First-trimester exposure to low-dose warfarin combined with enoxaparin did not significantly increase the risk of developmental delay or other major long-term adverse pediatric outcomes.
Cohort (n=32)
No
Does first-trimester exposure to low-dose warfarin plus enoxaparin improve long-term pediatric outcomes in children born to women with mechanical heart valves compared to enoxaparin alone?
First-trimester exposure to low-dose warfarin combined with enoxaparin in pregnant women with mechanical heart valves does not appear to increase the risk of long-term adverse pediatric outcomes compared to enoxaparin alone.
Absolute Event Rate: 10% vs 0%
p-value: p=0.7
Pregnant women with mechanical heart valves (MHVs) require continuous anticoagulation; however, first-trimester exposure to warfarin raises concerns regarding fetal safety. Data on long-term pediatric outcomes after low-dose warfarin exposure remain limited. This study aimed to evaluate long-term growth, neurodevelopmental, cardiac, and endocrine outcomes in children antenatally exposed to low-dose warfarin combined with enoxaparin, compared with enoxaparin alone. This single-center observational cohort study reports long-term pediatric follow-up outcomes of 32 children born to 30 women with MHVs who were enrolled at one participating center of the multicenter KYBELE study. Maternal data regarding anticoagulant therapy during pregnancy were obtained retrospectively from medical records, while pediatric data were collected through prospective clinical evaluations. Children underwent standardized assessments including physical examination, growth evaluation, Denver II developmental screening, skeletal radiography review, hearing and vision testing, electrocardiography, echocardiography, and thyroid and abdominal ultrasonography. Based on first-trimester anticoagulation regimen, children were classified as enoxaparin only (n = 12), enoxaparin plus warfarin 2.5 mg/day (n = 8), or enoxaparin plus warfarin 4 mg/day (n = 12). The median age at last follow-up was 61.5 months (range 9–168). No child had growth parameters below the 3rd percentile. The overall rate of prematurity was 19%. Although higher in children receiving enoxaparin plus warfarin (2.5 mg or 4 mg/day) compared with those receiving enoxaparin alone, the difference was not statistically significant (p = 0.6). Developmental delay on Denver II screening was identified in 2 of 32 children (p = 0.7), with no significant differences among groups. All children had normal hearing, vision, and thyroid function tests. Minor neonatal echocardiographic findings (e.g., patent ductus arteriosus or patent foramen ovale) were observed in 10 children (31%) and largely resolved during follow-up, with no child requiring cardiac intervention. No skeletal dysplasia or features suggestive of warfarin embryopathy were identified. In this single-center follow-up cohort of live-born children, first-trimester exposure to low-dose warfarin combined with enoxaparin was not associated with signals of major long-term adverse outcomes in growth, neurodevelopment, cardiac status, or thyroid function compared with enoxaparin alone. These findings support cautious use of low-dose warfarin when maternal indications exist, while underscoring the need for larger multicenter studies.
Arici et al. (2026) conducted a cohort in Pregnancies with mechanical heart valves (pediatric outcomes) (n=32). Low-dose warfarin plus enoxaparin vs. Enoxaparin alone was evaluated on Developmental delay on Denver II screening (p=0.7). First-trimester exposure to low-dose warfarin combined with enoxaparin did not significantly increase the risk of developmental delay or other major long-term adverse pediatric outcomes.