Increased risk of preterm birth in pregnant women exposed to chemotherapy during childhood, adolescence, or young adulthood: A systematic review and a network meta-analysis.
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OBJECTIVE: To assess the long-term impact of chemotherapy exposure on pregnancy outcomes in women treated during childhood, adolescence, or young adulthood (CAYA). DATA SOURCES: MEDLINE, Embase, and the Cochrane Library from 1990 to April 2023. METHODS: All studies reporting on pregnancy outcomes in adult females who had received chemotherapy or chemoradiotherapy during CAYA (<25 years) were included. The primary outcome was the live-birth rate. One of the secondary outcomes was preterm birth. For each outcome, a random-effect frequentist network meta-analysis (NMA) was carried out to estimate the risk ratios with 95 % confidence intervals. Sensitivity analyses were conducted by excluding studies at high risk of bias and the leave-one-out method. RESULTS: Eight studies were included in the meta-analysis on live-birth rates: 3,997 females became pregnant, leading to 2,878 live births. The NMA showed moderate heterogeneity or inconsistency (τ2 = 0.012, I2 = 58 % [11 %; 80 %]) and did not show any significant impact of treatments on live-birth rate. Six studies reported a total of 125 preterm births out of 1,976 started pregnancies and were included in the NMA (τ2 = 0.07, I2 = 19 % [0 %; 62 %]). Chemoradiotherapy was significantly associated with a higher risk of preterm birth when compared to the control group (3.44 [1.94; 6.09]) and the chemotherapy group (1.93 [1.19; 3.15]). Chemotherapy alone was associated with a statistically higher risk of preterm birth compared to the control group (1.78 [1.01; 3.13]). CONCLUSION: Although live-birth rate was similar in pregnant women with a history of CAYA chemotherapy or chemoradiotherapy, preterm birth was significantly increased.