Enrique M. Ostrea

Prevalence of fetal exposure to environmental toxins as determined by meconium analysis.

OBJECTIVE The primary objective was to determine whether environmental pollutants, specifically lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As) and organochlorine and organophosphate pesticides can be detected in meconium. STUDY DESIGN Prospective, cohort study. Infants were randomly recruited from the nurseries of five hospitals in Manila, Philippines. Their stools (meconium) were collected and analyzed for heavy metals by atomic absorption spectrophotometry and for pesticides by gas chromatography/mass spectrometry (GCMS). RESULTS A total of 426 infants were studied. The exposure rate (based on meconium analysis) and the median concentration of the pollutants in the positive samples were as follows: lead (26.5%; 35.77 microg/ml), cadmium (8.5%; 13.37 microg/ml), mercury (83.9%; 3.17 ng/ml), chlordane (12.7%; 22.48 microg/ml), chlorpyrifos (11.0%; 8.26 microg/ml), diazinon (34.3%; 12.96 microg/ml), DDT (26.5%; 12.56 microg/ml), lindane (73.5%; 2.0 microg/ml), malathion (53.0; 6.80 microg/ml), parathion (32.0%; 2.30 microg/ml) and pentachlorphenol (16.1%; 90.00 microg/ml). Some maternal and neonatal factors that were significantly associated with the presence of environmental toxins in meconium included multi-gravidity, multiparity, multiple gestation, meconium stained fluid, smoking, gestational age, low birth weight and infant gender. CONCLUSION Meconium analysis is a new and sensitive tool to detect fetal exposure to environmental toxins and its clinical use awaits further investigation.

A study of factors that influence the severity of neonatal narcotic withdrawal

1. History is unreliable in assessing maternal drug habit. Morphine was detected in significant amounts in maternal and fetal urine regardless of whether the mother was on a methadone program or whether she denied any use of heroin during the last trimester of pregnancy. 2. Infants born to drug-addicted mothers were, in general, of birthweight normal and appropriate for gestational age (i.e., greater that 10th percentile). The infants born to mothers on a methadone clinic program had a higher birthweight compared to those whose mothers were not on any methadone program. 3. In order of frequency, the signs and symptoms of withdrawal were: central nervous system manifestations-fist sucking, irritability, tremors, sneezing, high-pitch cry, hypertonia; vasomotor in the form of stuffy nose; and gastrointestinal in the form of sweating, diarrhea, vomiting and yawning. Convulsions were not noted. No death occurred. 4. The severity of neonatal narcotic withdrawal did not correlate with the infants gestational age, APGAR, sex or race; nor with maternal age, parity, duration of heroin addiction or duration of methadone intake. Also, it did not correlate with the total morphine level measured either in infants or mothers urine or in cord blood. The serum levels of calcium and glucose were normal and identical in either mild or severe withdrawal. 5. The severity of neonatal withdrawal correlated significantly with the methadone dose per day of the mother (in initial, final or average dose). A maternal methadone dose of more than 20 mg per day was associated with a higher incidence of moderate to severe withdrawal in their babies. As a corollary, it was also noted that infants whose mothers were on a high methadone dose (i.e., greater than 20 mg per day) had a greater postnatal weight loss despite a significantly higher birthweight initially, and stayed in the hospital longer. 6. Finally, the modification of the environment to reduce external stimuli to the infant born to a drug-dependent mother, does not prevent or diminish the severity of neonatal narcotic withdrawal. Thus, there is no need to manage these infants in a special nursery.

Sudden infant death syndrome among infants of drug-dependent mothers

F E W R E P O R T S describe an associat ion be tween sudden infant death and maternal prenatal addiction?, 2 Recognition of this association is essential for two reasons: (1) there is an increase in the incidence of drug abuse among women of childbearing age; and (2) methadone, the drug currently in use to treat opiate addiction, is also a narcotic. A combined maternal methadone and infant follow-up clinic provided the authors with the opportunity to follow infants born to drug-dependent mothers. The durgs principally Used by the women were heroin and methadone; the use of other drugs, however, namely diazepam. barbiturates, cocaine, amphetamines, and alcohol, was common. The reports of sudden infant death, as related by the addicted mothers, prompted us to investigate this problem.

Influence of breast-feeding on the restoration of the low serum concentration of vitamin E and β-carotene in the newborn infant

Vitamin E and beta-carotene are two important natural antioxidants. However, the mean (+/- SD) serum concentrations of beta-carotene in the cord blood of term (17.9 +/- 4.4 micrograms/dl) and preterm (14.04 +/- 4.7 micrograms/dl) infants are one eighth the concentration in the maternal serum (131 +/- 43 micrograms/dl). Likewise the serum concentrations of vitamin E in the term (0.31 +/- 0.09 mg/dl) and preterm (0.29 +/- 0.08 mg/dl) infants are one-third the concentration in the maternal serum (0.97 +/- 0.16 mg/dl). Human breast milk, particularly colostrum, contains very high concentrations of both vitamin E (3.28 +/- 2.93 mg/dl) and beta-carotene (213 +/- 166 micrograms/dl). Thus the breast-fed, term infant attains serum levels of both vitamin E and beta-carotene comparable to those in the adult within 4 to 6 days of breast-feeding. This study shows that the seeming barrier in the fetus to access to the antioxidants vitamin E and beta-carotene, in rapidly corrected and the substances are replenished postnatally through breast-feeding. This study therefore alludes to the possible role of breast-feeding in providing for the infants defense against oxygen toxicity.

Combined analysis of prenatal (maternal hair and blood) and neonatal (infant hair, cord blood and meconium) matrices to detect fetal exposure to environmental pesticides

OBJECTIVE The aim of this study was to determine optimum biomarkers to detect fetal exposure to environmental pesticides by the simultaneous analysis of maternal (hair and blood) and infant (cord blood, infant hair or meconium) matrices and to determine if a combination of these biomarkers will further increase the detection rate. PATIENTS AND METHODS Pregnant women were prospectively recruited from an agricultural site in the Philippines with substantial use at home and in the farm of the following pesticides: propoxur, cyfluthrin, chlorpyrifos, cypermethrin, pretilachlor, bioallethrin, malathion, diazinon and transfluthrin. Maternal hair and blood were obtained at midgestation and at delivery and infant hair, cord blood and meconium were obtained after birth. All samples were analyzed by gas chromatography/mass spectrometry (GC/MS) for the above pesticides and some of their metabolites. RESULTS A total of 598 mother/infant dyads were included in this report. The highest rates of pesticide exposure were detected in meconium (23.2% to propoxur, 2.0% to pretilachlor, 1.7% to cypermethrin, 0.8% to cyfluthrin, 0.7% to 1,1,1-trichloro-2,2-bis, p-chlorophenylethane (DDT) and 0.3% to malathion and bioallethrin) and in maternal hair (21.6% to propoxur, 14.5% to bioallethrin, 1.3% to malathion, 0.8% to DDT, 0.3% to chlorpyrifos and 0.2% to pretilachlor). Combined analysis of maternal hair and meconium increased detection rate further to 38.5% for propoxur and to 16.7% for pyrethroids. Pesticide metabolites were rarely found in any of the analyzed matrices. CONCLUSIONS There is significant exposure of the pregnant woman and her fetus to pesticides, particularly to the home pesticides, propoxur and pyrethroids. Analysis of meconium for pesticides was the single most sensitive measure of exposure. However, combined analysis of maternal hair and meconium significantly increased the detection rate. A major advantage of analyzing maternal hair is that prenatal pesticide exposure in the mother can be detected and intervention measures can be initiated to minimize further exposure of the fetus to pesticides.

Perinatal problems (excluding neonatal withdrawal) in maternal drug addiction: A study of 830 cases

However, not every child with ambiguous genitalia needs a bone marrow karyotype. Determination of the chromosomal sex is only one factor in the evaluation of such an infant, and the sex of rearing may depend on the prospect for functional repair, rather than the genetic sex. Bone marrow karyotyping on the first day of life, before a complete evaluation of the external and internal genitalia and the metabolic status have been carried out, could lead the parents to over-value this one piece of information and might interfere with their ability to make a rational decision in choosing the most appropriate gender for their child. We recommend that bone marrow chromosome analysis in newborn infants should be utilized only when the following three criteria have been met: (1) There is a strong clinical suspicion of a chromosomal syndrome known to be associated with a severe defect in brain development. (2) Immediate surgical treatment or assisted ventilation or both are required to sustain life. (3) The parents and physicians are prepared to take action depending on the outcome of the procedure.

Antenatal phenobarbital for the prevention of neonatal intracerebral hemorrhage

Forty-six pregnant women less than 35 weeks of gestation were enrolled in a prospective randomized controlled study evaluating the effects of antenatal phenobarbital on neonatal intracerebral hemorrhage. The women were randomly assigned to control (n = 22) or treatment (n = 24) groups; the treatment group received 500 mg of phenobarbital intravenously. The time interval between the dose of phenobarbital and delivery was 5.5 +/- 4.8 hours (mean +/- SD). The infants in the control group (n = 23) and those in the phenobarbital-treated group (n = 25) were comparable regarding birth weight, gestational age, and other obstetric and neonatal risk factors associated with intracerebral hemorrhage. The incidence of intracerebral hemorrhage was 56.5% (13 of 23 infants) in the control group and 32% (eight of 25 infants) in the phenobarbital-treated group (p = 0.08). Moderate or severe hemorrhage was diagnosed in six of 13 control infants and in none of the phenobarbital-treated infants (p less than 0.01). The mortality rate was significantly lower in the phenobarbital-treated group (two of 25 infants) than in the control group (eight of 23 infants; p less than 0.05). Our study suggests that antenatal phenobarbital administration results in a decrease in mortality and in the severity of intracerebral hemorrhage in the preterm neonate.

Postmortem drug analysis of meconium in early-gestation human fetuses exposed to cocaine: clinical implications.

Abstract Postmortem analysis of meconium from three human fetuses exposed to cocaine demonstrated the presence of cocaine in the meconium of a 17-week-old fetus and evidence that the concentration of cocaine in meconium is related to the amount and time of cocaine use by the mother during pregnancy. The latter observation was confirmed in a rat model. (J P ediatr 1994;124:477-9)

Vancomycin during pregnancy: Does it cause hearing loss or nephrotoxicity in the infant?

Vancomycin was administered intravenously to 10 pregnant women for the treatment of methicillin-resistant Staphylococcus aureus infections. Auditory brainstem response testing and renal function studies were performed on the 10 babies in the experimental group and 10 babies in each of two control groups to determine the safety of vancomycin use during pregnancy. Auditory brainstem responses were not normal at birth in six infants from the three different groups studied (N = 30) but were normal at 3 months in five. The sixth infant had conductive hearing loss unrelated to vancomycin use that spontaneously disappeared at 12 months of age. Renal function was normal in all infants. Vancomycin was detected in cord blood in two patients and in breast milk in one. Adequate serum levels were achieved with routine doses in eight mothers tested; no adverse reactions occurred. It appears that vancomycin use during the second and third trimesters of pregnancy does not produce sensorineural hearing loss or nephrotoxicity in the infant.

Association between prenatal pesticide exposures and the generation of leukemia-associated T(8;21)

This study was designed to investigate the relationship between prenatal pesticide exposures and the generation of leukemia‐associated t(8;21)(q22;q22), one of the most common cytogenetic abnormalities in childhood acute myeloid leukemia (AML).