Laura G. Greer

Pregnancy and laboratory studies: A reference table for clinicians

OBJECTIVE: To establish normal reference ranges during pregnancy for common laboratory analytes. DATA SOURCES: We conducted a comprehensive electronic database review using PUBMED and MEDLINE databases. We also reviewed textbooks of maternal laboratory studies during uncomplicated pregnancy. METHODS OF STUDY SELECTION: We searched the databases for studies investigating various laboratory analytes at various times during pregnancy. All abstracts were examined by two investigators and, if they were found relevant, the full text of the article was reviewed. Articles were included if the analyte studied was measured in pregnant women without major medical problems or confounding conditions and if the laboratory marker was measured and reported for a specified gestational age. TABULATION, INTEGRATION, AND RESULTS: For each laboratory marker, data were extracted from as many references as possible, and these data were combined to establish normal reference ranges in pregnancy. When possible, the 2.5 and 97.5 percentiles were reported as the normal range. In some of the reference articles, however, the reported range was based on the minimum and maximum value of the laboratory constituent. In those cases, the minimum to maximum range was used and combined with the 2.5 and 97.5 percentile range. We found that there is a substantial difference in normal values in some laboratory markers in the pregnant state when compared with the nonpregnant state. CONCLUSION: It is important to consider normal reference ranges specific to pregnancy when interpreting some laboratory results that may be altered by the normal changes of pregnancy.

Pharmacokinetic and pharmacodynamic comparison of two calcium supplements in postmenopausal women.

This randomized crossover study compared the single‐dose bioavailability and effects on parathyroid function of two commercially formulated calcium supplements containing 500 mg of elemental calcium. Twenty‐five postmenopausal women underwent three phases of study wherein they each took a single dose of calcium citrate with a standard breakfast (as Citracal® 250 mg + D), calcium carbonate (as Os‐Cal ®500 mg + D), or placebo at 8 a.m. Blood samples were drawn at baseline and hourly for 4 or 6 hours after each dose. Fasting and postload urine samples were also collected. Compared with calcium carbonate, calcium citrate provided a 46% greater peak‐basal variation and 94% higher change in area under the curve for serum calcium and a 41% greater increment in urinary calcium. Moreover, the decrement in serum parathyroid hormone concentration from baseline was greater after calcium citrate. In conclusion, calcium citrate is more bioavailable than calcium carbonate when given with a meal.

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

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.

Rapid Diagnostic Methods in Sexually Transmitted Infections

Sexually transmitted infections (STIs) are common infections throughout the developed and the developing world. It is estimated that worldwide there are 1 million new cases per day of curable bacterial STIs. As part of the World Health Organization 2001 Sexually Transmitted Diseases Diagnostics Initiative, the organization explored the need for simple, affordable, point-of-care STI testing for curable bacterial STIs. This article reviews the evidence supporting the implementation of currently available rapid tests for five common STIs: syphilis, gonorrhea, chlamydia, HIV, and herpes.

Pharmacokinetics of oseltamivir according to trimester of pregnancy

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.

Antithyroid antibodies and parity: further evidence for microchimerism in autoimmune thyroid disease

OBJECTIVE Fetal microchimerism may have a role in development of autoimmune thyroid disorders. Using parity as a surrogate for increasing fetal cell exposure, we analyzed its association with thyroid peroxidase antibody levels. STUDY DESIGN Secondary analysis of serum thyroid analytes determined in 17,298 women from a population-based prospective study between 2001 and 2003. Sera were assayed for thyrotropin, free thyroxine, and antithyroid peroxidase antibodies. We analyzed the relationship between thyroid peroxidase antibodies and increasing parity. RESULTS The incidence of abnormally elevated thyroid peroxidase antibody levels (>50 IU/mL) increased with advancing parity, but was not significant after adjustment for maternal characteristics. However, at higher thyroid peroxidase antibody levels (>500 IU/mL), a significant relationship with advancing parity persisted after adjustments (P = .002). CONCLUSION Advancing parity is associated with an increased risk for high serum concentrations of antithyroid peroxidase antibodies. This suggests fetal microchimerism may play a role in development of autoimmune thyroid disorders.

An Immunologic Basis for Placental Insufficiency in Fetal Growth Restriction

OBJECTIVE We sought to determine whether chronic villitis, an immunologic disease of the placenta, was related to fetal growth restriction. METHODS Beginning in October 1999, a protocol was instituted that required placentas of high-risk births be submitted for standardized histological examination. Chronic villitis was diagnosed when a lymphohistiocytic infiltrate involving placental villi was present and was graded according to the extent and location of the infiltrate. Fetal growth restriction was defined as weight less than 3rd, 5th, and 10th percentiles. Placental hypoplasia was defined as weight less than 10th percentile. RESULTS In the 10,204 placental examinations that were performed, low-grade and high-grade chronic villitis was associated with hypoplastic placentas and fetal growth restriction. Infants with placentas with low-grade and high-grade chronic villitis were more likely to require cesarean delivery for nonreassuring fetal heart rate compared with controls (27% and 25% versus 21%; p < 0.05). Fetal acidemia (umbilical artery pH < 7.0) was associated with high-grade chronic villitis compared with controls (4% versus 2%; p < 0.05). CONCLUSION Chronic villitis was associated with anatomic and functional placental insufficiency manifested as placental hypoplasia, growth restriction, increased risk of cesarean for nonreassuring fetal heart rate, and fetal acidemia. These findings support an immunologic basis for fetal growth restriction.

Pharmacokinetics of oseltamivir in breast milk and maternal plasma

OBJECTIVE Women in the postpartum period are at high risk for complications from influenza. Pharmacokinetic data of oseltamivir phosphate in postpartum women, however, are lacking. STUDY DESIGN Seven healthy patients within 48 hours of delivery were recruited. Each woman received 75 mg of oseltamivir phosphate. Plasma and breast milk samples were obtained at times 0, 0.5, 1, 2, 4, 8, 12, and 24 hours after the first dose. The samples were analyzed for oseltamivir and oseltamivir carboxylate levels. Using a noncompartmental model, area under the curve (AUC), maximum concentration (C(max)), time to maximum concentration, and half-life were estimated. RESULTS Oseltamivir phosphate and oseltamivir carboxylate were found in breast milk, although later and in lower levels than that found in plasma. The C(max) and AUC 0-24 was higher for the active metabolite than for the prodrug in both plasma and breast milk. CONCLUSION Oseltamivir carboxylate was present in breast milk but in concentrations significantly lower than considered therapeutic in infants.

Ampicillin resistance and outcome differences in acute antepartum pyelonephritis

Objective. To measure the incidence of ampicillin-resistant uropathogens in acute antepartum pyelonephritis and to determine if patients with resistant organisms had different clinical outcomes. Study design. This was a secondary analysis of a prospective cohort study of pregnant women admitted with pyelonephritis, diagnosed by standard clinical and laboratory criteria. All patients received ampicillin and gentamicin. Results. We identified 440 cases of acute pyelonephritis. Seventy-two percent (316 cases) had urine cultures with identification of organism and antibiotic sensitivities. Fifty-one percent of uropathogens were ampicillin resistant. The patients with ampicillin-resistant organisms were more likely to be older and multiparous. There were no significant differences in hospital course (length of stay, days of antibiotics, ECU admission, or readmission). Patients with ampicillin-resistant organisms did not have higher complication rates (anemia, renal dysfunction, respiratory insufficiency, or preterm birth). Conclusion. A majority of uropathogens were ampicillin resistant, but no differences in outcomes were observed in these patients.