Changing patterns in medication prescription for gestational diabetes during a time of guideline change in the USA: a cross-sectional study.

OBJECTIVE: To define patterns of prescription and factors associated with choice of pharmacotherapy for gestational diabetes mellitus (GDM), namely metformin, glyburide and insulin, during a period of evolving professional guidelines. DESING: Cross-sectional study. SETTING: US commercial insurance beneficiaries from Market-Scan (late 2015 to 2018). STUDY DESIGN: We included women with GDM, singleton gestations, 15-51 years of age on pharmacotherapy. The exposure was pharmacy claims for metformin, glyburide and insulin. MAIN OUTCOMES: Pharmacotherapy for GDM with either oral agent, metformin or glyburide, compared with insulin as the reference, and secondarily, consequent treatment modification (addition and/or change) to metformin, glyburide or insulin. RESULTS: Among 37 762 women with GDM, we analysed data from 10 407 (28%) with pharmacotherapy, 21% with metformin (n = 2147), 48% with glyburide (n = 4984) and 31% with insulin (n = 3276). From late 2015 to 2018, metformin use increased from 17 to 29%, as did insulin use from 26 to 44%, whereas glyburide use decreased from 58 to 27%. By 2018, insulin was the most common pharmacotherapy for GDM; metformin was more likely to be prescribed by 9% compared with late 2015/16, but glyburide was less likely by 45%. Treatment modification occurred in 20% of women prescribed metformin compared with 2% with insulin and 8% with glyburide. CONCLUSIONS: Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for GDM among a privately insured US population during a time of evolving professional guidelines. Further evaluation of the relative effectiveness and safety of metformin compared with insulin is needed. TWEETABLE ABSTRACT: Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for gestational diabetes mellitus in the USA.

Use of prophylactic antibiotics in women with previable prelabor rupture of membranes.

OBJECTIVE: To measure the effect of prophylactic antibiotics given at time of previable prelabor rupture of membranes (PROM) on latency. METHODS: Single center, retrospective cohort study of singleton pregnancies with previable (<23 0/7weeks) PROM. Antibiotics were given at clinician discretion. The primary outcome was latency, defined as duration of time between previable PROM and delivery. Secondary outcomes included delivery at ≥ 23weeks, infant survival, and maternal morbidity. Bivariate analysis compared maternal covariates between women who did and did not receive antibiotics. Antibiotic effect on latency was modeled using a Cox proportional hazards ratio. RESULTS: 213 women with previable PROM were identified; 77 (36%) remained pregnant and thus were included in this analysis. Forty (52%) of 77 received antibiotics. Compared to women who did not receive antibiotics, those who did had PROM at a later median (IQR) estimated gestational age, EGA, (22.2weeks [20.7, 22.5] vs. 19.3weeks [18, 20.7], p < 0.01). Median (IQR) latency was not different between women who did and did not receive antibiotics (2.2 [0.7, 3.9] vs. 1.5 [0.5, 4.6] weeks, p = 0.49). More infants survived to discharge among women who received antibiotics compared to those who did not [17(43%) vs. 3(8%), p < 0.01]. When adjusted for EGA at PROM, antibiotics were associated with longer latency (HR 0.57 [95% CI 0.33, 0.97], p = 0.01). Antibiotic use was not associated with differences in maternal morbidity. CONCLUSION: After adjusting for EGA at PROM, antibiotic receipt was associated with longer latency. Larger prospective studies are needed to define the utility of prophylactic antibiotics in previable PROM.

Lost in translation? English- and Spanish-speaking women's perceptions of gestational weight gain safety, health risks and counseling.

OBJECTIVE: To determine English- and Spanish-speaking women's perceptions on gestational weight gain (GWG) counseling. STUDY DESIGN: We administered a written survey to 279 pregnant women regarding GWG counseling and knowledge. We compared English- and Spanish-speaking women's responses using X(2)-tests and logistic regression analyses. RESULT: Seventy-four (27%) women completed the survey in Spanish and 205 (73%) in English. More Spanish compared with English speakers did not know if their provider recommended weight gain goals (26% vs 10%, odds ratio (OR) 3.2, confidence interval (CI) 1.5 to 6.5); if there are risks to excessive GWG for mother (27% vs 11%, OR 3.1, CI 1.5 to 6.4) or infant (38% vs 16%, OR 3.3, CI 1.7 to 6.3); or if exercise (15% vs 1%, OR 12.1, CI 3.0 to 69.1) or weight loss (35% v 12%, OR 4.0, CI 2.0 to 8.0) were safe during pregnancy. CONCLUSION: Significant differences exist between Spanish- and English-speaking women's perception of GWG counseling, which may be due to language or cultural barriers.

Bacterial infection promotes DNA hypermethylation.

Maternal oral infection, caused by bacteria such as C. rectus or P. gingivalis, has been implicated as a potential source of placental and fetal infection and inflammatory challenge, which increases the relative risk for pre-term delivery and growth restriction. Intra-uterine growth restriction has also been reported in various animal models infected with oral organisms. Analyzing placental tissues of infected growth-restricted mice, we found down-regulation of the imprinted Igf2 gene. Epigenetic modification of imprinted genes via changes in DNA methylation plays a critical role in fetal growth and development programming. Here, we assessed whether C. rectus infection mediates changes in the murine placenta Igf2 methylation patterns. We found that infection induced hypermethylation in the promoter region-P0 of the Igf2 gene. This novel finding, correlating infection with epigenetic alterations, provides a mechanism linking environmental signals to placental phenotype, with consequences for development.

Effect of betamethasone on maternal glucose.

OBJECTIVE: To determine the effect of single and multiple betamethasone courses on maternal fasting and postprandial glucose values. STUDY DESIGN: A prospective cohort study was performed in women receiving betamethasone at 24-34 weeks' gestation. Fasting and 1-h postprandial capillary glucose values were obtained daily following betamethasone therapy for hospitalized patients. A control group comprised outpatients who underwent weekly fasting and postprandial assessments for 3 weeks. Fasting and 1-h postprandial capillary glucose values were compared between control and betamethasone patients using an unpaired t test. RESULTS: Thirty-five women received a single course of therapy, 19 received multiple courses and 28 served as controls. Mean fasting glucose values for control patients fell within a narrow range of 81.6 +/- 10.3 to 82.2 +/- 6.4 mg/dl for weeks 1-3. Of women receiving betamethasone, 59% of fasting glucose values were greater than 90 mg/dl as compared to 16% of control fasting values (p < 0.00 1, chi2 test). Mean 1-h postprandial values for control women ranged from 107.7 +/- 15.1 to 112.3 +/- 20.0 mg/dl for weeks 1-3. Mean 1-h postprandial glucose values were < or = 140 mg/dl following one, two or three courses of betamethasone therapy. CONCLUSIONS: Betamethasone resulted in an acute increase in fasting glucose following a single course of betamethasone, whereas two or more courses of therapy resulted in a continuous elevation of fasting glucose values. One-hour postprandial values were not clinically abnormal.

Altered expression of TCR-CD3zeta induced by sera from women with preeclampsia.

OBJECTIVE: To investigate TCR-CD3zeta expression by cultured T lymphocytes exposed to midtrimester sera from pregnant women in whom preeclampsia developed at term compared with normotensive pregnant control subjects. STUDY DESIGN: Sera obtained at 24 to 28 weeks' gestation from 16 nulliparous women in whom preeclampsia developed at term and from 32 gestational age-matched control subjects without preeclampsia were evaluated for TCR-CD3zeta chain expression with use of Jurkat cells. Subsets of serum samples from 6 women with preeclampsia and 6 control subjects were then evaluated for their ability to induce apoptosis and to suppress interleukin-2 production. Groups were compared by use of the Kruskal-Wallis test, and P <.05 was considered significant. RESULTS: TCR-CD3zeta chain expression in cultured T lymphocytes was suppressed in approximately 60% of untreated control subjects after incubation with sera from normotensive pregnant women compared with 30% after incubation with sera from women with preeclampsia (P <.001). T-cell apoptosis was significantly higher after incubation with sera from normotensive control subjects, as was the expression of the proapoptotic regulator Bax, compared with sera from women with preeclampsia. Interleukin-2 levels were higher in T cells incubated with sera from women in whom preeclampsia later developed compared with sera from normotensive pregnant women (27.7 ng/mL versus 72.5 ng/mL; P <.001). CONCLUSIONS: Nulliparous women in whom preeclampsia developed did not suppress TCR-CD3zeta levels to the extent of normotensive control subjects, which may be linked to decreased lymphocyte apoptosis. This occurs remotely from the manifestation of clinical disease and suggests a deficiency in a serum factor in preeclampsia that may induce T cell zeta chain suppression in normal pregnancy.

Urinary interleukin-8 with asymptomatic bacteriuria in pregnancy.

OBJECTIVE: To evaluate urinary interleukin-8 (IL-8), an inflammatory cytokine, as a screening method for detecting asymptomatic bacteriuria in pregnancy. METHODS: Clean-catch urine samples from 200 pregnant women undergoing screening for asymptomatic bacteriuria were evaluated by urine culture, urine dipstick analysis, and measurement of IL-8. Interleukin-8 levels were measured by a chemiluminescent immunoassay (Immulite IL-8, Diagnostic Products Corp., Los Angeles, CA), and a receiver operating characteristic curve was used to determine the optimal cutoff point. Asymptomatic bacteriuria was defined as at least 100,000 colony-forming units of a single organism per mL. Dipstick testing included nitrite assessment as positive or negative and leukocyte esterase as negative, trace, 1+, 2+, or 3+. Dipstick testing was considered positive if nitrite was positive or leukocyte esterase was trace or greater. Sensitivities, specificities, positive and negative predictive values were determined for urinary leukocyte esterase and nitrite and compared with those of IL-8. chi(2) and Mann-Whitney U tests were used for statistical analyses. RESULTS: Twenty women were identified with asymptomatic bacteriuria by urine culture. The median urinary IL-8 levels for women with and without asymptomatic bacteriuria were 356 pg/mL and 125 pg/mL, respectively (P <.01, Mann-Whitney U test). Using an optimal cutoff point of 264 pg/mL, IL-8 had a sensitivity, specificity, positive and negative predictive value of 70%, 67%, 19%, and 95% for predicting asymptomatic bacteriuria. Urine dipstick analysis with either a positive leukocyte esterase or nitrite had a sensitivity, specificity, positive and negative predictive value of 45%, 62%, 12%, and 91%, respectively, for detecting asymptomatic bacteriuria. The differences between these testing methods were not statistically significant. CONCLUSION: Urinary interleukin-8 is not an acceptable screening method for asymptomatic bacteriuria in pregnancy because it fails to detect 30% of women with this condition.

Repeated fetal betamethasone treatment and birth weight and head circumference.

OBJECTIVE: To assess the effect of repeated courses of betamethasone on birth weight and head circumference. METHODS: We conducted a historical cohort study of inpatients receiving betamethasone therapy over 5 years. We compared birth weights and head circumferences of infants whose mothers received one course of betamethasone with those of infants whose mothers received multiple courses. Multiple regression analysis was used to adjust for potential confounding variables. Sufficient power (80%) existed to detect a 20% difference between the groups (alpha = 0.05). RESULTS: Mean birth weights (+/-SD) were 1717 +/- 707 g in the single-course group (n = 107) and 1783 +/- 647 g in the multiple-course group (n = 45) (P =.59, Student t-test). Mean head circumference was 28.2 +/- 3.6 cm in the single-course group and 29.2 +/- 2.9 cm in the multiple-course group (P =.15, Student t-test). In regression analysis, birth weights (1757 g and 1752 g) and head circumferences (28.5 cm and 29.0 cm) did not differ significantly different between the single-course and multiple-course groups. CONCLUSION: Multiple courses of betamethasone do not reduce birth weight or head circumference in neonates compared with single-course therapy.

Maternal periodontitis and prematurity. Part I: Obstetric outcome of prematurity and growth restriction.

Oral Conditions and Pregnancy (OCAP) is a 5-year prospective study of pregnant women designed to determine whether maternal periodontal disease contributes to the risk for prematurity and growth restriction in the presence of traditional obstetric risk factors. Full-mouth periodontal examinations were conducted at enrollment (prior to 26 weeks gestational age) and again within 48 hours postpartum to assess changes in periodontal status during pregnancy. Maternal periodontal disease status at antepartum, using a 3-level disease classification (health, mild, moderate-severe) as well as incident periodontal disease progression during pregnancy were used as measures of exposures for examining associations with the pregnancy outcomes of preterm birth by gestational age (GA) and birth weight (BW) adjusting for race, age, food stamp eligibility, marital status, previous preterm births, first birth, chorioamnionitis, bacterial vaginosis, and smoking. Interim data from the first 814 deliveries demonstrate that maternal periodontal disease at antepartum and incidence/progression of periodontal disease are significantly associated with a higher prevalence rate of preterm births, BW < 2,500 g, and smaller birth weight for gestational age. For example, among periodontally healthy mothers the unadjusted prevalence of births of GA < 28 weeks was 1.1%. This was higher among mothers with mild periodontal disease (3.5%) and highest among mothers with moderate-severe periodontal disease (11.1%). The adjusted prevalence rates among GA outcomes were significantly different for mothers with mild periodontal disease (n = 566) and moderate-severe disease (n = 45) by pair-wise comparisons to the periodontally healthy reference group (n = 201) at P = 0.017 and P < 0.0001, respectively. A similar pattern was seen for increased prevalence of low birth weight deliveries among mothers with antepartum periodontal disease. For example, there were no births of BW < 1000 g among periodontally healthy mothers, but the adjusted rate was 6.1% and 11.4% for mild and moderate-severe periodontal disease (P = 0.0006 and P < 0.0001), respectively. Periodontal disease incidence/progression during pregnancy was associated with significantly smaller births for gestational age adjusting for race, parity, and baby gender. In summary, the present study, although preliminary in nature, provides evidence that maternal periodontal disease and incident progression are significant contributors to obstetric risk for preterm delivery, low birth weight and low weight for gestational age. These studies underscore the need for further consideration of periodontal disease as a potentially new and modifiable risk for preterm birth and growth restriction.

Maternal periodontitis and prematurity. Part II: Maternal infection and fetal exposure.

Clinical data from the first 812 deliveries from a cohort study of pregnant mothers entitled Oral Conditions and Pregnancy (OCAP) demonstrate that both antepartum maternal periodontal disease and incidence/progression of periodontal disease are associated with preterm birth and growth restriction after adjusting for traditional obstetric risk factors. In the current study we present measures of maternal periodontal infection using whole chromosomal DNA probes to identify 15 periodontal organisms within maternal periodontal plaque sampled at delivery. In addition, maternal postpartum IgG antibody and fetal exposure, as indexed by fetal cord blood IgM level to these 15 maternal oral pathogens, was measured by whole bacterial immunoblots. The potential role of maternal infection with specific organisms within 2 bacterial complexes most often associated with periodontitis, conventionally termed "Orange" (Campylobacter rectus, Fusobacterium nucleatum, Peptostreptococcus micros, Prevotella nigrescens, and Prevotella intermedia) and "Red" (Porphyromonas gingivalis, Bacteroides forsythus, and Treponema denticola) complexes, respectively, to prematurity was investigated by relating the presence of oral infection, maternal IgG, and fetal cord IgM, comparing full-term to preterm (gestational age < 37 weeks). The prevalence of 8 periodontal pathogens was similar among term and preterm mothers at postpartum. There was a 2.9-fold higher prevalence of IgM seropositivity for one or more organisms of the Orange or Red complex among preterm babies, as compared to term babies (19.9% versus 6.9%, respectively, P = 0.0015, chi square). Specifically, the prevalence of positive fetal IgM to C. rectus was significantly higher for preterm as compared to full-term neonates (20.0% versus 6.3%, P = 0.0002, as well as P. intermedia (8.8% versus 1.1%, P = 0.0003). A lack of maternal IgG antibody to organisms of the Red complex was associated with an increased rate of prematurity with an odds ratio (OR) = 2.2; confidence interval (CI) 1.48 to 3.79), consistent with the concept that maternal antibody protects the fetus from exposure and resultant prematurity. The highest rate of prematurity (66.7%) was observed among those mothers without a protective Red complex IgG response coupled with a fetal IgM response to Orange complex microbes (combined OR 10.3; P < 0.0001). These data support the concept that maternal periodontal infection in the absence of a protective maternal antibody response is associated with systemic dissemination of oral organisms that translocate to the fetus resulting in prematurity. The high prevalence of elevated fetal IgM to C. rectus among premature infants raises the possibility that this specific maternal oral pathogen may serve as a primary fetal infectious agent eliciting prematurity.

Antepartum or postpartum isoniazid treatment of latent tuberculosis infection.

OBJECTIVE: To compare health outcomes and costs of different strategies for treatment of latent tuberculosis infection in pregnancy. METHODS: Using a Markov decision-analysis model, the following three strategies were evaluated for treatment of latent tuberculosis infection in pregnancy, defined as positive tuberculin skin reaction of 10 mm or greater and negative chest radiograph: no treatment, antepartum isoniazid administration, in which women were given 300 mg of isoniazid with pyridoxine beginning at 20 weeks' gestation for 6 months; and postpartum isoniazid, in which women were given isoniazid and pyridoxine for 6 months after delivery. Sensitivity analyses were performed for a wide range of probability and cost estimates, and considered discount rates. RESULTS: Under base-case assumptions, the fewest cases of tuberculosis within the cohort occurred with antepartum treatment (1400 per 100,000) compared with no treatment (3300 per 100,000) or postpartum treatment (1800 per 100,000). Antepartum treatment resulted in a marginal increase in life expectancy due to the prevented cases of tuberculosis, despite more cases of isoniazid-related hepatitis and deaths, compared with no treatment or postpartum treatment. Antepartum treatment was the least expensive. Only if the case-fatality rate for tuberculosis was tenfold lower than the base-case and the risk of fatal hepatitis tenfold higher did antepartum treatment become the least advantageous strategy. CONCLUSION: Rather than delaying treatment until postpartum, consideration for antepartum treatment of latent tuberculosis during pregnancy should be given. If isoniazid is not administered antepartum, then efforts to improve postpartum compliance should be instituted, as either antepartum or postpartum treatment is better than no treatment.

Differential localization of placental extracellular superoxide dismutase as pregnancy progresses.

OBJECTIVE: The aim of this study was to determine placental localization and activity of extracellular superoxide dismutase, a nitric oxide modulator, during early gestation and to correlate these characteristics with fetal vascular development. STUDY DESIGN: First-trimester (n = 10) and second-trimester (n = 10) villi were obtained at elective pregnancy termination. Extracellular superoxide dismutase was localized by means of an immunoperoxidase method. Activity was measured by determining the inhibition of cytochrome c reduction at pH 10 and messenger ribonucleic acid expression by in situ hybridization. RESULTS: Extracellular superoxide dismutase was intracellular within villous trophoblasts until 17 weeks' gestation, when it relocated to the villous extracellular matrix. Activities were similar between first- and second-trimester villi. In situ hybridization confirmed extracellular superoxide dismutase messenger ribonucleic acid within trophoblasts throughout gestation. CONCLUSION: Extracellular superoxide dismutase is produced by trophoblasts early in pregnancy, but it remains intracellular until 17 weeks' gestation, which may be related to fetal vascular development.

Extracellular superoxide dismutase localization and activity within the human placenta.

Maintenance of low vascular tone within the placenta is mediated by nitric oxide (NO). The half-life of NO is very short, as superoxide anion (O2-) rapidly inactivates NO to form peroxynitrite. Superoxide dismutases compete with NO for O2-. By scavenging O2-, superoxide dismutase promotes the vasodilatory action of NO. Extracellular superoxide dismutase (EC-SOD) is present in high concentrations within the extracellular matrix of systemic arteries and has been proposed to mediate vascular smooth muscle tone by increasing NO bioavailability. The localization and activity of EC-SOD within the human placenta has not been determined. Placental EC-SOD may be involved in placental vascular tone, and abnormal activity may lead to pre-eclampsia secondary to increased O2--mediated inactivation of NO. To investigate this possibility, the activity and localization of human placental EC-SOD was determined in normal women, and then compared to pre-eclamptic women. Placental EC-SOD localized within the villous extracellular matrix around arterioles, and there were no differences in distribution between normal and pre-eclamptic women. There were no differences in placental EC-SOD activity between normal and pre-eclamptic subjects in either center (33.7+/-4.1 versus 33.1+/-2.5, P=0.6), or peripheral (34.3+/-5.6 versus 34.0+/-3.5, P=0.9) samples. EC-SOD localization around villous vessels suggests that EC-SOD serves potentially to protect the fetal vasculature from O2-, in both normal and pre-eclamptic pregnancies. Placental EC-SOD distribution and activity is not different between pre-eclamptic and normal women, suggesting that EC-SOD is not involved in the vascular changes seen in pre-eclampsia.

Umbilical venous D-dimer concentrations with and without labor.

OBJECTIVE: To determine if labor activates the fetal fibrinolytic system. METHODS: A total of 59 umbilical venous blood samples were collecting following vaginal delivery at term (n = 20), cesarean delivery following labor at term (n = 12), vaginal delivery before term (n = 18), and cesarean delivery without labor (n = 9). D-dimer concentrations, a sensitive marker of fibrinolysis, were measured by enzyme-linked immunosorbent assay, and compared between groups by Kruskel-Wallis and Mann Whitney U tests, with significance defined as P < .05. RESULTS: There were no significant differences in median D-dimer concentrations between newborns delivered vaginally or by cesarean after term labor or preterm labor. There were significant differences in median umbilical venous D-dimer concentrations in subjects delivered vaginally or by cesarean after term or preterm labor compared with term subjects without labor delivered by cesarean (427, 773, and 326 versus 87 ng/mL, P = .01). CONCLUSION: Elevation of umbilical plasma D-dimer concentrations in laboring patients suggests activation of fetal fibrinolysis before delivery.

Placental pathology in patients using cocaine: an observational study.

OBJECTIVE: Although retroplacental hemorrhage is a major cause of fetal death, its etiology often remains obscure. In some reports, cocaine use by pregnant women has been associated with retroplacental hemorrhage and clinical abruptio placentae. This study was designed to assess the occurrence of chorionic villus hemorrhage, an entity shown recently to be associated with retroplacental hemorrhage, in the placentas of cocaine users. METHODS: Twenty-nine placentas from cocaine users and 15 placentas from drug-free controls, as determined by questionnaire and urine toxicology screen, were examined prospectively, and pathological findings documented. The prevalence of retroplacental hemorrhage, chorionic villus hemorrhage, edema, chorioamnionitis, funisitis, infarction, fetal vessel thrombosis, and intervillus hemorrhage was examined in the two groups. RESULTS: Chorioamnionitis was the most frequent finding in both groups (58% of cocaine users, 66% of controls). Edema of moderate severity or greater was found only in the cocaine-using group (17%). The prevalence of chorionic villus hemorrhage among women using cocaine also was 17%. CONCLUSION: Cocaine use during pregnancy may be associated with chorionic villus hemorrhage and villus edema, even in the absence of clinical abruptio placentae. The relationship between abnormal placental morphology and adverse perinatal outcomes remains to be determined.

Performance of a commercial polymerase chain reaction test for endocervical Chlamydia trachomatis infection in a university hospital population.

OBJECTIVES: To examine the accuracy of a commercial polymerase chain reaction (PCR) test (Amplicor CTR, Roche Diagnostic Systems, Branchburg NJ) for identification of endocervical chlamydial infections through both laboratory evaluation and among a diverse teaching hospital patient population. METHODS: Testing of reliable threshold inocula and reproducibility were carried out using laboratory stock organisms. Paired endocervical samples from patients with a wide range of indications were tested by PCR and an established culture procedure, and discrepant pairs were further analyzed to determine true results. RESULTS: Laboratory evaluation suggested that one copy of target DNA from a viable organism consistently yielded a positive result, and test reproducibility was very good, with an overall coefficient of variation of 15%. Compared to true results in 1,588 paired clinical samples from 1,489 women with a 10% prevalence of infection, the PCR test and culture yielded respective sensitivities of 87.4% and 78.0%, and negative predictive values of 98.6% and 97.6%. Specificity and positive predictive value for both tests were 100%. Cost per specimen was nearly identical at $18.84 and $18.88 respectively. Polymerase inhibitors and organisms lacking target DNA were not found in false-negative PCR samples. CONCLUSION: This commercial PCR test is accurate, cost-competitive, and much faster than culture for diagnosis of endocervical chlamydia infections in our population of intermediate prevalence of chlamydial infection.

Delivery of the nonvertex second twin: a review of the literature.

Twin gestations comprise approximately 1 percent of all pregnancies (1), and are associated with increased perinatal morbidity and mortality, mainly due to the increased incidence of prematurity and growth restriction (2). Hazards of twin delivery can be attributed to malpresentation, most often by the second twin. The vertex-nonvertex presentation occurs in approximately 40 percent of all twins (3, 4). Although there is consensus regarding the safety of vaginal delivery for twins when both are vertex (5), controversy exists over intrapartum management when the second twin is nonvertex. Some investigators advocate cesarean delivery, particularly when the second twin is nonvertex (6), or if the expected birth weight is < 2000 gm (6-8). This review aims to determine whether vaginal delivery of the nonvertex second twin, either by breech extraction or attempted external cephalic version, is associated with increased morbidity or mortality over cesarean delivery.

A randomized controlled trial of the effect of third-trimester calcium supplementation on maternal hemodynamic function.

OBJECTIVE: To determine the effect of third-trimester calcium supplementation on maternal hemodynamic function. METHODS: Pregnant women were randomized to receive either 1.5 g of elemental calcium or placebo for 6 weeks during the third trimester. Using Doppler technique, maternal hemodynamic characteristics were measured at baseline, at 2 hours after the first dose of study drug, and at the completion of 6 weeks. Serum, dietary, and urinary calcium levels were also assessed. Power calculation indicated the need to study ten subjects in each group to detect a 1.2 L (20%) difference in cardiac output between groups, assuming a mean of 6.2 +/- 1.0 L/minute. Data were analyzed by analysis of variance for repeated measures, Student t test, Mann-Whitney U test, and Fisher exact test. RESULTS: Twenty-three women enrolled, and 18 completed the study. There were no statistically significant differences in demographic characteristics or in serum, dietary, or urinary calcium levels between the two groups. There were also no statistically significant differences in hemodynamic function over time within the calcium supplementation or placebo group (P > .05; analysis of variance for repeated measures). After 6 weeks, there were no significant differences between the calcium- and placebo-treated subjects in any hemodynamic measurement. Specifically, there was not a statistically significant difference in cardiac output (7.3 +/- 1.2 L/minute versus 8.0 +/- 0.9 L/minute; P = .09) between the calcium- and placebo-treated groups. CONCLUSION: These findings suggest that third-trimester calcium supplementation does not significantly alter cardiac output. The mechanism by which calcium supplementation lowers blood pressure remains to be elucidated.

Maternal serum granulocyte-colony stimulating factor in preterm birth with subclinical chorioamnionitis.

Preterm birth has been linked with intrauterine infection and inflammation. Serum and amniotic fluid markers of inflammation, such as interleukin-1 (IL-1), IL-6, and granulocyte-colony stimulating factor (G-CSF), have been associated with clinical chorioamnionitis and preterm delivery. As G-CSF regulates the production and maturation of neutrophils, we sought to determine if maternal serum G-CSF levels are elevated in patients with preterm birth with subclinical histologic chorioamnionitis. Maternal serum G-CSF levels were significantly different among five groups of women studied (P < .001, Kruskall-Wallis test), and were highest in subjects with preterm labor who delivered preterm (P < .05, Mann-Whitney U test). Among women with preterm labor who delivered preterm, maternal serum G-CSF levels were significantly higher if histologic chorioamnionitis was present than when histologic evidence of infection was not present (P = 0.04, Mann-Whitney U test). Intrauterine infection may cause a local inflammatory process and initiate preterm labor. This inflammatory response may include production of G-CSF, which would enter the circulation and stimulate the migration of neutrophils to the site of infection. Our data support this concept, as maternal serum G-CSF is elevated with subclinical infection in association with preterm birth.

Herpes simplex virus type 2 detection by culture and polymerase chain reaction and relationship to genital symptoms and cervical antibody status during the third trimester of pregnancy.

OBJECTIVES: Our goal was to define the frequency of asymptomatic herpes simplex virus type 2 shedding by culture and polymerase chain reaction and to correlate our findings with cervical anti-herpes simplex virus type 2 immunoglobulin A production. STUDY DESIGN: Women who were seropositive for herpes simplex virus type 2 collected daily genital tract samples during the third trimester for culture and deoxyribonucleic acid quantitation by polymerase chain reaction. Cervical secretions were collected weekly for anti-herpes simplex virus type 2 immunoglobulin A. Asymptomatic shedding by culture versus polymerase chain reaction and anti-herpes simplex virus type 2 immunoglobulin A detection with and without genital shedding were compared by means of McNemar's chi 2 test. RESULTS: Asymptomatic shedding was more frequent by polymerase chain reaction than by culture (13.8% vs 2.3%, p < 0.0001). When cervical anti-herpes simplex virus type 2 immunoglobulin A was present, patients were more likely to have negative results by polymerase chain reaction than positive results (66.7% vs 26.7%, p = 0.001). Anti-herpes simplex virus type 2 immunoglobulin A was detected beyond 37 weeks in only one subject. CONCLUSIONS: Polymerase chain reaction was more sensitive than culture for detecting asymptomatic genital herpes simplex virus. The role of immunoglobulin A in clearing genital herpes simplex virus remains to be determined.