Neonatal Outcomes among Fetuses with an Abdominal Circumference <3rd %ile and Estimated Fetal Weight 3rd to 9th %ile Compared to Fetuses with an EFW <3rd %ile.

OBJECTIVE: Fetal growth restriction (FGR) is defined as an estimated fetal weight (EFW) or abdominal circumference (AC) <10th percentile (%ile) for gestational age (GA). An EFW <3rd %ile for GA is considered severe FGR (sFGR). It remains unknown if fetuses with isolated AC <3rd %ile should be considered sFGR. Our primary objective was to assess composite neonatal outcomes in fetuses with an AC <3rd %ile and overall EFW 3rd to 9th %ile compared with those with an EFW <3rd %ile. STUDY DESIGN: This retrospective cohort study was undertaken at a tertiary academic center from January 2016 to December 2021. Inclusion criteria were singleton fetuses with an EFW <3rd %ile (Group 1) or AC <3rd %ile with EFW 3rd to 9th %ile (Group 2) at 28 weeks' gestation or greater. Exclusion criteria were multiple gestations, presence of a major fetal anomaly, resolution of FGR, genetic syndrome, or infection. Composite neonatal outcome was defined by any of the following: neonatal intensive care unit admission >48 hours, necrotizing enterocolitis, sepsis, respiratory distress syndrome, mechanical ventilation, retinopathy of prematurity, seizures, intraventricular hemorrhage, stillbirth, or death before discharge. Small for gestational age (SGA) was defined as birth weight <10th %ile for GA. RESULTS: A total of 743 patients fulfilled our study criteria, with 489 in Group 1 and 254 in Group 2. The composite neonatal outcome occurred in 281 (57.5%) neonates in Group 1 and 53 (20.9%) in Group 2 (p < 0.01). The rates of SGA at birth were 94.9 and 75.6% for Group 1 and Group 2, respectively (OR 5.99, 95% confidence interval 3.65-9.82). CONCLUSION: Although AC <3rd %ile with EFW 3rd to 9th %ile is associated with a lower frequency of SGA and neonatal morbidity than EFW <3 %ile, fetuses with AC <3 %ile still exhibited moderate rates of these adverse perinatal outcomes. Consideration should be given to inclusion of an AC <3rd %ile with EFW 3rd to 9th %ile as a criterion for sFGR. However, prospective studies comparing delivery at 37 versus 38 to 39 weeks' gestation are needed to ensure improved outcomes before widespread adaptation in clinical practice. KEY POINTS: · The composite neonatal outcome occurred in 57.5% of fetuses with an overall EFW <3rd %ile and 20.9% of fetuses with an AC <3rd %ile but EFW 3rd to 9th %ile.. · Both groups demonstrated a high positive predictive value for SGA birth weight.. · Consideration should be given to inclusion of an AC <3rd %ile as a criterion for sFGR..

Utility of VerifyNow to assess the immediate pharmacodynamic response of chewed and swallowed aspirin: comparison with aggregometry.

VerifyNow (VN) test is a less laborious method to assess pharmacodynamics (PD) compared to light transmittance aggregometry (LTA). VN assay has not been used to study the immediate PD effects of acetylsalicylic acid (ASA). Ten healthy volunteers were randomly assigned to a single 162 or 650 mg dose of chewed and swallowed ASA. Pharmacodynamic and pharmacokinetic measurements were performed at baseline and serially up to 60 min after ASA administration. Onset by VN was 20 ± 7 min with 162 mg and 13 ± 7 min with 650 mg ASA (p = .07). Onset by 1 mM AA-induced PA was 13 ± 12 min with 162 mg and 7 ± 3 min with 650 mg ASA (p=NS). VN correlated with AA-induced PA (r = 0.80, p < .001) and serum TxB2 levels (r = 0.76, p < .001). 95% inhibition of serum TxB2 was achieved at 38 ± 22 min and 22 ± 8 min with the 162 and 650 mg ASA, respectively (p = .08). The onset and extent of the antiplatelet effect of 650 mg ASA is numerically faster and greater than the 162 mg dose. VN identifies the onset, extent, and dose response to ASA therapy. The ease of using VN should facilitate multicenter PD investigations of ASA.

Aspirin (acetylsalicylic acid) is an important drug widely used to prevent adverse ischemic events in patients with cardiovascular disease. Platelet aggregation and thromboxane B₂ levels in blood samples by complex laboratory methods are used to assess platelet response to aspirin. VerifyNow assay is a simple laboratory test that has not been used to assess the immediate effect of aspirin. In this study, conducted in 10 healthy volunteers, we compared the immediate platelet response to aspirin by serially assessing platelet aggregation by aggregometry and VerifyNow assay, and thromboxane B₂ levels. We also measured plasma levels of acetylsalicylic acid and salicylic acid. Our study demonstrated that the VerifyNow Aspirin test identifies the onset, extent, and dose-response to aspirin therapy. The ease of using the VerifyNow test should facilitate multicenter pharmacodynamic investigations of aspirin.

Early assessment of the pharmacokinetic and pharmacodynamic effects following acetylsalicylic acid loading: toward a definition for acute therapeutic response.

Despite decades of investigations, the optimal assessment of the "therapeutic response" to early after loading dose of acetylsalicylic acid (ASA) remains unclear. Limited information is available on the relation between pharmacodynamic (PD) and pharmacokinetic (PK) measurements assessed immediately after ASA administration. Serial PD and PK analyses were performed immediately after a single 162 or 650 mg dose of chewed and swallowed ASA in ten healthy adults. ASA response was defined as > 95% inhibition of serum thromboxane (Tx)B2, < 550 aspirin reaction units (ARU) by VerifyNow Aspirin (VN) test, and ≤ 20% arachidonic acid (AA)-induced platelet aggregation (PA). Correlation analyses between PK and PD measurements and receiver operating characteristic (ROC) curve analyses were performed. ASA response measured by VN test and AA-induced PA was achieved within 30 min of ASA administration. A correlation was observed between ARU and AA-induced maximum PA (r = 0.69, p < 0.001), serum TxB2 (r = 0.74 and p < 0.001), and serum TxB2 inhibition (r = 0.79, p < 0.001). In ROC curve analyses, ≤ 558 ARU and ≤ 7% AA-induced PA were associated with > 95% inhibition of TxB2. 686 ng/ml plasma ASA cut-off point was associated with > 95% inhibition of serum TxB2, ≤ 7% 1 mM AA-induced PA, and ≤ 585 ARU. A modest ~ 50% inhibition of TxB2 inhibition was associated with marked inhibition of 1 mM AA-induced platelet aggregation by LTA. Our analyses demonstrated important relationships between pharmacodynamic, and pharmacokinetic parameters measured immediately following oral ASA and cutoff values for ARU and AA-induced PA that is associated with > 95% inhibition of serum TxB2.