Charles E. L. Brown

Puerperal septic pelvic thrombophlebitis: Incidence and response to heparin therapy

OBJECTIVE Before the availability of modern imaging studies the diagnosis of septic pelvic thrombophlebitis causing prolonged puerperal fever was difficult to confirm without surgical exploration. With the use of computed tomography infection-related pelvic phlebitis can now be confirmed, and this study was designed to determine its incidence after delivery. We also designed a randomized clinical trial to evaluate the efficacy of heparin added to antimicrobial therapy for treatment of women with septic phlebitis. STUDY DESIGN We studied women who had pelvic infection and fever that persisted after 5 days despite adequate antimicrobial therapy with clindamycin, gentamicin, and ampicillin. After giving consent study participants underwent abdominopelvic computed tomographic imaging. Women with pelvic thrombophlebitis were randomly assigned to 1 of 2 management schemes that included continuation of antimicrobial therapy, either alone or with the addition of heparin, until the temperature was </=37.5 degrees C for 48 hours. RESULTS During the 3-year study period 44,922 women were delivered at Parkland Hospital; among these 8535 (19%) were delivered by the cesarean route. There were 69 women who met criteria for prolonged infection, and 15 (22%) of these were found to have septic pelvic thrombophlebitis. Four had infection after vaginal delivery and 11 had been delivered by the cesarean route. Of 14 women randomly assigned to therapy, 8 were assigned to receive continued antimicrobial therapy without the addition of heparin and the other 6 were assigned to receive heparin therapy in addition to the antimicrobial agents. According to an intent-to-treat analysis there was no significant difference between the responses of women with pelvic infection who were and were not given heparin therapy. Specifically, women not given heparin were febrile for 140 +/- 39 hours compared with 134 +/- 65 hours for women who received heparin (P =.83). Duration of hospitalization was also similar between the 2 groups at 10.6 +/- 1.9 days for those with thrombosis who were given antimicrobial agents alone and 11.3 +/- 1.2 days for women who also received heparin (P >.5). The 54 women with persistent fever but without computed tomographic evidence of septic pelvic thrombophlebitis were hospitalized for a mean of 12.0 +/- 4.1 days, compared with 10.9 +/- 2.9 days for women in whom thrombosis was diagnosed (P =.14). These women were followed up for >/=3 months post partum and none showed evidence of reinfection, embolic episodes, or postphlebitic syndrome. CONCLUSIONS The overall incidence of septic pelvic thrombophlebitis was 1:3000 deliveries. The incidence was about 1:9000 after vaginal delivery and 1:800 after cesarean section. Women given heparin in addition to antimicrobial therapy for septic thrombophlebitis did not have better outcomes than did those for whom antimicrobial therapy alone was continued. These results also do not support the common empiric practice of heparin treatment for women with persistent postpartum infection.

Low-dose aspirin: I. Effect on angiotensin II pressor responses and blood prostaglandin concentrations in pregnant women sensitive to angiotensin II

Decreased incidence of proteinuric hypertension after low-dose aspirin therapy is hypothesized to be a consequence of selective thromboxane A2 inhibition and sparing of prostacyclin. This study was designed to ascertain if low-dose aspirin therapy (81 mg/day for 1 week) alters vascular refractoriness to angiotensin II and the prostacyclin/thromboxane A2 ratio in pregnant women sensitive to angiotensin II (n = 17). Low-dose aspirin increased the effective pressor dose of angiotensin II from 5.9 +/- 2.4 to 10.2 +/- 5.5 ng/kg/min (p less than 0.01, mean +/- SD). Platelet-derived serum thromboxane B2 (a metabolite of thromboxane A2), a measure of therapy compliance, decreased from 1804 +/- 1771 to 132 +/- 206 pg/ml (p less than 0.01). Plasma thromboxane B2 decreased from 130 +/- 107 to 19 +/- 12 pg/ml (p less than 0.01). Inhibition was not selective because 6-keto-prostaglandin F1 alpha (a metabolite of prostacyclin) also decreased from 243 +/- 90 to 163 +/- 90 pg/ml (p = 0.039) and prostaglandin E2 was reduced from 155 +/- 67 to 95 +/- 40 pg/ml (p = 0.014). Decreases in thromboxane B2, however, were significantly greater (75% +/- 19%) than decreases in 6-keto-prostaglandin F1 alpha (21% +/- 33%) or prostaglandin E2 (29% +/- 36%); thus the 6-keto-prostaglandin F1 alpha/thromboxane B2 ratio increased from 3.1 +/- 2.0 to 12.4 +/- 9.9 (p less than 0.01). Although low-dose aspirin increases the effective pressor dose of angiotensin II, it does not return to normal pregnancy values. This observation is consistent with the hypothesis that this represents only a partial selective prostaglandin inhibition.

Predicting risk of preterm birth: the roles of stress, clinical risk factors, and corticotropin-releasing hormone.

The relationships and predictive abilities of perceived stress, selected clinical risk factors, and corticotropin-releasing hormone (CRH) levels in maternal plasma were investigated for their association with preterm labor (PTL), preterm birth, and gestational age at delivery. An exploratory, prospective, longitudinal research design was used to measure CRH 4 times over pregnancy, perceived stress at 24 and 32 weeks of pregnancy, clinical risk factors, and genitourinary infections in low-income women. Multiple regression analyses revealed that a model of measurement of perceived stress at 24 or 32 weeks, CRH at 24 or 32 weeks, and PTL (indicated by a diagnosis by the physicians on the medical record and greater than 5 contractions per hour on the fetal monitor) was predictive of as much as 0.23 to 0.27 of the variance in gestational age at birth. Entering ethnicity as a variable into a model did not improve the predictive value. An analysis of variance between Caucasian and Hispanic ethnic groups revealed differences in CRH levels. However, simple regression analysis of ethnicity as a predictor showed a weak r 2 with no significance for prediction. There was some evidence of an association of smoking with stress and both PTL and preterm birth. The measurement of stress combined with the measurement of CRH from maternal plasma may improve the prediction of which pregnant women are at risk for preterm birth. The measurement of CRH has potential as an early biological marker of preterm birth.

Relationships of cortisol, perceived stress, genitourinary infections, and fetal fibronectin to gestational age at birth.

The authors investigated the role of stress and cortisol with patients having pretermlabor (PTL) and preterm birth (PTB). The relationships of maternal cortisol, perceived stress, fetal fibronectin (fFN), and genitourinary infections to PTL and PTB were studied. A prospective, longitudinal, observational study (n = 78) was conducted in a private practice in central Texas. Subjects had 4 blood draws for cortisol measurements grouped by 15-19, 20-22, 23-26, 27-30, and 31-35 weeks of gestation. Subjects had 2 vaginal swabs for fFN, chlamydia, and bacterial vaginosis screens at 23-26 and 27-30 weeks with assessment of psychosocial stress at 23-26 and 31-35 weeks. Statistical analysis was by analysis of variance, Pearson correlations, Fisher exact test, and logistic regression. There were no significant differences between the PTB, PTL, and termgr oups on cortisol levels at any of the gestational periods. Cortisol concentrations at any gestational stage did not correlate with gestational age at birth. A relationship of cortisol to race was observed when comparing Caucasians to other ethnic groups. A correlation (r = 0.42, P < 0.001) between the change in Perceived Stress Scale (PSS) score and gestational age was observed. The greater the decrease in PSS scores, the longer was the gestational age. A significant increase in cortisol at 19-21 weeks (P < 0.04), 23-26 weeks (P < 0.05), and 31-35 weeks (P < 0.01) was observed in patients having genitourinary infection. PTL was also significantly increased in subjects having positive genitourinary infections at either 23-26 weeks or 27-30 weeks (P < 0.01). The sensitivity of fFN to predict PTL collected at 27-30 weeks was 40%, specificity 86%, positive predictive value 55%, and negative predictive value 83%. These results indicate that cortisol is a poor predictor of either PTL or PTB. A decrease in perceived stress during the 2nd trimester was associated with an increase in length of gestation, suggesting the possibility of stress reduction as an appropriate intervention for lengthening gestational age.

The effect of acculturation on progesterone/estriol ratios and preterm birth in hispanics

OBJECTIVE: To examine the Hispanic acculturation paradox by identifying the effect of acculturation on serum progesterone and estriol levels, the progesterone/estriol ratio, and preterm birth. METHODS: We used an observational, prospective design with 468 self-identified, low-income, pregnant Hispanic women. We used the Language Proficiency Subscale (from the Bidimensional Acculturation Scale for Hispanics) to measure acculturation. We measured progesterone and estriol in maternal serum at 22–24 weeks of pregnancy. We defined preterm birth as birth before 37 weeks of gestation. Statistical analysis was by Wilcox-Mann-Whitney and Kruskal-Wallis tests, analysis of variance, t tests, logistic regression, and structural equation modeling. RESULTS: English proficiency had an adjusted odds ratio of 4.03 (95% confidence interval 1.44–11.25), P<.001, and the lowest quartile of the progesterone/estriol ratio had an adjusted odds ratio of 2.93 (95% confidence interval 1.25–6.89), P<.001, to predict preterm birth. English proficiency was associated with a decrease in progesterone/estriol ratio and an increase in preterm birth. In structural equation modeling, the progesterone/estriol ratio mediated the relationship between acculturation and preterm birth. CONCLUSION: Hispanic woman have four times the risk of a preterm birth if they are more acculturated (ie, proficient in English). These findings demonstrate another possible aspect of obstetric risk, that of acculturation. Further refinement of the risk of acculturation is essential to clarify how we can adjust our clinical care to prevent increasing preterm birth with the increasing Hispanic population. LEVEL OF EVIDENCE: III

Acculturation, depressive symptoms, estriol, progesterone, and preterm birth in Hispanic women

We examined the effects of acculturation, depressive symptoms, progesterone, and estriol (E3) as predictors of preterm birth (PTB) in pregnant Hispanic women. This cross-sectional study recruited a sample of 470 Hispanic women between 22- and 24-week gestation from physician practices and community clinics. We used the CES-D to measure maternal depressive symptoms. We measured acculturation by English proficiency on the Bidimensional Acculturation Scale, residence index by years in the USA minus age, nativity, and generational status. Serum progesterone and E3 were analyzed by EIA. Ultrasound and medical records determined gestational age after delivery. In χ2 analysis, there were a significantly greater percentage of women with higher depressive scores if they were born in the USA. In a structural equation model (SEM), acculturation (English proficiency, residence index, and generational status) predicted the estriol/progesterone ratio (E/P), and the interaction of depressive symptoms with the E/P ratio predicted PTB. Undiagnosed depressive symptoms during pregnancy may have biological consequences increasing the risk for PTB.

Placental transfer of cefazolin and piperacillin in pregnancies remote from term complicated by Rh isoimmunization.

Although the administration of prophylactic antibodies for intrauterine transfusion is controversial, little information is available regarding placental transfer of antibiotics administered to the mother, or whether the presence of hydrops affects this placental transfer. Sixteen intravascular intrauterine transfusions were performed in 10 patients. Seven (10 procedures) patients were given 2 gm of cefazolin before the procedure and samples were obtained by fetal vascular access. Three patients (six procedures) were given 4 gm of piperacillin and samples were similarly obtained. Specimens were obtained for fetal serum, maternal serum, and amniotic fluid antibiotic concentration. The mean serum cefazolin concentration in hydropic fetuses was 18.04 +/- 3.37 micrograms/ml, and in nonhydropic fetuses the concentration was 21.02 +/- 17.8 micrograms/ml (p = 0.72). The mean fetal serum concentration of piperacillin was 22 +/- 12 micrograms/ml. The placental transfer of both drugs was similar. We conclude that the transplacental passage of these antibiotics is prompt and that the presence of hydrops does not significantly impair the passage of cefazolin.

The Utility of fFN for the Prediction of Preterm Birth in Twin Gestations

OBJECTIVE To determine the sensitivity, specificity, and positive predictive value (PPV) of fetal fibronectin (fFN) and to determine its usefulness, in conjunction with selected other clinical assessment measures, in the prediction of preterm birth for women with twin gestations. DESIGN A prospective, descriptive, longitudinal design. SETTING An obstetrical high-risk clinic that received patient referrals from several surrounding communities in central Texas. PATIENTS/PARTICIPANTS Forty-eight women identified with twin gestations prior to the 22nd week of pregnancy; primarily of Hispanic ethnicity. MAIN OUTCOME MEASURES A substantial number of outcome variables were assessed in this study. In the present report, data derived from weekly assessments for the identification of the presence of fFN, the diagnosis of bacterial vaginosis, and the measurement of cervical length were reviewed for their relationship to prematurity, birth weight, birth weight discordancy and placental chorionicity. RESULTS The relative risk of birth prior to 35 weeks gestation, fetal death, or discordance of twin birth weights of greater than 20% was 2.22 (CI: 1.09, 4.55, P < 0.015) when fFN was found to be positive at any weekly testing after 22 to 24 weeks gestation (sensitivity 76.82%, specificity 58.33%, PPV 66.7%). The presence of fFN was most highly predictive of preterm birth when performed during the 24th to 28th gestational week. Shorter cervical lengths were highly correlated with preterm birth (r = -0.6). An association between bacterial vaginosis and preterm birth was not demonstrated in this sample. CONCLUSION Sampling for the presence of fetal fibronectin can be easily accomplished by RNs in labor triage units and by advanced practice nurses in outpatient settings. The identification of fFN, particularly during the 24 to 28 weeks gestational time frame, is highly predictive of preterm birth, and particularly so for women with twin gestations.

Randomized, Double-Blinded, Placebo-Controlled Trial of Amoxicillin/Clavulanic Acid to Prevent Preterm Delivery in Twin Gestation

Objective: The objective of this study was to determine whether prophylactic treatment with oral broad-spectrum antimicrobial therapy improves pregnancy outcomes in twin gestations. Methods: Patients with twin gestations between 24 and 32 weeks were randomized to receive amoxicillin/clavulanic acid or placebo. Those patients randomized before 24 weeks received a 1-week course at 24 and at 28 weeks gestation. Those patients entered later than 24 weeks received a 1-week course either at 28 weeks or at enrollment (up to 32 weeks). Other than antibiotic use, the management of the groups was identical and unchanged from the routine care of twin gestations. Results: Of 149 twin pregnancies enrolled, 76 were randomized to the drug group and 73 to the placebo group. There was no significant difference in mean gestational age at delivery (35.9 vs. 35.7 weeks), birth weight (2,358 vs. 2,344 g), mean neonatal nursery stay (9.9 vs. 11.7 days), or respiratory distress syndrome (6/76 vs. 4/73) in the drug vs. placebo group, respectively. Conclusions: The addition of prophylactic oral broad-spectrum antimicrobial therapy to the standard antepartum management of twin gestations had no demonstrable effect on the gestational age at delivery, birth weight, or neonatal complications. There did not appear to be any beneficial effect of the prophylactic use of amoxicillin/clavulanic acid in this clinical setting.

Renal pelvicalyceal dilation in antepartum pyelonephritis: Ultrasonographic findings

The purpose of the present study was to determine whether pregnant women with pyelonephritis have differences of pelvicalyceal systems, compared with normal pregnant control subjects, that might predispose to upper urinary tract infection. Ultrasonographic examination of both kidneys in coronal and axial planes of 24 women with clinical pyelonephritis and positive urine cultures was compared with results in control subjects matched for gestational age, parity, and race. Women with right or bilateral pyelonephritis had increased dilation of the right calyceal system, compared with controls (1.7 cm vs 0.8 cm, p less than 0.001). Renal pelvis volume was increased as well (29.3 vs 5.5 cm3, p less than 0.001). Renal pelvicalyceal dilation in antepartum pyelonephritis was significantly increased compared with normal physiologic dilation of pregnancy. Follow-up nephrosonography in a small number of women (N = 10) after treatment of pyelonephritis did not reveal a consistent decrease in renal dilation, suggesting that dilation of the renal pelvis may antedate pyelonephritis. Further study of this phenomenon is warranted.