Neonatal Hair Research Articles

Maternal and Neonatal Scalp Hair Concentrations of Zinc, Copper, Cadmium, and Lead: Relationship to Some Lifestyle Factors

Postpartum scalp hair samples from 82 term-pregnancy mother/ neonate pairs were analyzed for their concentrations of zinc (Zn), copper (Cu), cadmium (Cd), and lead (Pb), using inductively coupled plasma-mass spectrometry. Maternal and neonatal Zn concentrations had geometric means (and 99% confidence intervals) of 122.5 microg/g (117.9--131.5 microg/g) and 146.9 microg (141.5--156.7 microg/g) respectively. Corresponding Cu values were 18.4 microg/g (17.6--23.8 microg/g) and 6.7 microg/g (6.3--7.6 microg/g). Those of Cd were 0.49 microg/g (0.47--0.69 microg/g) in the mothers and 0.57 microg/g (0.55--0.86 microg/g) in the neonates. For Pb, they were 7.95 microg/g (7.60--9.32 microg/g) and 4.56 microg/g (4.39--5.56 microg/g). Cigarette smoking, despite its relatively low prevalence (19.5%), was associated with lower Zn and higher Cd and Pb concentrations and in lower Zn/Cd and Zn/Pb molar concentration ratios. Smoking also altered interelemental relationships, particularly those of Zn with Cd and Pb and those between Cd and Pb. Smoking frequency appeared to show negative dose-response effects on maternal and neonatal Zn concentrations, Zn/Pb molar concentration ratios, and birth weight. Mothers with a history of oral contraceptive (OC) usage had significantly higher Cu concentrations and lower Zn/Cu molar concentration ratios than non users, with the highest Cu concentrations and lowest Zn/Cu values being associated with third-generation OCs. No similar effects were elicited in the respective neonatal Cu concentrations. Neither alcohol consumption nor prenatal supplementation with iron and/or folic acid had discernible effects on the maternal or neonatal elemental concentrations. The data from this study suggest that in a given population of term-pregnancy mothers and neonates, significant interindividual variations in hair trace element concentrations can occur, irrespective of commonality of general environment, and that lifestyle factors, including cigarette smoking and OC usage history, can be significant contributory factors to such variations. The data are discussed in relation to the effects of smoking-associated exposure to Cd and Pb exposure on Zn availability for placental transfer, as well as on the quantitative maternal Zn supply levels to the fetus resulting from the known tendency of smokers to have lower dietary intakes of Zn.

Molecular diversity of voltage-gated sodium channel alpha subunits expressed in neuronal and non-neuronal excitable cells

In order to investigate the role of molecular diversity of voltage-activated sodium channel α-subunits in excitability of neuronal and non-neuronal cells, we carried out patch-clamp recordings and single-cell RT-PCR on two different types of mammalian excitable cells i.e. hippocampal neurons and non-neuronal utricular epithelial hair cells. In each cell type, multiple different combinations of sodium channel α-subunits exist from cell to cell despite similar sodium current properties. The mRNA isoforms, Nav1.2 and Nav1.6, are the most frequently detected by single cell analysis in the two cell types while Nav1.3 and Nav1.7 are also moderately expressed in embryonic hippocampal neurons and in neonatal utricular hair cells respectively. By investigating the particular alternate splice isoforms of Nav1.6 occurring at the exon 18 of the mouse orthologue SCN8A, we revealed that this subunit co-exist in the two cell types under different alternative spliced isoforms. The expression of non-functional isoforms of Nav1.6 in utricular epithelial hair cells excludes the involvement of this subunit in supporting their excitability. Thus, from a functional point of view, the present results suggest that, at the single cell level, both neuronal and non-neuronal excitable cells expressed different and complex patterns of sodium channel gene transcripts but this diversity alone cannot explain the sodium current properties of these cell types.

The use of fatty acid ethyl esters in neonatal hair to identify infants affected by prenatal alcohol exposure: a baseline study

The identification of prenatal alcohol exposure is difficult due to the lack of a clear and consistent diagnostic marker. The usefulness of Fatty Acid Ethyl Esters (FAEE) as biomarkers for in utero alcohol exposure has been well established for meconium, however by extending the use of FAEE into neonatal hair, we can increase the window of detection for maternal drinking up to three months after birth. Using solid phase extraction and GC-MS in CI mode, we have successfully developed and validated a method for the quantitative analysis of FAEE in hair that can discriminate between adult heavy drinkers and non-drinkers. We now extend the use of this assay into neonatal hair. Baseline establishment for FAEE levels in neonatal hair is currently in progress to account for any endogenous FAEE levels found in the body. Hair samples were collected from non-drinking mothers and their neonates and analyzed for FAEE. Low levels of selected FAEE were detected in neonatal samples of our preliminary baseline cohort (n=13; mean cumulative FAEE=0.709±0.805 pmol/mg). Detection limits ranged from 0.01 to 0.04 pmol/mg. A baseline for the quantitative analysis of FAEE in neonatal hair will help define a reliable positive screening cut-off for in utero alcohol exposure. This novel neonatal hair test will aid a physician's ability to diagnose fetal alcohol spectrum disorder and provide intervention at stages where the effects of pre-natal alcohol exposure can be minimized or prevented. Clinical Pharmacology & Therapeutics (2004) 75, P25–P25; doi: 10.1016/j.clpt.2003.11.095

Cav1.3 (alpha1D) Ca2+ currents in neonatal outer hair cells of mice.

Outer hair cells (OHC) serve as electromechanical amplifiers that guarantee the unique sensitivity and frequency selectivity of the mammalian cochlea. It is unknown whether the afferent fibres connected to adult OHCs are functional. If so, voltage-activated Ca2+ channels would be required for afferent synaptic transmission. In neonatal OHCs, Ca2+ channels seem to play a role in maturation since OHCs from Cav1.3-deficient (Cav1.3-/-) mice degenerate shortly after the onset of hearing. We therefore studied whole-cell Ca2+ currents in outer hair cells aged between postnatal day 1 (P1) and P8. OHCs showed a rapidly activating inward current that was 1.8 times larger with 10 mM Ba2+ as charge carrier (IBa) than with equimolar Ca2+ (ICa). IBa started activating at -50 mV with Vmax = -1.9 +/- 6.9 mV, V0.5 = -15.0 +/- 7.1 mV and k = 8.2 +/- 1.1 mV (n = 34). The peak IBa showed negligible inactivation (3.6 % after 300 ms) whereas the ICa (10 mM Ca2+) was inactivated by 50.7 %. OHC IBa was reduced by 33.5 +/- 10.3 % (n = 14) with 10 microM nifedipine and increased to 178.5 +/- 57.8 % (n = 14) by 5 microM Bay K 8644. A dose-response curve for nifedipine revealed an IC50 of 2.3 microM, a Hill coefficient of 2.7 and a maximum block of 36 %. Average IBa density in OHCs was 24.4 +/- 10.8 pA pF-1 (n = 105) which is only 38 % of the value in inner hair cells. Single cell RT-PCR revealed expression of Cav1.3 in OHCs. In OHCs from Cav1.3-/- mice, Ba2+ current density was reduced to 0.6 +/- 0.5 pA pF-1 (n = 9) indicating that > 97 % of the Ca2+ channel current in OHCs flows through Cav1.3.

Voltage-gated Na+ channel activation induces both action potentials in utricular hair cells and brain-derived neurotrophic factor release in the rat utricle during a restricted period of development.

The mammalian utricular sensory receptors are commonly believed to be non-spiking cells with electrical activity limited to graded membrane potential changes. Here we provide evidence that during the first post-natal week, the sensory hair cells of the rat utricle express a tetrodotoxin (TTX)-sensitive voltage-gated Na+ current that displays most of the biophysical and pharmacological characteristics of neuronal Na+ current. Single-cell RT-PCR reveals that several alpha-subunit isoforms of the Na+ channels are co-expressed within a single hair cell, with a major expression of Nav1.2 and Nav1.6 subunits. In neonatal hair cells, 30 % of the Na+ channels are available for activation at the resting potential. Depolarizing current injections in the range of the transduction currents are able to trigger TTX-sensitive action potentials. We also provide evidence of a TTX-sensitive activity-dependent brain-derived neurotrophic factor (BDNF) release by early post-natal utricle explants. Developmental analysis shows that Na+ currents decrease dramatically from post-natal day 0 (P0) to P8 and become almost undetectable at P21. Concomitantly, depolarizing stimuli fail to induce both action potential and BDNF release at P20. The present findings reveal that vestibular hair cells express neuronal-like TTX-sensitive Na+ channels able to generate Na+-driven action potentials only during the early post-natal period of development. During the same period an activity-dependent BDNF secretion by utricular explants has been demonstrated. This could be an important mechanism involved in vestibular sensory system differentiation and synaptogenesis.

New Methods for Neonatal Drug Screening

After completing this article, readers should be able to: 1. Describe perinatal and neonatal complications of maternal use of cocaine, alcohol, opiates, and barbiturates in pregnancy. 2. List established cutoffs of conventional immunoassays of urine for common substances of abuse. 3. List the advantages of using meconium testing for substances of abuse. 4. Describe the role of fatty acid ethyl esters in detecting prenatal alcohol exposure. Maternal substance use during pregnancy can have direct consequences on both the developing fetus and the mother and is a significant public health concern. The prevalence of gestational use of drugs of abuse varies, depending on the study population and method of detection, but it generally ranges from 1% to 15%. (1) One of the largest epidemiologic studies conducted in the United States documented that although most pregnant women decrease the use of substances as the pregnancy progresses, a significant proportion of them remain regular users, even in the third trimester (eg, ethanol [13%], cannabis [9.3%], cocaine [10%], and heroin [1%]). (2) Various perinatal and neonatal complications can result from prenatal exposure to common drugs of abuse. (3) The use of cocaine during pregnancy is associated with increased risks of preterm labor, intrauterine growth retardation, and neurobehavioral abnormalities. Heavy alcohol use during pregnancy leads to fetal alcohol spectrum disorder, which is characterized by an array of congenital malformations, central nervous system abnormalities, and neurodevelopmental deficits. Neonates exposed to opiates, alcohol, and barbiturates in utero are at risk of developing neonatal abstinence syndrome, which is characterized by irritability, gastrointestinal dysfunction, respiratory distress, and other nonspecific symptoms. (1) Data in the literature conflict regarding adverse events in the immediate postnatal period that can be attributed to prenatal exposure to other illicit drugs. Thus, early identification of neonates in whom substance exposure is suspected is important for appropriate treatment intervention and …

Neonatal hair analysis contribution to establishing a gestational drug exposure profile and predicting a withdrawal syndrome.

Recently, interest in hair analysis in such fields as drug abuse, driving, or for clinical purposes (determination of drug-exposed neonates especially) has grown because of the highly sensitive method of detection (GC-MS) that can now be applied. Neonates born to drug-addicted mothers can suffer from neonatal withdrawal syndrome (NWS), which requires morphine treatment in its severe forms. To assess and measure toxicologic factors predicting the appearance and the severity of this syndrome, matrices such as urine, meconium, and hair are necessary. Cannabinoids, opiates, cocaine (and its metabolites), and methadone in particular were determined in the various matrices collected in 17 mother/neonate pairs. An immunologic screening method was used, and quantification was achieved with GC-MS. In spite of some bias (color, length, race) that might hinder an accurate interpretation, the results of hair analysis makes it possible to confirm a fetal drug exposure and to reinforce the diagnosis of the NWS observed, particularly when results obtained in other matrices are negative. Hair analysis contributes to our ability to predict a NWS.

Hair analysis of opiates in mothers and newborns for evaluating opiate exposure during pregnancy

The increasing interest in toxicological hair analysis as a marker of human exposure to xenobiotics such as illicit substances or therapeutic drugs, has been made feasible by the extension of mass spectrometry, a highly sensitive method of detection. A newborn exposed to drugs in utero can suffer from a varying degree of withdrawal syndrome, a few days after birth. If of opiate origin, the withdrawal syndrome can be treated with morphine, among other therapeutics, but it is not easy to diagnose because of atypical symptoms presented by neonates and especially when maternal drug addiction has not been revealed. To assess and measure toxicological factors linked with the appearance and the severity of this syndrome, maternal and neonatal matrices such as urine, meconium and hair were collected during a protocol approved by the ethical committee. Opiates in particular were measured with GC–MS and potential combined dependences (cannabis, cocaine, amphetamine, LSD and benzodiazepines) and/or substitutive therapeutics (methadone or buprenorphine) were also assessed in 17 mother/neonate couples. Gestational opiate exposure profiles were drawn up and linked with the observed withdrawal syndromes. A withdrawal syndrome seems to appear more frequently after foetal exposure to an association of opiates/substitutive molecules (8 out of 10 withdrawal syndromes observed in this study), although the impact of cocaine and benzodiazepines must also be taken into account. The results obtained in neonatal hair make it possible to affirm foetal drug exposure and are in accordance, for the majority, with the appearance of a neonatal withdrawal syndrome (NWS). Neonatal hair analysis could contribute to assess in utero exposure to opiates, particularly when results in urine and meconium are negative or when these matrices are not available.

Developmental changes in the expression of potassium currents of embryonic, neonatal and mature mouse inner hair cells

Developmental changes in electrophysiological membrane properties of mouse cochlear inner hair cells (IHCs) were studied from just after terminal differentiation up to functional maturity. As early as embryonic day 14.5 (E14.5) newly differentiated IHCs express a very small outward K+ current that is largely insensitive to 4-aminopyridine (4-AP). One day later the inward rectifier, IK1, is first observed. These immature cells initially exhibit only slow graded voltage responses under current clamp. From E17.5 spontaneous action potentials occur. During the first week of postnatal development, the outward K+ current steadily increases in size and a progressively larger fraction of the current is sensitive to 4-AP. During the second postnatal week, the activation of the 4-AP-sensitive current, by now contributing about half of the outward K+ current, shifts in the hyperpolarizing direction. Together with an increase in size of IK1, this hyperpolarizes the cell, thus inhibiting the spontaneous spike activity, although spikes could still be evoked upon depolarizing current injection. Starting at about the onset of hearing (postnatal day 12, P12) immature IHCs make the final steps towards fully functional sensory receptors with fast graded voltage responses. This is achieved mainly by the expression of the large-conductance Ca2+-activated K+ current IK,f, but also of a current indistinguishable from the negatively activating IK,n previously described in mature outer hair cells (OHCs). The 4-AP-sensitive current continues to increase after the onset of hearing to form the major part of the mature delayed rectifier, IK,s. By P20 IHCs appear mature in terms of their complement of K+ conductances.

Comparison of meconium and neonatal hair analysis for detection of gestational exposure to drugs of abuse

Background: Meconium and hair are two biological markers of in utero exposure to illicit drugs. Objective: To compare the sensitivity of the two tests for different drugs. Setting: Motherisk laboratory...

Maternal and neonatal hair mercury concentrations: the effect of dental amalgam

To evaluate maternal and fetal hair mercury levels in relation to the placement of dental amalgam tooth restorations. Cross sectional study involving women who never had dental amalgam restorations placed, women who had amalgam restorations placed before pregnancy and women who had restorations placed during the index pregnancy. North of England Maternity Hospital. Fifty-three healthy women who delivered healthy babies at term. Maternal and fetal hair was collected in a standardised manner in the first few days following delivery. Maternal and neonatal hair mercury concentrations. When compared with women without restorations, there was a significant increase in the maternal hair mercury concentration in women who had dental amalgam placed outside of the index pregnancy and also in women who had dental amalgam placed during the index pregnancy. The fetal hair mercury concentration was significantly higher in babies when mothers had been exposed to dental amalgam either before pregnancy or during pregnancy compared with unexposed babies. There was no difference in the maternal or fetal hair mercury levels in the groups of patients who had dental amalgam placed before or during pregnancy. Maternal and fetal hair mercury levels were significantly higher in women who previously had dental amalgam restorations placed. There was no evidence that placement of dental amalgam restorations in pregnant women who had already similar restorations increased the maternal or fetal hair mercury level.

Maternal and neonatal hair mercury concentrations: the effect of dental amalgam

Objective To evaluate maternal and fetal hair mercury levels in relation to the placement of dental amalgam tooth restorations. Design Cross sectional study involving women who never had dental amalgam restorations placed, women who had amalgam restorations placed before pregnancy and women who had restorations placed during the index pregnancy. Setting North of England Maternity Hospital. Sample Fifty-three healthy women who delivered healthy babies at term. Methods Maternal and fetal hair was collected in a standardised manner in the first few days following delivery. Main outcome measures Maternal and neonatal hair mercury concentrations. Results When compared with women without restorations, there was a significant increase in the maternal hair mercury concentration in women who had dental amalgam placed outside of the index pregnancy and also in women who had dental amalgam placed during the index pregnancy. The fetal hair mercury concentration was significantly higher in babies when mothers had been exposed to dental amalgam either before pregnancy or during pregnancy compared with unexposed babies. There was no difference in the maternal or fetal hair mercury levels in the groups of patients who had dental amalgam placed before or during pregnancy. Conclusion Maternal and fetal hair mercury levels were significantly higher in women who previously had dental amalgam restorations placed. There was no evidence that placement of dental amalgam restorations in pregnant women who had already similar restorations increased the maternal or fetal hair mercury level.

Developmental changes in the expression of potassium currents of embryonic, neonatal and mature mouse inner hair cells.

Developmental changes in electrophysiological membrane properties of mouse cochlear inner hair cells (IHCs) were studied from just after terminal differentiation up to functional maturity. As early as embryonic day 14.5 (E14.5) newly differentiated IHCs express a very small outward K+ current that is largely insensitive to 4-aminopyridine (4-AP). One day later the inward rectifier, IK1, is first observed. These immature cells initially exhibit only slow graded voltage responses under current clamp. From E17.5 spontaneous action potentials occur. During the first week of postnatal development, the outward K+ current steadily increases in size and a progressively larger fraction of the current is sensitive to 4-AP. During the second postnatal week, the activation of the 4-AP-sensitive current, by now contributing about half of the outward K+ current, shifts in the hyperpolarizing direction. Together with an increase in size of IK1, this hyperpolarizes the cell, thus inhibiting the spontaneous spike activity, although spikes could still be evoked upon depolarizing current injection. Starting at about the onset of hearing (postnatal day 12, P12) immature IHCs make the final steps towards fully functional sensory receptors with fast graded voltage responses. This is achieved mainly by the expression of the large-conductance Ca2+-activated K+ current IK,f, but also of a current indistinguishable from the negatively activating IK,n previously described in mature outer hair cells (OHCs). The 4-AP-sensitive current continues to increase after the onset of hearing to form the major part of the mature delayed rectifier, IK,s. By P20 IHCs appear mature in terms of their complement of K+ conductances.

Maternal and neonatal hair mercury concentrations—the effect of dental amalgam

We set out to evaluate the mercury burden in relation to the placement of dental amalgam tooth restorations by using maternal and fetal hair analysis. This was a cross-sectional study involving women who had never had dental amalgam restorations placed, women who had amalgam restorations placed before pregnancy and women who had restorations placed during pregnancy. Fifty-three maternal and fetal hair samples were collected in a standardised manner in the first few days following delivery. When compared with women without restorations there was a significant increase in the maternal hair mercury concentration in women who had dental amalgam placed outside the index pregnancy and also in women who had dental amalgam placed during the index pregnancy. The fetal hair mercury concentration was significantly higher in babies when mothers had been exposed to dental amalgam either before pregnancy or during pregnancy compared with unexposed babies. There was no difference in the maternal or fetal hair mercury levels in the patients who had dental amalgam placed before or during pregnancy.

Maternal smoking during pregnancy and nicotine and cotinine concentrations in maternal and neonatal hair.

Conflicting data have been reported in the association between maternal smoking and adverse effects during pregnancy and in neonates. Some studies, conducted on a limited number of patients have evaluated maternal consumption and fetal exposure by measuring nicotine and cotinine in the hair. Our aims were to evaluate the relationship among maternal cigarette consumption, fetal smoking exposure and outcome of pregnancy in a population of pregnant women who smoked. Mothers smoking during pregnancy were included at their first prenatal visit and followed prospectively. Maternal data (demographic variables, obstetrical history and cigarette consumption), neonatal data and birth indicators (number of weeks of gestation, type of delivery, weight) were collected. Hair samples from the mothers and the babies were collected at birth. The present study was conducted in the Department of Obstetrics of the University Hospital Robert Debré in Paris. A total of 254 women smokers were included in the study and 182 mother/neonate pairs were analyzed after exclusion of 50 babies whose hair samples were inadequate and 22 for various other reasons. Nicotine and cotinine concentrations in the maternal and neonatal hair were measured at birth by radio-immunoassay. Cigarette consumption was based on self reporting and quantified each trimester. It was expressed more precisely during the third trimester by the mean number per cigarette per day. Nicotine and cotinine concentrations in the maternal and neonatal hair at birth were also analysed. Nicotine and cotinine concentrations in maternal hair were associated with cigarette consumption during the third trimester of pregnancy (P < 0.003 and P < 0.01, respectively). In neonates, only cotinine concentrations were associated to maternal cigarette consumption (P < 0.0001). This association remained significant in a multivariate analysis, which included maternal cotinine hair concentrations and the ethnic group. Our results have shown a strong relationship between maternal cigarette consumption and fetal exposure to smoking measured by cotinine concentrations in neonatal hair. Further studies are required to look for associations between fetal exposure and adverse pregnancy outcome.

Maternal smoking during pregnancy and nicotine and cotinine concentrations in maternal and neonatal hair

Objective Conflicting data have been reported in the association between maternal smoking and adverse effects during pregnancy and in neonates. Some studies, conducted on a limited number of patients have evaluated maternal consumption and fetal exposure by measuring nicotine and cotinine in the hair. Our aims were to evaluate the relationship among maternal cigarette consumption, fetal smoking exposure and outcome of pregnancy in a population of pregnant women who smoked. Design Mothers smoking during pregnancy were included at their first prenatal visit and followed prospectively. Maternal data (demographic variables, obstetrical history and cigarette consumption), neonatal data and birth indicators (number of weeks of gestation, type of delivery, weight) were collected. Hair samples from the mothers and the babies were collected at birth. Setting The present study was conducted in the Department of Obstetrics of the University Hospital Robert Debré in Paris. Population A total of 254 women smokers were included in the study and 182 mother/neonate pairs were analyzed after exclusion of 50 babies whose hair samples were inadequate and 22 for various other reasons. Methods Nicotine and cotinine concentrations in the maternal and neonatal hair were measured at birth by radio-immunoassay. Main outcome measures Cigarette consumption was based on self reporting and quantified each trimester. It was expressed more precisely during the third trimester by the mean number per cigarette per day. Nicotine and cotinine concentrations in the maternal and neonatal hair at birth were also analysed. Results Nicotine and cotinine concentrations in maternal hair were associated with cigarette consumption during the third trimester of pregnancy ( P < 0.003 and P < 0.01, respectively). In neonates, only cotinine concentrations were associated to maternal cigarette consumption ( P < 0.0001). This association remained significant in a multivariate analysis, which included maternal cotinine hair concentrations and the ethnic group. Conclusions Our results have shown a strong relationship between maternal cigarette consumption and fetal exposure to smoking measured by cotinine concentrations in neonatal hair. Further studies are required to look for associations between fetal exposure and adverse pregnancy outcome.

E-cadherin and the Differentiation of Mammalian Vestibular Hair Cells

E-cadherin is expressed in vestibular, mechanosensory epithelia during early embryonic development. During late embryonic and neonatal stages it is expressed in supporting cells but down-regulated in differentiating sensory hair cells. We used a conditionally immortal cell line (UB/UE-1) from the neonatal mouse utricle to test the hypothesis that constitutive expression of E-cadherin inhibits the progression of hair cell differentiation. Under differentiating culture conditions, transfected E-cadherin inhibited expression of the cytoskeletal protein myosin VIIa and functional expression of both acetylcholine receptors and potassium channels, which are normally expressed by neonatal hair cells. However, it had no effect on the expression of the transcription factor Brn3c or the cytoskeletal protein fimbrin, which are also expressed by neonatal hair cells. The number of adherens junctions increased significantly under differentiating conditions but there was no detectable change in formation of tight junctions or gap junctions. However, E-cadherin expression led to density-dependent cell death under differentiating conditions. We have shown that E-cadherin is expressed in vestibular supporting cells, which form the basis of the sensory epithelium, but that constitutive expression inhibits the full differentiation of hair cells. Down-regulation of E-cadherin is thus likely to be a key element in the regeneration of hair cells.

Drug abuse’s smallest victims: in utero drug exposure

The social and economic impact of drug use on our global population continues to increase leaving no geographical, social or cultural group untouched. The National Institute on Drug Abuse (NIDA), in one of the few large surveys of maternal abuse, found that 5.5% of mothers reported taking an illicit substance during gestation. These figures certainly are underestimates due to the stigma of drug use during pregnancy and the accompanying legal, ethical and economic issues. Although drugs of choice and routes of administration vary by country, exposure of our most valuable resource, our children, to the developmental effects of drugs is an enormous problem. In utero drug exposure can have a severe impact not only on the development of the fetus, but also on the child during later stages of life. More than 75% of infants exposed to drugs have major medical problems as compared to 27% of unexposed infants. The cost of treating drug-affected infants was twice the cost of non-affected infants. Obstetrical complications including placental insufficiency, miscarriage, intrauterine death, and increased incidence of infectious and sexually-transmitted diseases are higher in the drug-abusing mother. Treatment for pregnant addicts should be a high priority for our governments. Increased awareness and improvement in our understanding of drug abuse in the medical, legal and social realms will enable us to reduce the barriers to treatment for this important population.Accurate identification of in utero drug exposure has important implications for the care of the mother and child, but can raise difficult legal issues. Society discourages prenatal care with the infliction of harsh criminal penalties. Maternal drug use during pregnancy can be monitored with urine, sweat, oral fluid and/or hair testing. Detection of in utero drug exposure has traditionally been accomplished through urine testing; however, the window of detection is short, reflecting drug use for only a few days before delivery. Monitoring exposure through testing of alternative matrices, such as neonatal meconium and hair, offers advantages including non-invasive collection and detection earlier in gestation. There are many unresolved issues in monitoring in utero drug exposure that urgently require research. These can be divided into research to definitively differentiate drug exposed and non-drug-exposed fetuses, determine the most efficient methods to routinely monitor women’s drug use, and determine how these drug test results relate to neonatal and maternal outcomes. Research in this area is difficult and expensive to perform, but necessary to assess accurately drug effects on the fetus. By increasing our understanding of the physiological, biochemical and behavioral effects of gestational drug exposure, we may ultimately provide solutions for better drug prevention, treatment and a reduction in the number of drug-exposed children.

Intracellular calcium regulation in inner hair cells from neonatal mice

The mechanisms that regulate the concentration of ionized intracellular calcium (Ca2+i) in the base of neonatal mouse inner hair cells, close to synaptic sites, were investigated using confocal microscopy combined with conventional patch-clamp electrophysiology. Cells were depolarized under whole-cell voltage clamp to load the cell with C a2+ through voltage-activated Ca2+ channels. Repeated depolarizations produced Ca2+i increases with similar amplitudes and time-courses of recovery. The rate of recovery from depolarization-induced Ca2+i loads was used to assess the mechanisms responsible for Ca2+i regulation. Removal of extracellular sodium had no effect on resting Ca2+i or the rate of recovery of Ca2+i suggesting no role for Na:Ca exchange in these cells. Inhibitors of intracellular store uptake such as thapsigargin, 2,5-di(tert-butyl)hydroquinone (BHQ) and cyclopiazonic acid (CPA) caused an increase in resting Ca2+i and slowed the rate of recovery, indicating that Ca2+ can be taken up intracellularly. However, 5mM caffeine failed to cause a detectable release of Ca2+ from intracellular stores. FCCP, a mitochondrial inhibitor, slowed the rate of recovery from Ca2+i loads, indicating a role for mitochondrial Ca2+ uptake. The largest effects were seen with intracellular vanadate (1mM) which caused an irreversible rise in resting Ca2+i and depolarization-induced increases in Ca2+i failed to recover fully. Together, these data indicate that both thapsigargin-sensitive stores and mitochondria can take up Ca2+i, but that Ca2+ efflux from the cell occurs solely via a plasma membrane Ca2+-ATPase.

Estimation of fetal exposure to drugs of abuse, environmental tobacco smoke, and ethanol.

Many women worldwide use recreational drugs and alcohol. Details on the amounts and schedule of such exposures in pregnancy are often unreliable because of recall issues and shame and fears of legal action. Even when the report on maternal dose is correct, it does not necessarily reflect the amount reaching the fetus. Drugs of abuse accumulate in meconium and are incorporated into fetal hair on its growth. Recent work has documented the sensitivity and specificity of these assays for cocaine and other recreational drugs. Dose-response relationships between cocaine as measured in neonatal hair and head circumference or neurologic sequelae have been recently established. For ethanol, which cannot be measured in hair or meconium, accumulation of its fatty acid ethyl esters in meconium is emerging as a promising test for heavy maternal drinking in the second part of pregnancy. The identification of biologic markers of intrauterine exposure to xenobiotics will allow better understanding of etiology and dose-response relationships.