Adverse and beneficial effects of tocolytic therapy.

In addition to questions raised about the efficacy of many tocolytics, appropriate concern has been voiced about the safety of these potent drugs. Although some degree of risk for adverse effects with drugs promising a strong therapeutic effect can be accepted, caution needs to be exercised when benefits are marginal or unproven. Unfortunately, some of the tocolytics, most notably the betamimetics and magnesium sulfate, have been found to have considerable potential for adverse maternal cardiovascular and respiratory effects. Although less clearly established, the use of indomethacin appears to be associated with increased fetal and neonatal risks. Concerning magnesium sulfate, in addition to the well-known maternal effects, the accumulating evidence showing an increased frequency of adverse outcomes in the fetus and neonate has led to the recommendations to abandon its use entirely as a tocolytic. Given the limitations of our current state of knowledge, nifedipine would appear to be among the more efficacious and safer tocolytics available to use when properly indicated.

Abnormality of calcium channel inhibitor released from fetal membranes in preterm labor.

OBJECTIVE: This study was undertaken to test the hypothesis that an inhibitor of uterine contractions acting at the level of the dihydropyridine receptor of the uterine L -type uterine calcium channel is released in greater amounts from fetal membranes before term than at term. STUDY DESIGN: Endogenous calcium channel inhibitor activity was generated with standardized 25-cm2 surface area fetal membrane samples from the following 4 categories of women: preterm in labor, preterm not in labor, term in labor, and term not in labor. The amount of inhibitor in each membrane category was quantified by means of a competitive binding assay. Inhibition of uterine contractions induced by Bay K 8644 (an L -type calcium channel agonist) was used as another test of endogenous calcium channel inhibitor activity released from fetal membranes of all 4 groups of patients. RESULTS: Endogenous calcium channel inhibitor activity was most variable but present in the greatest amount in fetal membranes of women who were preterm not in labor followed by those in women at term not in labor and at term in labor. Fetal membranes from women in preterm labor had the least amount of measured endogenous calcium channel inhibitor activity. Consistent with the competitive binding assay, endogenous calcium channel inhibitor activity from fetal membranes from women who were preterm not in labor, at term not in labor, and at term in labor inhibited Bay K 8644-induced uterine contractions. Fetal membranes from women in preterm labor did not inhibit Bay K 8644-induced contractions. Endogenous calcium channel inhibitor activity was present in the chorion, the decidua, and the placenta, with little activity in the amnion. CONCLUSION: The down-regulation of endogenous calcium channel inhibitor activity with advancing gestation is consistent with a potential role for this inhibitor in maintaining uterine quiescence and in regulating the transition into labor. One possible cause of idiopathic preterm labor may be an abnormally low amount of endogenous calcium channel inhibitor activity in fetal membranes.

Effect of dual tocolysis on the incidence of severe intraventricular hemorrhage among extremely low-birth-weight infants.

OBJECTIVE: Our purpose was to evaluate the null hypothesis that dual tocolysis with magnesium sulfate and indomethacin does not alter the rate of grade III or IV intraventricular hemorrhage. STUDY DESIGN: Fifty-six neonates weighing 500 to 800 gm from mothers who received tocolytic therapy with magnesium sulfate alone or in combination with indomethacin were the subjects of this retrospective study. Demographic variables were evaluated with a Student t test, chi(2) analysis, Fisher exact test, or Mantel-Haenszel chi(2) as appropriate. RESULTS: There was an increased incidence of grade III to IV intraventricular hemorrhage among patients treated with dual therapy (p = 0.02). Logistic regression showed that fetal age and dual tocolysis with indomethacin were the only independent prognostic factors for severe intraventricular hemorrhage. CONCLUSION: The results indicate that dual tocolysis with indomethacin may place extremely low-birth-weight infants at increased risk for grade III to IV intraventricular hemorrhage.

Placental pathologic conditions in anticardiolipin antibody positive women whose infants had congenital heart defects.

Anticardiolipin antibodies (ACLA) are present in 10% of women with recurrent pregnancy loss. Other associations with ACLA are arterial and venous thrombosis, cerebral infarction, pulmonary hypertension, preterm delivery, and fetal growth retardation. A previous prospective study of infants of mothers with positive ACLA identified an increased incidence of congenital heart disease in this population. As a follow-up, the placentas of the initial 40 ACLA-positive patients were studied to determine whether there was an increased incidence of infarct or thrombosis compared with that in control subjects matched for maternal age and gestational age within the same 2-year period. The age of ACLA-positive mothers was 30 +/- 5 years versus 29 +/- 5 years in the ACLA-negative mothers. Gestational age was 37 +/- 2 weeks in both groups; placental weight was 553 +/- 169 gm in the ACLA-positive group versus 593 +/- 117 gm in the ACLA-negative group. The birth weight was 2972 +/- 709 gm in infants of ACLA-positive mothers and 2920 +/- 674 gm in infants of ACLA-negative mothers. There was no statistically significant difference between the two groups in gestational age, maternal disease, placental histologic findings, placental weight, type of delivery, or type of ACLA. Twenty-seven ACLA-positive women were receiving prednisone. Chi square analysis showed the ACLA-positive mothers to have more spontaneous abortions (p = 0.02) and to have more children with congenital heart disease (5 ventricular septal defects and 2 atrial septal defects) (p = 0.006). In summary, infants born with congenital heart defects in women positive for ACLA did not have significant placental pathologic conditions when compared with control infants.

Etiology and outcome of extremely low-birth-weight infants.

OBJECTIVE: Our purpose was to determine whether the reason for delivery of extremely low-birth-weight infants influenced the immediate neonatal outcome. STUDY DESIGN: At a regional perinatal center a retrospective analysis of 111 neonates with birth weights between 500 and 800 gm and their respective mothers was performed. The mother-infant pairs were grouped according to the reason for delivery. Group 1 included those with idiopathic preterm labor. Group 2 included mothers with preterm rupture of membranes. Group 3 included those delivered for maternal or fetal indications. Group 4 included all multiple gestations. Maternal, intrapartum, and neonatal outcome variables were then evaluated for statistical significance by analysis of variance and chi2 methods and a p value of 0.05. RESULTS: The neonatal outcome variables (survival and incidence of major intraventricular hemorrhage, hyaline membrane disease, and fetal sepsis) were not found to be significantly different among the four groups tested. CONCLUSION: The reason for the delivery of extremely low-birth-weight infants does not have an impact on the immediate neonatal outcome in these neonates.

Establishing the criteria for anesthesia and other precautions for surgery during pregnancy.

Surgical procedures may be undertaken in the gravida with relatively little risk to the fetus or the continuation of pregnancy. The managing physician requires a thorough knowledge of the maternal physiologic adaptations to pregnancy to minimize maternal iatrogenic risks. The potential fetal effects of the planned procedure, diagnostic tests, therapeutic drugs, and anesthesia must be considered preoperative. Any potential fetal risks must be discussed with the patient and, in some cases, maternal need may obviate undertaking some procedures that place the fetus at some jeopardy. The outcome in most situations of surgery on the gravida is good for both the mother and the fetus.

Asymmetric intrauterine growth retardation: its association with preterm labor.

Premature newborns have been shown to have a lower birth weight than would be predicted from nomograms, suggesting an asymmetric pattern of intrauterine growth. The premature newborns of 95 patients were assessed for symmetry of growth utilizing the ponderal index (PI). Those patients were matched to 108 patients delivering at terms > 38 completed weeks. The PI determination of the preterm neonates was significantly lower than that of the term newborns, 2.31 +/- 0.35 versus 2.57 +/- 0.30, p < 0.001. These data suggest that fetuses delivered prematurely may have asymmetric patterns of intrauterine growth. Premature labor may alter normal substrate delivery to the fetus, producing an asymmetric weight-to-length ratio.

Emergency complications of labor and delivery.

The care of the pregnant patient presenting to the emergency department with labor or delivery complications requires an understanding of signs and symptoms of disease for the maternal and fetal patient. This article reviews management of common labor and delivery complications that may occur in the emergency department. The management of premature labor, premature rupture of the membranes, emergency delivery procedure, resolution of shoulder dystocia, prolapsed umbilical cord, and perimortem cesarean section are discussed.

Mediastinal cystic hygroma: prenatal decompression with neonatal resection and recurrence at 19 months of age.

A case of an anterior mediastinal cystic hygroma detected prenatally at 22 weeks' gestation is reported. Because of progressive nonimmune hydrops, cardiac compromise, and mediastinal shift compressing the lungs, in utero decompression was successfully performed at 24 weeks. This newborn infant was delivered at 37 weeks' gestation with no respiratory distress. Operative excision of a large thoracic cystic hygroma was performed shortly after birth. At 19 months of age, this patient appeared with unilateral wheezing and fever. Operative findings confirmed recurrence of a cystic hygroma.

Prenatal diagnosis of neonatal alloimmune thrombocytopenia using allele-specific oligonucleotide probes.

The prediction of neonatal alloimmune thrombocytopenia (NATP) in affected families has, in the past, been based on information about gene frequencies of the antigen systems involved, parental phenotyping, and fetal platelet counts. We explored the feasibility of allele-specific oligonucleotide probe typing for PIA antigens to determine the risk of second or subsequent fetuses in families where one infant had a diagnosis of anti-PIA1-mediated NATP. A total of eight families at risk for delivering an affected fetus were studied with both serologic and oligonucleotide typing. The correlation between serologic and oligonucleotide PIA types was 100%. Similarly, in an additional eight families not at risk for PIA1-mediated NATP, serologic and oligonucleotide typing maintained a perfect correlation. DNA isolated from fetal leukocytes as well as fetal amniocytes was successfully typed using this technology. Oligonucleotide-based typing of fetuses at risk for NATP whose fathers are heterozygous for the PIA antigens allows early recognition of affected fetuses so that prenatal therapy of mothers can be instituted if necessary. When fetuses are found to be unaffected, invasive, and/or expensive, prenatal interventions can be avoided.

Cardiac disease in pregnancy.

Pregnancy produces many hemodynamic alterations of the cardiovascular system. Consideration of these alterations must be given in the management of pregnant patients with cardiac disease. This article reviews the cardiovascular hemodynamic alterations of pregnancy, and the management of pregnant patients with specific cardiac lesions.

The partial association of uterine contractions with changes in electrocortical activity, breathing, and PaO2 in the fetal lamb: effects of brain stem section.

In intact fetal lambs near term there was a statistically significant relation between regular small uterine contractions and a change to high-voltage fetal electrocortical activity (excess above chance 15%) or arrest of breathing (excess 12%). Isocapnic hypoxia also arrested fetal breathing. After brain stem transection there was no relation between uterine contractions and the fetal electrocortical activity, but isocapnic hypoxia increased the rate and depth of fetal breathing. Similarly uterine contractions were to a small extent associated with the initiation of fetal breathing movements which continued for about as long as the contraction. We conclude that the occasional effects of uterine contractions are consistent with diminished fetal cranial oxygen supply.