Joseph A. Spinnato

Pain and discomfort thresholds in late pregnancy

&NA; Gintzler [6] found an abrupt increase in pain thresholds in rats during the last days of gestation. While some data suggest a similar increase in pain thresholds for pregnant women, Goolkasian and Rimer [7] have found, using signal detection procedures, that women are increasingly likely to report stimuli as painful during the last 2 weeks of pregnancy. The present studies were carried out to assess pain and discomfort thresholds in the last weeks of womens pregnancies. In the first study, daily measures of the pressure‐induced pain thresholds of 6 women who had spontaneous, vaginal births increased during the last 16 days of pregnancy and exceeded the 300 mm Hg maximum stimulus pressure for the last 9 days of pregnancy. In the second study, the discomfort thresholds of 6 women were measured each day during the last 11 days of pregnancy before spontaneous vaginal births. The discomfort thresholds of the pregnant women were higher than those of 6 non‐pregnant women whose discomfort thresholds were also measured each day. Pregnant womens thresholds increased before the onset of labor, while the discomfort thresholds of the non‐pregnant women were unchanged during the course of the study. These results extend Gintzlers findings of reduced sensitivity to pain shortly before parturition.

Antioxidant Therapy to Prevent Preeclampsia A Randomized Controlled Trial

OBJECTIVE: To study whether antioxidant supplementation will reduce the incidence of preeclampsia among patients at increased risk. METHODS: A randomized, placebo-controlled, double-blind clinical trial was conducted at four Brazilian sites. Women between 12 0/7 weeks and 19 6/7 weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomly assigned to daily treatment with both vitamin C (1,000 mg) and vitamin E (400 International Units) or placebo. Analyses were adjusted for clinical site and risk group (prior preeclampsia, chronic hypertension, or both). A sample size of 734 would provide 80% power to detect a 40% reduction in the risk of preeclampsia, assuming a placebo group rate of 21% and &agr;=.05. The &agr; level for the final analysis, adjusted for interim looks, was 0.0458. RESULTS: Outcome data for 707 of 739 randomly assigned patients revealed no significant reduction in the rate of preeclampsia (study drug, 13.8% [49 of 355] compared with placebo, 15.6% [55 of 352], adjusted risk ratio 0.87 [95.42% confidence interval 0.61–1.25]). There were no differences in mean gestational age at delivery or rates of perinatal mortality, abruptio placentae, preterm delivery, and small for gestational age or low birth weight infants. Among patients without chronic hypertension, there was a slightly higher rate of severe preeclampsia in the study group (study drug, 6.5% [11 of 170] compared with placebo, 2.4% [4 of 168], exact P=.11, odds ratio 2.78, 95% confidence interval 0.79–12.62). CONCLUSION: This trial failed to demonstrate a benefit of antioxidant supplementation in reducing the rate of preeclampsia among patients with chronic hypertension and/or prior preeclampsia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.ClinicalTrials.gov, NCT00097110 LEVEL OF EVIDENCE: I

The influence of epidural analgesia on cesarean delivery rates: A randomized, prospective clinical trial

OBJECTIVE The effects of epidural analgesia on the progress of labor are controversial. The objective of this study was to determine the effect of epidural analgesia on cesarean delivery rates in a population of patients randomly assigned to receive either epidural analgesia or intravenous opioids for intrapartum pain relief. STUDY DESIGN From January 1995 to May 1996, 318 spontaneously laboring, term, nulliparous patients were randomly assigned to receive either intravenous opioids or epidural analgesia for pain relief. Labor was managed according to the principles of active management of labor. Cesarean delivery was performed for obstetric indications. Data analysis was conducted on an intent-to-treat basis. A subanalysis was subsequently performed on patients who were compliant with the allocated form of treatment. RESULTS One hundred sixty-two patients were randomly assigned to receive intravenous meperidine and 156 were randomly assigned to receive epidural analgesia. Maternal age, gravidity, race, gestational age, and cervical dilatation at admission and at first analgesic dose did not differ between the groups. Intent-to-treat data analysis revealed no significant difference in the cesarean delivery rate between the 2 groups, being 13.6% in the opioid group and 9.6% in the epidural group (relative risk 0.70, 95% confidence interval 0.38-1.31, P >.05). Cesarean delivery rates for the indication of dystocia also did not differ, being 10.5% in the opioid group and 5.8% in the epidural group (relative risk 0.56, 95% confidence interval 0.26-1.21, P >.05). Subanalysis of the data from patients who were compliant with the allocated form of treatment revealed that patients in the epidural group (n = 147) were 3 times more likely to have an active phase duration >/=8 hours and were 10 times more likely to require >/=2 hours in the second stage of labor than were those in the opioid group (n = 78). There were no significant differences in cesarean delivery rates in this subanalysis, being 7.7% in the opioid group and 8.8% in the epidural group (relative risk 1.15, 95% confidence interval 0.45-2.91, P >. 05). The cesarean delivery rates for dystocia were also similar in the subanalysis, being 3.8% in the opioid group and 5.5% in the epidural group (relative risk 1.42, 95% confidence interval 0.39-5. 22, P >.05). CONCLUSION Epidural analgesia provides safe and effective intrapartum pain control and may be administered without undesirable effects on labor outcome.

Longitudinal study of platelet indices during normal pregnancy

The purpose of this longitudinal, prospective study was to define platelet indices during normal pregnancy and to compare them to normal nonpregnant values. Indices evaluated included platelet count, mean platelet volume, and platelet distribution width. No significant change occurred in the mean platelet count or mean platelet volume from the second to the third trimester; however, platelet distribution width increased progressively and significantly during this interval (p less than 0.0001). Mean platelet volume versus platelet count showed a significant inverse relationship (p less than 0.0001) and was congruent with normal nonpregnant values. Mean platelet volume versus platelet distribution width exhibited a significant direct relationship (p less than 0.03) that differed remarkably from normal nonpregnant values. These data support the concept of normal pregnancy as a compensated state of progressive platelet consumption. These findings may have important diagnostic and prognostic applications in discerning acute states of platelet consumption superimposed on the compensated consumption of normal pregnancy.

Serum inhibin A and angiogenic factor levels in pregnancies with previous preeclampsia and/or chronic hypertension: are they useful markers for prediction of subsequent preeclampsia?

OBJECTIVE Our objective was to determine whether measurement of placenta growth factor (PLGF), inhibin A, or soluble fms-like tyrosine kinase-1 (sFlt-1) at 2 times during pregnancy would usefully predict subsequent preeclampsia (PE) in women at high risk. STUDY DESIGN We analyzed serum obtained at enrollment (12(0/7) to 19(6/7) weeks) and follow-up (24-28 weeks) from 704 patients with previous PE and/or chronic hypertension (CHTN) enrolled in a randomized trial for the prevention of PE. Logistic regression analysis assessed the association of log-transformed markers with subsequent PE; receiver operating characteristic analysis assessed predictive value. RESULTS One hundred four developed preeclampsia: 27 at 37 weeks or longer and 77 at less than 37 weeks (9 at less than 27 weeks). None of the markers was associated with PE at 37 weeks or longer. Significant associations were observed between PE at less than 37 weeks and reduced PLGF levels at baseline (P = .022) and follow-up (P < .0001) and elevated inhibin A (P < .0001) and sFlt-1 (P = .0002) levels at follow-up; at 75% specificity, sensitivities ranged from 38% to 52%. Using changes in markers from baseline to follow-up, sensitivities were 52-55%. Associations were observed between baseline markers and PE less than 27 weeks (P < or = .0004 for all); sensitivities were 67-89%, but positive predictive values (PPVs) were only 3.4-4.5%. CONCLUSION Inhibin A and circulating angiogenic factors levels obtained at 12(0/7) to 19(6/7) weeks have significant associations with onset of PE at less than 27 weeks, as do levels obtained at 24-28 weeks with onset of PE at less than 37 weeks. However, because the corresponding sensitivities and/or PPVs were low, these markers might not be clinically useful to predict PE in women with previous PE and/or CHTN.

Eclampsia. IV. Neurological findings and future outcome.

Sixty-five patients with eclampsia were longitudinally evaluated regarding neurological abnormalities and maternal outcome (6 to 42 months) after eclampsia. Electroencephalograms were obtained on all patients during the subsequent 6 months. Computerized axial tomographic scans (n = 20) and cerebral arteriograms (n = 3) were obtained on patients with neurological deficits and/or those with an atypical clinical course. The electroencephalogram was abnormal in 49 patients (75%) at initial assessment but gradually returned to normal in all observed patients within 6 months. Cerebral arteriograms and computerized axial tomographic scans were normal in each patient studied. None of the patients had neurological deficits or subsequent convulsions on follow-up examination. Thirty-eight patients had one or more subsequent pregnancies without recurrent eclampsia, but 14 (37%) had pregnancy-induced hypertension. The findings suggest that neurological events of eclampsia are acute and transient and that long-term neurological deficit is rare in the properly managed patient. Computerized axial tomography and electroencephalography are rarely indicated in the management of such patients.

Induction of immune responses to ovarian tumor antigens by multiparity

Objective: Because epidemiologic data indicate a reduction in ovarian cancer risk with increased parity, the occurrence of maternal immunization against ovarian tumor-associated antigens during pregnancy was investigated. Methods: Sera were obtained from nulligravid and multiparous women and from men. Cellular proteins were isolated from four ovarian tumor cell lines as well as from normal ovaries. These proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the presence of cellular proteins reactive with each individuals serum was assessed by Westrn immunoblot. Tumor-reactive antibodies from two multiparous women were used to prepare immunoaffinity columns for the isolation of reactive proteins from ovarian turmor cells. These immunoaffinity-purified antigens were transferred electrophoretically to nitrocellulose membranes, stained with Ponceau S, and identified by amino acid sequencing. Results: Western immunoblot analysis of the cellular proteins from four established ovarian tumor cell lines using sera from multiparous women as the primary antibody indicated that these samples recognized multiple bands on ovarian tumors, ranging from 30 to 150 kD. Two commonly recognized proteins were isolated and subjected to microsequencing, which identified the 56-kD band protein as elongation factor-1α and the 38-kD protein as nucleophosmin/B23 protein. Both of these proteins play integral roles in cell growth. Conclusion: These findings suggest that certain antigens expressed by the fetus immunize women during pregnancy. This immune response may protect these women from the subsequent development of cancer.

Mechanism of action of intrauterine contraceptive devices and its relation to informed consent

The purposes of this review are to evaluate the available evidence for the mechanisms of action of copper-impregnated intrauterine contraceptive devices and to describe the informed consent consequences of those mechanisms. The medical literature was reviewed with the use of the Bioethics and Medline databases (1966 to present). Reports that supported or refuted the two major postulated mechanisms (interference with implantation of the fertilized ovum or spermicidal inhibition of fertilization) were assessed for their relative strength and support for the exclusivity of one or the other mechanism. The analysis of the evidence strongly suggests that the contraceptive effectiveness of intrauterine contraceptive devices is achieved by both a prefertilization spermicidal action and a postfertilization inhibition of uterine implantation. Patient informed consent for intrauterine contraceptive device insertion should include a discussion of these mechanisms of actions so as to avoid their use in patients with moral objections to postfertilization contraception.

Myometrial estradiol and progesterone receptor changes in preterm and term pregnancies

Objective To determine if labor is associated with changes in myometrial estradiol (E2) and progesterone receptors. Methods Lower myometrial segments were obtained from women undergoing cesarean deliveries at term in labor (n = 10), term not in labor (n = 10), preterm in labor (n = 9), and preterm not in labor (n = 11). Western immunoblotting was used to determine the presence and molecular size of E2 and progesterone receptor proteins. Immunocytochemistry was used to determine E2 and progesterone receptor changes in preterm and term pregnancies. Results Myometrium from pregnant women contained 74-kilodalton (kDa) E2 receptor and 94- and 110-kDa progesterone receptor proteins. These receptors are present in both myometrial smooth muscle and myometrial blood vessels. The nuclei of myometrial smooth muscle cells primarily contain both receptors. The immunostaining for progesterone receptors was less in patients in labor compared with those not in labor in preterm and term pregnancies. In comparing patients not in labor, the immunostaining for progesterone receptors was less at term compared with preterm pregnancy. Unlike the differences in progesterone receptors, there are no obvious differences in E2 receptor immunostaining in myometrial samples from all four groups of women. Conclusion A myometrial decrease in progesterone receptors, rather than an increase in E2 receptors, may play a role in the onset of labor in women with term or preterm pregnancies.

Social support during premature labor: effects on labor and the newborn

Prematurity is the single most frequent abnormality associated with birth, and is associated with both neonatal deaths and developmental deficits. In uncomplicated labors at term, the presence of a supportive companion has been found to lead to reduced length of labor, reduced need for medication for pain management, and improved neonatal well being. The relationships have not been explored in premature labor. Women in premature labor between 26 and 37 weeks of gestation were randomly assigned to a control group (n = 11) or to a supported group (n = 14), who were accompanied during labor by a supportive companion. Support during labor was associated with fewer abnormally long labors, less frequent use of medication for pain management during labor, and improved neonatal wellbeing.