Critical appraisal:Reulen RC, Zeegers MP, Wallace WH, Frobisher C, Taylor AJ, Lancashire ER, et al 2009

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Critical Appraisal

Article being appraised

Reulen RC, Zeegers MP, Wallace WH, Frobisher C, Taylor AJ, Lancashire ER, et al. Pregnancy outcomes among adult survivors of childhood cancer in the British Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev 2009 Aug;18(8):2239-47 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19661083.


Applicable clinical question

Key Facts

Study Design

cohort study

Study aims:

(1) quantify the risk of adverse pregnancy outcomes in survivors of childhood cancer in relation to cancer type and treatment, and (2) to assess live birth rates relative to the general population

Number of Patients:

10483

A questionnaire including questions enquiring about pregnancy outcomes was completed by 10,483 survivors of childhood cancer (who were at least 16 years of age). A total of 7,300 pregnancies were reported. Compared to general population of England & Wales.


Data from the British Childhood Cancer Survivor Study (BCCSS) - a large-scale cohort study that examines the late-effects of treatment of childhood cancer Dx between 1940-1991 in Britain, and survived >= 5years.
Reported outcome(s):

live birth, miscarriage, termination, stillbirth, premature birth, and low birth weight

Results of outcome(s):

-Of 10,483 survivors 31% sired at least one pregnancy (n=3,244) resulting in a total of 7,300 pregnancies. - -6,634 singleton pregnancies, of which 4,113 in female survivors and 2,521 by partners of male survivors.
-Of the 4,113 singleton pregnancies among female survivors 72.9% resulted in a live birth, 14.8% in a miscarriage, 11.8% in a termination, and 0.6% in a still birth. Of the 2,885 live born offspring for whom birth weight was known, 9% (n=262) had a low birth weight and of the 2,586 live births for whom the gestational week was known, 14% (n=368) were born prematurely.

FEMALE SURVIORS:
-exposed to abdominal irradiation had a significantly increased OR of delivering preterm (OR=3.2, 95%CI:2.1-4.7). Overall, 28.7% of survivors treated with abdominal irradiation reported a preterm birth versus 10.5% for survivors not treated with any radiotherapy. Abdominally irradiated Wilms’ tumour survivors demonstrated a 3.5-fold OR (95%CI:2.1-5.7) of delivering preterm relative to survivors treated without radiotherapy.
-exposed to abdominal irradiation had a significantly increased OR of producing offspring with a low birth weight (OR=1.9, 95%CI:1.1-3.2) adjusted for premature delivery. When those abdominally exposed were separated according to Wilms’/ non-Wilms’ then the OR for the Wilms’ group (OR=2.3, 95%CI:1.2-4.6) was significantly (p=0.03) greater than the non-Wilms’ group (OR=1.6, 95%CI:0.9,3.0). The percentage of offspring having a low birth weight for women exposed to abdominal irradiation was 22.3% versus 7.6% for women not exposed to irradiation. The latter percentage is comparable to
the 7-8% observed in the general population of England and Wales.
-An increased OR of miscarriage was also associated with abdominal radiotherapy (OR=1.4, 95%CI:1.0-1.9).
-heritable retinoblastoma had significantly increased odds of terminating a pregnancy relative to leukaemia survivors (OR=2.1, 95%CI:1.1-3.7).
-For all combined, number of live births was 2/3 of that expected (O/E=0.64, 95%CI: 0.62-0.66). Survivors of CNS tumours (O/E=0.50, 95%CI: 0.46-0.54) and heritable retinoblastoma (O/E=0.49, 95%CI:0.40-0.61) produced only half the live births expected. Live births was smallest in Hodgkin’s lymphoma (O/E=0.88, 95%CI:0.78-0.99) and non-heritable retinoblastoma survivors (O/E=0.81, 95%CI: 0.69-0.94). Survivors treated with abdominal or brain radiotherapy each produced almost 50% fewer offspring than expected (O/E=0.55, 95%CI:0.50-0.61; O/E=0.52, 95%CI: 0.48-0.56, respectively). Although at all ages female survivors produced fewer offspring than expected, the deficit decreased with increasing maternal age (p-trend<0.001).

MALE SURVIORS:
-Of 2,521 singleton pregnancies, 80.2% resulted in a live birth, 11.8% in a miscarriage, 7.5% in an termination, and 0.5% in a still birth.
-6% (n=113) of the 1,776 live born offspring for whom birth weight was known had a low birth weight, and 13.5% (n=202) of the 1,498 live born offspring for whom gestational week was known were born prematurely.

Comments on results:

- based on self-report (potential for under-reporting or recall bias)
- some missing data
- treatment between 1940-1991 (so old Tx protocols?)


Evidence ratings

Level of evidence

III-3

Risk of bias
High risk of bias Comments: Although from a registry, this was a questionnaire based study - with a 71% response rate - so potential for selection bias etc.
Result of appraisal

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Completed by

Dr Jessica Harris

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Article
Reulen RC, Zeegers MP, Wallace WH, Frobisher C, Taylor AJ, Lancashire ER, et al. Pregnancy outcomes among adult survivors of childhood cancer in the British Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev 2009 Aug;18(8):2239-47 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19661083.
Assigned to
User:Michelle.peate
Topic area
Guidelines:COSA:Cancer fertility preservation guidelines/Impact of cancer on fertility
Clinical question
Form
Form:Critical appraisal


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