Brain proton magnetic resonance spectroscopy in children exposed to methamphetamine in utero.

OBJECTIVE: To examine the possible neurotoxic effects of prenatal methamphetamine exposure on the developing brain using 1H-MRS. METHODS: Methamphetamine-exposed children (n = 12) and age-matched unexposed control subjects (n = 14) were evaluated with MRI, localized 1H-MRS, and a Child Behavior Checklist. Metabolite concentrations of N-acetyl-containing compounds (NA), total creatine (Cr), choline-containing compounds, myoinositol, and glutamate + glutamine were measured in the frontal white matter and striatum. RESULTS: Despite an absence of visible structural abnormalities in either group, children exposed to methamphetamine in utero had higher [Cr] (+10%, p = 0.02) in the striatum. [NA], primarily a measure of N-acetylaspartate, was normal in both regions, which suggests no significant neuronal loss or damage in the two brain regions examined. There were no differences in reported behavior problems among the methamphetamine-exposed children relative to the unexposed group. CONCLUSIONS: The authors found increased [Cr] in the striatum with relatively normal [NA] in children exposed to methamphetamine. These findings suggest an abnormality in energy metabolism in the brains of children exposed to methamphetamine in utero.

Brain proton magnetic resonance spectroscopy and imaging in children exposed to cocaine in utero.

OBJECTIVE: The effects of prenatal cocaine exposure have been examined using neurobehavioral and brain structural evaluations; however, no study has examined the effects of prenatal cocaine on brain metabolism. Proton magnetic resonance spectroscopy ((1)H-MRS) is a noninvasive method to examine the biochemistry of various brain regions. The purpose of this study was to examine the possible neurotoxic effects of prenatal cocaine exposure on the developing brain using (1)H-MRS. METHODS: Cocaine-exposed children (n = 14) and age-matched unexposed control participants (n = 12) were evaluated with MRI and localized (1)H-MRS. Metabolite concentrations of N-acetyl-containing compounds (NA), total creatine (Cr), choline-containing compounds, myoinositol, and glutamate + glutamine were measured in the frontal white matter and striatum. RESULTS: Despite an absence of structural abnormalities in either group, children exposed to cocaine in utero had significantly higher Cr (+13%) in the frontal white matter. NA, primarily a measure of N-acetyl aspartate and neuronal content, was normal in both regions examined by (1)H-MRS. Normal NA suggests no significant neuronal loss or damage in the 2 brain regions examined in children exposed to cocaine prenatally. CONCLUSIONS: Consistent with findings in abstinent adult cocaine users, we found increased Cr in the frontal white matter, with normal NA in children exposed to cocaine. These findings suggest the need to investigate further possible abnormalities of energy metabolism in the brain of children exposed to cocaine in utero. In addition, this study demonstrates the feasibility of using (1)H-MRS to investigate the effects of prenatal drug exposure on the developing brain.

Human immunodeficiency virus-1 seroprevalence among parturients in Los Angeles County public hospitals.

To estimate the prevalence of human immunodeficiency virus type 1 (HIV-1) among parturients in an area with a high cumulative incidence of AIDS, an HIV seroprevalence study was conducted in 1988 in Los Angeles County. Test results were available from 8485 (86.1%) of the 9860 women delivering at four public hospitals. The test results were linked to demographic and medical information available from routinely collected delivery records. Three specimens were HIV-positive, for a seroprevalence of 3.5 per 10,000. The seropositive women were all Latina. The prevalence of HIV among women delivering at all hospitals in Los Angeles County has been shown to be relatively low compared with that of other metropolitan areas with a high number of AIDS cases, such as New York city, but appears to be even lower among women delivering at public hospitals during this time period. This low prevalence is attributed to the predominance of Latinas, who may have lower levels of infection, among public hospital parturients. The relatively low prevalence of HIV among injection drug users in Los Angeles County may contribute to the overall lower prevalence among women in Los Angeles County compared with those in New York city. This study supplements county-specific data obtained from statewide blinded neonatal testing by providing details on HIV seroprevalence among the catchment populations of public hospitals in Los Angeles County.

An intravaginal controlled-release prostaglandin E2 pessary for cervical ripening and initiation of labor at term.

The purpose of this randomized, double-blind study was to evaluate the efficacy and safety of a new controlled-release hydrogel pessary for ripening the cervix and initiating labor. Subjects had an entry Bishop score of 4 or less and gestational age of 37 or more weeks. One hundred fourteen women received a placebo pessary and 101 received the hydrogel pessary, containing 10 mg of prostaglandin (PG) E2. Compared with the placebo group, those given the PGE2 pessary were more likely to have an increase in Bishop score of 3 or more (60 or 59% versus 21 or 18%; P less than .0001), change to a Bishop score of 6 or higher (59 or 58% versus 18 or 16%; P less than .0001), and active labor (68 or 67% versus 15 or 13%; P less than .0001). Including the crossover study, uterine hyperstimulation (28 of 182, 15%) and fetal heart rate abnormalities (18 of 182, 10%) in PGE2-treated subjects were reversed on removal of the pessary with no apparent harm to the mother or fetus. These temporary adverse effects appeared while the pessary was in place and after the onset of active labor. Oxytocin was unnecessary in 89 of 182 (49%) of the PGE2-treated cases and was used more often to augment than to induce labor. We conclude that the described controlled-release PGE2 vaginal pessary induces appreciable cervical ripening and frequently initiates active labor with little or no need for oxytocin. The pessary may cause uterine hyperstimulation or fetal heart rate abnormalities, but these would be expected to reverse on removal of the pessary.

The effect of maternal cocaine use on the fetus: changes in antepartum fetal heart rate tracings.

Fetal heart rate tracings of pregnancies complicated by cocaine use were analyzed to evaluate the effects of subacute maternal cocaine use on the fetus. Nonstress tests were performed twice weekly on patients from the perinatal substance abuse clinic with screening of maternal urine samples for cocaine, amphetamines, phencyclidine, and opiates at the time of each examination. Nonstress tests performed when the urine toxicology screen was positive for cocaine alone (positive cocaine nonstress tests) were paired with those from the same patient but performed when the screen was negative (negative cocaine nonstress tests). The nonstress tests were analyzed with the Lyons scoring system, which evaluates the baseline heart rate, the oscillatory amplitude of the baseline, the oscillatory frequency, decelerations, and accelerations. Twenty pairs of nonstress tests from 20 patients were analyzed. The total score was higher on the negative cocaine nonstress test in 70% of the pairs and equal in the remaining 30% (p less than 0.001). Significant differences occurred in the oscillatory amplitude (p less than 0.001), frequency (p = 0.002), and acceleration scores (p = 0.03) but not the fetal heart rate baseline or the deceleration scores. The observed changes may reflect alterations in fetal central nervous system neurotransmitters and fetal state regulation, which may affect the developing central nervous system of cocaine-exposed fetuses and in turn play a role in the developmental and behavioral abnormalities observed in cocaine-exposed infants.

The association between Chlamydia trachomatis and ectopic pregnancy. A matched-pair, case-control study.

We performed a case-control study of the association of past exposure to Chlamydia trachomatis and ectopic pregnancy with 306 case patients with an ectopic pregnancy and 266 pregnant patients who served as controls. The geometric mean antichlamydial antibody titer among cases was 75 +/- 10.2 vs 13 +/- 11.0 among controls. The matched-pair odds ratio for ectopic pregnancy and IgG titer of 1:64 or greater to C trachomatis was 3.0 (95% confidence interval, 2.1 to 4.4). Adjusting for age at first intercourse, total lifetime partners, douching, history of infertility, and parity yielded a relative risk of 2.4 (95% confidence interval, 1.5 to 3.3). Current douching remained an independent risk factor after controlling for chlamydial exposure, with an adjusted relative risk of 2.1 (95% confidence interval, 1.3 to 3.5). The population attributable fraction for chlamydial infection was 0.47 and that for douching was 0.45. The results stress the need for control of C trachomatis infections and for further study of specific douching behaviors as risk factors for ectopic pregnancy.

Perinatal outcome associated with PCP versus cocaine use.

Phencyclidine (PCP) remains a widely used illicit drug, especially among adolescents and young adults. The pharmacologic effects of PCP are similar to those of cocaine; therefore, in this retrospective study 37 PCP-intoxicated parturients were matched for ethnicity, tobacco use, age, gravidity, and degree of prenatal care with 37 cocaine-intoxicated parturients. Infants exposed to PCP in utero, like those exposed to cocaine, had a high incidence of intrauterine growth retardation (32 vs 19%, N.S.), precipitate labor (43 vs 27%, N.S.), symptoms of neonatal drug withdrawal/intoxication, and prolonged neonatal hospitalizations. Moreover, they were more likely to have meconium-stained amniotic fluid (30 vs 19%, p = .05) and less likely to be born prematurely as cocaine-exposed infants. The comparison between the long-term developmental outcome of these groups awaits further study.

Epidemic listeriosis associated with Mexican-style cheese.

In Los Angeles County, California, 142 cases of human listeriosis were reported from January 1 through August 15, 1985. Ninety-three cases (65.5 percent) occurred in pregnant women or their offspring, and 49 (34.5 percent) in nonpregnant adults. There were 48 deaths: 20 fetuses, 10 neonates, and 18 nonpregnant adults. Of the nonpregnant adults, 98 percent (48 of 49) had a known predisposing condition. Eighty-seven percent (81 of 93) of the maternal/neonatal cases were Hispanic. Of the Listeria monocytogenes isolates available for study, 82 percent (86 of 105) were serotype 4b, of which 63 of 86 (73 percent) were the same phage type. A case-control study implicated Mexican-style soft cheese (odds ratio, 5.5; 95 percent confidence interval, 1.2 to 24.8) as the vehicle of infection; a second case-control study showed an association with one brand (Brand A) of Mexican-style soft cheese (odds ratio, 8.5; 95 percent confidence interval, 2.4 to 26.2). Laboratory study confirmed the presence of L. monocytogenes serogroup 4b of the epidemic phage type in Brand A Mexican-style cheese. In mid-June, all Brand A cheese was recalled and the factory was closed. An investigation of the cheese plant suggested that the cheese was commonly contaminated with unpasteurized milk. We conclude that the epidemic of listeriosis was caused by ingestion of Brand A cheese contaminated by one phage type of L. monocytogenes serotype 4b.

The treatment of endomyometritis.

The mainstay of treatment for postpartum endometritis is a combination of antibiotics, such as clindamycin plus an aminoglycoside. In an effort to save time and reduce the cost of treating this infection, researchers have investigated monotherapy with a beta-lactam antibiotic. Twenty-five patients with postcesarean endometritis and three with postpartum endometritis were studied at two sites for the effectiveness of 3.1 g ticarcillin disodium/clavulanate potassium administered every four or six hours for a minimum of four days. Eighteen of the 25 postcesarean endometritis patients (72%) were judged clinical cures, 6 (24%) were clinical failures, and 1 had therapy discontinued because of diarrhea. In the postpartum course of all the patients there were no wound infections and three (12%) instances of bacteremia. The majority of the enterococci were sensitive to ticarcillin disodium/clavulanate potassium, as were all of the Escherichia coli, Klebsiella pneumoniae, Bacteroides bivius, Bacteroides fragilis and other Bacteroides species.

Treatment of postcesarean endomyometritis.

Improved understanding of the microbiology of postcesarean endometritis has dramatically changed the approach to its antibiotic therapy. Initial therapy should include broad-spectrum anaerobic coverage, including against all Bacteroides species, as well as gram-positive and gram-negative aerobic coverage. Moreover, ideally initial therapy should also include coverage of Chlamydia trachomatis. Furthermore, although the use of antibiotic prophylaxis for high-risk patients undergoing cesarean section has significantly decreased their incidence of febrile morbidity, one must remember that prophylactic antibiotics have important bacteriologic effects that may limit the efficacy of monotherapy for the treatment of endometritis in prophylaxis failures.

Clinical manifestations of epidemic neonatal listeriosis.

We report the broad spectrum of clinical manifestations in 23 infants with positive cultures for Listeria monocytogenes who were treated in our hospital during a recent epidemic. The majority of infants (70%) were preterm and none was small for gestational age. Thirteen (56%) had respiratory distress at birth with evidence of congenital pneumonia. Four of the 5 deaths occurred among these infants. Four infants considered healthy after resuscitation developed fever and lethargy within 36 hours after birth. Only one of these infants had evidence of pneumonia. We conclude that congenital pneumonia with respiratory distress at birth is the major cause of mortality and morbidity from L. monocytogenes infection in the neonate.

Factors affecting psychological adjustment to a fetal death.

The loss of a child in utero can be a tragic experience. The purpose of the present study was to examine some patient characteristics that may predict which women are likely to have problems in adjusting to the loss and to examine the effectiveness of interventions by care providers in facilitating emotional recovery. Twenty-eight women who were no more than 4 weeks post partum from a fetal death were interviewed while waiting to see their physicians at the fetal demise clinic at Los Angeles County Women's Hospital. It was found that women were less depressed after the loss if they already had children, if they did not blame themselves for the death, and if they received a picture of the infant or were allowed to see the infant. Women benefited from sympathy from the medical personnel and being kept informed of problems as they developed.

Serologic evidence of prior chlamydial infection in patients with tubal ectopic pregnancy and contralateral tubal disease.

Oviductal damage from infectious salpingitis is a principle cause of ectopic pregnancy. To examine the role of Chlamydia trachomatis in patients with ectopic pregnancy, 24 patients undergoing laparotomy for ectopic pregnancy were evaluated by assessment of chlamydial serology and chlamydial cultures of tubal biopsy specimens. The patients were divided into two groups based on the presence or absence of gross abnormalities in the fallopian tube contralateral to the ectopic gestation. Ten patients in group I showed gross evidence of chronic salpingitis in the contralateral tube; 14 patients in group II had normal-appearing contralateral tubes. Chlamydial cultures were negative in both groups. Chlamydial immunoglobulin M antibodies assayed by indirect microimmunofluorescence were negative in both groups (less than or equal to 1:32). Mean geometric immunoglobulin G titers for C. trachomatis were significantly higher in the patients with evidence of contralateral chronic salpingitis (78.9 versus 13.1). These findings suggest that C. trachomatis may be a major cause of oviductal damage, which predisposes to ectopic pregnancy.

Uteroplacental unit as a source of elevated circulating prorenin levels in normal pregnancy.

Circulating levels of inactive renin, that is, prorenin, are increased in normal pregnant women. To determine whether the uteroplacental unit secretes prorenin into the maternal circulation, we measured enzymatically active and inactive renin in plasma simultaneously obtained from the radial artery and uterine vein of 12 normotensive, nonlaboring patients undergoing elective cesarean section at term. We also measured these forms of renin in the umbilical arterial and venous blood of these patients. Our data reveal that the levels of inactive renin in both arterial and uterine venous blood of normal pregnant women are significantly higher than in peripheral venous blood of nonpregnant, normotensive control subjects; normotensive term patients have a ratio of plasma inactive to active renin of 9:1 in contrast to the 1:1 ratio in normotensive nonpregnant subjects; there is a significant uterine arteriovenous difference of prorenin (66.2 +/- 24.4 ng/ml/hr, p less than 0.05) but not of active renin (1.8 +/- 1.5 ng/ml/hr, not significant). These results suggest that the uteroplacental unit contributes to the elevated prorenin levels at term pregnancy.

Epidemic perinatal listeriosis at autopsy.

Seven cases of listeriosis identified at perinatal autopsy are described. The cases occurred during the time of a 1985 Los Angeles, California, epidemic of listeriosis from suspected food contamination by Listeria monocytogenes. In only one of seven cases were gross pathologic lesions encountered. Microscopic lesions in six cases consisted of rare, localized microabscesses or granuloma-like lesions in multiple organs and contained histiocytes, monocytes, lymphocytes, and polymorphonuclear leukocytes with variable necrosis. One case had no gross or microscopic findings. Organomegaly was uncommon. The diagnosis was confirmed in three cases by postmortem blood culture. Complete perinatal autopsy is important for confirmation of listeriosis when microbiologic, gross, or microscopic findings alone may not yield characteristic features.

Perinatal listeriosis (early-onset): correlation of antenatal manifestations and neonatal outcome.

Listeria monocytogenes is an underdiagnosed and underreported cause of congenital sepsis. Twenty mother/infant pairs from whom Listeria was isolated were studied at the University of Southern California School of Medicine and Women's Hospital during the last ten years to delineate antepartum factors indicative of a fetus at high risk for perinatal Listeria sepsis. The combination of high maternal leukocyte count, fetal tachycardia, decreased fetal heart rate variability, and, especially, the absence of intrapartum fetal heart rate accelerations was associated with a complicated course for the neonate with congenital Listeria sepsis. Intrapartum administration of antibiotics decreased fetal morbidity and mortality but did not impair recovery of the organism.

Fetal injury prior to labor: does it happen?

Major advances have been made in the identification and prevention of perinatal factors that lead to long-term handicap or neurologic deficits. When the infant or child exhibits a major handicap, scrutiny of the pregnancy management often occurs in an attempt to define the causal factors. The medical goal of this inquiry is to prevent injuries and, when possible, to eliminate these factors. In the litigious sense, any deviation from optimal, ideal care or any unusual observations, such as unusual or atypical fetal heart rate patterns, are often causally linked to the adverse outcome. There are at least four categories of major fetal injury that probably occur prior to labor. An awareness of, and a diligent search for, details will no doubt clarify the legitimate origins of many so-called birth injuries. Hence the common tendency to fixate on minor deviations and/or deficiencies of labor and delivery management as causing catastrophic injuries will be successfully challenged.

Perinatal mortality associated with intrauterine infection due to pseudomonads.

Pseudomonads are common causes of nosocomial infections but are rarely implicated in perinatal disease. In a retrospective autopsy study we found that 9% of all acute congenital bacterial infections were due to Pseudomonas species. Premature rupture of membranes occurred in half the cases and clinical maternal amnionitis in two-thirds. One case was apparently nosocomial in origin. No known risk factors were implicated in any other case. Seven infants were stillborn and two died within a few hours. Congenital pneumonia, funisitis, and chorioamnionitis were found at autopsy. Intrauterine infection due to the pseudomonads poses a serious problem that has not been previously recognized.

Preinduction cervical priming with PGE2 intracervical gel.

A prospective, randomized, controlled clinical trial was conducted to evaluate the safety and efficacy of a single, 0.5-mg dose of prostaglandin E2 gel in a shelf-stable triacetin base administered intracervically in patients with an unfavorable cervix (Bishop score less than or equal to 4) 12 hours prior to oxytocin-induction of labor. forty-eight evaluable patients were enrolled, 25 in the PGE2 group and 23 in the control group. PGE2 gel treatment resulted in a significant improvement in the mean Bishop score compared to control (3.14 versus 0.70, P less than .00005). Sixty-four percent of the patients treated with PGE2 had regular uterine contractions during the 12-hour preinduction period beginning 2.18 +/- 2.0 hours after gel insertion, compared to 9% in the control group, P = .0001. Moreover, 12% (3/25) of the patients receiving PGE2 progressed into active labor and delivered during the preinduction period. The duration of oxytocin infusion required for the induction or augmentation of labor was significantly shorter for patients who received intracervical PGE2 gel compared to the control group (13.1 +/- 8.1 versus 19.0 +/- 8.7, P less than .05). However, there was no significant difference in the incidence of cesarean section between the two study groups (40 and 22% in the PGE2 and control groups, respectively). No episodes of uterine hypertonus or hyperstimulation or gastrointestinal side effects occurred as a result of PGE2 gel treatment.(ABSTRACT TRUNCATED AT 250 WORDS)