Safety of preventive acetylsalicylic acid use in patients at high risk for major obstetrical syndromes

Introduction. Prophylactic use of low-dose acetylsalicylic acid (ASA) is widely implemented in pregnant women at high risk for major obstetrical syndromes (MOS); however, the safety profile of the drug regarding fetal and neonatal outcomes remains a subject of ongoing scientific debate.

Aim: to conduct a comparative analysis of obstetric and perinatal outcomes following preventive ASA use in high-risk patients, while evaluating its efficacy in preeclampsia (PE) and fetal growth restriction (FGR) preventing and assessing safety of antenatal exposure on the fetus and neonate.

Materials and Methods. This retrospective case-control study enrolled 236 mother-infant pairs stratified as follows: main group consisted of pairs in which 136 patients at high risk for PE and/or FGR received 150 mg of ASA daily. This cohort was subdivided into two overlapping subgroups: 103 and 77 mothers predisposed to PE and FGR, respectively, including cases with combined risks. In control group, 100 pairs with general population risk profile not receiving ASA were enrolled.

Results. Preventive ASA therapy demonstrated high clinical efficacy, with incidence of FGR in target subgroup (n = 77) comprising 2.6 %, which corresponds to general population levels. In the at high PE risk (n = 103), the rate of its manifestation was 25.2 %, with all cases presenting exclusively as late-onset PE. No statistically significant differences were observed regarding obstetric blood loss volume or incidence of neonatal intraventricular hemorrhage, including cases of preterm birth. Notably, 6 cases of hypospadias were verified in male subgroup of the study cohort (7.0 % vs. 0,0 % in the control group; p = 0.088), which exceeds the standard population rate (0.2–0.8 %).

Conclusion. The initiation of low-dose ASA therapy within the recommended gestational window (12–16 weeks) in high-risk patients provides effective prevention against early-onset PE and FGR, without increasing hemorrhagic risks for either the mother or the fetus. However, the observed elevation in hypospadias incidence above the general population level suggests a potential vulnerability in urethrogenesis during the second trimester, thereby justifying a need for conducting further large-scale cohort studies.

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