Cervical cancer, leukaemia survivors face heightened risks during pregnancy

Pregnancies in women who have survived cervical cancer or leukaemia should be considered high-risk due to the potential for multiple severe obstetric complications, as reported in a study.

In The Teenage and Young Adult Cancer Survivor Study (TYACSS) cohort, a total of 21,437 births were recorded among 13,886 female survivors, which was lower than expected (observed-to-expected ratio, 0.68, 95 percent confidence interval [CI], 0.67–0.69; p<0.0001). [Lancet Oncol 2024;25:1080-1091]

“Survivors of cervical cancer had one of the lowest birth rates of all survivors of cancer (observed-to-expected ratio, 0.42, 95 percent CI, 0.40–0.44; p<0.0001), and those who gave birth were at a higher risk of a whole range of obstetric complications [relative to the general population],” the investigators said.

Specifically, there was an excess risk of malpresentation of the foetus during labour (standardized incidence ratio [SIR], 1.31, 95 percent CI, 1.11–1.54), obstructed labour (SIR, 1.72, 95 percent CI, 1.38–2.13), disorders of the amniotic fluid and membranes (SIR, 2.49, 95 percent CI, 1.96–3.18), premature rupture of membranes (SIR, 1.57, 95 percent CI, 1.38–1.78), preterm delivery (SIR, 2.74, 95 percent CI, 2.44–3.08), placental disorders (SIR, 1.53, 95 percent CI, 1.09–2.15) including placenta praevia (SIR, 1.60, 95 percent CI, 1.09–2.33), and antepartum haemorrhage (SIR, 1.45, 95 percent CI, 1.05–2.00).

Survivors of leukaemia also had a large deficit in births (observed-to-expected ratio, 0.42, 95 percent CI, 0.40–0.44; p<0.0001) and were likewise at risk of several obstetric complications, the investigators noted.

The risk of preterm delivery (SIR, 1.50, 95 percent CI, 1.11–2.02) was elevated, as was that of obstructed labour (SIR, 1.65, 95 percent CI, 1.05–2.58), postpartum haemorrhage (SIR, 1.25, 95 percent CI, 1.00–1.56), and retained placenta and membranes (SIR, 1.97, 95 percent CI, 1.06–3.66).

“Survivors of all other specific cancers had no more than two obstetric complications that exceeded an observed-to-expected ratio of 1.25 or more, providing reassurance for almost all survivors of adolescent and young adult cancer concerning their risks in pregnancy,” the investigators said.

The analysis included 200,945 individuals who received a diagnosis of any of 17 specific types of adolescent and young adult cancer at age 15–39 years and survived for a minimum of 5 years. A total of 27 specific obstetric complications were ascertained using the English Hospital Episode Statistics database. The median follow-up duration was 11.9 years.

The toll of cancer treatments

The biological mechanisms underlying the increased risk of multiple obstetric complications in survivors of cervical cancer and leukaemia are complex and not fully understood, according to the investigators. For cervical cancer survivors, while advancements in treatment have improved fertility outcomes, fertility-sparing procedures including radical trachelectomy can introduce new risks such as cervical incompetence or scarring or stenosis of the cervix, which in turn contribute to the risk of obstetric complications. [Fertil Steril 2016;106:1195-1211.e5; J Clin Med 2023;12:2614]

For leukaemia survivors, the link to obstetric complications is less clear. However, the investigators pointed to the involvement of exposure of the uterus to total body irradiation as part of hematopoietic stem cell transplantation. This exposure, they said, may induce fibrotic changes or affect muscular or vascular functioning of the uterus, potentially increasing the risk of complications during pregnancy and childbirth. [JCI Insight 2023;8:e163704]

“We provide important evidence to inform the development of clinical guidelines for the management of pregnancies among women with a history of adolescent and young adult cancer, particularly for survivors of cervical cancer and leukaemia, because current formal guidelines are absent,” the investigators said. 

Given the observed risk of several serious obstetric complications, pregnancies in women with a history of cervical cancer or leukaemia require close medical monitoring and specialized care, they added.