Population Pharmacokinetics of Cefazolin in Serum and Adipose Tissue From Overweight and Obese Women Undergoing Cesarean Delivery.

The optimal antibiotic prophylaxis dosing regimen of cefazolin for cesarean delivery (CD) in overweight and obese women is unknown. This study was done to compare the duration that cefazolin concentrations remain above the minimum inhibitory concentration (MIC) in adipose tissue (AT). Serum and AT concentrations from 3 previous studies in CD patients were comodeled using the nonparametric adaptive grid algorithm in Pmetrics. AT concentrations for 5000 overweight and obese patients receiving 1-, 2-, and 3-g cefazolin regimens were simulated to calculate the probability that free drug concentrations remained above an MIC of 2 µg/mL at 1, 1.5, and 2 hours after administration. Sixty-seven patients (mean body mass index 38.7 kg/m2 ; range 25.5-55.8 kg/m2 ) provided data. A 2-compartment model with 1 of the compartments representing AT fit the data best. Final model parameters were clearance 7.38 ± 5.34 L/h, volume of central compartment 11.8±9.36 L, and AT volume of distribution 80.12 ± 55.47 L. The mean±SD (median) penetration ratio of cefazolin into AT was 0.81 ± 2.06 (0.62). At 1.5 and 2 hours, 1-, 2-, and 3-g regimens achieved AT concentrations above the MIC in 71.2%, 92.4%, and 94.7%, and 55.7%, 86.8%, and 91.7%, respectively, of simulated patients. Cefazolin achieved good penetration into AT. Because CD duration is commonly less than 1.5 hours, a 2-g dose has a high probability of providing AT concentrations above the target pathogens' MIC for overweight and obese females. A second dose may be considered for longer surgeries.

Vasa previa: diagnosis and management.

BACKGROUND: Vasa previa is a rare condition that is associated with a high rate of fetal or neonatal death when not diagnosed antenatally. The majority of available studies are either small, do not include antepartum data, limited to single institutions, or are biased by inclusion of patients from registries and online vasa previa support groups. OBJECTIVE: The purpose of this study was to investigate the diagnostic and management strategies for this potentially catastrophic entity and to describe further maternal and placental risk factors that may aid in the establishment of a screening protocol for vasa previa. STUDY DESIGN: This was a retrospective multicenter descriptive study that included all pregnancies that were complicated by vasa previa that delivered between January 1, 2000, and December 31, 2012. Nine maternal fetal medicine practices and the hospitals in which they practice participated in data collection of diagnosis, treatment, and maternal-neonatal outcomes. RESULTS: Sixty-eight pregnancies were identified that included the diagnosis of vasa previa or "possible vasa previa" either in the ultrasound record or in the hospital record at the time of delivery. Four cases (5.8%) appeared to resolve on repeat ultrasound examination. Fifteen of the 64 cases that were suspected of having vasa previa could not be verified or were not documented at delivery. Of the remaining 49 cases, where vasa previa was documented, 47 cases (96%) were diagnosed by ultrasound scanning antenatally. Known risk factors for vasa previa were present in 41 of 47 cases (87%). Of the 49 cases, 41 were delivered by planned cesarean delivery at a mean gestational age of 34.7 weeks, and 8 cases required emergent cesarean delivery at a mean gestational age of 34.6 weeks (range, 32.4-36.0 weeks gestation). Seven of these emergent cesarean deliveries had been diagnosed previously; 1 case had not. All of the emergent cesarean deliveries were for vaginal bleeding; 1 case was also for a concerning fetal heart rate, but only 1 of the known cases had a documented ruptured fetal vessel. None of these cases were found to have cervical shortening before the onset of bleeding. One of the undiagnosed cases resulted in a ruptured fetal vessel and a baby with no heart beat at birth who survived but had periventricular leukomalacia at 1 month of age with mild white-matter atrophy. Of the remaining neonates in this group, there were no deaths and no major complications beyond mild respiratory distress syndrome in 9 cases. There were no other major neonatal complications, which included no cases of periventricular leukomalacia, neonatal sepsis, necrotizing enterocolitis, or any grade of intraventricular hemorrhage in the confirmed cases of vasa previa. CONCLUSION: This study confirms most current recommendations that include risk-based ultrasound screening, early hospitalization at 30-34 weeks gestation, antenatal corticosteroids at 30-32 weeks gestation, and elective delivery at 33-34 weeks gestation. Thus, with these recommendations for current identification and management of vasa previa in this series of geographically diverse mostly private practice maternal fetal medicine practices, we have confirmed recent reports that show a dramatic improvement in neonatal survival and complications compared with earlier reports.

Placental α-Microglobulin-1 in Vaginal Secretions of Women with Evidence of Preterm Labor.

OBJECTIVE: To evaluate the presence of placental α-microglobulin-1 (PAMG-1) in vaginal secretions in women with symptoms of preterm labor and assess its use as a predictor of preterm birth. STUDY DESIGN: A prospective cohort study of women between 16 and 34 weeks of gestation with symptoms of preterm labor and intact membranes was conducted. The presence of PAMG-1 was determined using a commercially available kit (AmniSure, AmniSure International LLC, Boston, MA). RESULTS: A total of 100 women were enrolled, of which 86 had outcome data available. PAMG-1 was detected in 19/86 (22.1%) subjects. These women were more likely to deliver within 7 days than those without PAMG-1 detected (6/19 [31.6%] vs. 5/67 [7.5%]; odds ratio 5.6; 95% confidence interval 1.5-21.6). These findings persisted after adjusting for potential confounders. The sensitivity was 54.6%, specificity was 82.7%, positive predictive value was 31.6%, and the negative predictive was 92.5%. CONCLUSION: The presence of PAMG-1 is associated with an increased likelihood of delivery within 7 days.

Increased 3-gram cefazolin dosing for cesarean delivery prophylaxis in obese women.

OBJECTIVE: The purpose of this study was to determine tissue concentrations of cefazolin after the administration of a 3-g prophylactic dose for cesarean delivery in obese women (body mass index [BMI] >30 kg/m(2)) and to compare these data with data for historic control subjects who received 2-g doses. Acceptable coverage was defined as the ability to reach the minimal inhibitory concentration (MIC) of 8 µg/mL for cefazolin. STUDY DESIGN: We conducted a 2-phase investigation. The current phase is a prospective cohort study of the effects of obesity on tissue concentrations after prophylactic 3-g cefazolin doses at the time of cesarean delivery. Concentration data after 3-g were compared with data for historic control subjects who had received 2-g. Three grams of parenteral cefazolin was given 30-60 minutes before skin incision. Adipose samples were collected at both skin incision and closure. Cefazolin concentrations were determined with the use of a validated high-performance liquid chromatography assay. RESULTS: Twenty-eight obese women were enrolled in the current study; 29 women were enrolled in the historic cohort. BMI had a proportionally inverse relationship on antibiotic concentrations. An increase of the cefazolin dose dampened this effect and improved the probability of reaching the recommended MIC of ≥8 µg/mL. Subjects with a BMI of 30-40 kg/m(2) had a median concentration of 6.5 µg/g (interquartile range [IQR], 4.18-7.18) after receiving 2-g vs 22.4 µg/g (IQR, 20.29-34.36) after receiving 3-g. Women with a BMI of >40 kg/m(2) had a median concentration of 4.7 µg/g (IQR, 3.11-4.97) and 9.6 µg/g (IQR, 7.62-15.82) after receiving 2- and 3-g, respectively. With 2 g of cefazolin, only 20% of the cohort with a BMI of 30-40 kg/m(2) and none of the cohort with a BMI of >40 kg/m(2) reached an MIC of ≥8 µg/mL. With 3-g, all women with a BMI of 30-40 kg/m(2) reached target MIC values; 71% of the women with a BMI of >40 kg/m(2) attained this cutoff. CONCLUSION: Higher adipose concentrations of cefazolin were observed after the administration of an increased prophylactic dose. This concentration-based pharmacology study supports the use of 3 g of cefazolin at the time of cesarean delivery in obese women. Normal and overweight women (BMI <30 kg/m(2)) reach adequate cefazolin concentrations with the standard 2-g dosing.

Pregnancy outcomes in the super obese, stratified by weight gain above and below institute of medicine guidelines.

OBJECTIVE: To examine the association of antenatal weight gain above and below the 2009 Institute of Medicine (IOM) guidelines in the super-obese population (body mass index [BMI] of 50 or higher) on the maternal and neonatal morbidities of gestational hypertension or preeclampsia (pregnancy-induced hypertension), gestational diabetes mellitus, cesarean delivery, birth weight more than 4,000 g and more than 4,500 g, low birth weight, and preterm birth. METHODS: The effect of gestational weight gain was assessed in this retrospective cohort study using California birth certificate and patient discharge diagnosis data. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) as a function of antenatal weight gain. Weight gain within 2009 IOM guidelines (11-20 pounds) served as the reference group. RESULTS: The study population consisted of 1,034 women. Women gaining below, within, and above IOM guidelines accounted for 38.3, 23.5, and 38.2%, respectively. Weight gain below IOM guidelines was not associated with a statistically increased odds of preterm birth (OR 1.82, 95% CI 0.60-5.59) or low birth weight (OR 1.20, 95% CI 0.57-2.49); however, birth weight more than 4,000 g was significantly reduced (OR 0.50, 95% CI 0.32-0.77). Excessive weight gain statistically increased the odds of pregnancy-induced hypertension (OR 1.96, 95% CI 1.26-3.03) and cesarean delivery (OR 1.40, 95% CI 1.00-1.97) while not appearing to protect against the delivery of low-birth-weight neonates (OR 0.84, 95% CI 0.40-1.78). CONCLUSION: Weight gain below the current guidelines in the super-obese cohort is not associated with an increase in maternal or neonatal risk while decreasing the odds of delivering a macrosomic neonate. Women with BMIs of 50 or higher may warrant separate gestational weight gain recommendations.

The impact of change in pregnancy body mass index on macrosomia.

OBJECTIVE: To examine the impact of change in body mass index (BMI) during pregnancy on the incidence of macrosomia. METHODS: This is a retrospective cohort study using 2007 linked birth certificate and discharge diagnosis data from the state of California. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated for the outcome of macrosomia, as a function of a categorical change in pregnancy BMI: BMI loss (<-0.5), no change (-0.5 to 0.5), minimal (0.6 to 5), moderate (5.1 to 10), and excessive (>10). The impact of pregnancy change in BMI was determined for the entire cohort and then stratified by prepregnancy BMI category. Minimal BMI change served as the reference group. RESULTS: The study population consisted of 436,414 women. Overall, women with moderate and excessive BMI changes had aORs of 1.66 and 3.21, respectively, for macrosomia, when compared with women with minimal BMI change. When stratified by prepregnancy BMI, normal (aOR 3.85) and overweight women (aOR 2.96) with antenatal BMI change greater than 10 had the highest odds of macrosomia. CONCLUSIONS: Excessive change in pregnancy BMI results in an increased odds of macrosomia. This finding was most pronounced in the normal and overweight women.

Patient-prosthesis mismatch in pregnancy.

BACKGROUND: Patient-prosthesis mismatch is a known and severe complication after aortic valve repair in the general population. There is a paucity of literature regarding this condition in pregnancy. CASE: We present the clinical course of a pregnant woman with severe patient-prosthesis mismatch after aortic valve replacement. After extensive workup, the patient underwent aortic valve replacement, enlargement of the aortic root, and placement of a larger prosthetic valve at 21 weeks of gestation. Her postoperative course was complicated by fetal death. CONCLUSION: Cardiopulmonary bypass and aortic valve replacement present a multitude of risks to maternal and fetal health. The obstetrician managing pregnant women with prosthetic heart valves should be aware of the complications that may arise, including patient-prosthesis mismatch.

The impact of change in pregnancy body mass index on cesarean delivery.

OBJECTIVE: To examine the impact of pregnancy changes in body mass index (BMI) on the incidence of cesarean delivery. METHODS: This is a retrospective cohort study using linked birth certificate and discharge diagnosis data from the year 2007. Adjusted odds ratios (aOR) were calculated for the outcome of cesarean delivery, as a function of a categorical change in pregnancy BMI (kg/m(2)): BMI loss (BMI change<-0.5), no change (-0.5 to 0.5), minimal (0.6 to 5), moderate (5.1 to 10) and excessive (>10). The impact of pregnancy change in BMI was determined for the entire cohort and then stratified by prepregnancy BMI category. RESULTS: The study population consisted of 436 414 women with singleton gestations. When compared to women with no net change in BMI, women with excessive BMI changes collectively had a 80% increased incidence of cesarean delivery (aOR = 1.78). By prepregnancy obesity class, the aOR for cesarean delivery in women with excessive BMI change were: normal weight (aOR = 2.25), overweight (aOR = 2.39), obese class I (aOR = 2.23), obese class II (aOR = 2.56) and obese class III (aOR = 2.08). CONCLUSIONS: The odds of cesarean delivery were uniformly increased in all prepregnancy BMI categories as net BMI change increased. These data illustrate that all women, not just the overweight and obese, are at significantly increased risk of cesarean delivery with excessive BMI change during pregnancy.

Management of interstitial ectopic pregnancies with a combined intra-amniotic and systemic approach.

BACKGROUND: Approximately 2% of all pregnancies are ectopic; of these, 4% are interstitial or cervical. There exists no clear consensus as to whether surgical or medical management is superior. CASE: We present three cases of advanced nonfallopian tube ectopic pregnancies from 6 to 8 weeks of gestation. Our first two cases were managed with a combined intrafetal, intra-amniotic and systemic approach using methotrexate and potassium chloride, whereas our third case was managed with an intra-amniotic approach alone. Our combined approach cases were successful, with resolution of human chorionic gonadotropin in 50 and 34 days, whereas our single approach case re-presented with bleeding requiring uterine artery embolization and operative removal of products of conception. CONCLUSION: Patients presenting with advanced interstitial or cervical pregnancies who are clinically stable can be offered medical management with a combined approach.