About 5% of babies are born postterm (that is, delivered after 42 completed weeks of gestation). Postterm infants experience more morbidity and mortality than term infants, prompting routine (and expensive) antenatal testing and active management of postterm pregnancies. This article reviews the epidemiology of postterm delivery. A few congenital conditions associated with disruption of the fetal-pituitary-adrenal axis as well as a rare maternal enzyme deficiency have long been identified with postterm delivery. In recent literature, environmental pollution, diet, and pharmaceutical agents have been associated with postterm birth. Very little systematic research has focused on identifying risk factors for this poorly understood birth outcome.
Augmented renal clearance (ARC) has been reported in approximately 30-65% of patients in the intensive care unit (ICU) despite the presence of a normal serum creatinine concentration. In certain ICU patient populations (e.g., patients with sepsis or trauma), the incidence increases to roughly 50-85%. Risk factors for ARC include the following: age younger than 50-55 years, male sex, higher diastolic blood pressure, fewer comorbidities, and a lower Acute Physiology and Chronic Health Evaluation II (APACHE II) or modified Sequential Organ Failure Assessment (SOFA) score at ICU admission. In addition, patient populations with the highest reported incidence of ARC include those with major trauma, sepsis, traumatic brain injury, subarachnoid hemorrhage, and central nervous system infection. Due to the high incidence of ARC in patients with a normal serum creatinine concentration, clinicians should consider screening ICU patients deemed high risk by using the ARC scoring system or the identification and assessment algorithm provided in this review. In addition, an 8-hour continuous urine collection should be considered to assess a measured creatinine clearance for evaluating the necessity of medication dosage adjustments. There is a clear association between ARC and subtherapeutic antibiotic concentrations as well as literature suggesting worse clinical outcomes; thus, the risk of underdosing antibiotics in a patient with ARC could increase the risk of treatment failure. This review examines strategies to overcome ARC and summarizes current pharmacokinetic and pharmacodynamic literature in patients with ARC in an effort to provide dosing guidance for this patient population.
Phthalates are plasticizers that are added to polyvinyl chloride (PVC) products to impart flexibility and durability. They are produced in high volume and generate extensive though poorly defined human exposures and unique childhood exposures. Phthalates are animal carcinogens and can cause fetal death, malformations, and reproductive toxicity in laboratory animals. Toxicity profiles and potency vary by specific phthalate. The extent of these toxicities and their applicability to humans remains incompletely characterized and controversial. Two phthalates, diethylhexyl phthalate (DEHP) and diisononyl phthalate (DINP), have received considerable attention recently because of specific concerns about pediatric exposures. Like all phthalates, DEHP and DINP are ubiquitous contaminants in food, indoor air, soils, and sediments. DEHP is used in toys and medical devices. DINP is a major plasticizer used in children's toys. Scientific panels, advocacy groups, and industry groups have analyzed the literature on DEHP and DINP and have come to different conclusions about their safety. The controversy exists because risk to humans must be extrapolated from animal data that demonstrate differences in toxicity by species, route of exposure, and age at exposure and because of persistent uncertainties in human exposure data. This report addresses sensitive endpoints of reproductive and developmental toxicity and the unique aspects of pediatric exposures to phthalates that generate concern. DEHP and DINP are used as specific examples to illustrate the controversy.
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