Mark C. Maberry

Fetal lung maturation in congenital diaphragmatic hernia

OBJECTIVE Our purpose was to determine whether congenital diaphragmatic hernia is associated with abnormalities of fetal lung maturation. STUDY DESIGN We measured surfactant protein A and saturated phosphatidylcholine in amniotic fluid from 19 pregnancies with a prenatal diagnosis of congenital diaphragmatic hernia (gestational age 16 to 40 weeks) and 48 control pregnancies (gestational age 16 to 39 weeks). Results were compared by analysis of covariance. RESULTS Beyond 34 weeks of gestation there was a progressive rise in amniotic fluid surfactant protein A and saturated phosphatidylcholine in control pregnancies, whereas in most fetuses with prenatal diagnosis of congenital diaphragmatic hernia these values remained low (p < 0.01). Amniotic fluid surfactant protein A was lower in fetuses with congenital diaphragmatic hernia who died or required extracorporeal membrane oxygenation than in survivors treated with conventional management (4.9 +/- 2.9 vs 16.8 +/- 5.7 micrograms/ml surfactant protein A, respectively, p < 0.05 by Mann-Whitney U test). CONCLUSIONS There are decreased surfactant components in amniotic fluid in many pregnancies complicated by congenital diaphragmatic hernia, which may reflect fetal lung immaturity or hypoplasia.

Obstetric clavicular fracture: The enigma of normal birth

Objective To determine the main risk factors involved in neonatal clavicular fracture, the most common injury to the neonate. Methods Two hundred fifteen cases of clavicular fracture of 65,091 vaginal deliveries (0.4%) occurring between January 1983 and December 1988 were pair-matched with controls based on mode and date of delivery, race, and maternal age. Incidences, odds ratios, and stratified analysis were used to identify and control for confounding between risk factors. Results Shoulder dystocia, increasing birth weight, and increasing gestational age were identified as risk factors. Within the range of normal birth weights, there is a biologic gradient of increasing risk for clavicular fracture. Although shoulder dystocia is the strongest risk factor identified, the magnitude of its point estimate is probably affected to a large extent by differential ascertainment. The use of forceps, prolonged second stage of labor, and nulliparity status were not significantly associated with neonatal clavicular fracture. Conclusions Neonatal clavicular fracture occurs commonly in an obstetric population. Obstetric clavicular fracture is an unpredictable, unavoidable complication of normal birth.

Antibiotic Concentration in Maternal Blood, Cord Blood and Placental Tissue in Women with Chorioamnionitis

Mark C. Maberry, MD, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9032 (USA) Introduction Acute chorioamnionitis or intra-amniotic infection remains an important disease entity in obstetrics, and with an incidence of approximately 1-3% of all pregnancies, it remains an important contribution to maternal and perinatal morbidity [1, 2]. Although recent information has emphasized the need for immediate antibiotic therapy once the diagnosis is made [3,4], there is no unanimity of opinion on the ideal antibiotic regimen to treat the infection. Many antibiotic regimens have been used in the treatment of chorioamnionitis, but little is known regarding the antibiotic concentrations in the fetus and placental tissues. We have previously published data regarding the levels of several different antibiotics in maternal and cord blood, as well as in placental tissue [5]. The purpose of the present study was to ascertain the concentrations of several relatively new broad-spectrum antibiotics in maternal and fetal blood and placental tissue. These new antibiotics might prove clinically useful for the treatment of acute chorioamnionitis. All antibiotic assays were determined using high-pressure liquid-chromatography methods as previously described [3]. All assays were done using UV detection at wavelengths of 229 nm for ß-lactam antibiotics, and 313 nm for the ß-lactamase inhibitors. Prior to assay, all ß-lactamase inhibitors were derivatized with imidazole. Instruments used were a Waters 481 detector, an autosampler and a 10-MV recorder. All procedures were validated and had a coefficient of variation of less than 10 % and recoveries of greater than 90 %, as calculated by linear leastsquares regression analysis. Results The results of the antibiotic penetration studies are summarized in table 1. All three antibiotics were found in cord blood and placental tissue. Both ampicillin-sulbac-tam and cefotaxime achieved equal levels in maternal and cord blood (ratios of cord to maternal blood were approximately 1.0). Ticarcillin-clavulanic acid cord to maternal blood ratios were about 25%

17β-Hydroxysteroid oxidoreductase activity in human maternal and umbilical cord sera

The specific activity of 17 beta-hydroxysteroid oxidoreductase (17 beta-HSOR) in human umbilical cord arterial serum has been reported to be similar to that of maternal serum and 5- to 15-times higher than that of cord venous serum. Based on these findings, it was proposed that 17 beta-HSOR in cord arterial serum arises from fetal tissue sources other than placenta. In the course of studies of the role of 17 beta-HSOR in the modulation of bioactive estrogen levels in the human fetus, we determined that: (i) the specific activity of 17 beta-HSOR in maternal serum is 2.1- to 55-times higher than that in either umbilical cord venous serum or cord arterial serum; (ii) the specific activity of 17 beta-HSOR in umbilical cord venous and cord arterial sera are similar; (iii) anti-human placental cytosolic 17 beta-HSOR antibody inactivates the 17 beta-HSOR in maternal, umbilical cord arterial, and cord venous sera but not in maternal or fetal erythrocytes; (iv) the specific activity of 17 beta-HSOR in maternal serum (expressed per mg protein) is higher than that in umbilical cord serum and maternal and fetal erythrocytes, and is approximately 700-times lower than that of the placental microsomal enzyme; (v) the preferred cofactor for maternal serum 17 beta-HSOR is NADP+; (vi) 17 beta-HSOR is associated with the high speed supernatant fraction of maternal serum rather than with the particulate fraction; and, (vii) the patterns of binding of [3H]estradiol-17 beta to proteins in maternal and umbilical cord arterial sera and those of 17 beta-HSOR activity, determined in corresponding fractions obtained after sucrose density gradient centrifugation, are approximately coincidental at S20, omega 4.6-5. The findings of higher 17 beta-HSOR levels in maternal serum compared with umbilical cord arterial serum and the inactivation of the cord arterial serum enzyme by an antibody that recognizes human placental cytosolic 17 beta-HSOR is suggestive that 17 beta-HSOR in cord arterial serum is of placental origin.

Trimethoprim and Sulfamethoxazole Transfer in the in vitro Perfused Human Cotyledon

Utilizing the in vitro human placental model, we studied the placental transfer of trimethoprim and sulfamethoxazole. At trimethoprim concentrations of 7.2 micrograms/ml, only 1.4 micrograms/ml was transported across the placenta after 1 h, and at concentrations of 1.0 microgram/ml, one half the usual serum level, only 0.08 microgram/ml was transported across the placenta. Maternal concentrations of sulfamethoxazole of 29.6 and 127.7 micrograms/ml resulted in concentrations of 5.1 and 14.8 micrograms/ml on the fetal side, respectively. Thus, it would appear that trimethoprim is slowly transported across the placenta and in low concentrations whereas sulfamethoxazole readily crosses the placenta. The combination of these drugs is useful for treatment of bacteriuria. It may also prove to be especially useful for Pneumocystis carinii infections in pregnant women with AIDS. With a half-life of 13 h for trimethoprim and 6 h for sulfamethoxazole, the drugs are not likely to achieve toxic levels in the fetal compartment. Thus, it would appear that trimethoprim and sulfamethoxazole may be both efficacious and safe for the treatment of both these infections during pregnancy.

Intrapartum asphyxia in pregnancies complicated by intra‐amniotic infection

Intra-amniotic infection has been reported to be associated with intrapartum asphyxia; however, the criteria used to define asphyxia have been imprecise. In the present study of 123 women with intra-amniotic infection and 6769 women without infection, the mean umbilical artery pH was 7.28 in both groups. The frequency of acidemia (umbilical artery pH less than 7.20) was not significantly different between the infection group and controls (15 versus 10% P=.12). Likewise, there was no significant difference between the groups when a lower umbilical artery pH value (less than 7.15) was used to define acidemia. None of the infants from infected mothers had metabolic acidemia with a pH of less than 7.15 and none had a pH of less than 7.00. Significantly more (P<.05) infants in the infected group did have low 1-minute (20 versus 5%) and 5-minute (3 versus 1%) Apgar scores of 6 or less, criteria often used to define asphyxia. However, none of the newborns from the infected group had recently proposed criteria for the diagnosis of birth asphyxia (ie, leading to neurologic impairment) such as metabolic acidemia, seizures in the immediate newborn period, and low Apgar scores (3 or less). Birth asphyxia is rarely associated with intra-amniotic infection, and in the absence of other signs of fetal jeopardy such as an ominous fetal heart rate pattern, an immediate cesarean to prevent asphyxia does not appear justified once the diagnosis of chorioamnionitis is made.

Chorioamnionitis: A harbinger of dystocia

The impact of Chorioamnionitis on the course of labor is controversial. Some clinicians believe the infection has stimulatory effects, whereas others suspect inhibitory influences. Two hundred sixty-six pregnancies with Chorioamnionitis requiring labor stimulation with oxytocin were matched to uninfected women for maternal age, race, parity, gestational age, oxytocin dosage regimen, indication for labor stimulation, type of labor stimulation, cervical dilatation at initiation of oxytocin, and time from rupture of membranes to initiation of labor stimulation. Chorioamnionitis diagnosed before oxytocin infusion was associated with shorter oxytocin initiation-to-delivery intervals (4.3 versus 5.6 hours; P = .04) and had no significant impact on the cesarean rate compared with matched controls. In contrast, pregnancies complicated by Chorioamnionitis detected late in labor were associated with markedly longer oxytocin initiation-to-delivery intervals (12.6 versus 7.9 hours; P < .0001) and a fourfold increase in cesarean for dystocia compared with matched controls (40 versus 10%; P < .0001). Thus, the impact of Chorioamnionitis on the course of labor can be divided into two clinical presentations. That diagnosed before labor stimulation does not increase the use of cesarean, whereas that diagnosed after oxytocin stimulation may be a sign of abnormal labor, as it was associated with a marked increase in abdominal delivery for dystocia.

Megadose carbamazepine during the period of neural tube closure

Background: Analyses of the frequency of congenital anomalies among infants born to women who used carbamazepine during organogenesis have not yielded consistent results. Because the drug is used to treat epilepsy, any association is confounded by the underlying condition. Case: A nonepileptic 44‐year‐old multigravid woman attempted suicide by ingesting 24 200‐mg carbamazepine tablets (approximately 4.8 g). By last menstrual period and sonogram dates, the megadose occurred during the third to fourth week post‐conception. Maternal drug levels were elevated above therapeutic ranges for 2 days. Maternal serum alpha‐fetoprotein was elevated, and high‐resolution fetal sonography demonstrated a large myeloschisis that was verified at autopsy. No family history of neural tube defects or any other malformations was reported by the patient. Megadose carbamazepine ingestion during the period of neural tube closure was the only known risk factor. Conclusion: Although no other published reports of megadose carbamazepine during pregnancy were located, the neural tube defect is consistent with the recently reported risks for congenital anomalies in infants born to women who used this anticonvulsant in therapeutic doses during pregnancy. (Obstet Gynecol 1993;82:705‐8)

Examination of amniotic fluid in diagnosing congenital syphilis with fetal death

The diagnosis of congenital syphilis is difficult, particularly in stillborn fetuses, who are often macerated and have undergone autolysis. These changes can obscure both syphilitic histologic findings and special stains for spirochetes in tissue specimens used to confirm the diagnosis of congenital syphilis. Five gravidas with untreated syphilis and fetal deaths underwent sonographic examination and amniocentesis. In all five cases, dark-field microscopic examination of the amniotic fluid showed spirochetes with morphology and motility characteristic of Treponema pallidum. Organisms were infrequent, but easily identified at 400x magnification and confirmed using an oil-immersion objective yielding a 900x magnification. After delivery, fetal-placental examination and autopsy showed clinical findings typical of congenital syphilis in all five cases. Histologic changes compatible with syphilis were found in all four autopsied fetuses. Silver impregnation stains were positive in two of five tissue specimens, and anti-treponemal monoclonal antibody immunofluorescence assays were positive in one of three amniotic fluid specimens examined retrospectively, further strengthening the specificity of the dark-field microscopic identification of spirochetes. This technique, which can make the diagnosis of congenital syphilis, is recommended for women with syphilis and a fetal death, especially if sonographic hydrops and/or edema is present or if an autopsy will not be performed.