Lindsay Maggio

Cefazolin prophylaxis in obese women undergoing cesarean delivery: a randomized controlled trial.

OBJECTIVE: To compare adipose tissue concentration among obese women receiving 2 g compared with 3 g of precesarean cefazolin prophylaxis. METHODS: This was a double-blind randomized controlled trial of women with singleton gestations and body mass indexes (BMIs) of 30 or greater at their first prenatal visit undergoing cesarean delivery at term. Women were randomly allocated, stratified by BMI, to receive 2 g or 3 g of cefazolin. Subcutaneous adipose tissue was harvested twice: before (opening) fascial incision and after (closing) fascial closure. The primary outcome was opening adipose tissue cefazolin concentration, measured by high-pressure liquid chromatography. RESULTS: From April 2013 to July 2014, 58 women were enrolled, 57 included in the analysis: 28 in the 2-g group and 29 in the 3-g group. Baseline characteristics were similar between groups. Median opening adipose tissue concentration was similar between the 2-g and 3-g groups (9.4 [interquartile range 5.1–13.4] compared with 11.7 [interquartile range 7–18.3] micrograms/g, P=.12). The percentage of women with opening concentrations above 8 micrograms/g, the minimally inhibitory concentration of cefazolin for Staphylococcus species, was similar (61% compared with 72%, P=.35). All samples were above 2 micrograms/g, the minimally inhibitory concentration for Enterobacteriaceae. Closing adipose tissue concentrations and stratified analyses were consistent with the overall analysis. CONCLUSION: In obese women undergoing cesarean delivery, prophylaxis with 3 g of cefazolin did not significantly increase adipose tissue concentration. Thus, our data do not support recommendations for 3-g dosing. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01810354. LEVEL OF EVIDENCE: I

Iatrogenic Preterm Premature Rupture of Membranes after Fetoscopic Laser Ablative Surgery

Introduction: To describe the incidence and risk factors for iatrogenic premature preterm rupture of membranes (iPPROM) after fetoscopic laser surgery for the twin-to-twin-transfusion syndrome. Materials and Methods: This is a retrospective review of all patients who have undergone fetoscopic laser surgery at a single fetal treatment center since 2000. We defined iPPROM as spontaneous rupture of membranes before the onset of labor prior to 34 weeks of gestation. The iPPROM cohort was compared to the cohort without iPPROM for several preoperative, operative, and delivery characteristics. Results: Ninety-two consecutive patients were reviewed. The overall rate of iPPROM was 18.5% (n = 17). The rates of iPPROM within 1 and 4 weeks were 5.4 and 10.9%, respectively. The median interval from surgery to delivery was significantly shorter in the iPPROM group (21 vs. 62 days, p = 0.01). The mean gestational age at delivery (27.0 vs. 31.1 weeks, p = 0.02) was lower in the iPPROM group. No other characteristics studied differed significantly between the groups. Discussion: The incidence of iPPROM was substantially lower than in recent multicenter reports; however, no risk factors of iPPROM could be identified. Whether this is related to variations in surgical or anesthetic management will require further investigation.

Perinatal outcomes with normal compared with elevated umbilical artery systolic-to-diastolic ratios in fetal growth restriction.

OBJECTIVE: To compare the composite neonatal morbidity of pregnancies with fetal growth restriction (estimated fetal weight less than the 10th percentile) and normal compared with elevated umbilical artery systolic-to-diastolic ratios. METHODS: This was a retrospective cohort study of all pregnancies complicated by fetal growth restriction with normal compared with elevated umbilical artery systolic-to-diastolic ratios from January 2008 to July 2012 at a single center. Exclusions were multiple gestation, prenatally diagnosed fetal anomalies, delivery at outside institution, and absent or reversed end diastolic flow. Maternal characteristics and perinatal outcomes including composite neonatal morbidity were compared between groups. RESULTS: Of 11,785 pregnancies evaluated, 789 (7%) were diagnosed with fetal growth restriction. Among 512 that met inclusion criteria, 394 (77%) had normal and 118 (23%) had elevated umbilical artery systolic-to-diastolic ratios. When fetal growth–restricted pregnancies with elevated umbilical artery systolic-to-diastolic ratios were delivered at 37 weeks of gestation were compared with those with normal umbilical artery systolic-to-diastolic ratios delivered at 39 weeks of gestation, there was no difference in the rate of neonatal intensive care unit admission (101 [25.7%] compared with 51 [43.2%]; crude odds ratio [OR] 2.5, 95% confidence interval 1.5–4.0; adjusted OR 1.37, 95% CI 0.69–2.71) or composite neonatal morbidity (60 [15.2%] compared with 24 [20.3%]; crude OR 1.42, 95% CI 0.84–2.40; adjusted OR 0.91, 95% CI 0.45–1.84). CONCLUSION: Composite neonatal morbidity is comparable in fetal growth–restricted pregnancies with elevated compared with normal umbilical artery systolic-to-diastolic ratios when delivered at 37 and 39 weeks of gestation, respectively. Planning delivery of pregnancies with fetal growth restriction and elevated systolic-to-diastolic ratios and without other complications at 37 weeks of gestation results in good outcomes. LEVEL OF EVIDENCE: II

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.

Treatment of severe insulin resistance in pregnancy with 500 units per milliliter of concentrated insulin.

OBJECTIVE: To evaluate glycemic control and pregnancy outcomes among pregnant women with severe insulin resistance treated with 500 units/mL concentrated insulin. METHODS: Retrospective analysis of gravid women with severe insulin resistance (need for greater than 100 units of insulin per injection or greater than 200 units/d) treated with either 500 units/mL concentrated insulin or conventional insulin therapy. We performed a two-part analysis: 1) between gravid women treated with and without 500 units/mL concentrated insulin; and 2) among gravid women treated with 500 units/mL concentrated insulin, comparing glycemic control before and after its initiation. RESULTS: Seventy-three pregnant women with severe insulin resistance were treated with 500 units/mL concentrated insulin and 78 with conventional insulin regimens. Patients treated with 500 units/mL concentrated insulin were older and more likely to have type 2 diabetes mellitus. Average body mass index was comparable between both groups (38.6 compared with 40.4, P=.11) as were obstetric and perinatal outcomes and glycemic control during the last week of gestation. Within the 500 units/mL concentrated insulin cohort, after initiation of this medication, fasting and postprandial blood glucose concentrations improved. However, the rates of blood glucose values less than 60 mg/dL and less than 50 mg/dL were higher in the 500 units/mL concentrated insulin group after initiation than before, 4.8% compared with 2.0% (P<.01) and 2.0% compared with 0.7% (P<.01), respectively. CONCLUSION: The use of 500 units/mL concentrated insulin in severely obese insulin-resistant pregnant women confers similar glycemic control compared with traditional insulin regimens but may increase the risk of hypoglycemia. LEVEL OF EVIDENCE: II

Early term versus term delivery in the management of fetal growth restriction: a comparison of two protocols.

OBJECTIVE This study aims to compare two management protocols in pregnancies diagnosed with fetal growth restriction (FGR). STUDY DESIGN All singleton pregnancies diagnosed and managed with FGR at our institution during two protocol periods were analyzed. The early term protocol (January 2008-February 2010) specified delivery at 37(0/7) weeks if antenatal testing was reassuring, but did not specify the timing of delivery if umbilical artery (UA) Doppler systolic:diastolic (S:D) ratios were elevated (>95th percentile for gestational age [GA]). The term protocol (March 2010-July 2012) specified delivery at 39(0/7) weeks with normal S:D ratios and 37(0/7) weeks with elevated S:D ratios when antenatal testing was reassuring. RESULTS There were 228 and 312 women in the early term and term protocol, respectively, who met inclusion criteria. Compared with the early term group, the term group had an increased median GA at delivery (37.1 vs. 38.6%, p < 0.001), decreased deliveries less than 37(0/7) weeks (37 vs. 24%, p = 0.01) and decreased neonatal intensive care unit (NICU) admissions (38 vs. 28%, p = 0.02). CONCLUSION A protocol specifying delivery at 39(0/7) weeks when UA S:D ratios are normal and delivery at 37(0/7) weeks when UA S:D ratios are elevated when other antenatal testing is reassuring in FGR: (1) prolonged gestation, (2) decreased preterm births, and (3) decreased NICU admissions.

Gestational Diabetes Mellitus and Frequency of Blood Glucose Monitoring

OBJECTIVE To assess whether testing blood glucose four times daily compared with four times every other day would lead to similar birth weights among patients with gestational diabetes mellitus (GDM). METHODS This noninferiority randomized controlled trial was conducted at five centers. After receiving a diagnosis of GDM, women tested their blood glucose every day for 7 days. After that period, compliant women without hyperglycemia requiring treatment were randomized to either blood glucose testing four times a day or every other day. Noninferiority would be declared if the mean birth weight in the every-other-day group was no higher than 165 g (5% difference assuming an average birth weight of 3,296 g) compared with the four times a day group. A total sample size of 286 women allowed noninferiority to be tested (one-sided .05 level of significance). RESULTS From May 2013 to May 2016, of the 293 women with GDM who were randomized, 149 (51%) were tested four times a day and 144 (49%) were tested every other day. Between the two groups, there were no significant differences with regard to need for medical treatment, induction, gestational age at delivery, mode of delivery, rate of preeclampsia, or shoulder dystocia. Birth weight was similar between both groups and the upper bound of the 90% confidence interval (CI) was less than 165 g, establishing noninferiority with a mean difference of -41 g (90% CI -137 to 54 g). Rate of compliance with blood glucose testing was higher in the every-other-day group (89% compared with 92%, P<.01). The differences in rates of macrosomia and birth weight greater than the 95th percentile were not clinically significant. Neonatal outcomes including neonatal hypoglycemia were similar. CONCLUSION Among patients with well-controlled GDM, testing blood glucose values every other day did not increase birth weight, although it did increase compliance with testing when compared with women who tested every day. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT01818557.

Prenatal Screening for Thrombophilias: Indications and Controversies, an Update

Pregnancy is associated with increased clotting potential and decreased fibrinolysis. Women with thrombophilias have an increased risk of venous thromboembolism during pregnancy. At least 50% of cases of venous thromboembolism in pregnant women are associated with an inherited or acquired thrombophilia. Acquired thrombophilias have also been linked with adverse pregnancy outcomes such as recurrent pregnancy loss, intrauterine fetal demise, early onset severe preeclampsia, placental abruption, and fetal growth restriction. This article addresses indications for thrombophilia testing, the appropriate laboratory tests, and timing of testing to ensure reliability of results.

Evidence-Based Cesarean Delivery for the Nonobstetrician

Cesarean delivery (CD) is one of the most common major surgeries performed in the United States and worldwide. Surgical techniques evaluated in well-designed randomized controlled trials (RCTs) that demonstrate maternal benefit should be incorporated into practice. The objective of this review is to provide a summary of surgical techniques of the procedure and review the evidence basis for them for the nonobstetrician. The following techniques with the strongest evidence should be commonly performed, when feasible: (1) prophylactic antibiotics with a single dose of ampicillin or first-generation cephalosporin prior to skin incision; (2) postpartum hemorrhage prevention with oxytocin infusion of 10 to 40 IU in 1 L crystalloid over 4 to 8 hours; (3) low transverse skin incision; (4) blunt or sharp subcutaneous and fascial expansion; (5) blunt, cephalad-caudad uterine incision expansion; (6) spontaneous placental removal; (7) blunt-tip needle usage during closure; (8) subcutaneous suture closure (running or interrupted) if thickness is ≥2 cm; and (9) skin closure with suture. Although the number of RCTs designed to optimize maternal and neonatal outcomes of this common procedure is encouraging, further work is needed to minimize surgical morbidity. Optimal methods for postpartum hemorrhage prevention, adhesion prevention, and venous thromboembolism prophylaxis remain ongoing areas of active research, with outcomes that could markedly improve maternal morbidity and mortality. If evidence of a surgical technique appears preferred over another, clinicians should be comfortable adopting the evidence-based technique when performing and teaching CD.

Effects of Routine Screening for Gonorrhea and Chlamydia Before Intrauterine Device Insertion

INTRODUCTION: The objective of this study was to identify the incidence of gonorrhea and chlamydia in women presenting for intrauterine device (IUD) insertion in an academic community clinic and to evaluate the current “two-visit” practice for IUD insertion. METHODS: A retrospective chart review was conducted from 2009 to 2010 at Peoples Community Health Center, the primary community clinic of an academic residency training program in Houston, Texas. Study participants were identified from a list of all patients who had gonorrhea and chlamydia testing as those who presented for IUD insertion. Subsequent encounters were reviewed to identify participants who presented for IUD placement, were lost to follow-up, or presented with a pregnancy. RESULTS: There were 720 patients who met inclusion criteria. The average age was 30.3 years (standard deviation [SD] 23.28–37.32), average gravidity 2.89 (SD 1.29–4.49), and parity 2.5 (SD 1.2–3.8). The average education was 9.34 years (SD 12.79–5.89). The patients were predominantly Hispanic (82.78%) and married (70.56%). The incidence of gonorrhea was 0.56% and of chlamydia was 2.5%. Overall, 484 patients (69.74%) returned and received an IUD. The rate of pregnancy was significantly higher in those that did not represent for IUD placement (32.4% compared with 1.9%, P<.001). CONCLUSIONS: Like previously reported studies in other populations, the incidence of gonorrhea and chlamydia in our patients is low; however, rates of failure to return and pregnancy are high. Current “two-visit” protocols should be amended to allow for immediate placement of IUDs in similar populations to prevent delay in contraceptive services and unintended pregnancy.