Bertis B. Little

Diagnosis of birth asphyxia on the basis of fetal pH, Apgar score, and newborn cerebral dysfunction

Imprecise diagnosis of birth asphyxia coupled with uncertainties about causal factors for neurologic abnormalities in the newborn have greatly fueled the current litigation crisis in obstetrics. Our goal was to more precisely define birth asphyxia based on fetal condition as measured by umbilical artery blood pH, Apgar scores, and neurologic condition of newborns. We selected for study 2738 patients with singleton pregnancies with cephalic presentations who were delivered of infants at term to avoid complications such as prematurity, which may affect infant outcome independent of birth condition. The basis for study of these particular patients were defined criteria for high risk and an indicated arterial cord pH value. A total of five infants demonstrated cerebral dysfunction as evidenced by seizures during the neonatal period. Infection was linked to seizures in three of these infants; one infant had neonatal asphyxia and only one infants clinical course could be attributed solely to birth events (uterine rupture). Stratification of umbilical artery blood pH values, Apgar scores, and combinations of these dependent variables in relation to newborn clinical outcomes revealed that infants must be severely depressed at delivery before birth asphyxia can be reliably diagnosed. Such depression includes Apgar scores less than or equal to 3 at 1 and 5 minutes plus umbilical artery pH values less than 7.00.

Pharmacokinetics during pregnancy: evidence-based maternal dose formulation

OBJECTIVEnTo review the literature regarding how drug pharmacokinetics differ between pregnant and nongravid women.nnnDATA SOURCESnArticles published between 1963 and 1997 were retrieved from the database of the National Library of Medicine for review, using the key words pregnancy, pharmacokinetics, and human. Additional articles and book chapters were identified from the bibliographies of articles retrieved.nnnMETHODS OF STUDY SELECTIONnArticles had to include primary data that were not previously published. Data abstracted from articles meeting the inclusion criteria included: sample size, estimated gestational age, area under the curve, volume of distribution, maximum plasma concentration, steady-state concentration, half-life, time to maximum plasma concentration, clearance, and data from nonpregnant controls.nnnTABULATION, INTEGRATION, AND RESULTSnOf more than 1000 articles published, 61 articles and book chapters reported relevant pharmacokinetic data, such as those listed, based on primary data. Only two studies synthesized pharmacokinetic data into guidelines for individualized clinical regimens.nnnCONCLUSIONnAvailable data regarding the pharmacokinetics of therapeutic regimens during pregnancy do not provide clinically relevant guidelines for the formulation of therapy for individual patients. Pharmacokinetic investigations during pregnancy that produce evidence-based guidelines for treating individual patients were identified as a major area of need. Minimum requirements are recommended for reporting pharmacokinetic studies in obstetrics.

Metabolism of cocaine by human placentas: Implications for fetal exposure

To assess placental metabolism of cocaine, placentas were obtained at the time of delivery and the microsomes were extracted by ultracentrifugation within 2 hours. Placental microsomes were cultured with cocaine at physiologic plasma concentrations similar to those of cocaine users (0.75 micrograms/ml). Two control groups were established. In the first group an anticholinesterase was added to the culture to suppress enzyme activity, and in the second cocaine was cultured alone without placental microsomes to obtain baseline spontaneous conversion of the drug. The results indicate that cocaine is biotransformed by the human placenta, presumably by cholinesterase activity. This suggests that the placenta may provide a moderate degree of protection from cocaine-induced morbidity, such as abruptio placentae and fetal growth retardation, by converting cocaine into less active metabolites. These results also have pharmacogenetic implications because cholinesterase activity varies among individuals. Hence placentas that cannot transform the drug may place the conceptus at greater risk of developmental abnormalities.

Prediction of the severity of meconium aspiration syndrome

OBJECTIVEnMeconium aspiration syndrome is associated with increased neonatal morbidity and mortality. We sought to determine whether the need for neonatal mechanical ventilation or prolonged ventilation (> or = 3 days) was predictable from antepartum, intrapartum, and immediate neonatal events.nnnSTUDY DESIGNnBetween 1987 and 1989, 8003 of 43,906 (18%) live infants had meconium-stained amniotic fluid; 82 of these infants had clinical and radiographic evidence of meconium aspiration, and of these 82, 39 (48%) required mechanical ventilation. Predictors of ventilation or prolonged ventilation were determined by means of stepwise logistic regression.nnnRESULTSnPredictors of neonatal ventilation included fetal tachycardia, interval from meconium detection to delivery, low 5-minute Apgar score, respiratory distress necessitating intubation in the delivery suite, and delivery by cesarean section. Sensitivity was 72%, and specificity was 64%; the model was incorrect in 32% of the cases. Predictors of prolonged ventilation were ominous fetal heart rate tracing, umbilical arterial pH < 7.20, birth weight > 90th percentile, nulliparity, and Apgar score > 4 at 1 minute and < or = 6 at 5 minutes. Sensitivity was 67%, and specificity was 91%; prolonged ventilation was incorrectly predicted in 17% of the cases.nnnCONCLUSIONSnUse of these models to determine the need for mechanical ventilation or prolonged ventilatory assistance will enhance identification of infants at risk of severe meconium aspiration and will lead to early transfer to the neonatal intensive care unit for intense observation and management.

Placental transfer of selected substances of abuse

The placenta was classically considered a barrier, but in 1957 this notion was shattered. This organ is only a selective filter and metabolic site. In this review, the placental transfer of the top 17 substances of abuse are analyzed. In the National Library of Medicine only 41 papers that documented placental transfer of the major substances of abuse could be located, and these data excluded approximately one-sixth of the most commonly abused substances. Nonetheless, it was possible to evaluate placental transfer of all substances of abuse based on their physical chemical properties. It is with despair that it must be reported that virtually all substances of abuse freely cross the placenta, exposing the embryo/fetus to whatever substances the mother may be using.

Body size, fatness, and leanness of Mexican American children in Brownsville, Texas: changes between 1972 and 1983.

Changes in the height, weight, body mass index, triceps skinfold, and arm and estimated midarm muscle circumferences in lower socioeconomic Mexican American children, 6 through 17 years of age, from Brownsville, Texas, were documented on the basis of surveys done in 1972 and 1983. With the exception of height in youths ages 14-17, all parameters show gains at most ages, and in particular an increase in fatness. Brownsville Mexican American youth are similar in height, weight, and the body mass index to Mexican American youth in other areas of Texas. These trends confirm the large proportion of relatively short but heavy children among Mexican Americans.

Comparison of the Impact of Short (<1 Year) and Long-Term (≥1 Year) Clopidogrel Use Following Percutaneous Coronary Intervention on Mortality

The optimal duration of clopidogrel administration after percutaneous coronary intervention (PCI) remains unknown. Clopidogrel is currently recommended for minimums of 1 and 12 months after bare-metal stent and drug-eluting stent implantation, respectively. To determine the impact of clopidogrel discontinuation 1 year after PCI, the outcomes of 530 consecutive patients who underwent PCI from January 2004 to July 2006, were free of cardiovascular events for 6 months after PCI, and had follow-up available for >12 months were examined. The outcomes of patients who received clopidogrel for > or =1 year were compared with those of patients who received it for <1 year. The mean age was 65 +/- 9 years. Patients often presented with acute coronary syndromes (57%), and 85% received drug-eluting stents. Clopidogrel was used for > or =1 year and for <1 year in 341 and 189 patients, respectively. During a mean follow-up period of 2.4 +/- 0.8 years, 40 patients (8%) died, 21 (4%) had acute myocardial infarctions, and 89 (17%) underwent repeat coronary revascularization. Compared with patients with clopidogrel administration for <1 year after PCI, those who received clopidogrel for > or =1 year had lower mortality (14.8% vs 3.5%, p <0.001). On multivariate analysis, clopidogrel use for > or =1 year was associated with lower mortality (hazard ratio 0.28, 95% confidence interval 0.14 to 0.59), independent of traditional cardiovascular risk factors, clinical presentation, and the use of drug-eluting stents. In conclusion, the use of clopidogrel for > or =1 year after PCI was associated with lower mortality.

Pilot Trial of Cryoplasty or Conventional Balloon Post-Dilation of Nitinol Stents for Revascularization of Peripheral Arterial Segments: The COBRA Trial

OBJECTIVESnThe purpose of this study is to compare post-dilation strategies of nitinol self-expanding stents implanted in the superficial femoral artery of diabetic patients with peripheral arterial disease.nnnBACKGROUNDnEndovascular treatment of superficial femoral artery disease with nitinol self-expanding stents is associated with high rates of in-stent restenosis in patients with diabetes mellitus.nnnMETHODSnWe conducted a prospective, multicenter, randomized, controlled clinical trial of diabetic patients to investigate whether post-dilation of superficial femoral artery nitinol self-expanding stents using a cryoplasty balloon reduces restenosis compared to a conventional balloon. Inclusion criteria included diabetes mellitus, symptomatic peripheral arterial disease, and superficial femoral artery lesions requiring implantation of stents>5 mm in diameter and >60 mm in length. Primary endpoint was binary restenosis at 12 months, defined as ≥2.5-fold increase in peak systolic velocity by duplex ultrasonography.nnnRESULTSnSeventy-four patients, with 90 stented superficial femoral artery lesions, were randomly assigned to post-dilation using cryoplasty (n=45 lesions) or conventional balloons (n=45 lesions). Mean lesion length was 148±98 mm, mean stented length was 190±116 mm, mean stent diameter was 6.1±0.4 mm, and 50% of the lesions were total occlusions. Post-dilation balloon diameters were 5.23±0.51 mm versus 5.51±0.72 mm in the cryoplasty and conventional balloon angioplasty groups, respectively (p=0.02). At 12 months, binary restenosis was significantly lower in the cryoplasty group (29.3% vs. 55.8%, p=0.01; odds ratio: 0.36, 95% confidence interval: 0.15 to 0.89).nnnCONCLUSIONSnAmong diabetic patients undergoing implantation of nitinol self-expanding stents in the superficial femoral artery, post-dilation with cryoplasty balloon reduced binary restenosis compared to conventional balloon angioplasty. (Study Comparing Two Methods of Expanding Stents Placed in Legs of Diabetics With Peripheral Vascular Disease [COBRA]; NCT00827853).

Environmental influences cause menstrual synchrony, not pheromones

To assess the influence of environmental conditions on the pattern of menstrual variation among women, data on menstrual cycles were recorded longitudinally from 127 university women who lived in a group of houses surrounding a central courtyard. Adequate follow‐up was available on 76 women, among whom menstrual synchrony occurred in a short period of time. During the first month of coresidence, the day of menstrual onset deviated from the mean by an average of 13.7 days. During the next month, however, this average deviation declined to 2.6days. Moreover, it was found that menstrual synchrony occurred in the overall sample regardless of the house of residence, although synchrony occurred to a greater extent in some houses than in others. It would thus appear that common environmental influences play an important role in the overall pattern of menstrual cyclicity.

Early repair of episiotomy dehiscence associated with infection.

OBJECTIVEnThe purpose of our study was to examine early repair of episiotomy dehiscences in a large urban hospital setting serving a predominantly indigent population.nnnSTUDY DESIGNnSince September 1, 1989, we have proceeded with early repair in the immediate postpartum period. The medical records of 34 of 35 patients who underwent early repair were reviewed.nnnRESULTSnOf the 34 patients, 21 (62%) had midline and 13 (38%) had mediolateral episiotomies. Dehiscence was associated with episiotomy infection in 27 (79%) of the 34 patients: 18 (86%) in the midline group and 9 (69%) in the mediolateral group. Repair was accomplished from 3 to 13 days (mean = 6.4) after dehiscence. Successful repairs were accomplished in 32 (94%) of 34 patients. Two (6%) patients with initial third-degree episiotomies had a subsequent breakdown of their repairs and were allowed to heal by secondary intention.nnnCONCLUSIONSnAlthough most dehiscences in our population were associated with infection, early repair in this population is associated with a satisfactory outcome in the vast majority.