Jill K. Davies

Subcutaneous Tissue Reapproximation, Alone or in Combination With Drain, in Obese Women Undergoing Cesarean Delivery

OBJECTIVE: To compare the efficacy of subcutaneous suture reapproximation alone with suture plus subcutaneous drain for the prevention of wound complications in obese women undergoing cesarean delivery. METHODS: We conducted a multicenter randomized trial of women undergoing cesarean delivery. Consenting women with 4 cm or more of subcutaneous thickness were randomized to either subcutaneous suture closure alone (n = 149) or suture plus drain (n = 131). The drain was attached to bulb suction and removed at 72 hours or earlier if output was less than 30 mL/24 h. The primary study outcome was a composite wound morbidity rate (defined by any of the following: subcutaneous tissue dehiscence, seroma, hematoma, abscess, or fascial dehiscence). RESULTS: From April 2001 to July 2004, a total of 280 women were enrolled. Ninety-five percent of women (268/280) had a follow-up wound assessment. Both groups were similar with respect to age, race, parity, weight, cesarean indication, diabetes, steroid/antibiotic use, chorioamnionitis, and subcutaneous thickness. The composite wound morbidity rate was 17.4% (25/144) in the suture group and 22.7% (28/124) in the suture plus drain group (relative risk 1.3, 95% confidence interval 0.8–2.1). Individual wound complication rates, including subcutaneous dehiscence (15.3% versus 21.8%), seroma (9.0% versus 10.6%), hematoma (2.2% versus 2.4%), abscess (0.7% versus 3.3%), fascial dehiscence (1.4% versus 1.7%), and hospital readmission for wound complications (3.5% versus 6.6%), were similar (P > .05) between women treated with suture alone and those treated with suture plus drain, respectively. CONCLUSION: The additional use of a subcutaneous drain along with a standard subcutaneous suture reapproximation technique is not effective for the prevention of wound complications in obese women undergoing cesarean delivery. LEVEL OF EVIDENCE: I

Predictors of glyburide failure in the treatment of gestational diabetes.

OBJECTIVE: Our objective was to identify among women with gestational diabetes mellitus (GDM) the patient characteristics that predict treatment failure with glyburide. METHODS: Historical cohort of 95 GDM women offered glyburide after dietary failure with defined entry criteria. RESULTS: From November 2000 to May 2005, 118 women had 124 pregnancies and were offered glyburide therapy by the 2 codirectors of our Diabetes Clinic. All but 2 women elected glyburide, and 27 pregnancies were excluded due to criteria defined a priori to the study. A cohort of 95 women with 95 pregnancies were included for analysis. Nineteen percent failed glyburide. Significant predictors of failure were maternal age (34 years compared with 29 years, P = .001), earlier diagnosis of GDM (23 weeks compared with 28 weeks, P = .002), higher gravidity (P = .01) and parity (P = .03), and a higher mean fasting blood glucose (112 compared with 100 mg/dL; P = .045) compared with those successfully treated. After adjustment in the multivariable logistic regression analysis, GDM women diagnosed at a gestational age less than 25 weeks were 8.3 times more likely to fail glyburide compared with those diagnosed after 25 weeks. Maternal and fetal outcomes were favorable with a cesarean delivery rate of 25% and macrosomia rate of 7%. CONCLUSION: Glyburide was more likely to fail in women diagnosed earlier in pregnancy, of older age and multiparity, and with higher fasting glucoses, suggesting that earlier glucose intolerance and a reduced capacity to respond to an insulin secretagogue may distinguish this group. The time for glyburide as an alternative treatment has come; however, it should be prescribed after careful consideration of these patient characteristics to minimize the likelihood of failure. LEVEL OF EVIDENCE: II-2

Single versus weekly courses of antenatal corticosteroids in preterm premature rupture of membranes

OBJECTIVE: This study was performed to evaluate the efficacy of weekly courses of antenatal corticosteroids compared with a single course in women with preterm premature rupture of membranes (PROM). METHODS: A planned secondary analysis of women with preterm PROM who participated in a multicenter, randomized trial of weekly courses of antenatal corticosteroids versus single-course therapy was performed. After their first course of standard antenatal steroid therapy, administered between 24 to 32–6/7 weeks of gestation, consenting women were randomly assigned to receive betamethasone versus placebo injections weekly until 34–0/7 weeks of gestation. Maternal and neonatal morbidities were compared between the 2 groups. RESULTS: Of the 161 women with preterm PROM, 81 women were assigned to receive weekly courses of steroids and 80 to the single-course group. There were no significant differences in composite morbidity between the groups (27 [34.2%] of 81 patients versus 33 [41.8%] of 80 patients, P = .41). Chorioamnionitis was higher in patients who received weekly courses of antenatal steroids (39 [49.4%] of 81 patients versus 25 [31.7%] of 80 patients, P = .04). CONCLUSION: Weekly courses of antenatal steroids in women with preterm PROM did not improve neonatal outcomes beyond that achieved with single-course therapy and was associated with an increased risk of chorioamnionitis. Antenatal steroid therapy should not be routinely repeated in patients with preterm PROM. LEVEL OF EVIDENCE: I

Acute intrauterine infection results in an imbalance between pro- and anti-inflammatory cytokines in the pregnant rabbit.

PROBLEM: Intrauterine infection results in an increase in cytokines. This study compared the time courses for the pro‐ and anti‐inflammatory cytokine responses in 33 pregnant rabbits at 70% gestation. Pro‐inflammatory markers were activated nuclear factor‐kappa B (NF‐κB) in placenta and tumor necrosis factor‐alpha (TNF‐α) in amniotic fluid. These were compared to the anti‐inflammatory cytokine, interleukin‐1 receptor antagonist (IL‐1ra), in placenta and uterus.
 METHOD OF STUDY: Does were endoscopically inoculated with Escherichia coli through their cervices and sacrificed at six intervals between 0 and 30 hr post‐inoculation.
 RESULTS: Activated NF‐κB, determined by electromobility gel shift assay, increased significantly 16 hr after bacterial inoculation (P≤0.05). This was directly mirrored by TNF‐α concentrations, determined by bioassay, in the amniotic fluid. However, IL‐1ra levels, determined by enzyme‐linked immunosorbent assay, did not increase in response to infection.
 CONCLUSION: Intrauterine infection results in an imbalance between pro‐ and anti‐inflammatory cytokines that may potentiate infection‐induced preterm delivery.

Obstetric Factors Associated with Infections in the Fetus and Newborn Infant

Early-onset neonatal infection often has its origin in utero. Thus, risk factors for neonatal sepsis include prematurity, premature rupture of the membranes (PROM), and maternal fever during labor (which may be caused by clinical intra-amniotic infection). This chapter focuses on these major obstetric conditions. Included in addition to these three “classic” topics is a discussion of new information indicating that intrauterine exposure to bacteria is linked to major neonatal sequelae, including cerebral palsy, bronchopulmonary dysplasia (BPD), and respiratory distress syndrome (RDS).

Safety and Tolerability of Antiretrovirals during Pregnancy

Combination antiretroviral therapy (CART) dramatically decreases mother-to-child HIV-1 transmission (MTCT), but maternal adverse events are not infrequent. A review of 117 locally followed pregnancies revealed 7 grade ≥ 3 AEs possibly related to antiretrovirals, including 2 hematologic, 3 hepatic, and 2 obstetric cholestasis cases. A fetal demise was attributed to obstetric cholestasis, but no maternal deaths occurred. The drugs possibly associated with these AE were zidovudine, nelfinavir, lopinavir/ritonavir, and indinavir. AE or intolerability required discontinuation/substitution of nevirapine in 16% of the users, zidovudine in 10%, nelfinavir in 9%, lopinavir/ritonavir in 1%, but epivir and stavudine in none. In conclusion, nevirapine, zidovudine, and nelfinavir had the highest frequency of AE and/or the lowest tolerability during pregnancy. Although nevirapine and nelfinavir are infrequently used in pregnancy at present, zidovudine is included in most MTCT preventative regimens. Our data emphasize the need to revise the treatment recommendations for pregnant women to include safer and better-tolerated drugs.

Kinetics and determining factors of the virologic response to antiretrovirals during pregnancy.

HIV-infected pregnant women with undetectable plasma HIV RNA concentrations at delivery pose a minimal risk of vertical transmission. We studied the kinetics and the determinants of the virologic response to antiretroviral therapy in 117 consecutive pregnancies. Patients who initiated therapy during pregnancy had a VL decrease of 2 and 2.5 log10 after 4 and 24 weeks, respectively. Therapeutic drug monitoring (TDM) of the protease inhibitors administered in doses recommended for nonpregnant adults resulted in below-target concentrations in 29%, 35%, and 44% of 1st, 2nd, and 3rd trimester measurements, respectively, but low drug concentrations did not correlate with virologic failure. Demographic characteristics, antiretroviral experience prior to pregnancy, baseline VL, or use of specific antiretrovirals did not affect the virologic response. Adherence to ≥95% of prescribed doses and utilization of psychosocial services were associated with undetectable plasma HIV RNA at delivery. In conclusion, the virologic responses of pregnant and nonpregnant adults share similar charactersitics.

A randomized controlled trial of interleukin-1 receptor antagonist in a rabbit model of ascending infection in pregnancy

Objective: To determinewhether treatment with interleukin-1 receptor antagonist (IL1-ra) would affect amniotic fluid concentrations of tumor necrosis factor alpha (TNF-α) and prostaglandins or clinical or microbiological outcomes in a model of ascending bacterial infection in pregnancy. Methods: Timed pregnant New Zealand white rabbits at 70% of gestation underwent endoscopic inoculation of the cervices with 106–106 cfu Escherichia coli . Animals were randomly assigned in a blinded manner to a 5-h intravenous infusion of human IL1-ra (10 mg/kg) or placebo beginning 1 – 2 h after inoculation. Blood was drawn fromthe does for assay of serum IL1-ra concentration before inoculation, at mid-infusion, after the infusion ended and at necropsy. At necropsy, temperature and cultures were taken, and aspirated amniotic fluid was pooled for assays of TNF-α, prostaglandin E2 (PGE2) and IL1-ra. Results: Serum IL1-ra concentrations rose to a mean of 2 mg/ml at mid-infusion and fell markedly after the infusion to concentrations barely detectable at necropsy. Between the two groups, there were no significant differences in the rates of fever or positive cultures or in amniotic fluid concentrations of PGE2 or TNF-α.One unique finding was the demonstration that administration of human IL1-ra to the does resulted inmeasurable concentrationsof human IL1-ra in the amniotic fluid. Conclusions: Treatment with an intravenous infusion of human IL1-ra after cervical inoculation with E. coli did not affect clinical or microbiological outcomes or amniotic fluid concentrations of TNF-α or PGE2. This experiment provides the first demonstration of passageof human IL1-ra from the maternal bloodstreamto the amniotic fluid.

A randomized trial of conjugated group B streptococcal type Ia vaccine in a rabbit model of ascending infection.

OBJECTIVE Maternal vaccination may become a central strategy in the prevention of early-onset group B Streptococcal sepsis. Unlike earlier group B streptococcal polysaccharide vaccines that were poorly immunogenic, newer vaccines conjugated to tetanus toxoid have been developed and have improved immunogenicity. We sought to evaluate a conjugated vaccine using our rabbit model of ascending infection. STUDY DESIGN Rabbit does were randomized to receive either conjugated group B streptococcal type Ia (Ia-tetanus toxoid) or conjugated group B streptococcal type III (III-tetanus toxoid) vaccine. Does were vaccinated 7 days before conception and 7 and 21 days after conception. On days 28 to 30 of a 30-day gestation, does were inoculated intracervically with 10(6) colony-forming units of type Ia group B Streptococcus. Labor was induced if does were undelivered after 72 hours. Does were observed up to 7 days after inoculation. Offspring were observed up to 4 days. We obtained maternal cultures from the uterus, peritoneum, and blood and offspring cultures from the mouth, anus, and blood. Antibody levels were also determined. RESULTS Offspring survival was significantly improved in the group receiving Ia-tetanus toxoid (P =.047). Outcomes such as maternal sepsis and severe illness, although not reaching statistical significance, showed a trend toward improved outcomes in the Ia-tetanus toxoid group. CONCLUSIONS This is the first study to evaluate the conjugated group B streptococcal vaccine by using any model of ascending infection. The Ia-tetanus toxoid vaccine led to improved survival and was immunogenic but fell short of its expected efficacy in preventing ascending group B streptococcal disease under these experimental conditions.

Using LEAN Methodology to Improve Patient Flow in OB Diabetes Clinic in a Single Academic Center [18H]

INTRODUCTION: Patient satisfaction is an increasingly meaningful metric in our current health care system. Our objective was to evaluate patient flow in OB Diabetes Clinic at our safety net institution, known internally as a slow running clinic with complicated patients. METHODS: The Diabetic OB clinic at Denver Health Medical Center is a referral clinic for our city wide health care system. Because of the complex medical conditions of our patients, this clinic was overbooked and often ran late. DHMC was the first health care system to utilize LEAN methodology in health care delivery. In Fall 2014, we sponsored a 32 hour LEAN rapid improvement event to evaluate patient flow in Diabetic OB clinic utilizing procedures such as current state map, root cause analysis, present and ideal state development. Clinic observations were performed; action plans were created then implemented after the event. Pre/post surveys of patient/provider satisfaction and patient cycle time measurements were tabulated. RESULTS: Patient cycle time improved 29% (77 min to 55 min), patient satisfaction by 7% (from 3.2/4 to 3.45/4) and staff satisfaction 49% (from 2/4 to 3.9/4). Patient wait time to see the provider decreased by 45% (from 20 min to 11 min). CONCLUSION: Utilizing LEAN methodology for the first time in Diabetic OB clinic, we were able to significantly improve patient flow this subspecialty clinic. We measurably decreased patient wait time and improved both patient/provider satisfaction. In a health care system where patient satisfaction is increasingly valued, our structured event and actions improved these outcomes.