Morgan Swank

Effects of maternal obesity on tissue concentrations of prophylactic cefazolin during cesarean delivery.

OBJECTIVE: To estimate the adequacy of antimicrobial activity of preoperative antibiotics at the time of cesarean delivery as a function of maternal obesity. METHODS: Twenty-nine patients scheduled for cesarean delivery were stratified according to body mass index (BMI) category, with 10 study participants classified as lean (BMI less than 30), 10 as obese (BMI 30–39.9), and nine as extremely obese (BMI 40 or higher). All patients were given a dose of 2 g cefazolin 30–60 minutes before skin incision. Antibiotic concentrations from adipose samples, collected after skin incision and before skin closure, along with myometrial and serum samples, were analyzed with microbiological agar diffusion assay. RESULTS: Cefazolin concentrations within adipose tissue obtained at skin incision were inversely proportional to maternal BMI (r=−0.67, P<.001). The mean adipose concentration was 9.4 plus or minus 2.7 micrograms/g in the lean group of women compared with 6.4 plus or minus 2.3 micrograms/g in the obese group (P=.009) and 4.4 plus or minus 1.2 micrograms/g in the extremely obese group (P<.001). Although all specimens demonstrated therapeutic cefazolin levels for gram-positive cocci (greater than 1 microgram/g), a considerable portion of obese and extremely obese did not achieve minimal inhibitory concentrations of greater than 4 micrograms/g for Gram-negative rods in adipose samples at skin incision (20% and 33.3%, respectively) or closure (20.0% and 44.4%, respectively). No significant difference in cefazolin concentration was observed in mean closure adipose, myometrial, or serum specimens across the BMI categories. CONCLUSION: Pharmacokinetic analysis suggests that present antibiotic prophylaxis dosing may fail to provide adequate antimicrobial coverage in obese patients during cesarean delivery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00980486. LEVEL OF EVIDENCE: II

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.

The impact of change in pregnancy body mass index on the development of gestational hypertensive disorders.

Objective:To examine the impact of change in body mass index (BMI) during pregnancy on the incidence of gestational hypertension/preeclampsia.Study Design:This is a retrospective cohort study using linked California birth certificate and discharge diagnosis data from the year 2007. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated for the outcome of gestational hypertension/preeclampsia, 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 change in pregnancy BMI was evaluated for the entire cohort and then as a function of prepregnancy BMI category. Women with no change in pregnancy BMI served as the reference group.Result:The study population consisted of 436 414 women with singleton gestations. Overall, women with excessive BMI change had a nearly twofold increased odds of gestational hypertension/preeclampsia (aOR=1.94; 95% CI=1.72 to 2.20). By prepregnancy BMI class, overweight and obese women who had a moderate change in pregnancy BMI also had increased odds of developing gestational hypertension/preeclampsia with aOR ranging from 1.73 to 1.97.Conclusion:Regardless of prepregnancy BMI category, women with excessive BMI change have a higher chance of developing gestational hypertension/preeclampsia. Overweight and obese women with moderate BMI change may also be at increased risk.

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. LEVEL OF EVIDENCE: II

The impact of change in pregnancy body mass index on macrosomia

To examine the impact of change in body mass index (BMI) during pregnancy on the incidence of macrosomia.

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

Abstract 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/m2): 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.

Necrotizing pancreatitis associated with severe preeclampsia.

BACKGROUND: Necrotizing pancreatitis is rare in pregnancy and usually is associated with symptomatic cholelithiasis. We present a case of fatal necrotizing pancreatitis in a patient with severe preeclampsia. CASE: A 25-year old primigravid woman at 35 weeks of gestation presented with decreased fetal movement, pruritus, and malaise. Intrauterine fetal demise was diagnosed in the context of severe thrombocytopenia, hypertension, proteinuria, hemolysis, elevated transaminases, and renal failure. Postpartum, the patient developed metabolic acidosis, hyperglycemia, and hypoxemia followed by cardiopulmonary arrest and death. Autopsy revealed extensive acute pancreatic necrosis, pleural effusions, ascites, and fatty liver without evidence of microthrombi. The cause of death was acute necrotizing pancreatitis resulting from severe preeclampsia. CONCLUSION: Severe preeclampsia may cause widespread end-organ damage and may affect the gastrointestinal system, resulting in fatal necrotizing pancreatitis.

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.

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.

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.