Comparing pregnancy outcomes in the exposed and unexposed group, similar rates of miscarriage (22 [1.7%] compared with 16,878 [2.2%]) were recorded in both groups while ectopic pregnancies were more frequent in cancer survivors (38 [2.9%] compared with 6,534 [0.9%], P<.001). More legal termination of pregnancies were performed in the unexposed group (153,233 [20.3%]) compared with the exposed group (145 [10.9%], (P<.001)).
The mean age at delivery was 29 years (SD 5.66) and 26 years (SD 5.62) in the exposed and unexposed groups, respectively (P<.001). More women in the cancer group delivered between 1995 and 2004 (55%) compared with the comparison cohort—most of whom delivered between 1980 and 1989 (54%). The median birth weight and median gestational age of neonates born to the exposed group were 3,360 g (IQR 3,000–3,711 g) and 40 weeks (IQR 23–43 weeks) and in the unexposed group were 3,330 g (IQR 3,000–3,650 g) and 40 weeks (IQR 24–43 weeks) (P=.080 and P=.459, respectively).
Obstetric and perinatal complications in both groups of women are shown in Table 3. The unadjusted odds of preterm premature rupture of membranes, preterm delivery of less than 37 and 34 weeks of gestation, instrumental vaginal delivery (forceps and vacuum extraction), cesarean delivery, and operative delivery overall (abdominal or vaginal) were significantly higher in women with a history of cancer. Rates of induction of labor were not significantly different between the two groups. Of those women who delivered by cesarean, there was no significant difference in the proportion having an elective as compared with an emergency cesarean delivery between the two groups (OR 1.20, 95% CI 0.88–1.65). After adjustment for maternal age and year of delivery, the risk of postpartum hemorrhage, preterm delivery of less than 37 weeks of gestation, instrumental vaginal delivery, and operative delivery (abdominal or vaginal) were each significantly higher in women who had survived cancer. The association with delivery by cesarean was no longer statistically significant; the apparent excess risk being entirely explained by the effects of maternal age and year of delivery.
When simultaneous adjustment was made for all statistically significant confounders and outcomes (maternal age, year of delivery, preterm delivery of less than 37 weeks of gestation, postpartum hemorrhage, operative delivery), postpartum hemorrhage (OR 1.45, 95% CI 1.03–2.12, P=.042) and operative delivery (OR 1.26, 95% CI 1.08–1.47, P=.003) remained significantly higher in the cancer group. Preterm delivery of less than 37 weeks of gestation was no longer statistically significantly different between the two groups (OR 1.30, 95% CI 0.99–1.72, P=.063).
Numbers needed to harm were calculated for those outcomes where the (maternal age and year of delivery) adjusted odds ratios demonstrated statistically significant differences between the exposed and unexposed groups. This calculation estimates that, for every six women with cancer, one additional woman is delivered operatively; every 18 women with cancer results in an additional instrumental vaginal delivery; every 146 results in an extra case of postpartum hemorrhage; and every 46 with cancer leads to one extra preterm delivery.
This study suggests that women delivering their first pregnancies after surviving cancer are older and have a 56% higher risk of postpartum hemorrhage, a 33% higher risk of operative delivery (abdominal or vaginal), and a 33% higher risk of preterm delivery of less than 37 weeks of gestation than their peers.
This study is strengthened by its use of national, routinely collected data which allowed us to generate population-based figures. We are, however, limited by the paucity of data about the precise nature of cancer treatment which precludes subgroup analysis by mode of therapy (surgery, chemotherapy, and radiotherapy) and the small numbers in each group which preclude subgroup analysis by diagnosis. We were unable to adjust for confounders such as smoking, as the data were not available in either of the routine datasets. We were also unable to explore fertility in all survivors of cancer as details of fertility treatment including in vitro fertilization and gamete donation are not routinely available.
All malignant neoplasms have been included in this analysis resulting in a profile appropriate to this age distribution, which includes female survivors of cancer occurring not just in childhood, but up to the end of the reproductive years. While this has resulted in a relatively large proportion of skin cancers, we did not feel it was appropriate to eliminate any specific groups, as we did not have details of treatment on any group to allow us to be selective.
Practice both in oncology and obstetrics has changed substantially over the last 2 decades. Given that the two comparison groups we compared differed substantially in terms of their year of delivery and knowing that the frequency of both pregnancy complications and outcomes have changed over the 25 years covered by this study, we adjusted for year of delivery to alleviate the confounding associated with these temporal effects. In addition, for those outcomes which were shown to be statistically significant, we found no evidence of interaction between exposure and year of delivery.
There are a limited number of studies of pregnancy outcomes among cancer survivors, and many are based on small numbers of women. Female survivors of Wilm’s tumor treated with abdominal irradiation7–10 have been found to be at risk of a variety of reproductive problems, including miscarriage, low birth weight, preterm birth, and increased perinatal mortality rate. While we did not find a significant excess of miscarriage, these are known to be under reported in hospital-based data as many women are not admitted to hospital after such an event.
The largest study to date, the Childhood Cancer Survivor Study followed up 1,915 female survivors of childhood cancer with 4,029 pregnancies (63% resulting in live births) by questionnaire.11 The survivor group were less likely to have their pregnancy result in a live birth than the female sibling comparison group, and the risk of offspring of low birth weight was greater among women who had received pelvic radiation. Further analysis on the births of 2,201 children born to 1,264 female survivors showed these were more likely to be born preterm, but not smaller than the offspring of their siblings.12
A Norwegian study13 based on registry linkage data showed that infants born to women with a cancer history were on average 130 g lighter and delivered 6 days earlier compared with the general population and were more likely to be delivered by cesarean. In our study, the risk of offspring being born preterm showed a 33% increase among the cancer group. The odds ratio estimate remained relatively unchanged after adjusting for maternal age and year of delivery. However, since our analysis had only 50% power to detect an odds ratio of 1.3 as statistically significant, the possibility of a causal association cannot, on this basis, be excluded.
We had no specific prior hypotheses relating to postpartum hemorrhage, but it is of note that this finding cannot be explained by the excess of cesarean deliveries experienced by the cancer survivors group. Both factors were mutually adjusted for in the final model. Since we looked at multiple outcomes, this could be a chance finding. However, blood loss at delivery is often subjectively measured and generally underestimated14,15 and it may be that this finding reflects more accurate measurement in women perceived to be high risk.
Radiotherapy and chemotherapy have been identified as potentially harmful to the reproductive system. The level of damage is dependent on the age at time of treatment, the site and dose of irradiation, or drug regimen.16 Pelvic or abdominal irradiation has been shown to affect uterine volume,17 endometrial thickness, and blood flow18,19 while cranial irradiation may lead to damage to the hypothalamic–pituitary axis.20 While these biological changes after treatment could potentially result in poorer obstetric outcomes, reasons for complications such as postpartum hemorrhage are still largely speculative. A history of cancer also makes these women more likely to encounter increased surveillance and a lower threshold for intervention, as previously noted in other groups perceived as high risk.21,22 Further, the women themselves may see the pregnancy as particularly precious, possibly having considered that they would never achieve childbearing, and so may be less likely to be passive regarding the management of their pregnancy. This would help explain the higher rates of intervention shown in this population even after adjustment for maternal age.
This work provides information for health professionals involved in the effective obstetric management of the increasing numbers of women who become pregnant after treatment for cancer. It also provides data which will help address some of these women’s concerns before and during pregnancy. Understanding the effects of cancer on future childbearing may assist in the strategic targeting of resources to give these women the best care and access to treatment.
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© 2007 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.
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