Scott W. Roberts

Fetal acidemia associated with regional anesthesia for elective cesarean delivery

Objective To determine the prevalence, magnitude, and type of fetal acidemia associated with contemporary obstetric anesthetic techniques. Methods Umbilical artery blood gases were obtained in 1601 singleton pregnancies delivered by elective cesarean. Results General anesthesia was used in 371 (23%) women, epidural in 286 (18%), combined spinal-epidural in 659 (41%), and spinal in 231 (14%). Approximately 18% of infants exposed to regional anesthetics had umbilical artery blood pH values 7,19 or less, 42 (3%) infants had pH values less than 7.10, and nine (1%) had values 6.99 or less. The incidence of fetal acidemia was greater in spinal and combined spinal-epidural procedures compared to epidural anestheics. Fetal acidemia was predominantly respiratory in type because carbon dioxide pressure was abnormally increased when fetal acidemia was diagnosed. Conclusions Regional anesthesia is associated with fatal acidemia, occasionally severe, and has features of an acute respiratory type of acidemia. Fetal acidemia is less frequent with epidural anesthesia compared to subarachnoid techniques.

Valacyclovir prophylaxis to prevent recurrent herpes at delivery: A randomized clinical trial

OBJECTIVE: To measure the efficacy of valacyclovir suppression in late pregnancy to reduce the incidence of recurrent genital herpes in labor and subsequent cesarean delivery. METHODS: A total of 350 pregnant women with a history of genital herpes were assigned randomly to oral valacyclovir 500 mg twice a day or an identical placebo from 36 weeks of gestation until delivery. In labor, vulvovaginal herpes simplex virus (HSV) culture and polymerase chain reaction (PCR) specimens were collected. Vaginal delivery was permitted if no clinical recurrence or prodromal symptoms were present. Neonatal HSV cultures and laboratory tests were obtained, and infants were followed up for 1 month after delivery. Data were analyzed using &khgr;2 and Student t tests. RESULTS: One hundred seventy women treated with valacyclovir and 168 women treated with placebo were evaluated. Eighty-two percent of the women had recurrent genital herpes; 12% had first episode, nonprimary genital herpes; and 6% had first episode, primary genital herpes. At delivery, 28 women (8%) had recurrent genital herpes requiring cesarean delivery: 4% in the valacyclovir group and 13% in the placebo group (P = .009). Herpes simplex virus was detected by culture in 2% of the valacyclovir group and 24% of the placebo group (P =.02). No infants were diagnosed with neonatal HSV, and there were no significant differences in neonatal complications. There were no significant differences in maternal or obstetric complications in either group. CONCLUSION: Valacyclovir suppression after 36 weeks of gestation significantly reduces HSV shedding and recurrent genital herpes requiring cesarean delivery. LEVEL OF EVIDENCE: I

Clinical presentation of community-acquired methicillin-resistant Staphylococcus aureus in pregnancy

Objective: The objective of this study was to review the presentation and management of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) in pregnant women. Methods: This was a chart review of pregnant patients who were diagnosed with MRSA between January 1, 2000, and July 30, 2004. Data collected included demographic characteristics, clinical presentation, culture results, and pathogen susceptibilities. Patients’ pregnancy outcomes were compared with the general obstetric population during the study period. Results: Fifty-seven charts were available for review. There were 2 cases in 2000, 4 in 2001, 11 in 2002, 23 in 2003, and 17 through July of 2004. Comorbid conditions included human immunodeficiency virus and acquired immunodeficiency syndrome (13%), asthma (11%), and diabetes (9%). Diagnostic culture was most commonly obtained in the second trimester (46%); however 18% of cases occurred in the postpartum period. Skin and soft tissue infections accounted for 96% of cases. The most common site for a lesion was the extremities (44%), followed by the buttocks (25%), and breast (mastitis) (23%). Fifty-eight percent of patients had recurrent episodes. Sixty-three percent of patients required inpatient treatment. All MRSA isolates were sensitive to trimethoprim-sulfamethoxazole, vancomycin, and rifampin. Other antibiotics to which the isolates were susceptible included gentamicin (98%) and levofloxacin (84%). In comparison with the general obstetric population, patients with MRSA were more likely to be multiparous and to have had a cesarean delivery. Conclusion: Community-acquired MRSA is an emerging problem in our obstetric population. Most commonly, it presents as a skin or soft tissue infection that involves multiple sites. Recurrent skin abscesses during pregnancy should raise prompt investigation for MRSA. Level of Evidence: II-3

Effect of influenza vaccination in the first trimester of pregnancy

OBJECTIVE: To estimate the effect of first-trimester influenza vaccination on fetal and neonatal outcomes. METHODS: This was a retrospective cohort study examining delivery and neonatal outcomes after antepartum exposure to the seasonal trivalent inactive influenza vaccine. Data were collected and entered into an established computerized database. Outcomes by trimester of vaccination were then compared with women who did not receive the vaccine. RESULTS: During the 5-year study period, 10,225 women received the seasonal influenza vaccine antepartum; 8,690 of these delivered at our institution, 439 in the first trimester and 8,251 in the second and third trimesters. Women vaccinated antepartum were significantly older with higher parity than women who declined vaccination. Neonates born to mothers receiving the vaccine in any trimester did not have an increase in major malformations regardless of trimester of vaccination (2% regardless of vaccination group, P=.9). Stillbirth (0.3% compared with 0.6%, P=.006), neonatal death (0.2% compared with 0.4%, P=.01), and premature delivery (5% compared with 6%, P=.004) were significantly decreased in the vaccinated group. CONCLUSION: Influenza vaccination in the first trimester was not associated with an increase in major malformation rates and was associated with a decrease in the overall stillbirth rate. This information will aid in counseling women regarding the safety of influenza vaccination in the first trimester. LEVEL OF EVIDENCE: II

Markers of acute and chronic asphyxia in infants with meconium-stained amniotic fluid

OBJECTIVE Cord blood pH, lactate, hypoxanthine, and erythropoietin levels have all been used as markers of either acute or chronic asphyxia. We sought to determine whether these index values were significantly different in infants with or without meconium-stained amniotic fluid. STUDY DESIGN Fifty-six pregnant women in spontaneous labor at term were divided into two groups on the basis of the presence or absence of meconium-stained amniotic fluid. All meconium-stained fluid was centrifuged, and the volume percentage of particulate matter (i.e., meconium) was recorded. Umbilical artery blood and mixed arterial and venous cord blood were obtained at each delivery. Lactate, hypoxanthine, and erythropoietin levels were measured. Statistical analysis included Student t test and rank sum statistics where appropriate. Normal and Spearman correlation coefficients were also used. RESULTS There were no significant differences in mean umbilical artery pH (7.26 +/- 0.06 vs 7.25 +/- 0.10), lactate levels (32.8 +/- 10 mg/dl vs 30.4 +/- 14.2 mg/dl), and hypoxanthine levels (13.4 +/- 6.7 mumol/L vs 14.0 +/- 6.0 mumol/L) in newborns with meconium (n = 28) compared with controls (n = 28). Erythropoietin levels were significantly greater in newborns with meconium (median 39.5 mIU/ml vs 26.8 mIU/ml, p = 0.039). There was no correlation between the amount of particulate matter and any marker of asphyxia. CONCLUSIONS There was no correlation between markers of acute asphyxia (i.e., umbilical artery blood pH, lactate, or hypoxanthine) and meconium. However, erythropoietin levels were significantly elevated in newborns with meconium-stained amniotic fluid. This latter marker may better correlate with chronic asphyxia.

Maternal and neonatal outcomes after antepartum treatment of influenza with antiviral medications

Pregnant women are at increased risk of severe morbidity and mortality, secondary to influenza infection. Vaccination programs are the cornerstone of influenza preventive efforts and when they fail, 2 classes of antiviral drugs are important for both postexposure prophylaxis and treatment. The first class, the M2 ion channel inhibitors, includes amantadine and rimantadine, and is effective for the prophylaxis and treatment of influenza A. The second class, the neuraminidase inhibitors, includes oseltamivir, which is effective against both influenza A (including novel H1N1) and B. Because of increasing resistance to oseltamivir, this drug has been used with M2 ion channel inhibitors as 2-drug therapy for influenza A. Little data are not available on the safety of these 2 drug classes when used for treatment of influenza in pregnant women. This retrospective cohort study compared the maternal and neonatal outcomes of pregnant women treated antepartum for influenza with M2 ion channel inhibitors (amantadine, rimantadine), oseltamivir, or a control group. The study was conducted during 5 influenza seasons at a hospital in Texas. The comparative data showed that antepartum treatment with M2 ion channel inhibitors (n = 104), oseltamivir (n = 135), and a control group (n = 82,097) were not associated with increased rates of the following outcomes: gestational diabetes (P = 0.388), preterm birth (P = 0.190), premature rupture of the membranes (P = 0.154), or preeclampsia (P = 0.209). No differences were found among the 3 groups regarding the duration of hospital stay for the mother or the infant, the incidence of fever in labor, stillbirth, or major or minor malformations. Moreover, there were no significant differences among singleton live-born neonates without major malformations in fetal weight (P = 0.186), number of neonates who required intubation (P = 0.552) or intensive care nursery admission (P = 0.418), or the incidence of hyperbilirubinemia (P = 0.282). There were no neonatal deaths among live-born singletons and none had grade 3 or 4 intraventricular hemorrhages or seizures. Two preterm neonates exposed to antivirals in the second trimester developed necrotizing enterocolitis. One was exposed to amantadine and the other to oseltamivir. These findings show that antepartum-antiviral exposure does not increase the risk of adverse maternal or neonatal outcomes.

Cost-effectiveness of Universal Influenza Vaccination in a Pregnant Population

OBJECTIVE: The purpose of this study was to estimate whether universal influenza vaccination of pregnant women was cost-effective in the management of influenza-like illness during influenza season. METHODS: A decision analysis model was developed to investigate the cost-effectiveness of providing inactivated trivalent influenza vaccine to all pregnant women. This scenario was compared with providing supportive care only on a case-by-case basis to the unvaccinated pregnant population. RESULTS: Vaccination of 100% of pregnant women would save approximately

Community-acquired methicillin-resistant staphylococcus aureus among patients with puerperal mastitis requiring hospitalization

50 per woman, resulting in a net gain of approximately 45 quality-adjusted hours relative to providing supportive care only. CONCLUSION: Universal vaccination with inactivated trivalent influenza vaccine is cost-saving relative to providing supportive care alone in the pregnant population. LEVEL OF EVIDENCE: III

Pharmacokinetics of oseltamivir according to trimester of pregnancy

OBJECTIVE: To estimate the incidence of puerperal mastitis requiring hospital admission and to describe demographic and obstetric risk factors for this condition. We also sought to identify trends in bacteriology among isolates obtained from breast abscesses and breast-milk aspirates, with a focus on treatment strategies used for community-acquired methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Patients with puerperal mastitis who were admitted to a county-based teaching hospital between January 1997 and December 2005 were identified by International Classification of Diseases, 9th Revision, codes (675.1, 675.2). Data collected included demographic characteristics, clinical presentation, treatment, duration of admission, premorbid antibiotic exposure, and bacteriology. Demographic variables and obstetric outcomes were compared with all other pregnant women delivered at our hospital. RESULTS: One hundred twenty-seven of 136,459 women delivered at our teaching hospital were admitted for puerperal mastitis (9.3 [95% confidence interval (CI) 7.8–11.1] per 10,000 deliveries). The incidence of mastitis only during the study period was 6.7 (95% CI 5.4–8.3) per 10,000 deliveries, and the incidence of mastitis with breast abscess was 2.6 (95% CI 1.8–3.6) per 10,000 deliveries. Puerperal mastitis was significantly associated with younger women (23.4 years compared with 25.1 years, P<.001) and decreased parity (P=.02). Clinically significant breast abscess (n=35, 28%) was seen most commonly with community-acquired MRSA (n=18, 67%) during the data-collection period. The majority (15 [56%]) of women with culture-proven MRSA did not receive antibiotic therapy to which this organism was sensitive. They were discharged without complication, and there were no treatment failures. CONCLUSION: Community-acquired MRSA was most commonly associated with breast abscess. The empiric use of antibiotics ineffective against community-acquired MRSA did not adversely affect the outcomes in this study. LEVEL OF EVIDENCE: III

The Metabolism and Transplacental Transfer of Oseltamivir in the Ex Vivo Human Model

The purpose of this study was to determine pharmacokinetic parameters for oseltamivir in all trimesters of pregnancy. Thirty pregnant women, 10 per trimester, who were receiving oseltamivir phosphate (75 mg) were recruited to study first-dose pharmacokinetics. Plasma samples were obtained at 0, 0.5, 1, 2, 4, 8, and 12 hours after the first dose. Samples were analyzed for oseltamivir and oseltamivir carboxylate levels. With the use of a noncompartmental model, we estimated the area-under-the-curve, maximum concentration, time-to-maximum concentration, and half-life. There were no significant differences in the pharmacokinetics of oseltamivir by trimester, except for an increased half-life in the first trimester for oseltamivir phosphate and an increased maximum concentration in the third trimester for oseltamivir carboxylate. The levels of oseltamivir carboxylate that were observed were within the range that was needed to achieve inhibitory concentrations at 50% for pandemic H1N1. The pharmacokinetics of oseltamivir does not change significantly according to trimester of pregnancy.