RESUMO
OBJECTIVE: To conduct a pilot randomized controlled trial of unfractionated heparin (UFH) in women considered at high risk of placental insufficiency in the second trimester. METHODS: Women with either false-positive first trimester (pregnancy-associated placental protein-A [PAPP-A] < 0.35 MoM) or second trimester (alpha-fetoprotein [AFP] > 2.0 MoM, inhibin > 3.0 MoM, human chorionic gonadotropin > 4.0 MoM) serum screening tests or medical/obstetric risk factors were screened for placental insufficiency by sonographic evaluation of the placenta and uterine artery Doppler between 18 and 22 weeks. Thrombophilia screen-negative women with two or three abnormal test categories were randomized by 23+6 weeks to self-administration of subcutaneous unfractionated heparin (UFH) 7500 IU twice daily until birth or 34 weeks, or to standard care. Maternal anxiety and other maternal-infant outcomes were determined. RESULTS: Thirty-two out of 41 eligible women consented, with 16 women randomized to UFH and 16 to standard care. There was no statistically significant difference identified between the two treatment groups (standard care vs. UFH) for the following: maternal anxiety score (mean [standard deviation]), 14.2 [± 1.6] vs. 14.0 [± 1.8]; birth weight (median [range]), 1795 [470-3295]g vs. 1860 [730-3050]g; perinatal death, 3 vs. 0; severe preeclampsia, 2 vs. 6; placental weight < 10th percentile, 7 vs. 4; or placental infarction, 4 vs. 3. CONCLUSION: Our study design identified women at high risk of adverse maternal-infant outcomes attributable to placental insufficiency. Women with evidence of placental insufficiency were willing to undergo randomization and self-administration of UFH without increased maternal anxiety.
Assuntos
Anticoagulantes/administração & dosagem , Heparina/administração & dosagem , Insuficiência Placentária/tratamento farmacológico , Adulto , Ansiedade/etiologia , Estudos de Viabilidade , Feminino , Humanos , Injeções Subcutâneas , Pessoa de Meia-Idade , Ontário , Projetos Piloto , Insuficiência Placentária/diagnóstico por imagem , Gravidez , Resultado da Gravidez , Segundo Trimestre da Gravidez , Autoadministração/psicologia , Resultado do Tratamento , Ultrassonografia Doppler , Ultrassonografia Pré-NatalRESUMO
OBJECTIVES: Screening studies for trisomy 21 demonstrate that low maternal serum pregnancy-associated plasma protein-A (PAPP-A) at 11-13 weeks' gestation is associated with stillbirth, intrauterine growth restriction (IUGR) and pre-eclampsia in chromosomally normal fetuses. However, the strength of these associations is too weak to justify screening for these placental insufficiency syndromes. Our objective was to evaluate placental size and uterine artery (UtA) Doppler imaging as second-stage screening tests for women with low PAPP-A. METHODS: We prospectively studied 90 normal singleton pregnancies with first-trimester PAPP-A = 0.30 multiples of the median. Maternal serum alpha-fetoprotein (AFP) at 15-18 weeks' gestation, and second-trimester placental size and UtA Doppler indices were assessed as predictors of pregnancy outcome. RESULTS: The risks of IUGR, preterm delivery before 32 weeks' gestation and stillbirth were significantly associated with small placental size (relative risk (RR), 3.96; 95% CI, 2.21-5.98; RR, 3.96; 95% CI, 2.21-5.98; and RR, 6.44, 95% CI, 2.74-14.54, respectively) and elevated AFP (RR, 3.67; 95% CI, 1.78-7.71; RR, 2.48; 95% CI, 1.23-4.94; and RR, 5.14; 95% CI, 1.66-16.85, respectively), but not with abnormal UtA Doppler indices. The combination of elevated AFP and small placental size further increased the risk of IUGR (RR, 4.88; 95% CI, 2.88-5.31), delivery before 32 weeks' gestation (RR, 4.25; 95% CI, 2.38-4.98) and stillbirth (RR, 7.44; 95% CI, 3.04-3.75). CONCLUSIONS: Small placental size and elevated AFP, but not UtA Doppler indices, identify women with low PAPP-A at high risk of IUGR, extreme preterm delivery and stillbirth. These additional screening tests may directly improve perinatal outcomes in women with low PAPP-A.