Trauma in pregnancy remains one of the major contributors to maternal and fetal morbidity and mortality. Potential complications include maternal injury or death, shock, internal hemorrhage, intrauterine fetal demise, direct fetal injury, abruptio placentae, and uterine rupture. The leading causes of obstetric trauma are motor vehicle accidents, falls, assaults, and gunshots, and ensuing injuries are classified as blunt abdominal trauma, pelvic fractures, or penetrating trauma. Many of the assessment and management aspects of obstetric trauma are unique to pregnancy, although initial evaluation and resuscitation should always be maternally directed. Once maternal stability is established, vigilant evaluation of fetal well-being becomes warranted. Continuous fetal heart monitoring, ultrasonography, computed tomography, open peritoneal lavage, and/or exploratory laparotomy may be indicated in a case of obstetric trauma. In view of the significant impact of trauma on the pregnant woman and her fetus, preventive strategies are paramount.
Background
Use of standard adult lopinavir/ritonavir (LPV/RTV) dosing (400/100 mg) during the third trimester of pregnancy results in reduced LPV exposure. The goal of this study was to determine LPV exposure during the third trimester of pregnancy and 2 weeks postpartum with a higher LPV/RTV dose.
Methods
The Pediatric AIDS Clinical Trials Group Protocol 1026s is an ongoing, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving LPV/RTV 400/100 mg twice daily during the second trimester and 533/133 mg twice daily during the third trimester through 2 weeks postpartum. Intensive steady state 12-hour pharmacokinetic profiles were performed during the third trimester and at 2 weeks postpartum and were optional during the second trimester. LPV and RTV were measured by reverse-phase high-performance liquid chromatography with a detection limit of 0.09 µg/mL.
Results
Twenty-six HIV-infected pregnant women were studied. Median LPV area under the plasma concentration-time curve (AUCs) for the second trimester, third trimester, and postpartum were 57, 88, and 152 µg·h−1·mL−1, respectively. Median minimum LPV concentrations were 1.9, 4.1, and 8.3 µg/mL.
Conclusions
The higher LPV/RTV dose (533/133 mg) provided LPV exposure during the third trimester similar to the median AUC (80 µg·h−1·mL−1) in nonpregnant adults taking standard doses. However, the AUC on this increased dose at 2 weeks postpartum was considerably higher. These data suggest that the higher LPV/RTV dose should be used in third trimester pregnant women; that it should be considered in second trimester pregnant women, especially those who are protease inhibitor experienced; and that postpartum LPV/RTV dosing can be reduced to standard dosing by 2 weeks after delivery.
Discordance places twins at increased risk for some adverse perinatal outcomes, whether they are AGA or SGA. Discordance was not an independent risk factor for serious neonatal morbidity or mortality; however, this study was underpowered to detect those differences.
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