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.

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.

Interstitial deletions 4q21.1q25 and 4q25q27: phenotypic variability and relation to Rieger anomaly.

We describe clinical and chromosomal findings in two patients with del(4q). Patient 1, with interstitial deletion (4)(q21.1q25), had craniofacial and skeletal anomalies and died at 8 months of hydrocephalus. Patient 2, with interstitial deletion (4)(q25q27), had craniofacial and skeletal anomalies with congenital hypotonia and developmental delay. These patients shared certain manifestations with other del(4q) patients but did not have Rieger anomaly. Clinical variability among patients with interstitial deletions of 4q may be related to variable expression, variable deletion, or imprinting of genes within the 4q region.

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.

Congenital cytomegalovirus infection presenting as cerebral ventriculomegaly on antenatal sonography.

Antenatal sonography in two cases demonstrated cerebral ventriculomegaly and decreased head circumference, subsequently found to be secondary to cytomegalovirus (CMV) infection. In both cases, the lateral ventricles were enlarged and lissencephaly was diagnosed in the neonatal period. The findings of ventriculomegaly and decreased head circumference on antenatal sonography warrant further investigation for CMV via amniotic fluid cultures or fetal blood, given the poor prognosis in infants with symptomatic infection.

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 for 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 less than .0001) and a fourfold increase in cesarean for dystocia compared with matched controls (40 versus 10%; P less than .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.

Pregnancy complicated by hereditary spherocytosis.

Hereditary spherocytosis is a spectrum of inherited erythrocyte membrane defects that result in hemolysis and varying degrees of anemia. Among 50 pregnancies in 23 women with spherocytosis, maternal complications were infrequent except for anemia, and perinatal outcomes were generally good. In six women, blood volume expansion estimated by 51chromium-tagged erythrocytes was similar to that for normal pregnant women. Mean red cell survival measured during seven pregnancies in six women ranged at 30-90 days, consistent with the heterogeneity of this disorder.

Effect of type of anesthesia on blood loss at elective repeat cesarean section.

It has recently been reported that the use of halogenated agents during balanced general anesthesia may result in an increase in blood loss associated with cesarean section. This report has been criticized for failure to control for a variety of other factors that may have contributed to the increased blood loss, particularly the indication for and type of cesarean section. The present study was designed in an attempt to resolve this criticism. Blood loss was evaluated in uncomplicated patients undergoing elective repeat cesarean section under either general anesthesia using a halogenated agent (isoflurane) or regional anesthesia (spinal/epidural). All 117 singleton term, nonlaboring women underwent repeat low transverse cesarean section performed through a midline abdominal incision. Exclusion criteria included maternal medical complications, abnormal placentation, polyhydramnios, presence of uterine leiomyomas, and intraoperative complications. Seventy-five patients (64%) received regional and 42 (36%) received general anesthesia. A greater proportion of women undergoing general anesthesia experienced a postoperative decrease in hematocrit of 5 vol% or more compared with patients receiving regional anesthesia (10 of 42 versus 5 of 75, p = 0.018). Thus, we conclude that women undergoing uncomplicated elective repeat cesarean section under general anesthesia supplemented with a halogenated agent are at risk for increased blood loss compared with those women receiving regional anesthesia. However, the increased blood loss was not clinically significant in this study, since none of the patients required transfusion.

Anaerobic coverage for intra-amnionic infection: maternal and perinatal impact.

Although intrapartum antibiotics are beneficial to both the mother and newborn, there is no consensus as to the most efficacious antibiotic regimen in the treatment of intra-amnionic infection, especially with regard to anaerobic coverage. We randomized pregnant women with intra-amnionic infection to receive either dual agent therapy (ampicillin and gentamicin) or triple agent therapy (ampicillin, gentamicin, and clindamycin). The frequency of vaginal and cesarean delivery was similar in both groups. There was no significant difference in the incidence of endometritis between the two groups (10 of 69 versus 5 of 64; p = NS). There were no significant differences in either neonatal morbidity or mortality. The addition of clindamycin to provide anaerobic coverage for intra-amnionic infection does not significantly alter the incidence of endometritis in women delivered by cesarean section, although it may have an impact on women delivering vaginally.

Intrapartum antibiotic therapy for suspected intraamniotic infection: impact on the fetus and neonate.

Acute chorioamnionitis occurs relatively frequently in pregnancy and may result in significant fetal and neonatal morbidity. Although there is no unanimity of opinion regarding the most efficacious antibiotic regimen for the treatment of this complication, there is a consensus, at least among obstetricians, that maternal treatment may have an impact on neonatal outcome. It appears that the fetus and neonate benefit from "intrauterine" treatment. Virtually all antibiotics cross the placenta, and fortunately most are relatively safe for use during pregnancy.

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.

Alpha-thalassemia: prenatal diagnosis and neonatal implications.

Homozygous alpha-thalassemia major, or Bart's hemoglobinopathy, is the most common etiology of nonimmune hydrops in those of Oriental descent. The prenatal diagnosis can now be made utilizing DNA hybridization technique from fetal cells obtained by either amniocentesis or chorionic villus sampling. A case is reviewed documenting the utilization of DNA studies in managing patients known or suspected to have a history of alpha-thalassemia major.

Pregnancy complicated by hemoglobin CC and C-beta-thalassemia disease.

The outcomes of 72 pregnancies in 20 women with either hemoglobin CC or C-beta-thalassemia are described. Except for mild to moderate hemolytic anemia, maternal complications caused by the hemoglobinopathy were infrequent and perinatal outcomes were generally good. In eight women, blood volume expansion determined by 51chromium-tagged erythrocytes was similar to that for normally pregnant women. Mean red-cell survival was determined 11 times in eight women, and the red-cell half-life of 22 days was significantly shorter than that of 35 days for normally pregnant women.

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 less than .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.

Transfer of ceftizoxime surpasses that of cefoperazone by the isolated human placenta perfused in vitro.

The transfer of cefoperazone and ceftizoxime across the human placenta was compared using the in vitro, bidirectionally perfused human placental lobule. The mean (+/- SEM) clearance indices for ceftizoxime and cefoperazone were 0.124 +/- 0.02 and 0.037 +/- 0.01, respectively (P = .0013). Cefoperazone concentration plateaued at a fetal concentration of 4-5 micrograms/mL in a recirculating perfusion system. No evidence of a decreasing slope of ceftizoxime transfer to the fetal compartment was noted after 60 minutes of perfusion. In a closed-closed perfusion system with equal concentrations of ceftizoxime in each compartment, a 1.1:1 fetal gradient was noted. These data indicate that ceftizoxime crosses the placenta significantly better than does cefoperazone and support our in vivo study documenting preferential concentration of ceftizoxime in the fetal compartment.

17 beta-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.

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.