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Cancer during pregnancy associated with stillbirth, neonatal mortality
Women who had cancer either during pregnancy or in the year after pregnancy faced a greater risk for neonatal mortality and stillbirth, according to researchers in Sweden.
“Cancer during pregnancy is a rare event,” Donhao Lu, MD, of the department of medical epidemiology and biostatistics at Karolinska Institutet, Stockholm, and colleagues wrote. “Whether prenatal exposure to a maternal malignancy and its treatment during pregnancy impair fetal development and neonatal health is, however, of great clinical concern.”
Lu and colleagues reviewed national health registries in Sweden to examine 3,947,215 single births between 1973 and 2012. The researchers defined exposure to cancer as maternal cancer diagnosed during pregnancy (n = 984), or cancer diagnosed during the year after pregnancy (n = 2,723).
The researchers compared exposed births with unexposed births to calculate incidence rate ratios (IRR) for stillbirths and infant mortality. Incidence of small-for-gestational age births and preterm births served as secondary outcomes.
Maternal cancer during pregnancy appeared associated with stillbirth (IRR = 2.5; 95% CI, 1.2-5). This consisted mainly of stillbirths assessed as small for gestational age (IRR, 4.9; 95% CI, 2.2-11). Maternal cancer also appeared associated with preterm small-for-gestational age births (RR = 3; 95% CI, 2.1-4.4).
Both maternal cancer during pregnancy and the year after pregnancy associated with neonatal mortality (IRR = 2.7; 95% CI, 1.3-5.6 during pregnancy; IRR = 2; 95% CI, 1.2-3.2 the year after pregnancy) and preterm birth (IRR = 5.8; 95% CI, 5.3-6.5 during pregnancy; IRR = 1.6; 95% CI, 1.4-1.8 the year after pregnancy). The researchers attributed the association with preterm birth to iatrogenic, rather than spontaneous, preterm birth. Overall, preterm birth accounted for 89% of the association between maternal cancer during pregnancy and neonatal mortality.
“Maternal cancer diagnosed during pregnancy was associated with increased risks [for] stillbirths assessed as small for gestational age and preterm small for gestational age live birth, suggesting that cancer and its treatment during pregnancy may impair fetal growth,” Lu and colleagues wrote. “Careful monitoring of fetal growth and cautious decision-making on the choices, as well as the timing of preterm delivery, should therefore be reinforced in these pregnancies.” – by Andy Polhamus
Disclosure: Lu reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
Perspective
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The report byLu and colleagues represents a thoughtfully designed and impressively executed study aimed at answering a highly significant clinical question: Is maternal cancer during pregnancy associated with stillbirth and infant mortality? The researchers also examined important secondary outcomes, including small for gestational age and preterm birth. Prior to this report, limited data were available on this topic. The large, nationwide, cohort study by Lu and colleagues examined nearly 4 million births in Sweden over nearly 4 decades. This study is the first of its kind, highlighting an underappreciated risk in the pregnant patient with cancer: morbidity and mortality in her offspring.
Among the nearly 4 million births examined, approximately 3,700 births occurred in the context of a maternal cancer. When looking at birth outcomes, the researchers distinguished between maternal cancer diagnosed during pregnancy — for which the mothers may have been treated during pregnancy — and those diagnosed the year following pregnancy, largely without cancer treatment during pregnancy. Investigators found an association between maternal cancer diagnosed during pregnancy and stillbirths — primarily small-for-gestational-age stillbirths — and preterm live births that were small for gestational age. This indicated that cancer and cancer-directed treatments during pregnancy may impair growth of the fetus. Maternal cancer diagnosed during and in the year following pregnancy both appeared associated with neonatal mortality, or infants dying within the first 27 days of life, and preterm births. Most of the preterm births were iatrogenic, or medically recommended. Importantly, among patients diagnosed with cancer during pregnancy, preterm birth explained 89% of the association of maternal cancer during pregnancy with neonatal mortality. These iatrogenic preterm births may have occurred, for example, in order to speed up cancer treatment. However, the fact that preterm birth and neonatal mortality were also seen with maternal cancer diagnosed after pregnancy suggests that cancer may have effects on the fetus.
This important work by Lu and colleagues underscores the importance of close monitoring of fetal growth and thoughtful decision-making of the timing of planned preterm delivery in pregnant women with cancer, because preterm delivery can be associated with a previously unappreciated degree of neonatal mortality. Maternal cancer during pregnancy is associated with risks for both the mother and her offspring. Joint and careful consideration on the part of oncologists and obstetricians is critical to achieve the best possible health outcomes.