Pharmacokinetics of betamethasone in twin and singleton pregnancy.

OBJECTIVE: The aims of the study were to compare the pharmacokinetics of betamethasone in singleton pregnancy with the pharmacokinetics in twin pregnancy and to assess the adrenal suppression produced by betamethasone. STUDY DESIGN: We measured serial betamethasone and cortisol levels in 30 singleton and 21 twin pregnancies after the first dose of betamethasone and calculated the pharmacokinetic parameters for betamethasone including volume of distribution, half-life, and clearance. We also measured cord and maternal blood levels of betamethasone at the birth of infants of 13 singleton and 9 twin pregnancies. RESULTS: The half-life of betamethasone in mothers with twin pregnancies was significantly shorter than that in mothers with singleton pregnancies (7.2 +/-2.4 versus 9.0 +/- 2.7 hours; P <.017). Clearance of betamethasone in the twin pregnancies appeared greater than in singleton pregnancies (8.4 +/- 6.4 versus 5.7+/- 3.1 L/h; P =.06) but did not reach statistical significance. Volume of distribution was similar in the two groups. Because the time between the last dose of betamethasone and birth varied widely (range, 2-158 hours), mothers with a longer interval after treatment tended to have a higher cord-to-maternal betamethasone ratio than did mothers with a shorter interval in both twin and singleton pregnancies. This finding indicated delayed fetal clearance, but the correlation was weak (R (2) = 0.29 for twins and 0.08 for singletons). CONCLUSION: The shorter half-life of betamethasone in twin pregnancy than in singleton pregnancy may cause the level of betamethasone to be subtherapeutic for lung maturation in twin pregnancy.

Management of failed prostaglandin abortions.

Midtrimester abortion was induced in 529 patients by administration of the naturally occurring prostaglandins E2 and F2alpha as well as the 15-methyl analogs, 15-ME-PGE2 and 15-ME-PGF2alpha. Ten patients failed to abort with prostaglandin therapy, even in association with intravenous oxytocin, a failure rate of 1.9%. Two failures were related to uterine malformation; 1 patient had the pregnancy in a blind uterine horn, and the second patient was pregnant in one horn of a uterus didelphys. Five of the 10 patients who failed to abort during prostaglandin administration were subsequently found to have uterine distortion due to myomata uteri. When abortion induced by prostaglandin fails to occur within the expected time for the agent and technic employed, the presence of uterine malformation or abnormality should be considered. Evaluation with ultrasonography is indicated along with a repeat test to confirm the pregnancy. If the sonogram is suggestive of uterin malformation, a hysterosalpinogram should be obtained to determine if there is communication between the cervix and the gestational sac. If no communication is present, an intravenous pyelogram should be performed in view of the 90% correlation of urogenital abnormalities, and an exploratory laparotomy should be performed. When a communication exists between the cervix and the gestational sac, the 24 hours of uterine activity induced by the prostaglandin will have resulted in cervical changes so that the cervix can easily be dilated to either a 14 or 16 Hegar dilator and the conceptus can be removed in parts with minimal bleeding.

Translocation of the Dalkon Shield into the broad ligament.

Perforation of the uterus is a serious complication in users of intrauterine devices for contraception. The incidence varies with the type of device. The perforation can occur in different parts of the uterine wall. Perforation into the broad ligament is rare; only 4 cases have been described. Two additional cases, both occurring with the Dalkon Shield, are reported here.

PIP: A serious complication following the insertion of an IUD is perforation of the uterus and translocation of the device into the abdominal cavity. Uterine perforation can be divided into "primary" ones, the most common, which are related to the insertion procedure, and "secondary" ones, which are caused by uterine contractions. A rare type of secondary perforation is to the broad ligament. Heretofore, only 4 such cases have been reported. 2 additional cases, occurring with the Dalkon shield, are reported here. Although the translocation of an IUD into the leaves of the broad ligament is rare, this complication should be considered whenever an IUD cannot be removed by pulling the strings. 2 possible complications--rupturing of the uterine vessels causing serious intraabdominal bleeding and infection, with potential danger of peritonitis and sepsis--could greatly endanger the patient's life. The 2 cases reported here were resolved satisfactorially.

Pregnancy and pulmonary tuberculosis.

There are 1565 premature and full-term deliveries in patients with tuberculosis at The New York Hospital included in this report. About 10% of the patients had active pulmonary tuberculosis immediately before or during gestation. The obstetric management of the patient with inactive tuberculosis is similar to that of the nontuberculous woman. In patients with active or recently active tuberculosis, delivery under regional anesthesia, with forceps when necessary to avoid excessive straining during the second stage of labor, is advised. Tuberculosis is not an indication for cesarean section. Chemotherapy is now the cornerstone of all therapy for tuberculosis; the various regimens and modifications depend on the type and extent of the disease. The best combination of drugs is isoniazid and ethambutol. Therapy in all cases must be multiple drug, continuous, and long-term. Prophylactic isoniazid is used infrequently during pregnancy and only in special circumstances. Results of treatment with the newer antituberculosis drugs show that the disease progressed in less than 1% of patients between 1957 and 1972 compared to 3 to 4% of patients from 1933 to 1956. Infants born to the 1565 tuberculous mothers reported here were of average weight, and none of the 1588 infants (23 sets of twins) had congenital tuberculosis. Patients should be carefully followed postpartum with sputum tests and x-rays. They should also be given medical and socioeconomic counseling.

Amniotic fluid transfer of meperidine from maternal plasma in early pregnancy.

Concurrent samples of maternal plasma and amniotic fluid were collected from 40 subjects during the second trimester of pregnancy following a single intramuscular dose of meperidine (100 mg). Maternal meperidine plasma levels were highest in samples collected from 15 to 50 minutes after drug administration. Thereafter the level declined during the next 2 hours. Meperidine was not detected in amniotic fluid until 30 minutes after the intramuscular dose. We estimated that an apparent equilibrium was reached between plasma and amniotic fluid at 120 to 155 minutes after the drug was given to the mother. Normeperidine was not detected in either maternal plasma or amniotic fluid during the time course of this study.

Herpes simplex in the amniotic fluid of an unaffected fetus.

A woman with a 7-year history of herpes progenitalis was delivered by cesarean section after herpes simplex virus was isolated from the cervix 2 weeks prior to delivery. No overt signs of herpes progenitalis had been observed during this pregnancy. At amniocentesis done the day of delivery to assess fetal maturity, herpes simplex virus was isolated from the amniotic fluid. An unaffected infant was delivered; she remains healthy at 18 months of age. Immunoglobulin levels in fetal serum and amniotic fluid did not indicate fetal infection.

Infants of mothers treated with ethanol for premature labor.

Presented is a retrospective study of the newborn infants of mothers who were treated with ethanol in order to arrest premature labor, in comparison with matched control infants. In regard to neonatal mortality, there was no statistical difference between the study and the control infants. However, infants born within 12 hours after administration of ethanol had a significantly lower 1-minute Apgar score and a higher incidence of respiratory distress syndrome. This indicates that treatment with ethanol should be discontinued as soon as it becomes evident that labor cannot be arrested.

Perinatal monitoring of fetal well-being in the presence of congenital heart block.

We present a case of congenital complete heart block associated with maternal autoantibodies in which a normal labor and delivery could safely be allowed to proceed despite the absence of the usual tool of electronic fetal heart rate monitoring for fetal distress, by the technique of rupturing membranes and using a fetal scalp electrode electrocardiographic tracing to assess the fetal atrial rate.

The relationship between prematurely ruptured membranes and fetal immunoglobulin production.

Cord blood and maternal sera were studied in a series of 227 cases of prematurely ruptured membranes (PRM) with respect to: (1) fetal immunoglobulin (lg) synthesis associated with PRM, (2) the interrelationship between different lg classes during infection, and (3) the relationship between lg values and the duration of PRM prior to the onset of labor. A preliminary report from this laboratory, which indicated that a humorla fetal immune response occurred in some but not all cases of PRM, and that significant increases in either IgA or IgM could be found, was confirmed. There was both clinical and immunologic evidence of one peak of infection one to 12 hours after onset of PRM and another after 72 hours after onset of PRM, suggesting that some patients were infected before the clinical onset of PRM symptomatology. Increased IgA and/or IgM was found in 16.3% of infants with clinical evidence of infection. This was comparable to the 18.5% of patients with PRM who had elevated IgA and/or IgM without clinical evidence of infection. Further, there was no correlation between the severity of infection and the presence of lg elevation. Based on the data in the present series, lg determination in cord blood cannot be used to distinguish cases of PRM with and without fetal infection.

Immunohistologic detection of antigen related to primate type C retrovirus p30 in normal human placentas.

This study reports the immunohistologic detection of SSAV/GaLV type C retrovirus p30-related antigen in unfixed cryostat sections of normal human term placentas by the indirect immunofluorescence method. Goat anti-SSAV p28 serum reacted specifically with 10 of 10 anatomic specimens of human placenta. Goat anti-GaLV p29 serum reacted similarly with 8 of 10 specimens. Goat anti-BaEV p28, anti-RD-114 p28, anti-FeLV p27, anti-R-MuLV p30, and anti-MPMV p27 gave no specific reaction with placenta. The anti-SSAV p28 and anti-GaLV p29 reactive antigen was located in the placenta mainly at the basal aspect of syncytiotrophoblast near the underlying trophoblastic basement membrane where type C retroviruslike particles have been found electronmicroscopically. The specific antibody activity of anti-SSAV p28 serum against placenta was removed by critical absorption with disrupted SSAV or GaLV but not RD-114 or MuLV. These results suggest the presence in human placenta of a putative type C retroviral protein which cross-reacts with the p30 protein of the SSAV/GaLV type C retrovirus group.

Changes in active and inactive renin throughout normal pregnancy.

Active and inactive renin were measured sequentially in 16 women throughout pregnancy and again post-partum. By 12 weeks, inactive renin was elevated 14-fold and fell slightly thereafter. By 12 weeks, active renin was 3.5-fold elevated. It continued to rise in 8 patients (Group A) until term, it remained stable in 6 (Group B) and in 2 it was quite variable. Between 12 and 32 weeks PRA and plasma aldosterone increased in Group A from 7.0 to 17.1 ng/ml/hr, and 20.0 to 95.7 ng/dl respectively and both were unchanged in Group B (6.5 to 8.1 ng/ml/hr and 26.5 to 24.6 ng/dl respectively). Inactive renin was higher in Group B than in Group A at 12 weeks (224 v 126 ng/ml/hr) but fell thereafter to the same stable but elevated level. Group A were younger (24 +/- 1.8 S.E. v. 30 +/- 2.2 years). These studies demonstrate that active and inactive renin increase early in pregnancy and remain elevated thereafter. In certain younger subjects, further increases in active renin and aldosterone sometimes occur and appear necessary for the maintenance of normal blood pressure.

Organization of amniocentesis for antenatal genetic diagnosis.

In spite of the rapid development of amniocentesis for genetic diagnosis, it is still only a small fraction of the mothers at risk who are having the procedure performed. The medical and public health problems associated with genetic amniocentesis are discussed on the basis of the experience gathered in a major medical center.

Fetal immune response following prematurely ruptured membranes.

Concentrations of immunoglobulins (Ig)A1, and IgA2, IgD, IgE, IgG, and IgM have been determined in cord blood, amniotic fluid, and maternal serum in a group of patients with a history of prematurely ruptured membranes (PRM) prior to the onset of labor and in a control group of patients undergoing normal delivery and without a history of infection during pregnancy. IgA and IgD were determined by sensitive hemagglutination-inhibition tests; IgG and IgM, by radial immunodiffusion; IgE, by a radioimmunoassay. There was evidence for an immune response in 10 of 16 cases of PRM: five of 16 had increased IgA but normal IgM; three of 16 had increased IgA and IgM; two of 16 had high IgM and normal IgA in cord blood. In patients with significantly increased levels of either IgA or IgM or both, there was a decreased level of IgD. These changes are most likely the result of the immune response to ascending infection from the maternal genitals. The sensitive testing method employed could demonstrate the presence of IgD in 53 per cent of normal cord blood samples and 72 per cent of amniotic fluid samples obtained at term. IgE was found in all normal cord blood and amniotic fluid samples tested. By concentrating the amniotic fluid up to 180-fold, IgM was demonstrated in all normal samples tested. The potential importance of IgA determinations in cord blood in addition to IgM determination for detection of intrauterine infections is stressed.