Maternal and perinatal outcomes in high compared to low risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection (phase 2): the World Association of Perinatal Medicine working group on coronavirus disease 2019.

BACKGROUND: It has still to be ascertained whether severe acute respiratory syndrome coronavirus 2 infection in pregnancy is associated with worse maternal and fetal outcomes compared to low risk gestations. OBJECTIVE: This study aimed to evaluate maternal and perinatal outcomes in high- and low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: This was a multinational retrospective cohort study involving women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection from 76 centers from 25 countries in Europe, the United States, South America, Asia, and Australia from April 4, 2020, to October 28, 2020. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit, use of mechanical ventilation, or death. The secondary outcome was a composite measure of adverse perinatal outcome, including miscarriage, fetal loss, neonatal and perinatal death, and admission to the neonatal intensive care unit. All outcomes were assessed in high- and low-risk pregnancies. Pregnancies were considered high risk in case of either preexisting chronic medical conditions in pregnancy or obstetrical disorders occurring in pregnancy. The Fisher exact test and logistic regression analysis were used to analyze the data. RESULTS: A total of 887 singleton pregnancies who tested positive for severe acute respiratory syndrome coronavirus 2 infection using reverse transcription-polymerase chain reaction of nasal and pharyngeal swab specimens were included in the study. The risk of composite adverse maternal outcomes was higher in high-risk pregnancies than in low-risk pregnancies (odds ratio, 1.52; 95% confidence interval, 1.03-2.24; P=.035). In addition, women carrying high-risk pregnancies were at higher risk of hospital admission (odds ratio, 1.48; 95% confidence interval, 1.07-2.04; P=.002), presence of severe respiratory symptoms (odds ratio, 2.13; 95% confidence interval, 0.41-3.21; P=.001), admission to the intensive care unit (odds ratio, 2.63; 95% confidence interval, 1.42-4.88), and invasive mechanical ventilation (odds ratio, 2.65; 95% confidence interval, 1.19-5.94; P=.002). When exploring perinatal outcomes, high-risk pregnancies were at high risk of adverse perinatal outcomes (odds ratio, 1.78; 95% confidence interval, 0.15-2.72; P=.009). However, such association was mainly because of the higher incidence of miscarriage in high-risk pregnancies compared with that in low-risk pregnancies (5.3% vs 1.6%, P=.008); furthermore, there was no difference in other explored outcomes between the 2 study groups. At logistic regression analysis, maternal age (odds ratio, 1.12; 95% confidence interval, 1.02-1.22; P=.023) and high-risk pregnancy (odds ratio, 4.21; 95% confidence interval, 3.90-5.11; P<.001) were independently associated with adverse maternal outcomes. CONCLUSION: High-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection were at higher risk of adverse maternal outcomes than low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection.

Creating and validating a warfarin pharmacogenetic dosing algorithm for Colombian patients.

PURPOSE: Warfarin is an oral anticoagulant associated with adverse reaction to drugs due to wide inter- and intra-individual dosage variability. Warfarin dosage has been related to non-genetic and genetic factors. CYP2C9 and VKORC1 gene polymorphisms affect warfarin metabolism and dosage. Due to the central role of populations' ethnical and genetic origin on warfarin dosage variability, novel algorithms for Latin American subgroups are necessary to establish safe anticoagulation therapy. PATIENTS AND METHODS: We genotyped CYP2C9*2 (c.430C > T), CYP2C9*3 (c.1075A > C), CYP4F2 (c.1297G > A), and VKORC1 (-1639 G > A) polymorphisms in 152 Colombian patients who received warfarin. We evaluated the impact on the variability of patients' warfarin dose requirements. Multiple linear regression analysis, using genetic and non-genetic variables, was used for creating an algorithm for optimal warfarin maintenance dose. RESULTS: Median weekly prescribed warfarin dosage was significantly lower in patients having the VKORC1-1639 AA genotype and poor CYP2C9*2/*2,*2/*3 metabolizers than their wild-type counterparts. We found a 2.3-fold increase in mean dose for normal sensitivity patients (wild-type VKORC1/CYP2C9 genotypes) compared to the other groups (moderate and high sensitivity); 31.5% of the patients in our study group had warfarin sensitivity-related genotypes. The estimated regression equation accounted for 44.4% of overall variability in regard to warfarin maintenance dose. The algorithm was validated, giving 45.9% correlation (R 2=0.459). CONCLUSION: Our results describe and validate the first algorithm for predicting warfarin maintenance in a Colombian mestizo population and have contributed toward the understanding of pharmacogenetics in a Latin American population subgroup.