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Impact of maternal brain tumours on perinatal and maternal management and outcome: a single referral centre retrospective study

European Journal of Obstetrics & Gynecology and Reproductive Biology, pages 132 - 136

Abstract

Objective

To evaluate the impact of maternal brain tumours on perinatal and maternal management and outcome.

Study design

We performed a retrospective cohort study in a single referral centre with departments of obstetrics, neurology, and neurosurgery from January 2003 to July 2011. Cases were retrieved from our hospital databases, excluding pituitary adenomas, metastasis, and vascular tumours. Postnatal follow-up was of at least 6 months. Studied parameters were tumour type, gestational age at diagnosis if applicable, neurological events, obstetrical complications, pregnancy outcome, mode of delivery, peripartum analgesia, need for specific treatments, and maternal morbidity and mortality.

Results

20 women (23 pregnancies) diagnosed with a brain tumour. Overall, there were 4 terminations of pregnancy, 4 elective premature caesarean deliveries, 15 live births ≥37 WG (9 caesarean and 6 vaginal deliveries), and 4 maternal deaths within 6 months postpartum. The brain tumour was diagnosed during pregnancy in 7 cases (group A), before pregnancy with preconception counselling in 10 (group B), and before pregnancy without preconception counselling in 6 (group C). In group A, there were 1 termination of pregnancy (TOP), 3 preterm elective caesarean deliveries, 3 live births ≥37 WG with one vaginal delivery, and 2 maternal deaths. In group B, there were 1 elective premature caesarean delivery and 7 live births ≥37 WG with 4 vaginal deliveries. In group C, there were 3 TOP, 3 live births ≥37 WG with one vaginal delivery, and 2 maternal deaths.

Conclusions

Poor perinatal outcome and maternal death were associated with unplanned pregnancies and tumours diagnosed during pregnancy. Vaginal birth with epidural analgesia was nevertheless observed in all groups.

Keywords: Brain tumour, Neurosurgery, Preconception counselling, Vaginal delivery, Epidural analgesia.

Introduction

Management of a central nervous system (CNS) tumour during pregnancy often presents complex challenges. Population based studies showed that brain tumours are associated with an increased risk of maternal mortality, premature delivery, intra uterine growth restriction (IUGR), and caesarean delivery [1] .

Pregnancy is known to speed-up the growth of meningioma whereas exposure to estrogens might decrease the incidence of gliomas[2], [3], [4], [5], [6], [7], and [8]. Moreover, the literature is very poor in data helping professionals counsel patients and take decisions concerning the mode of delivery and type of analgesia.

In order to improve understanding of obstetrical risks in these patients and to assist with treatment, counselling, and monitoring during delivery, we performed a retrospective study of pregnancies associated with brain tumours managed over a 9-year period in a single centre.

Materials and methods

We searched the database of the department of obstetrics and gynaecology using “brain tumour”, and “neurosurgery”, as key words between January 2003 and July 2011. We excluded pituitary adenomas and vascular tumours. Cases were included regardless of pregnancy or maternal outcome. Obstetrical, neurological, and neurosurgical files were reviewed for the studied parameters.

We stratified our series according to when the tumour was diagnosed, and to whether the women had preconception counselling. This resulted in 3 subgroups: tumour diagnosed during pregnancy (group A), tumour diagnosed before pregnancy with preconception counselling by a neurologist or neurosurgeon and an obstetrician (group B), and tumour diagnosed before pregnancy without preconception counselling (group C).

The following parameters were recorded: tumour type, size, location, gestational age at diagnosis if applicable, treatment before pregnancy neurological events during pregnancy (seizures, intracranial hypertension, neurosurgery), obstetrical complications (premature delivery or IUGR), pregnancy outcome, mode of delivery and analgesia, the need for specific treatments, maternal morbidity and mortality with a postpartum follow up of at least 6 months.

Results

Over the study period, a total of 23 pregnancies were identified, with a wide spectrum of tumour types ( Table 1 ). Median maternal age at the onset of pregnancy was 33.5 years (26–42).

Table 1 Medical history and pregnancy course in women with brain tumour or history of brain tumour.

Pregnancy n° Group WG at diagnosis for group A Maternal age Tumour type Benign/malignant Neurological treatment before pregnancy Treatment at conception Treatment during pregnancy
3 A 25WG 33 Oligodendroglioma grade III Malignant 0 0 Ventricular derivation antiepileptic drugs a and corticosteroids
5 A 39WG 35 Meningioma Benign 0 0 Corticosteroids
7 A 32WG 36 Cerebellopontine angle chondroma Malignant 0 0 Corticosteroids
10 A At onset of pregnancy but symptomatic at 32WG 30 Neurocytoma Malignant 0 0 0
15 A 37WG 26 Arachnoid cyst Benign 0 0 Antiepileptic drugs b
18 A 14WG 38 Glioblastoma Malignant 0 Antiepileptic drugs c Antiepileptic drugs b + d and corticosteroids
21 A 29WG 27 Meningioma Benign 0 0 Antiepileptic drugs b and corticosteroids
1 B   35 Arachnoid cyst Benign 0 Antiepileptic drugs e Antiepileptic drugs e
22 B   37 Arachnoid cyst Benign 0 Antiepileptic drugs e Antiepileptic drugs e
4 B   37 Oligodendroglioma grade II Malignant Chemotherapy (Temozolomide) 0 0
11 B   29 Astrocytoma Malignant Surgery and ventricular derivation 0 Ventricular derivation
13 B   42 Astrocytoma Malignant Surgery Antiepileptic drugs f Antiepileptic drugs f
14 B   35 Oligo astrocytoma grade II Malignant Surgery Antiepileptic drugs g + d Antiepileptic drugs g + d
16 B   34 Neurocytoma Malignant Surgery 0 0
23 B   36 Neurocytoma Malignant Surgery 0 0
17 B   28 Astrocytoma Malignant Surgery 0 0
20 B   32 Neuroepithelial dysembryoplastic tumour Benign Radiotherapy Antiepileptic drugs f Antiepileptic drugs f
2 C   30 Pinealoblastoma Malignant Ventricular derivation 0 Surgery, radiotherapy, antiepileptic h drugs, and corticosteroids
6 C   33 Glioma Malignant Surgery, chemotherapy and radiotherapy 0 0
8 C   32 Glioblastoma Malignant Surgery, chemotherapy and radiotherapy 0 0
9 C   34 Craniopharyngioma Benign 0 0 0
12 C   41 Glioma grade II Malignant Chemotherapy and radiotherapy Chemotherapy (Temozolomide) Chemotherapy (Temozolomide)
19 C   31 Neuroepithelial dysembryoplastic tumour Benign 0 0 0

a Clonazepam.

b Levetiracetam.

c Oxcarbazepine.

d Clobazam.

e Carbamazepine.

f Valproic acid.

g Lamotrigine.

h Phenobarbital.

Pregnancies number 1 and 22, 16 and 23, and 19 and 20 occurred in the same 3 patients within the study period.

The diagnosis of brain tumour was made during pregnancy in 7 women (group A), one in the first, two in the second, and four in the third trimester. Symptoms leading to diagnosis during pregnancy were balance disorder, blurred vision and hearing disorder (patient n°3), diplopia (patient n°5, 7 and 21), headache (patient n°7, 10 and 21), epilepsy (patient n° 15 and 18), and facial paralysis (patient n° 18).

Brain tumour had been diagnosed prior to pregnancy in 16 women (70%). Ten of them had had preconception counselling (group B), and 6 had not (group C).

Overall, there were 4 terminations of pregnancy (TOP) and 19 live births.

The four TOP were motivated by a need for treatment early in pregnancy. Two of these patients died during the follow-up period despite aggressive treatments. One of the other two patients, case n°19, was treated by surgery and radiotherapy and had another pregnancy (case n°20) a year later after preconception counselling with a favourable outcome.

Epidural or spinal anaesthesia was contraindicated in 6 cases, because of intracranial hypertension and risk of brain herniation.

Delivery was achieved by caesarean in 13 cases, either elective (n = 11), or during labour (n = 2). There were 6 spontaneous vaginal deliveries, although 2 were considered to have a contraindication to push. Labour was induced in 5 cases ( Table 2 ).

Table 2 Pregnancy outcome and postpartum in women with brain tumour or history of brain tumour.

Pregnancy n° Group Pregnancy outcome (LB: live birth; TOP: termination of pregnancy) Gestational age at outcome Hospitalization during pregnancy in neuro surgery (days) Mode of delivery Reason for obstetrical intervention Analgesia Maternal post partum course Survival post partum
3 A LB 30 89 Caesarean Urgent maternal treatment Spinal and epidural Transferred to neurosurgery Maternal death (63 days)
5 A LB 39 11 Vaginal spontaneous No specific intervention Epidural Transferred to ICU Survival > 6 months
7 A LB 37 33 Caesarean Risk of brain herniation General anaesthesia Uneventful Survival > 6 months
10 A LB 33 37 Caesarean Risk of brain herniation General anaesthesia Transferred to neurosurgery Survival > 6 months
15 A LB 39 0 Caesarean Fetal distress during labour Epidural Uneventful Survival > 6 months
18 A TOP 17 44 Dilatation and evacuation Urgent maternal treatment General anaesthesia Transferred to ICU Maternal death (40 days)
21 A LB 34 22 Caesarean Risk of brain herniation General anaesthesia Transferred to ICU Survival > 6 months
1 B LB 39 0 Caesarean Risk of brain herniation General anaesthesia Uneventful Survival > 6 months
22 B LB 39 0 Caesarean Risk of brain herniation General anaesthesia Uneventful Survival > 6 months
4 B LB 40 0 Caesarean Failure to progress Epidural Uneventful Survival > 6 months
11 B LB 35 41 Caesarean Risk of brain herniation General anaesthesia Transferred to ICU Survival > 6 months
13 B LB 38 0 Vaginal spontaneous No specific intervention Epidural Uneventful Survival > 6 months
14 B LB 41 0 Vaginal spontaneous No specific intervention Epidural Uneventful Survival > 6 months
16 B LB 39 0 Caesarean Maternal choice Spinal anaesthesia Uneventful Survival > 6 months
23 B LB 39 0 Caesarean Maternal choice Spinal anaesthesia Uneventful Survival > 6 months
17 B LB 41 0 Vaginal spontaneous No specific intervention Epidural Uneventful Survival > 6 months
20 B LB 39 0 Vaginal spontaneous No specific intervention Epidural Uneventful Survival > 6 months
2 C LB 38 158 Vaginal spontaneous No specific intervention Epidural Admitted for radiotherapy Maternal death (77 days)
6 C LB 38 0 Caesarean Scarred uterus General anaesthesia Uneventful Survival > 6 months
8 C TOP 7 7 Dilatation and evacuation Urgent maternal treatment General anaesthesia   Maternal death (178 days)
9 C LB 39 0 Caesarean Breach and pushing contra indication Epidural Uneventful Survival > 6 months
12 C TOP 6 0 Dilatation and evacuation Urgent maternal treatment General anaesthesia Transferred to ICU Survival > 6 months
19 C TOP 17 0 Dilatation and evacuation Urgent maternal treatment General anaesthesia Transferred to ICU Survival > 6 months

There were 4 premature births. All neonates were of appropriate weight for gestational age,i.e.there were no IUGR. One infant was admitted to neonatal care unit, the others remained with their mother in the postpartum ward.

During pregnancy, 10 women were exposed to antiepileptic drugs, 6 to corticosteroids and 3 required neurosurgery (2 ventricular derivation and one brain tumour surgery). Delivery was prompted in 4 patients to allow for postpartum treatment: 3 for surgical procedures (2 ventricular derivation and 1 brain tumour surgery) and one for chemotherapy.

There were 4 maternal deaths. Maternal outcome was favourable in all 19 remaining pregnancies. Six patients required long term antiepileptic drugs.

In our series all four deaths were related to uncontrollable tumour growth. Of the four women who died in the six months after pregnancy, there were one oligodendroglioma, one pinealoblastoma and two glioblastoma. In two of these patients the tumour was diagnosed during pregnancy. One woman in whom the diagnosis was made in the first trimester elected to terminate the pregnancy whereas another patient decided to continue the pregnancy after the diagnosis of tumour had been made at 25 weeks.

Only one patient in our series had chemotherapy during pregnancy for brain tumour. She subsequently had a termination of pregnancy on her demand early in the first trimester of pregnancy. One other patient had radiotherapy alone on the brain and spine during pregnancy, but only down to the cervical spine level, completed down to S1–S2 only after delivery.

Maternal and paediatric outcome were favourable in all women in group B (planned pregnancies). In contrast maternal deaths and premature deliveries occurred in groups A and C ( Table 3 ).

Table 3 Perinatal and maternal outcome comparing plannedversusunplanned pregnancy.

  Group B (planned) n = 10 Groups A and C (unplanned) n = 13
Maternal deaths (<6 months post partum) 0 4
Live births 10 9
TOP 0 4
Elective premature CS 1 3
Trials of labour 6 4
Vaginal deliveries 4 2
Hospitalization in neurological ward during pregnancy 1 8

Comments

The low incidence of brain tumours in a young female population and the wide range of histological types, leading to various treatments and survival rates, are major limits to getting a global image of the maternal and neonatal mortality and morbidity when a brain tumour is diagnosed before or during pregnancy.

In our series, pregnant women with brain tumour had high rates of maternal death (19%), premature delivery (23%), and caesarean birth (56%). In the subgroup with planned pregnancies however, maternal and neonatal outcomes were favourable.

All maternal deaths in our series were directly related to brain tumours. Our methodology is not adapted to study the role of pregnancy on brain tumours, but the natural evolution of the tumours could itself explain our mortality rate.

Our results suggest that the increased prematurity rates observed by Terry et al. [1] might result from iatrogenic prematurity, elective premature delivery being indicated to allow active neurological management in the third trimester.

Short-term maternal mortality was high in our series (19%), but similar to those reported by Isla et al. [9] and Lynch et al. [10] . The size of our series precludes analysing the impact of tumour type on outcome, but mortality rates of up to 50% have been reported in malignant brain tumours associated with pregnancy[1] and [11].

These high mortality rates may be in part related to pregnancy hormones stimulating tumour growth, a phenomenon documented for meningioma[2], [3], [4], [5], [6], [7], and [8]and glioma [12] . When the tumour is diagnosed during pregnancy, the diagnosis may have been delayed, tumour symptoms such as headache or nausea being wrongly attributed to pregnancy.

The numbers in our series are too small to identify an increase risk of IUGR, but we might speculate that the 2.9 OR for IUGR reported by Terry et al. [1] might be related to drug therapy during pregnancy considering that all the neonates in our series were of appropriate weight for gestational age,i.e.there were no IUGR. Patients in our series received relatively few drugs regarding the severity of the medical condition for many of them.

There is very little data in the literature on the mode of delivery and use of spinal or epidural analgesia in labouring women with brain tumours. By describing cases in our series with both vaginal delivery and epidural analgesia, we bring some support for discussion and counselling options.

The findings of our study emphasize the potential benefits of preconception counselling, when the diagnosis of brain tumour is made beforehand. Preconception counselling is recommended for many chronic diseases (cardiac, diabetes, lupus,etc.). It should also be offered to women with brain tumours. In our series, preconception counselling against pregnancy might have avoided the 4 TOP we reported. We are aware, however, that pregnancy outcome is difficult to foresee and that preconception counselling cannot avoid an unpredictable adverse outcome, even when the tumour size is stable, or the tumour seems totally ablated, and the tumour is not expected to be hormone sensitive.

Management of brain tumours in pregnancy emphasizes the importance of providing optimal care for the patients although treatments can interfere with pregnancy [13] . Diagnosis of brain tumour during pregnancy can be a difficult challenge since some symptoms, which are suggestive in the non-pregnant population, are common. Nausea and vomiting can be misdiagnosed as hyperemesis gravidarum [14] . Migraines are common during pregnancy [15] .

The use of antiepileptic drugs during pregnancy is also often a problem. Whenever possible treatment should be optimized before pregnancy and the effectiveness assessed before conception by a neurologist. Monotherapy, with the lowest teratogenic potential drugs are the best option when possible. Valproate and multiple drugs should be avoided whenever possible [16] . Some patients in our series were under drugs that are usually avoided during pregnancy; these drugs were used only after failure of other antiepileptic drugs. Adaptation of drugs was not always done through plasmatic level in our series but the neurologists adapted the treatment on clinical symptoms.

The timing of surgery, when needed, should depend on the situation. When surgery is an emergency procedure, it should be performed irrespective of the gestational age. When timing of surgery is an option, and cannot wait until after pregnancy, the second trimester seems for some authors the best option [13] . When surgery is indicated after 32 weeks of gestation, elective delivery seems a reasonable option to provide optimal care to the mother, due to the favourable neonatal outcome at that gestational age.

The attitude concerning chemotherapy and radiotherapy is similar. It should be provided anytime during pregnancy when maternal health depends on these treatments. Otherwise, after the first trimester of pregnancy, when organogenesis is completed, chemotherapy seems to have little influence on fetal neurological development, but long-term toxic effects are not well evaluated. Brain tumours being rarely chemosensitive, it sometimes seems reasonable to wait until delivery to start chemotherapy[10] and [17].

Overall, poor perinatal outcome and maternal death were associated with unplanned pregnancies and tumours diagnosed during pregnancy. Vaginal births with epidural analgesia were nevertheless observed in all groups. Preconception counselling could help choosing the best time for a woman to become pregnant,i.e.when tumour growth is under control, and regimen have been optimized. A larger prospective study is needed to confirm the positive impact of preconception counselling in women with brain tumours.

Funding

None.

References

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Footnotes

Department of Obstetrics and Gynecology, Groupe Hospitalier Pitié Salpêtrière, Université Pierre et Marie Curie-Paris 6, Paris, France

lowast Corresponding author at: Department of Obstetrics and Gynecology, GH Pitié Salpetrière 83, boulevard de l’hôpital, 75013 Paris, France. Tel.: +33 1 42 17 77 01; fax: +33 1 42 17 77 02.