Meconium-stained amniotic fluid and the meconium aspiration syndrome. An update

Over the past 5 years, increasing understanding about the pathophysiology of meconium-stained amniotic fluid (MSAF) and the meconium aspiration syndrome (MAS) has occurred. Many new therapies are being used in an attempt to prevent MAS and to treat the disorder. The authors review the current status of knowledge concerning the MSAF and MAS and management of these entities.     

Hyperphenylalaninemia due to dihydropteridine reductase deficiency. Assay of the enzyme in fibroblasts from affected infants, heterozygotes, and in normal amniotic fluid cells

Two infant siblings with modest elevations of serum phenylalanine concentrations had seizures and developmental regression: they died in their second year. Dihydropteridine reductase activity, which can be measured in normal cultured skin fibroblasts, was measured in the younger sibling and was absent. Parents of the two siblings and parents of a previously reported patient all showed 50% or less of the normal dihydropteridine reductase activity in their cultured fibroblasts. Dihydropteridine reductase activity is also present in normal cultured amniotic fluid cells, offering the possibility of prenatal diagnosis. Absence of dihydropteridine reductase results not only in a defect in the conversion of phenylalaning to tyrosine, but also in the biosynthesis of the neurotransmitters, dopamine, norephinephrine, and serotonin. Since deficiencies in these neurotransmitters would not be alleviated by a phenylalanine-restricted diet, it is important to establish the nature of the enzymatic defect in all suspected variants of phenylketonuria.     

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.     

Reactivity and regulation in children prenatally exposed to cocaine.

Children prenatally exposed to cocaine may be at elevated risk for adjustment problems in early development because of greater reactivity and reduced regulation during challenging tasks. Few studies have examined whether cocaine-exposed children show such difficulties during the preschool years, a period marked by increased social and cognitive demands and by rapid changes in reactivity and regulation. The authors addressed this question by examining frustration reactivity and regulation of behavior during a problem-solving task in cocaine-exposed and -unexposed preschoolers. Participants were 174 4.5-year-olds (M age = 4.55 years, SD = 0.09). Frustration reactivity was measured as latency to show frustration and number of disruptive behaviors, whereas regulation was measured as latency to approach and attempt the problem-solving task and number of problem-solving behaviors. Results indicated that cocaine-exposed children took longer to attempt the problem-solving task but that cocaine-exposed boys showed the most difficulties: They were quicker to express frustration and were more disruptive. Effect sizes were relatively small, suggesting both resilience and vulnerabilities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alterations in the reinforcing efficacy of cocaine in adult rats following prenatal exposure to cocaine.

Adult male rats gestationally exposed to cocaine and nonexposed control offspring were examined for differences in operant responding for cocaine and sucrose reinforcement. Offspring were derived from dams that had received subcutaneous injections of 40 mg/kg/3cc cocaine hydrochloride daily on gestational Days 8–20 and nontreated control dams. Although no prenatal treatment differences were seen when the animals lever pressed for sucrose pellets on a progressive-ratio (PR) schedule, adult offspring prenatally exposed to cocaine were observed to exhibit an enhanced rate of cocaine intravenous self-administration on a fixed-ratio 5 (FR-5) schedule along with a marked decrease in break point on the PR reinforcement schedule. These results suggest that the reinforcing efficacy of cocaine may be reduced in animals with a prenatal history of cocaine exposure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Passage of mannitol from mother to amniotic fluid and fetus

Ten pregnant women and three pregnant sheep received mannitol intravenously. The results show that during late pregnancy this substance appears in amniotic fluid, and when the fetus is alive, its concentration increases with time, reaching values which are higher than those simultaneously obtained in maternal plasma. The experiments performed in sheep show that in fetal urine the concentration of mannitol reached values 10 to 20 times higher than those found in fetal plasma. This supports the hypothesis that the fetal kidney has an important role in the transference of this type of substance from the mother to the amniotic fluid.     

Differences among mothers of infants judged to differ in security.

38 12-mo-old infants were seen with their mothers in a strange situation test. On the basis of reunion behavior in this situation, each infant was judged securely attached to the mother, insecurely attached to the mother, or intermediate in security. When the infants were 21 mo, research assistants blind to strange situation behavior rated maternal behavior from videotapes of a mother–child free play session. Mothers of securely attached infants were significantly more sensitive, accepting, and expressive of affect than mothers of insecurely attached infants. Mothers of insecurely attached infants were found to be more angry. (3 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cerebrospinal fluid concentrations of somatostatin and biogenic amines in grown primates reared by mothers exposed to manipulated foraging conditions

The glycopeptide antibacterial drugs, vancomycin and teicoplanin, are widely used in hospitals for therapy of severe or multiresistant infection that has a positive results on Gram's stain test. Although vancomycin resistance is common in some hospital-acquired Enterococcus sp and resistance to teicoplanin occurs among Staphylococci sp glycopeptides remain the cornerstone of therapy for infection due to methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative Staphylococcus organisms, and infection related to implanted devices. Therapeutic drug monitoring (TDM) of these agents remains controversial, but advances in our understanding of their pharmacodynamics and further clinical studies are helping clarify the situation. In the future, a more rational approach to monitoring will probably result in less intensive monitoring of vancomycin but more intensive monitoring of teicoplanin.     

Olfactory function in the human fetus: Evidence from selective neonatal responsiveness to the odor of amniotic fluid.

This study was aimed at characterizing the level of specificity of the human newborn's response to an odor experienced in utero. Three groups of breast-fed infants and 3 groups of bottle-fed infants were examined on Postnatal Day 3 for their differential head-turning response when exposed to paired-choice tests contrasting the odors of either familiar (f) amniotic fluid (AF) or nonfamiliar (nf) AF or either of these AF odors and a control (C) stimulus. In fAF versus nfAF tests, the infants oriented preferentially to the odor of fAF, regardless of their feeding regimen (i.e., of their postnatal reexposure to AF-like cues in maternal milk). The fAF or nfAF versus C tests showed that this response pattern was caused by a true positive orientation toward fAF and not by avoidance from nfAF odor. This highly selective neonatal response to fAF odor is consistent with the hypothesis that the human fetus can detect and store the unique chemosensory information available in the prenatal environment and that this information becomes coupled with positive control of behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Detection of 1,N6-ethenoadenine in rat urine after chloroethylene oxide exposure

The four etheno adducts of vinyl chloride formed in DNA, 1,N6-ethenoadenine (epsilonA), 3,N4-ethenocytosine, 1,N2-ethenoguanine and N2,3-ethenoguanine were previously reported to be released from DNA by a family of enzymes in the base-excision repair pathway (Dosanjh et al., Proc. Natl Acad. Sci. USA, 91, 1024-1028, 1994; Hang et al., Carcinogenesis, 17, 155-157, 1996; Hang et al., Proc. Natl Acad. Sci. USA, 94, 12869-12874, 1997). Adducts excised from DNA by glycosylases are usually excreted in urine and have been reported to be potential biomarkers of DNA damage in exposed individuals. In this study, we report the detection of epsilonA in the urine of rats exposed to chloroethylene oxide (CEO) using immunoaffinity columns made with specific monoclonal antibodies for enrichment, followed by quantitation by HPLC with fluorescence detection. Chemical analysis of urine samples revealed the presence of a compound chromatographically identical to authentic epsilonA standard. This compound was confirmed by mass spectral analysis. EpsilonA was present in urine of control and CEO-treated rats, with the latter having up to 50-fold greater amounts. The cumulative excretion of epsilonA reached a plateau between 24 and 48 h post-exposure. While it is clear that CEO treatment results in increased excretion of epsilonA, the exact source of the adduct is unknown. When rats were administered epsilonA i.v., approximately 10% of the administered dose was excreted in urine. This research demonstrates that urinary excretion of epsilonA may be a potential biomarker for in vivo alkylation of DNA and nucleotide pools.     

Gestational methylmercury exposure selectively increases the sensitivity of operant behavior to cocaine.

Developmental methylmercury (MeHg) exposure alters dopamine neurotransmitter systems, but the selectivity of this and the effects of low, environmentally relevant MeHg exposure regimens are poorly understood. In previous reports, some including littermates of animals studied here, chronic, low-level exposures affected performance on reversal tasks and enhanced reinforcer efficacy. Using high- and low-rate operant behavior under a fixed interval (FI) schedule, sensitivity was examined to drugs that target noradrenergic and dopaminergic neurotransmitter systems. Female rats were exposed in utero to 0, 0.5, or 5 ppm of mercury, as MeHg, via maternal drinking water. Selenium (Se) is thought to attenuate MeHg's neurotoxicity, so animals consumed a diet containing 0.06 or 0.6 ppm of Se. At 11 months, they lever-pressed under a FI 120” schedule of sucrose reinforcement. Acute dose-effect curves were generated with cocaine, desipramine, SKF-38393, quinpirole, SCH-23390, and sulpiride. As compared with unexposed animals, those exposed to 5 ppm mercury, regardless of Se exposure, were 2 to 3 times more sensitive to the rate-reducing effects of high doses of cocaine and did not show increased responding earlier in the interval following moderate cocaine doses. Cocaine's effects in the 0.5 ppm Hg groups depended on dietary Se: low Se diet resulted in a rightward shift in the DEC compared to controls, whereas a high Se diet did not. No differential effects of MeHg were seen with the other drugs. Gestational MeHg exposure produces irreversible sensitivity to dopamine, but not norepinephrine, reuptake inhibitors and not to drugs that target D1 or D2 receptors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Factors associated with decisions about return to work in mothers of infants.

To better understand career-related choices made by mothers of infants, 82 mothers were interviewed in the maternity ward and 3 times in the next 12 mo. Mothers who were consistent in their plans not to work, from the maternity ward through the next 12 mo, were compared with mothers who in the maternity ward said they were not going to work but later changed their minds. The groups were similar in their anxiety about separation from their infants; they differed significantly with respect to accepting and adapting to infant discontent, beliefs about their babies' attachment, and the importance of a job or career in their lives. (2 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enduring effects of prenatal cocaine exposure on attention and reaction to errors.

Rats exposed to cocaine prenatally were administered a series of 3-choice visual attention tasks, with the most pronounced deficits seen in a task in which the onset time, location, and duration of a visual cue varied unpredictably between trials. The cocaine-exposed rats were less accurate than controls but did not differ in the rate of premature responses or omission errors. The pattern of errors, coupled with response latency data, implicated deficits in the ability to rapidly engage attention and maintain a high level of alertness to the task. The cocaine-exposed rats also exhibited a blunted reaction to an error on the previous trial, possibly reflecting an alteration in emotional regulation and/or error monitoring. Implications for underlying neuropathology are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neonatal exposure to cocaine enhances the reward-potentiating properties of the drug in young adult animals.

Either cocaine (20 mg/kg) or saline vehicle was administered to rat pups once daily on postnatal days 1–8. The enhancement of braid stimulation reward (BSR) by acute administration of cocaine (2.5, 5, and 10 mg/kg ip) was assessed in adult offspring (70–90 days of age) using a rate-frequency curve-shift paradigm. Acute administration of cocaine produced orderly dose-related shifts of the rate-frequency function toward lower frequencies in all groups indicating a reward-enhancing effect of the drug on BSR. However, offspring neonatally exposed to cocaine displayed a greater drug-induced potentiation of BSR. Of particular note, the small but significant enhancement of the reward-potentiating properties of cocaine was more pronounced in female offspring neonatally exposed to the drug. These findings indicate that the rewarding properties of cocaine were altered by neonatal exposure to the drug in a sexually dimorphic fashion. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Concentration of mercury in hair of indigenous mothers and infants from the Amazon basin

HSV-1 mutants in the RL-1 gene encoding the ICP34.5 protein have been demonstrated to have diminished neurovirulence in brain yet replicate as efficiently as parental virus in transformed tissue culture cells. Thus they have been proposed as candidates viruses for human brain tumor therapies. Evaluation of their replicative properties and pathogenesis within the nervous system has been limited. As most patients undergoing therapies for brain tumors are likely to be immunocompromised, it will be important to understand the pathogenesis of these viruses in immunocompromised hosts. To this end, the lateral ventricle of nude mice was injected with high (2.5 x 10(7) PFU), medium (10(5) PFU), or low dose (10(3) PFU) HSV-1 variant-1716, which has a deletion in the RL-1 gene. Ten of 10 mice died within 2-3 days following the high titer infection. Six of 19 animals with medium titer infection died within 9 days, and viral antigens were seen in ependymal cells as well as neurons within the brainstem and thalamus. Although only two of 19 animals became moribund 18 days after medium titer viral infection, many neocortical and hippocampal neurons were positive for HSV-1 antigens. However, plaque-purified viral isolates recovered from brain homogenates of these animals demonstrated no increase in pathogenicity. Nine of 20 animals died following low dose infection; six of these animals, from which tissue was analyzed, all had many HSV antigen-positive neurons in the neocortex and hippocampus. These data imply that if this type of virus is used for human brain tumor therapy immunosuppressed patients may suffer from significant viral pathogenesis outside the tumor.     

Stress exposure and stress generation in children of depressed mothers.

Two hypotheses were tested: (1) One mechanism contributing to the high rate of disorder in children of women with affective disorders is elevated exposure to stressful events and conditions, and (2) the children of depressed women, particularly women with unipolar depression, contribute to event occurrence because of increased interpersonal conflict. Life stress interview assessments were made at 6-mo intervals for 3 yrs on 53 children of unipolar, bipolar, medically ill, and normal women. Both hypotheses were confirmed. Transactional models of risk and further studies of the interpersonal functioning of children at risk for depression are needed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of prenatal exposure to cocaine on conditional discrimination learning in adult rats.

Adult male rats that were gestationally exposed to cocaine and control offspring were trained on an instrumental conditioning task for assessment of the acquisition and reversal of an appetitive conditional discrimination based on olfactory cues. Offspring were derived from Sprague-Dawley dams that had received subcutaneous/ly (sc) injections of 40 mg/kg/3 cc cocaine hydrochloride (C40) daily on Gestational Days 8–20, pair-fed (PF) dams that were injected with saline, nutritional control dams (NC) that received saline injections, and nontreated control dams (LC). There were no differences among the prenatal treatment groups in acquisition of the barpress response or response rate throughout all phases of training. All prenatal treatment groups required approximately the same number of sessions to criterion on the initial odor discrimination. In contrast, adult C40 offspring required more sessions to acquire the reversal of the conditional discrimination than did animals from the other treatment groups (PF, NC, and LC). In addition, even at criterion performance for acquisition of the reversal discrimination, C40 animals exhibited lower accuracy on the 1st 10 responses and made significantly more errors before the 1st reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fluorides in the body of the mother and in the fetus. III. Fluorides in amniotic fluid

Fluoride concentrations in amniotic fluid as well as in venous and arterial cord blood serum were determined in 20 women during the perinatal period. The mean concentrations of fluoride from amniotic fluid, venous cord blood serum and arterial cord blood serum were 1,6 +/- 0,18 mumol/l, 3,2 +/- 0,28 mumol/l and 2,9 +/- 0,39 mumol/l respectively. Amniotic fluid fluoride concentrations were significantly higher in the older age group of pregnancies (39-42 weeks) in comparison with the younger age group of pregnancies (34-38 weeks) p < 0,01. The reasons for mentioned relations were discussed.     

Enrolling and retaining mothers of substance-exposed infants in drug abuse treatment.

This study provided an experimental test of a drug abuse treatment enrollment and retention intervention in a sample of 103 Black mothers of substance-exposed infants. Significantly more women assigned to the Engaging Moms Program enrolled into drug abuse treatment than did women assigned to the control condition (88% vs. 46%). Sixty-seven percent of participants in the Engaging Moms Program received at least 4 weeks of drug abuse treatment compared with 38% of the control women. However, there were no differences between the groups 90 days following treatment entry. Logistic regressions revealed that readiness for treatment predicted both short-term and long-term treatment retention. The Engaging Moms Program has considerable promise in facilitating treatment entry and short-term retention, but it did not influence long-term retention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Children's cognitive ability from 4 to 9 years old as a function of prenatal cocaine exposure, environmental risk, and maternal verbal intelligence.

This study examined the effects of prenatal cocaine exposure, environmental risk, and maternal verbal intelligence on children's cognitive ability. Gender and age were examined as moderators of potential cocaine exposure effects. The Stanford-Binet IV intelligence test was administered to 231 children (91 cocaine exposed, 140 unexposed) at ages 4, 6, and 9 years. Neonatal medical risk and other prenatal exposures (alcohol, cigarettes, and marijuana) were also examined for their unique effects on child IQ. Mixed models analysis indicated that prenatal cocaine exposure interacted with gender, as cocaine-exposed boys had lower composite IQ scores. Age at assessment did not moderate this relation, indicating that cocaine-exposed boys had lower IQs across this age period. A stimulating home environment and high maternal verbal IQ also predicted higher composite IQ scores. Cocaine-exposed boys had lower scores on the Abstract/Visual Reasoning subscale, with trends for lower scores on the Short-Term Memory and Verbal Reasoning subscales, as exposure effects were observed across domains. The findings indicate that cocaine exposure continues to place children at risk for mild cognitive deficits into preadolescence. Possible mechanisms for the Exposure × Gender interaction are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)