient was infected by her cat or dog, in whom P. multocida was cultured from saliva. Pasteurellamultocida is part of the commensal flora of the respiratory and gastrointestinal tracts of cats and dogs, and is not a common cause of infections in humans.
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Bacterial meningitis during pregnancy is an uncommon disease, with substantial mortality for both mother and child. In a 6-year period we identified six cases of community-acquired pneumococcal meningitis during pregnancy in the Netherlands. No episodes of bacterial meningitis due to other microorganisms were found in a nationwide cohort study performed from 2006 to 2009, in which four out of six pneumococcal meningitis episodes were identified . Combining our data with previous reports we found S. pneumoniae in 52% and L. monocytogenes in 16% of bacterial meningitis episodes during pregnancy.
Patients in our cases-series were relatively old compared with previous studies of pneumococcal meningitis during pregnancy [7–17]: four of six women were over 35 years. This is probably explained by the higher age of childbearing in the Netherlands .
All patients in our study and all patients reported after 1962 with pneumococcal meningitis were multigravida, in contrast to meningitis in pregnancy caused by other bacteria. Maternal age and parity have previously not been associated with an increased rate of other pneumococcal infections such as pneumonia . Otitis was found to be the most important risk factor in developing pneumococcal meningitis in pregnant women. Combining our results with previous reports, the incidence of otitis and sinusitis in pregnant patients was 54% . The incidence of otitis and sinusitis during pregnancy is unclear, but has not been reported to be increased compared with the normal population.
A previous study suggested pregnancy to be a predisposing condition for pneumococcal meningitis . However, as B-cell immunity during pregnancy is normal, susceptibility to infections by S. pneumoniae is unchanged . The small number of reported cases in the literature does not support a higher incidence of pneumococcal meningitis in pregnancy. The annual birth rate in the Netherlands is approximately 200 000/year , resulting in an estimated incidence of 0.5 cases of pneumococcal meningitis per 100 000 successful pregnancies. This rate is lower than the overall incidence of pneumococcal meningitis in adults (1.3/100 000) .
In our patients and previous studies pneumococcal meningitis occurring in the first trimester appears to have a relatively good prognosis, as no deaths occurred in a total of five reported patients [7,9,15]. However, miscarriages are common in these women as three of five had spontaneous abortions (60%). The cause of spontaneous abortion in these women was unknown. Miscarriages have been described following other pneumococcal infections such as pneumonia but the incidence and mechanism are unknown . Septic shock and multi-organ failure in the mother have been described as possible mechanisms for foetal death, but these conditions do not apply to the patient in our case series .
In our literature review, we identified L. monocytogenes as the second most common cause of bacterial meningitis during pregnancy [18,19]. Pregnancy has been identified as a risk factor for Listeria monocytogenes infection and maternal infection may result in foetal loss, stillbirth or invasive disease in the newborn . It is estimated that 16% of invasive L. monocytogenes infections occur in pregnant women . Maternal illness is usually mild, and often asymptomatic or self-limited . The mortality rate in pregnant patients with bacterial L. monocytogenes meningitis was, however, substantial, with two deaths in seven patients (29%). This is higher than the 17% described in non-pregnant adults with L. monocytogenes meningitis . The rate of foetal loss was high: in four of seven cases (57%) there was a neonatal death, which is considerably higher than the reported 23% neonatal mortality in L. monocytogenes infections in general .
The incidence of L. monocytogenes meningitis in pregnant women is unclear. In our literature review we identified only seven case reports [18,19]. However, a study of 283 episodes of L. monocytogenes infections, including 128 cases of meningitis and encephalitis, included 15 pregnant women . This study did not specify how many of the pregnant women had meningitis and could therefore not be included in our review. In a nationwide prospective study on L. monocytogenes meningitis none of the included 30 episodes occurred during pregnancy . Although the incidence is probably low, empirical therapy in pregnant women with bacterial meningitis should cover L. monocytogenes based on our literature review.
Pathogens other than S. pneumoniae and L. monocytogenes causing bacterial meningitis during pregnancy are rare and only reported in isolated cases. Some of these cases were associated with specific risk factors, such as sexually transmitted disease (N. gonorrhoea) or exposure to animal saliva (P. multocida). However, no specific risk factors could be identified in meningitis cases due to Group A and B streptococci, H. influenzae and N. meningitidis. No cases of bacterial meningitis during pregnancy due to organisms other than S. pneumoniae were identified in a nationwide prospective cohort study in the Netherlands, including 518 episodes . The risk of meningitis due to organisms other than S. pneumoniae and L. monocytogenes is therefore considered to be very low.
Current standard therapy for bacterial meningitis includes adjunctive dexamethasone . Two out of six patients with pneumococcal meningitis in our study did not receive adjunctive dexamethasone; one patient because of antibiotic use prior to admission and the second patient for unknown reasons. Physicians might be hesitant to administer dexamethasone in pregnant women as it has been associated with oral clefts when administered in the first trimester . In late pregnancy few side effects have been reported and corticosteroids are frequently used to improve foetal lung maturation in impending preterm birth. Because of the beneficial effect of adjunctive dexamethasone on survival in pneumococcal meningitis and its limited side-effects, its use in pregnant woman seems appropriate .
We conclude that bacterial meningitis during pregnancy is rare and mostly caused by S. pneumoniae. Otitis and sinusitis are important predisposing conditions in these patients. Miscarriages are frequent in pregnant women with pneumococcal meningitis in their first trimester. The second most common cause is L. monocytogenes, which is associated with a high rate of neonatal death. Empirical therapy for bacterial meningitis in pregnant women should therefore cover S. pneumoniae and L. monocytogenes. Despite optimal antibiotic treatment bacterial meningitis during pregnancy can have a rapidly fatal outcome for mother and child.