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Biomedical subjects

M G Neerhof

Publications and source records attributed to M G Neerhof.

At least 19 recordsLinked to original sources

Lamellar body counts compared with traditional phospholipid analysis as an assay for evaluating fetal lung maturity.

OBJECTIVE: To compare lamellar body counts with the lecithin/sphingomyelin ratio and phosphatidylglycerol analysis in terms of assessment of risk of respiratory distress syndrome (RDS). METHODS: Lamellar body counts, lecithin-sphingomyelin ratios (L/Ss), and phosphatidylglycerol levels were assessed in 1611 amniotic fluid samples obtained at four clinical sites from pregnant women whose fetuses were at risk for RDS. Cases in which delivery occurred within 72 hours of sample collection (n = 833) were analyzed. Specific cutoffs for predicting the likelihood of RDS for both the lamellar body count and the L/S had been derived previously at each of the clinical sites based on receiver operating characteristic curves using unrelated samples, whereas phosphatidylglycerol was reported as either mature (present) or immature (absent). Standard clinical and radiographic criteria were used to diagnose RDS, and the diagnosis was confirmed by review of newborn records. RESULTS: One hundred (12.0%) of the 833 infants delivered within 72 hours of sample collection developed RDS. The negative predictive value of the lamellar body count (97.7%) was similar to that of the L/S (96.8%) and slightly better than that of phosphatidylglycerol analysis (94.7%) (P =.048). The lamellar body count performed as well as phospholipid analysis irrespective of gestational age or patient population. CONCLUSION: The lamellar body count compares favorably with traditional phospholipid analysis as an assay for assessment of fetal lung maturity. Lamellar body counts are preferable because they are faster, more objective, less labor intensive, less technique dependent, and less expensive and because they can be performed with equipment available in every hospital laboratory.

Amniocentesis↗

Lamellar body counts: a consensus on protocol.

Lamellar bodies, concentrically layered "packages" of phospholipid that represent the storage form of surfactant, can be counted in the platelet channel of most electronic cell counters. The lamellar body count has been used for more than a decade and performs as well as traditional phospholipid analysis as an assay for evaluating fetal lung maturity. It is preferable to phospholipid analysis because it is rapid, objective, and inexpensive and can be performed in any hospital laboratory. The current methodologies for specimen preparation vary widely among laboratories, most notably with respect to centrifugation, resulting in differences in maturity cutoffs used. Our goal was to establish a consensus regarding a standardized methodology for the lamellar body count. Institutions that previously had published their results with lamellar body counts were invited to contribute. The consensus of the four participating institutions includes the following: centrifugation is not a necessary step and should be abandoned, maturity is suggested by a count of 50,000/microL or greater, and immaturity is suggested by a count of 15,000/microL or lower. As the lamellar body count gains wider acceptance as a primary assay for assessing fetal lung maturity, the test must be performed uniformly and accurately, given the implications of acting on a falsely negative test resulting from improper methodology.

Amniotic Fluid↗

Endothelin and blood pressure regulation in the female rat: studies in normal pregnancy and with nitric oxide synthase inhibition-induced hypertension.

OBJECTIVE: To evaluate the role of endothelin (ET) in blood pressure regulation in normal pregnant and nonpregnant rats and with nitric oxide synthase (NOS) inhibition. METHODS: Pregnant and nonpregnant Sprague-Dawley rats were treated for 7 days with an ET(A)-selective (A-127722 or FR-139317), ET(B)-selective (A-192621), or ET(A)/ET(B) nonselective (A-182086) endothelin receptor antagonist, and/or with the NOS inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME, 2. 5 mg/kg/h). In pregnant rats, the ET antagonists and L-NAME were administered from gestational day 14 through day 21 (term = 22 days). All rats received indwelling arterial catheters for blood pressure measurement. Mean arterial pressures were recorded on infusion days 1, 4, and 7 and these data were compared by analysis of variance among experimental groups with p < 0.05 considered significant. RESULTS: The ET(A) receptor antagonism lowered blood pressure in both pregnant and nonpregnant rats (p < 0.05), whereas ET(B) antagonism resulted in hypertension (p < 0.001). ET(B) antagonism-induced hypertension was attenuated by pregnancy (p < 0. 001). Hypertension was induced in all rats treated with L-NAME (p < 0.001). Endothelin receptor antagonism, regardless of specificity, did not ameliorate L-NAME-induced hypertension in pregnant or nonpregnant female rats. The only observed effect of ET(A) antagonism on NOS inhibition-induced hypertension was the prevention of a continued rise at infusion day 7 in nonpregnant rats. CONCLUSIONS: Endothelin, acting via both the ET(A) and ET(B) receptors, contributes to blood pressure homeostasis in pregnant and nonpregnant rats. Endothelin receptor antagonism does not ameliorate NOS-inhibition-induced hypertension in pregnant rats.

Animals↗

Timing of labor induction after premature rupture of membranes between 32 and 36 weeks' gestation.

OBJECTIVE: The objective was to determine a consensus gestational age for labor induction after premature rupture of membranes between 32 and 36 weeks' gestation on the basis of the relative frequencies of adverse neonatal outcomes. STUDY DESIGN: A retrospective review was undertaken of all patients with premature rupture of membranes between 32 and 36 weeks' gestation. These patients were managed expectantly whenever possible. Neonatal outcomes were stratified by gestational age at rupture of membranes. RESULTS: Two hundred thirty-six patients with rupture of membranes between 32 and 36 weeks' gestation were managed expectantly. Prolongation of pregnancy by >/=1 week was infrequent in all cases, particularly if membrane rupture occurred after 34 weeks' gestation. Reductions in the neonatal length of stay and the incidence of hyperbilirubinemia were observed at 34 weeks' gestation with respect to younger gestational ages. No perinatal deaths occurred among the study cases. CONCLUSIONS: A "break point" in neonatal morbidity was observed at 34 weeks' gestation, which supports induction of labor at this gestational age. The short latencies observed limit the potential benefits of expectant management.

Adult↗

Endothelin receptor A antagonism prevents hypoxia-induced intrauterine growth restriction in the rat.

OBJECTIVE: Our purpose was to investigate the hypothesis that endothelin plays a critical role in maternal hypoxia-induced intrauterine growth restriction. STUDY DESIGN: Chronic indwelling venous and arterial catheters were placed on day 17 of a 22-day gestation in timed-pregnant Sprague-Dawley rats. Twelve rats were infused with saline solution and 12 with 6 mg/kg per day FR139317, an endothelin receptor A-specific antagonist. For gestational days 18 to 21 half the rats in each infusion group were housed in a normoxic environment and the other half in a hypoxic (14% oxygen) environment. On day 21 an arterial blood gas level was determined, the rats were then anesthetized, and a hysterotomy was performed. The weight of each pup and its corresponding placenta was recorded. Statistical significance was determined by analysis of variance. RESULTS: Among the rats receiving saline solution infusions, fetal weights were 20% less and placental weights were 11% less for those housed in a hypoxic environment compared with those housed in a normoxic environment (p < 0.003). Among the rats receiving FR139317 infusions, fetal and placental weights were not significantly different for those in a hypoxic environment compared with those in a normoxic environment. The fetal and placental weights for the rats receiving FR139317 infusion in hypoxic or normoxic environments were similar to those receiving saline solution in a normoxic environment. CONCLUSIONS: Endothelin plays a critical role in hypoxia-induced intrauterine growth restriction. Infusion of an endothelin antagonist prevents the intrauterine growth restriction caused by chronic hypoxia.

Animals↗

Pregnancy in the chronically hypertensive patient.

The majority of patients with mild chronic hypertension have successful pregnancy outcomes. Most perinatal morbidity is secondary to superimposed preeclampsia. Antihypertensive therapy does not appear to significantly affect pregnancy outcome, nor the incidence of superimposed preeclampsia in mild chronic hypertensives. The maternal and fetal risks are considerably higher for severe chronic hypertension and for those patients with target organ disease. These patients ideally should be counseled regarding their risks prior to pregnancy. Antihypertensive therapy should be instituted at diastolic pressures greater than or equal to 100 mm Hg.

Antihypertensive Agents↗

Randomized trial of antenatal dexamethasone in surfactant-treated infants delivered before 30 weeks' gestation.

OBJECTIVE: To determine if an additive effect exists between antenatal corticosteroid administration and postnatal surfactant therapy in the prevention of respiratory distress syndrome (RDS) in preterm infants. METHODS: A randomized, double-blind trial was conducted from April 1990 to June 1994, in which dexamethasone (5 mg every 12 hours for a total of four doses) or saline was given to women at risk for delivery at 24-29 weeks' gestation. At birth, prophylactic surfactant was administered to all study infants. Main outcome measures were RDS occurrence and severity. Secondary clinical end points included bronchopulmonary dysplasia, pneumothorax, patent ductus arteriosus, necrotizing enterocolitis, retinopathy, intraventricular hemorrhage, and death. RESULTS: Seventy-five of the 124 randomized subjects delivered 96 infants within the studied gestational age range (dexamethasone, n = 54; placebo, n = 42). Similar maternal demographics and obstetric complications were noted between study groups. A greater population of infants were delivered from multi-fetal gestations in the dexamethasone cohort (26 of 54 versus 12 of 42 newborns; P = .05). There were no significant differences in the occurrence or severity of RDS between the dexamethasone and placebo infants (none or mild, 67 versus 67%; moderate, 24 versus 26%; severe, 9 versus 7%, respectively), or differences in any of the secondary clinical outcomes. The study size was sufficient to exclude a 50% reduction in RDS incidence as a consequence of dexamethasone exposure. An analysis restricted to singletons (dexamethasone, n = 28; placebo, n = 30) revealed similar overall occurrence of intraventricular hemorrhage (12 of 28 versus ten of 30; P = .63), but significantly fewer grade 3 and 4 intraventricular hemorrhages in dexamethasone-exposed neonates (two of 12 versus six of ten; P = .048). CONCLUSION: Antenatal dexamethasone does not appear to decrease the incidence or severity of RDS in surfactant-treated infants delivered at 24-29 weeks' gestation, but may be associated with reduced severity of intraventricular hemorrhages in surfactant-treated singletons in this gestational age range.

Adult↗

Congenital diaphragmatic hernia. In utero therapy and ethical considerations.

Despite advances in neonatal medicine, the mortality rate for congenital diaphragmatic hernia remains high. The results of work in animal models suggest that this anomaly may be amenable to in utero surgical correction. In this article, the natural history of congenital diaphragmatic hernia in humans is reviewed, and the development of antenatal management strategies is traced. The ethical issues surrounding the management of fetuses with diaphragmatic hernias are also discussed. The ground-breaking nature of the development of strategies for management of congenital diaphragmatic hernia underscores the importance of establishing scientific and ethical guidelines for future endeavors with in utero therapy.

Animals↗

Amniotic fluid lamellar body count: a rapid and reliable fetal lung maturity test.

OBJECTIVE: To evaluate the lamellar body count as a predictor of fetal lung maturity. METHODS: We conducted a prospective clinical outcome study. Amniocentesis was performed for evaluation of fetal lung maturity status within 72 hours of delivery in 130 patients. A lamellar body count was performed on each specimen, and a lecithin-sphingomyelin ratio and lung phospholipid profile were performed when possible (insufficient sample or contamination in eight cases). Each infant was evaluated for evidence of respiratory distress syndrome (RDS). RESULTS: A lamellar body count exceeding 30,000/microL predicted pulmonary maturity correctly in all cases (negative predictive value 1.00). All 16 cases of RDS had counts of 30,000/microL or less. If the lamellar body count was less than 10,000/microL, the positive predictive value for RDS was 67%, and the likelihood of a mature result from chromatographic phospholipid analysis was low (one of 14, 7%). Values between 10,000-30,000/microL indicated intermediate risk (four of 39, 10%) for developing RDS. Phospholipid analysis indicated fetal lung maturity in 35 of 39 (90%) cases with lamellar body counts in the intermediate risk range. CONCLUSIONS: The lamellar body count compares favorably with traditional phospholipid testing in the prediction of fetal lung maturity. Phospholipid analysis is not needed with lamellar body counts greater than 30,000/microL or less than 10,000/microL, but may be of benefit for values in the intermediate risk range. Advantages of this test include speed, objectivity, small sample volume required, and universal availability of instrumentation.

Amniocentesis↗

Midtrimester Rh sensitization associated with circulating anticardiolipin antibodies and elevated maternal serum alpha-fetoprotein. A case report.

The incidence of antepartum Rh isoimmunization has been limited by third-trimester Rh immune globulin (RhIg) administration. Prophylactic failures are uncommon but can occur if sensitization takes place prior to the 28th week of gestation. We report a case of midtrimester Rh sensitization in an anticardiolipin antibody-positive primipara coincident with the discovery of an elevated maternal serum alpha-fetoprotein value, oligohydramnios and fetal growth retardation. This case suggests that fetal-maternal hemorrhage and subsequent sensitization may be facilitated by anticardiolipin antibody-induced placental damage. Prophylactic midtrimester RhIg administration might avoid sensitization in similar cases.

Adult↗

Causes of intrauterine growth restriction.

IUGR is a relatively common problem and a potential cause of significant perinatal morbidity and mortality. There are many possible causes of IUGR, and some cases may involve more than one (Table 1). Although an underlying cause may not always be identifiable, it it important to consider all of these factors because identification of the underlying cause of the IUGR may impact short-term management as well as long-term prognosis. The cornerstone of management for IUGR involves close antenatal surveillance with a well-timed delivery. Antenatal testing in the form of fetal heart rate monitoring, ultrasonographic evaluation, and, on occasion, umbilical blood sampling allows for ongoing surveillance of the growth-retarded fetus. Intrapartum management should include close fetal heart rate monitoring because the ability of the growth-restricted fetus to tolerate labor generally is low and the risk for acidosis is high. A pediatric team should attend the delivery because the risk of meconium aspiration and the frequency of low Apgar scores and metabolic disorders are high. The biochemical mediators reviewed in this article are not likely to be independent causative factors in IUGR; it is more likely they are important mediators of a pathologic process set in motion by other agents or insults. A better understanding of how these mediators contribute to the pathophysiology of IUGR will improve our understanding of this disorder and may allow for therapeutic interventions in the underlying pathophysiologic process.

Acidosis↗

Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients.

OBJECTIVE: We compared the use of aspirin alone with combined therapy (prednisone plus aspirin) in antiphospholipid antibody-positive obstetric patients with prior adverse pregnancy outcome. STUDY DESIGN: Thirty-nine patients meeting specific laboratory and clinical inclusion criteria were randomized to receive either combined therapy (prednisone plus low-dose aspirin, n = 17) or aspirin alone (n = 22). The daily aspirin dose was 81 mg; prednisone was begun at 20 mg/day and increased or decreased on the basis of observed changes in serial antibody levels. Perinatal outcomes were compared between groups. Evaluation of treatment-related maternal complications and serial antibody titers was also accomplished. RESULTS: Thirty-four randomized subjects were evaluable (prednisone plus low-dose aspirin, n = 12 vs aspirin only, n = 22); no perinatal losses were observed in the study cohort. Preterm delivery was experienced by significantly more patients receiving prednisone plus low-dose aspirin than aspirin only (8/12 vs 3/22, respectively; p = 0.003), and prednisone exposure appeared to be an independent risk factor for preterm birth. CONCLUSIONS: The use of prednisone therapy in conjunction with low-dose aspirin does not appear to improve outcome and may provoke obstetric complications in antiphospholipid antibody-positive patients.

Adult↗

Heparin therapy for congenital antithrombin III deficiency in pregnancy.

A patient with congenital antithrombin III deficiency and a history of thromboembolic events prior to pregnancy was successfully treated with subcutaneous heparin alone throughout two pregnancies. Although adjuvant antithrombin III infusions may have a role in the treatment of this disorder, especially in the peripartum period, there is no evidence that this approach is superior to heparin therapy alone. We present this case as further evidence that heparin therapy alone appears to be a safe and effective treatment for pregnant patients with this rare but serious disorder.

Adult↗

Idiopathic aldosteronism in pregnancy.

This is the first reported case of the idiopathic type of primary aldosteronism in pregnancy. The severely hypertensive patient was unresponsive to treatment with high doses of four antihypertensive agents administered concurrently. A drastic improvement in blood pressure was noted within 24 hours of beginning enalapril maleate, although subsequent deterioration in fetal status led to delivery at 26 weeks' gestation. Alternatives to standard medical therapy may be necessary for this rare but potentially life-threatening disease during pregnancy.

Adult↗

Fetal supraventricular tachycardia and hydrops fetalis: combined intensive, direct, and transplacental therapy.

A 25-week fetus with severe hydrops fetalis secondary to supraventricular tachycardia was treated with fetal intramuscular injections of digoxin in conjunction with maternal intravenous digoxin, followed by oral digoxin and subsequently by oral procainamide therapy. Fetal umbilical blood sampling revealed poor placental transfer of digoxin, even after 2 weeks of therapeutic maternal levels. This case suggests that direct fetal therapy is of value in the treatment of some fetuses with supraventricular tachycardia, and lends further evidence that the role of transplacental digoxin therapy is limited in the compromised fetus. It also demonstrates that resolution of hydrops may require a prolonged period.

Adult↗

Cocaine abuse during pregnancy: peripartum prevalence and perinatal outcome.

The frequency of cocaine abuse during pregnancy has increased markedly in recent years. Cocaine abuse during pregnancy has been associated with significant perinatal morbidity and mortality. In this study a large population of pregnant women were tested for drug use at the time of their admission to the hospital for labor and delivery. During the study period a total of 138 (8%) of 1776 patients who were delivered of infants had positive urine toxicologic screening tests for cocaine. Moreover, the prevalence of peripartum cocaine abuse increased considerably during the study period. The perinatal outcomes of the 138 patients whose urine samples yielded positive test results for cocaine were compared with those of the 88 control patients with negative results. Cocaine use was associated with lower gestational age at delivery and higher incidences of preterm delivery, premature rupture of the membranes, and small-for-gestational-age infants. When compared with control infants, infants of mothers who used cocaine had more instances of neonatal morbidity and longer hospitalizations. In this study peripartum cocaine abuse was common, increased during the study period, and was associated with perinatal morbidity.

Abnormalities, Drug-Induced↗

Hepatic rupture in pregnancy.

Hepatic rupture is a rare and serious complication of pregnancy. A case of hepatic rupture is presented along with a review of the recent literature.

Adult↗