Perinatal outcomes for infants exposed to systemic cancer treatment during gestation: a systematic review and meta-analysis.
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OBJECTIVES: The incidence of cancer diagnosed during pregnancy is increasing, but data relating to perinatal outcomes for infants exposed to systemic cancer treatment in utero remain limited. This systematic review and meta-analysis aimed to synthesise evidence from the available literature to investigate whether perinatal outcomes for babies born to women with gestational cancer differ based on whether they are exposed to systemic cancer treatment in utero. DESIGN: A systematic review was conducted according to PRISMA-P guidelines. We extracted raw data from the eligible studies to calculate ORs and 95% CIs for perinatal outcomes reported in the included studies. DATA SOURCES: A comprehensive search of Medline, Embase, Cochrane Library and CINAHL databases identified studies published between January 2001 and May 2025. ELIGIBILITY CRITERIA: Studies were eligible for inclusion in the review that reported on both a study group (women with gestational cancer who received systemic therapy during pregnancy) and a comparison group (women with gestational cancer who did not receive systemic therapy during pregnancy). DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data. Perinatal outcomes included spontaneous abortion, pregnancy termination, intrauterine growth restrictions (IUGR), stillbirth, intrauterine foetal death, neonatal mortality, preterm birth (<37 weeks), Apgar score at 5 min, small for gestational age (SGA), low birth weight, congenital anomalies, admission to neonatal intensive care (NICU) and long-term infant and child outcomes (cognitive skill and academic achievement) following systemic therapy. Raw data were extracted from the eligible studies to calculate ORs and 95% CIs for perinatal outcomes, and the ROBINS-I tool was used to assess bias. RESULTS: Five cohort studies (a total of 416 women and 427 neonates exposed to systemic therapy in utero) met the inclusion criteria. Across these studies, a higher rate of preterm birth was consistently observed among exposed neonates compared with those unexposed, with reported ORs ranging from 1.85 to 24.00. Although effect sizes varied and CIs were wide, the overall trend suggests a potential association between in utero exposure to systemic therapy and increased risk of preterm birth. No significant differences were observed in the rates of spontaneous abortion, congenital anomalies, stillbirth, IUGR or SGA births between exposed and non-exposed babies. CONCLUSION: Very few studies have compared outcomes of systemic therapy-exposed and non-exposed babies of women with gestational cancer. These studies are of limited quality. The available evidence suggests that while some studies indicate a possible association between systemic cancer therapy and increased risk of preterm birth, the overall findings should be interpreted cautiously given the small sample sizes, lack of adjusted analyses, and clinical heterogeneity among included studies. Further research is required to better understand the impact of systemic therapy exposure in utero on perinatal outcomes.