Prenatal maternal indomethacin use resulting in prolonged neonatal renal insufficiency

The short-term use of indomethacin has been shown to be relatively safe and effective in halting premature labor. Its use has been associated with adverse renal effects in both the fetal and newborn periods that are generally transient and resolve on discontinuation of the drug. However, limited data suggest that prolonged prenatal exposure to indomethacin may be harmful to the fetus. We report a case of prolonged severe renal dysfunction characterized by oligohydramnios and postnatal anuria, azotemia, and ultrasonographic kidney abnormalities associated with the long-term prenatal use of indomethacin. Although partial resolution was observed, a moderate decrease in renal function persists. Prenatal maternal indomethacin use represents a potential cause of renal dysfunction in the newborn infant that may be only partially reversible.     

Pharmacologic management of psychiatric illness during pregnancy: dilemmas and guidelines

OBJECTIVE: Given concerns about use of psychotropic medication during pregnancy, the authors reviewed the literature regarding the effects of prenatal exposure to psychotropic medications on fetal outcome. METHOD: A MEDLINE search of all articles written in English from 1966 to 1995 was performed to review information on the effects of psychotropic drug use during pregnancy on fetal outcome. Where sufficient data were available and when methodologically appropriate, meta-analyses were performed to assess risk of fetal exposure by psychotropic medication class. RESULTS: Three primary effects are associated with medication use during pregnancy: 1) teratogenicity, 2) perinatal syndromes (neonatal toxicity), and 3) postnatal behavioral sequelae. For many drug classes there are substantial data regarding risk for teratogenicity. Tricyclic antidepressants do not seem to confer increased risk for organ dysgenesis. The available data indicate that first-trimester exposure to low-potency phenothiazines, lithium, certain anticonvulsants, and benzodiazepines may increase the relative risk for congenital anomalies. However, the absolute risk of congenital malformations following prenatal exposure to most psychotropics is low. CONCLUSION: Exposure to certain psychotropic drugs in utero may increase the risk for some specific congenital anomalies, but the rate of occurrence of these anomalies even with the increased risk remains low. Use of psychotropic medications during pregnancy is appropriate in many clinical situations and should include thoughtful weighing of risk of prenatal exposure versus risk of relapse following drug discontinuation. The authors present disorder-based guidelines for psychotropic drug use during pregnancy and for psychiatrically ill women who wish to conceive.     

Tocopherols, retinol, beta-carotene and fatty acids in fat globule membrane and fat globule core in cows'' milk

To develop and characterize a murine model for investigating the long-term effects of prenatal cocaine exposure, the present study established the route of drug administration and the doses to be used for pregnant C57BL/6 mice. Comparison of the effects of a high dose of cocaine (60 mg/kg) when gavaged or injected subcutaneously (SC) established patterns of pathology characteristic of administration route but no dominating logic for selecting one over the other route for prenatal studies; however, because of the fourfold greater brain levels, with no evidence of greater pathology, the SC route was selected. When injected daily during gestation days 12-18, the period of prenatal development of dopamine systems, cocaine at doses producing plasma concentrations consistent with its stimulatory effects reduced food ingestion and weight gains during pregnancy and fetal body and brain weights at term. The extent of these reductions was comparable to reports on babies exposed to cocaine prenatally. Furthermore, the present study suggests that maternal undernutrition is not a likely mediator of these perinatal effects and that differences in the amount of cocaine exposure may cause the contrasting effects of maternal cocaine noted in the human literature.     

The effect of gestational ethanol exposure on voluntary ethanol intake in early postnatal and adult rats.

Clinical and epidemiological studies provide strong data for a relationship between prenatal ethanol exposure and the risk for abuse in adolescent and young adult humans. However, drug-acceptance results in response to fetal exposure have differed by study, age at evaluation, and experimental animal. In the present study, the authors tested whether voluntary ethanol intake was enhanced in both the infantile and adult rat (15 and 90 days of age, respectively), as a consequence of chronic fetal drug experience. Experimental rats were exposed in utero by administering ethanol to a pregnant dam in a liquid diet during gestational Days 6-20. Compared with those for isocaloric pair-fed and ad lib chow control animals, the results for experimental animals demonstrated that fetal exposure significantly increased infantile affinity for ethanol ingestion without affecting intake patterns of an alternative fluid (water). Heightened affinity for ethanol was absent in adulthood. Moreover, the results argue against malnutrition as a principal factor underlying the infantile phenomenon. These data add to a growing literature indicative of heightened early postnatal acceptance patterns resulting from maternal use or abuse of ethanol during pregnancy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prenatal diagnosis of triploidy and trisomy 21 through fetal erythroblasts isolated from maternal blood

BACKGROUND: A long-sought goal of medical genetics has been the development of prenatal diagnostic procedures that do not endanger the conceptus. The safety of noninvasive methods for prenatal diagnosis would be especially attractive because they could be extended to all pregnant women, regardless of their ages or histories. Noninvasive prenatal diagnosis for the entire population might be possible recovering fetal cells from maternal blood. For this purpose, we have studied fetal erythroblasts. MATERIALS AND METHODS: To evaluate the potential of the method for clinical use, we studied maternal blood samples from 11 women referred to us for prenatal diagnosis between 15 and 20 weeks of gestation. For simple and effective enrichment of fetal nucleated erythrocytes from peripheral maternal blood, we combined a triple density gradient and magnetic-activated cell sorting (MACS) of anti-CD71 transferrin receptor antibody labeled cells. The isolated cells were analysed by using dual-colour interphase fluorescent in situ hybridization (FISH) with X-, Y-, 18- and 21-specific DNA probes. RESULTS: Chromosomal abnormalities detected on enriched fetal cells include trisomy 21 and triploidy. CONCLUSIONS: Based on the current results it is suggested that the technique described here is a simple, fast, efficient and reliable method for non invasive prenatal diagnosis.     

Detection of cocaine exposure in the neonate. Analyses of urine, meconium, and amniotic fluid from mothers and infants exposed to cocaine

Cocaine and its metabolites were measured in urine, meconium, and amniotic fluid specimens collected from 30 maternal-infant pairs with histories of prenatal cocaine use. Cocaine, benzoylecgonine, and ecgonine methyl ester were measured by isotope dilution gas chromatography-mass spectrometry. Mothers were interviewed at delivery regarding their cocaine use during pregnancy. There was qualitative agreement between the results of drug determinations in maternal urine, amniotic fluid, infant urine, and meconium. Although all of the mothers in this study admitted to using cocaine during their pregnancy, cocaine or its metabolites were detected only in the 20 cases in which cocaine was used within 3 weeks before delivery. We conclude that when sufficiently sensitive analytic methods are used, maternal urine, infant urine, and meconium analyses yield equivalent results for detection of prenatal cocaine exposure. Importantly, neither meconium nor urinary drug measurements detected cocaine exposure when the last reported use was prior to 3 weeks before delivery.     

Identification of multiprotein complexes containing DNA replication factors by native immunoblotting of HeLa cell protein preparations with T-antigen-dependent SV40 DNA replication activity

Adequate prenatal care has been linked to improved birth outcomes in general populations but has not been assessed in HIV-infected women. We examined longitudinal claims files and vital statistics records for women in the New York State Medicaid HIV/AIDS data base delivering a singleton from 1985 through 1990. Adequacy of the self-reported number of prenatal visits was assessed by the Kessner index. In logistics models, we estimated the association of prenatal care, illicit drug use, and other maternal characteristics with three outcomes; low birth weight, preterm birth, and small-for-gestational-age. Of 2,254 singletons delivered by this HIV-infected cohort, 28% were low birth weight, 23% were preterm birth, and 20% were small for gestational age. Two-thirds had inadequate prenatal care. Non-drug users had 57 and 26% lower adjusted odds of low birth weight and preterm delivery than drug users. The adjusted odds of low birth weight and preterm birth for women with an adequate number of prenatal visits were, respectively, 48 and 21% lower than for women with inadequate care. Adequate prenatal care was also associated with a 43% reduction in the odds of small-for-gestational-age. An adequate number of prenatal visits by women in this HIV cohort was associated with a significant reduction in all three adverse birth outcomes, but most had inadequate prenatal care. These data support strengthening efforts to bring pregnant, HIV-infected women into care.     

Fetal cells in the maternal blood: a step towards non-invasive prenatal diagnosis? Review of the literature

Prenatal diagnosis of genetic abnormalities requires nucleated fetal cells which are currently obtained by invasive techniques such as amniocentesis, chorionic villus sampling and percutaneous umbilical blood sampling. Each of these entails a risk to the foetus and sometimes to the mother. Nucleated fetal cells have been reported to be present in maternal blood. Recovery of fetal cells from maternal blood would allow a noninvasive prenatal diagnosis. Their rarity (1 fetal cell for 10(6) to 10(8) maternal cells) presents a technical challenge. Due to the small number of fetal cells, sensitive analysis techniques such as PCR and FISH are necessary. Some degree of fetal cells enrichment in the maternal blood sample often precedes the analysis. Different techniques are used for the enrichment: discontinuous density gradient, magnetic activated cell sorting, fluorescence activated cell sorting, micromanipulator.... Several prenatal diagnosis have already been performed from maternal venous blood samples: diagnosis of gender, RhD blood genotype, Duchenne muscular dystrophy and hemoglobinopathy by PCR, diagnosis of gender and chromosome aneuploidy by FISH. Many teams are working on this subject. It is difficult to compare the studies because the techniques of enrichment and analysis vary. We review the different strategies chosen for prenatal diagnosis from maternal blood and discuss the results.     

Maternal adrenalectomy eliminates a surge of plasma dehydroepiandrosterone in the mother and attenuates the prenatal testosterone surge in the male fetus

Previous work has established a number of sex-related deficits in immune function, behavior, and endocrine responses to stress in the offspring of dams exposed to ethanol. To examine the potential role of maternal glucocorticoids as a mediator of these sexually dimorphic effects in the fetus, we examined the influence of prenatal alcohol exposure in the presence or absence of maternal glucocorticoids on fetal plasma corticosterone (CORT) production. An additional question to be addressed by these studies was whether maternal adrenalectomy could eliminate the known inhibition by ethanol of the prenatal surge of plasma testosterone in male fetuses. Pregnant dams were adrenalectomized (ADX) or sham-adrenalectomized on gestational day (G) 7 and placed on a liquid diet containing 35% ethanol-derived calories or pair-fed an isocaloric control diet throughout the experiment. On G18, G19, and G21, plasma levels of CORT, testosterone, and dehydroepiandrosterone (DHEA) were measured in male and female fetuses and their mothers. Ethanol administration consistently increased maternal plasma CORT levels but did not significantly alter CORT levels in the fetus. Maternal ADX resulted in compensatory increases in fetal CORT levels that were lower in fetuses of ADX dams on alcohol, suggesting a direct effect of ethanol on fetal pituitary-adrenal activity. There were no significant sex differences in fetal plasma CORT levels in response to any of these manipulations. A novel surge of maternal plasma DHEA was found on G19 that was absent in plasma from ADX dams. In spite of the absence of a surge on G19, plasma DHEA levels of ADX dams rose from very low levels at G18 to levels on G21 that were significantly higher than in Sham dams. A normal testosterone surge was observed in male fetuses on G18 and G19 from sham-adrenalectomized dams administered the pair-fed diet. However, this surge was greatly attenuated in males administered ethanol and also in male fetuses from ADX dams. These results reveal a direct inhibitory influence of ethanol on fetal CORT secretion as well as on the prenatal testosterone surge in males. Furthermore, these studies demonstrate the presence of a surge of DHEA in the pregnant rat. Overall, these data suggest that there is a critical adrenal factor in the rat that regulates the maternal surge of DHEA on G19 and the prenatal testosterone surge of male fetuses on G18-19.     

Epilepsy in pregnancy

Family physicians who provide obstetric care may periodically encounter a patient with a history of epilepsy, which may manifest before or after pregnancy. In either case, several issues need to be addressed. Pregnant women with epilepsy may have an increased frequency of seizures, with the potential for resultant maternal and fetal morbidity and mortality. Teratogenic effects of antiepileptic drugs include craniofacial abnormalities and neural tube defects. Management strategies include the prenatal use of folic acid and vitamin K, monotherapy with a single antiepileptic drug, and obtaining at least monthly free serum drug levels. Fortunately, with close monitoring and proper management, more than 90 percent of pregnancies in women with epilepsy will be uncomplicated.     

Prenatal intervention for hydronephrosis

PURPOSE: The widespread use of prenatal ultrasound results in an increased recognition of fetal hydronephrosis and technological advances now make fetal intervention possible. However, efficacy is unknown, and there have been errors in diagnosis, and associated morbidity and mortality. This review focuses on the current status of prenatal diagnosis and management of hydronephrosis. MATERIALS AND METHODS: The relevant literature on prenatal physiology, prenatal diagnosis, experimental obstruction and clinical series of prenatal intervention was reviewed. RESULTS: Prenatal ultrasound is a poor discriminator of physiological hydronephrosis, obstruction, renal dysplasia and reflux. Persistent early onset oligohydramnios is the best predictor of poor neonatal outcome. New minimally invasive techniques may aid diagnostically but they may not improve outcome. Dysplasia is often present by the time hydronephrosis is detected and it is not reversible in experimental models. Prenatal intervention is technically feasible but the survival rate is only 47%, and catheter placement and open fetal surgery have significant fetal and maternal risks. Complications occur in up to 45% of fetuses. CONCLUSIONS: Prenatal intervention for hydronephrosis remains an experimental technique. The most important question is whether prenatal therapy for obstructive uropathy improves survival and decreases long-term morbidity and mortality in affected fetuses.     

Potential role of transforming growth factor-beta 1 in terminating the immune response in patients with Guillain-Barré syndrome

Currently, amniocentesis, chorionic villus sampling (CVS) and fetal blood sampling are used to obtain fetal cells for genetic diagnosis. These invasive procedures pose a small but not negligible risk for the fetus. Efforts have been directed towards the enrichment of fetal cells, such as erythroblasts, from maternal blood and progress has been made in the diagnosis of some chromosomal disorders and in sex determinations. We now report the detection of point mutations in single gene disorders using this method of prenatal diagnosis by enriching fetal cells from maternal blood by magnetic cell sorting followed by isolation of pure fetal cells by microdissection. In two pregnancies at risk for sickle cell anaemia and beta-thalassaemia, we successfully identified the fetal genotypes. Thus, prenatal diagnosis of single gene disorders by recovering fetal cells from maternal circulation appears to be a feasible approach.     

Fetal cells in the peripheral blood of pregnant women express thymidine kinase: a new marker for detection

Fetal cells occur in maternal blood in a substantial proportion of normal pregnancies. Several different approaches have been used to detect and enrich these cells for non-invasive prenatal diagnosis. However, before these fetal cells can routinely be used for prenatal diagnosis, perfectly reproducible procedures for detection and enrichment need to be established. We found that these fetal cells express high intracellular levels of the DNA precursor pathway enzyme thymidine kinase. Since normal adult peripheral blood cells do not exhibit any thymidine kinase activity, this enzyme is a potent new marker to detect and enrich fetal cells from maternal blood. We further describe the first successful application of a cytofluorometric thymidine kinase assay to detect fetal cells in the maternal circulation by virtue of their high thymidine kinase activity.     

Methadone maintenance improves cognitive performance after two months of treatment.

Methadone maintenance (MM) has received little scientific attention regarding neurocognitive effects. The present study examined cognitive function in 17 opiate-dependent subjects at baseline and after 2 months of MM treatment. Subjects demonstrated significant improvements from baseline on measures of verbal learning and memory, visuospatial memory, and psychomotor speed and reduced frequency of drug use (Addiction Severity Index) relative to baseline, although the total percentage of urine samples positive for additional illicit substances was slightly increased. No effect of illicit drug use was observed when the sample was stratified by urine toxicology results, suggesting that improvements in cognition were not associated with additional illicit drug use. Results suggest that opiate-dependent subjects exhibit significant improvement in cognitive function after MM treatment. Future investigations are needed to confirm these findings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prenatal medicine: development, current status and future perspectives

Prenatal diagnosis and therapy are based mainly on the progress of diagnostic ultrasound and laboratory methods in genetics. There is a general tendency to replace second trimester fetal diagnoses by first trimester approaches. Transvaginal sonography and chorionic villus sampling in particular have been proven helpful in this context. The aim of all prenatal diagnostic measures is fetal therapy in time to prevent untreatable abnormalities. There has been some progress in this area; in particular, the application of stem cells for the correction of single cell diseases seems to be promising. Because all prenatal interventions involve a risk to the mother and especially the fetus, there is a concentrated effort to develop non-invasive screening or diagnostic methods. Extensive work on the isolation of fetal cells from the maternal circulation has revealed that such cells are present physiologically in pregnancy, but further trials need to show whether this method is safe enough for routine diagnostic use.     

Prenatal cocaine exposure impairs selective attention: Evidence from serial reversal and extradimensional shift tasks.

This study assessed the effects of prenatal cocaine exposure on cognitive functioning, using an intravenous (IV) rodent model that closely mimics the pharmacokinetics seen in humans after smoking or IV injection and that avoids maternal stress and undernutrition. Cocaine-exposed males were significantly impaired on a 3-choice, but not 2-choice, olfactory serial reversal learning task. Both male and female cocaine-exposed rats were significantly impaired on extradimensional shift tasks that required shifting from olfactory to spatial cues; however, they showed no impairment when required to shift from spatial to olfactory cues. In-depth analyses of discrete learning phases implicated deficient selective attention as the basis of impairment in both tasks. These data provide clear evidence that prenatal cocaine exposure produces long-lasting cognitive dysfunction, but they also underscore the specificity of the impairment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neonatal outcome in infants with evidence of fetal exposure to opiates, cocaine, and cannabinoids

This study evaluated the neonatal outcome of infants with evidence of fetal exposure to cocaine, opiates, and cannabinoids. Subjects were from the newborn nursery of an inner-city university teaching hospital. Meconium from 141 infants admitted to the full-term nursery was analyzed for metabolites of opiates, cocaine, and cannabinoids. The population was 72% African-American; 82% had medical assistance; history of drug use was reported in the medical records in 18%; mean maternal age was 24.2 years; mean birth weight was 3,234 +/- 502 g; and neonatal abstinence syndrome was reported in 7%. Meconium analysis data showed the following: 52.5% were drug-free; cocaine was present in 31%, opiates in 18% (cocaine and/or opiates 39%), and cannabinoids in 17%. In 38 infants in whom urine toxicology was obtained for clinical indications, meconium was more sensitive than urine in detecting drug exposure (55.3% vs 31.5%). There was no significant difference between cocaine/opiate-exposed and drug-free infants in race, socioeconomic status, maternal age, birth weight, head circumference, length, and Apgar scores. Cocaine/opiate-exposed infants had greater length of stay and increased frequency of maternal sexually transmitted diseases during pregnancy, with a trend toward a higher percent with fetal distress.     

1988 National Maternal and Infant Health Survey: methods and response characteristics

OBJECTIVES: The 1988 National Maternal and Infant Health Survey (NMIHS) was conducted by the National Center for Health Statistics to study factors related to poor pregnancy outcome, such as adequacy of prenatal care; inadequate and excessive weight gain during pregnancy; maternal smoking, drinking, and drug use; and pregnancy and delivery complications. METHODS: The NMIHS is a nationally representative sample of 11,000 women who had live births, 4,000 who had late fetal deaths, and 6,000 who had infant deaths in 1988. Questionnaires were mailed to mothers based on information from certificates of live birth, reports of fetal death, and certificates of infant death. Information supplied by the mother, prenatal care providers, and hospitals of delivery was linked with the vital records to expand knowledge of maternal and infant health in the United States. RESULTS: The response rates in all three components of the NMIHS differed according to the mothers' characteristics. Mothers were more likely to respond if they were 20-39 years of age, were white, were married, had fewer than four children, entered prenatal care early, had more prenatal visits, had more years of education, or resided in the Midwest Region. The percent of respondents was lower for teenage mothers, mothers of races other than white, and mothers with four or more children, little prenatal care, or fewer years of education. Mothers whose infants weighed less than 2,500 grams were less likely to respond in the live-birth and infant-death components than mothers whose infants weighed 2,500 grams or more. CONCLUSIONS: The NMIHS will provide an invaluable tool for researchers and practitioners seeking solutions to perinatal and obstetric problems.     

The impact of maternal drinking during and after pregnancy on the drinking of adolescent offspring

OBJECTIVE: The impact of prenatal maternal drinking on alcohol consumption in adolescent offspring was examined among boys and girls separately. METHOD: A prospective longitudinal sample of 185 mother-firstborn child dyads was used to examine the impact of maternal self-reported alcohol consumption during pregnancy on adolescent self-reported lifetime and current drinking, controlling for potential confounding factors. RESULTS: In this representative general population sample, maternal drinking during pregnancy, particularly continuous moderate to heavy consumption, had a significant positive effect on adolescent daughters' current drinking, but a slight negative effect on sons' lifetime drinking. The sex-specific prenatal effect on current drinking persisted with controls for prenatal maternal cigarette smoking, current maternal drinking, child-rearing practices (i.e., maternal-child closeness, monitoring and a rule against drinking) and the adolescent's problem behaviors in childhood. Prenatal maternal smoking was also associated with elevated rates of adolescent drinking, particularly current drinking. Of the child-rearing variables, only a rule against drinking decreased adolescent drinking. CONCLUSIONS: Selected prenatal factors may constitute risks for alcohol consumption among adolescent daughters. The results are discussed in light of animal models that document increased vulnerability among female offspring to the deleterious effects of gestational alcohol exposure. Implications for understanding the risk factors associated with adolescent alcohol use are discussed.     

Power spectral analysis of EEG in a multiple-bedroom, multiple-polygraph sleep laboratory

Although scientific and policy statements regarding drugs often suggest that there are grave problems of drug use within America's inner cities, the evidence that supports these statements is often based on anecdotal or incomplete data. This study of African-American adults from the Woodlawn study followed longitudinally partially fills that gap, at least for learning more about those who spend some or all of their childhood within an inner city neighborhood. We found few differences between the lifetime prevalence of drug use and a national representative sample of adults of the same age range. Furthermore, a national household survey of African-Americans of similar age living in six central cities also reported low lifetime rates of illicit drug use. Nevertheless, those from the Woodlawn cohort had higher rates of use of illicit drugs in the past year than the national sample, especially those still living in areas with high rates of poverty. Additionally, reports of heavy drug trafficking were much greater in the inner city areas than in the suburbs.