Use of the Griffiths Mental Development Scales in an agro-industrial province in the Philippines.

BACKGROUND: There is a need to assess neurobehavioral performance of children in developing countries using standardized developmental tools. METHODS: The Griffiths Mental Development Scales was evaluated in the Philippines by comparing the performance of 742 Filipino children longitudinally at 6, 12 and 24 months old to those of their British counterparts. RESULTS: The mean general and subquotient scores of Filipino children were all within average for age. Comparison with British children showed that except for performance subscales, Filipino children had significantly higher developmental subquotients at 6 months old. As the Filipino infants grew older, their developmental subquotients in all subscales were significantly lower, except for personal and social skills at 24 months old. The genetic predisposition as evidenced by modest maternal scores on the Wechsler Intelligence Scales and lack of familiarity with test materials are factors that may influence the developmental patterns of Filipino children. CONCLUSION: Although the performance of the Filipino children in the Griffiths test were within average with age, their performance on developmental subquotients at later ages of 12 and 24 months were significantly lower than British children and may have been influenced by differences in ethnicity, cultural traditions and limited environmental resources.

Effect of ibuprofen L-lysinate on bilirubin binding to albumin as measured by saturation index and horseradish peroxidase assays.

OBJECTIVE: To demonstrate, in vitro, the influence of increasing ibuprofen (IBU) concentration on bilirubin-albumin (B-A) binding. STUDY DESIGN: The influence of IBU on B-A binding was measured by saturation index and horseradish peroxidase assays. B-A solutions were prepared at B:A ratios of 0.5, 1.0, 1.5 and 2.0 and bilirubin concentrations of 5 and 10 mg per 100 ml. Drug concentrations used were 142.5, 200 and 285 mg l(-1) for IBU and 100 and 200 mg l(-1) for acetyl salicylic acid (ASA). Similar tests were performed on premature newborn sera with bilirubin concentrations of 5 to 10 mg per 100 ml. RESULT: By the saturation index test, significant displacement of bilirubin from albumin with IBU was demonstrated only on B-A solution with high B:A ratio of 2.0 and IBU concentration of 285 mg l(-1) and was less as compared to ASA. No displacement was observed in the sera of jaundiced neonates. By the horseradish peroxidase assay using B-A solutions, free bilirubin was significantly increased at (1) increasing concentrations of bilirubin in solution and (2) increasing B:A ratios in a solution containing 5 mg per 100 ml of bilirubin. In the sera of jaundiced neonates, significantly higher free bilirubin concentrations were observed when IBU was added to serum with bilirubin concentration of 10 mg per 100 ml as compared to 5 mg per 100 ml (0.062+/-0.004 versus 0.026+/-0.005, P<0.001 by Student's t-test). CONCLUSION: Displacement of bilirubin was demonstrated only at high IBU concentration and high B:A ratio. However, free bilirubin levels were not shown to increase with increasing IBU concentration.

Detection of Exposure to Environmental Pesticides During Pregnancy by the Analysis of Maternal Hair Using GC-MS.

Several classes of pesticides were extracted from maternal hair by solid-liquid extraction. Analysis of their selected metabolites involved a methanolic/hydrochloric acid methyl ester derivatization and liquid-liquid extraction. Gas chromatography electron impact mass spectrometry was used to detect and quantify the pesticides and metabolites. Recovery of parent compounds and metabolites from the analysis of spiked hair ranged from 87 to 112% with coefficients of variation less than 11%. Limits of detection ranged from 0.031 to 5.88 µg g(-1). Analysis of hair samples from pregnant women in the Philippines showed maternal exposure during pregnancy to bioallethrin, propoxur, chlorpyrifos, pretilachlor and malathion.

Detection of prenatal exposure to several classes of environmental toxicants and their metabolites by gas chromatography-mass spectrometry in maternal and umbilical cord blood.

We developed a sensitive method to detect several classes of pesticides and their metabolites in maternal and cord whole blood using electron-impact gas chromatography-mass spectrometry (GC-MS). The method can detect parent and metabolite compounds at levels of <0.10 and 0.20mug/mL, respectively, with high accuracy and recovery. Analysis of blood from mother-infant dyads from an area of high pesticide use in the Philippines showed detectable levels of propoxur, 3-phenoxybenzoic acid (3-PBA), and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) in maternal and umbilical cord blood. GC-MS analysis of several classes of parent pesticides and their metabolites in maternal and cord blood provides a sensitive and specific method to detect pesticide exposure during pregnancy.

Detection of Several Classes of Pesticides and Metabolites in Meconium by Gas Chromatography-Mass Spectrometry.

A solid phase extraction method was developed to isolate multiple classes of parent pesticides from meconium. A methanolic/hydrochloric acid methyl ester derivatization with liquid-liquid extraction technique was also developed for the analysis of metabolites. Identification and quantitation was by electron impact gas chromatography-mass spectrometry. For the parent compounds and metabolites, recoveries in spiked meconium ranged between 72-109%, with coefficients of variation ranging from 1.55-16.92% and limits of detection between 0.01-4.15 µg g(-1). Meconium samples obtained from infants in the Philippines were assayed using these methods, and propoxur, cypermethrin, pretilachlor, malathion, 4,4'-dichlorodiphenyltrichloroethylene, bioallethrin, and cyfluthrin were detected.

Analysis of nonsteroidal antiinflammatory drugs in meconium and its relation to persistent pulmonary hypertension of the newborn.

OBJECTIVE: The objective of this study was to detect fetal exposure to nonsteroidal antiinflammatory drugs (NSAIDs) by meconium analysis and to determine the relationship between fetal exposure to NSAIDs and the development of persistent pulmonary hypertension of the newborn (PPHN). METHODS: In a case-control study of the inborn and outborn nurseries of a large urban medical center, meconium was collected from 101 newborn infants (40 with the diagnosis of PPHN based on clinical or echocardiographic criteria and 61 randomly selected, healthy, term infants [control]) and analyzed for NSAIDs (ibuprofen, naproxen, indomethacin, and aspirin) by gas chromatography/mass spectrometry. The risk of developing PPHN was determined in infants who were exposed antenatally to NSAID. RESULTS: Infants with PPHN (n = 40) had a mean gestation of 38.9 weeks and birth weight of 3524 g, which were similar to the those of the control group (n = 61). However, the incidence of low Apgar scores (

Estimates of illicit drug use during pregnancy by maternal interview, hair analysis, and meconium analysis.

OBJECTIVE: To compare the sensitivity and specificity of maternal interview, maternal hair analysis, and meconium analysis in detecting perinatal exposure to cocaine, opiate, and cannabinoid. DESIGN/METHODS: The use of cocaine, opiate, and cannabinoid during pregnancy was determined prospectively in 58 women by 3 methods: structured maternal interview, maternal hair analysis, and meconium analyses. The results of the 3 methods were compared with one another. RESULTS: The maternal interview showed the lowest sensitivity in detecting cocaine and opiate exposures (65% and 67%, respectively), but it had the highest sensitivity in detecting cannabinoid exposure (58%). Both hair and meconium analyses had high sensitivity for detecting cocaine or opiate exposures. Hair analysis had a sensitivity of 100% for cocaine and 80% for opiate detection. However, it had a false-positive rate of 13% for cocaine and 20% for opiate, probably as a result of passive exposure. Meconium analysis had a sensitivity of 87% for cocaine and 77% for opiate detection, but unlike hair analysis, it had no false-positive test results for cocaine. Both hair and meconium analyses had low sensitivity in detecting cannabinoid exposure (21%-22.7%), most probably because of the sporadic use of cannabinoid. CONCLUSION: Meconium and hair analyses had the highest sensitivities for detecting perinatal use of cocaine and opiate, but not for cannabinoid. The principal drawback of hair analysis is its potential for false-positive test results associated with passive exposure to drugs. Maternal interview is a time-consuming test of low sensitivity. The high sensitivity of meconium analysis and the ease of collection make this test ideal for perinatal drug screening.

Understanding drug testing in the neonate and the role of meconium analysis.

The use of illicit drugs during pregnancy is a problem that affects a significant number of pregnant women or women of childbearing age. For many reasons, the identification of the drug exposed mother and her infant is a necessary, albeit difficult, task. This article will discuss drug testing to detect the antenatal exposure of the newborn infant to illicit drugs and review the different laboratory methods that are used and the role of meconium analysis in neonatal drug testing.

The Tagum study I: analysis and clinical correlates of mercury in maternal and cord blood, breast milk, meconium, and infants' hair.

OBJECTIVES: To compare the indicators and levels of mercury (Hg) exposure in the mother with those in the fetal compartments, and determine its effects on the newborn. METHODS: Hg levels using atomic absorption spectrophotometry were determined in maternal blood, breast milk, cord blood, infants' hair, and meconium of 78 consecutive mother-infant pairs in a community with high Hg pollution. The prevalence and levels of Hg both in meconium and in cord blood were correlated with maternal and infant risk factors. RESULTS: The prevalence of Hg in the fetal compartments was higher than in the maternal fluid compartments. Hg was present in 6.4% of maternal blood and 6.4% of breast milk, as compared with 16.7% of cord blood, 31.6% of infants' hair, and 46.1% of meconium. Forty-six percent of infants with Hg in cord blood had none in meconium, whereas 80.6% with Hg in meconium had none in cord blood. Hg was not present in the maternal blood of all infants (n = 36) with Hg in their meconium. Among those with detectable Hg, the mean levels were: mothers' blood 24 parts per billion +/- 5.47, cord blood 53.3 parts per billion +/- 37.49, and meconium 48.6 +/- 43.48. Quantitative measurement in hair was not done because of insufficient sample. Paired comparisons were all significant between Hg levels in the mothers' blood and meconium, mothers' blood and cord blood, and cord blood and meconium. Regression analysis showed Hg levels in meconium to be correlated with prevalence of Hg in infants' hair, length of stay in Tagum, and meconium-stained amniotic fluid. Fisher's Exact probability test showed that the prevalence of Hg in meconium was significantly related to the prevalence of Hg in the mothers' blood and length of stay in Tagum. The prevalence of Hg in cord blood was significantly related to the prevalence in the mothers' blood. Regression analysis of levels of Hg in cord blood showed a significant relation to levels in mothers' blood (.0001), prevalence in infants' hair (.0126), gestational age (GA) (.0091), and head circumference (HC) (.0469). By quadrant analysis of weight against HC in 66 full-term infants all of 4 infants weighing an average of >3000 g at birth and with HCs lower than the fifth percentile had Hg in meconium. CONCLUSION: The higher prevalence and levels of Hg in the fetal compartments reflect the ease of placental transfer with fetal trapping. Hg determinations in the mothers' blood underestimate the degree and extent of fetal exposure. There is a significant difference in each compartment's ability to reflect Hg exposure of the fetus. A small HC may be associated with the presence of Hg in meconium. Hg in meconium should be measured in addition to cord blood to determine the load of fetal Hg.

Detection of cytomegalovirus in the meconium of infected newborns by polymerase chain reaction.

OBJECTIVE: Congenital cytomegalovirus (CMV) infection is a leading cause of hearing loss and mental retardation throughout the world. Detection of the CMV DNA by polymerase chain reaction (PCR) offers a sensitive, rapid, and specific means of identification. Meconium, the stool formed in utero, may be an ideal specimen for CMV detection. The objective of this study was to develop a PCR-based methodology for the detection of CMV in the meconium of neonates. METHODS: Meconium was collected from 10 newborn infants (seven with positive viral cultures and three uninfected infants born to CMV-seropositive mothers). For each, DNA was isolated from meconium by organic extraction and attachment to a DNA-binding matrix, and PCR was performed using amplimers specific for the major intermediate early (MIE) and late antigenic (LA) regions of CMV. RESULTS: Gel electrophoresis demonstrated an anticipated PCR product of 250 base pairs (bp) corresponding to the MIE region of CMV in all infected and positive control meconium samples. Furthermore, a single band of 150 bp corresponding to the LA region of CMV was also amplified in several of the infected infants. Conversely, no amplification of these antigenic regions was noted in either uninfected infants born to CMV-seropositive mothers or negative controls. CONCLUSIONS: CMV is present within the meconium of infected neonates and is readily detectable by PCR.

Spectrum of gestational exposure to illicit drugs and other xenobiotic agents in newborn infants by meconium analysis.

OBJECTIVE: To detect the spectrum of gestational exposure to illicit drugs and other xenobiotic agents in neonates by meconium analysis. METHOD: Meconium was collected from 98 neonates and analyzed for illicit drugs and other xenobiotic agents by high-performance liquid chromatography and gas chromatography/mass spectrometry. RESULTS: Eighty-one (82.7%) infants tested positive for xenobiotic agents, and each infant had from 1 to 9 drugs present. These included local anesthetics (30%) such as lidocaine and mepivacaine; food additives (25%) such as ionol (butylated hydroxytoluene); illicit drugs (11%), especially cocaine and morphine; analgesics (10%) such as meperidine; and fewer (< 10%) other drugs such as antihistamines, antidepressants, adrenergics, anticonvulsants, cough medications, analeptics, hypnosedatives, and cardiotonics. CONCLUSION: We demonstrated substantial exposure of neonates to xenobiotic agents, ranging from exposure to food additives, prescribed or over-the-counter medications, and drugs of abuse.

Meconium drug screening of stillborn infants: a feasibility study.

OBJECTIVE: Meconium drug testing of liveborn infants is highly sensitive (87%) and specific (100%). Accurate knowledge of drug use in mothers of stillborns would be beneficial. We determined the feasibility of noninvasive meconium drug screening for opiates and cocaine in stillborns. METHODS: Stillborn infants delivered at our hospital had meconium collected using a 4-mm spatula inserted into the anus. Specimens were analyzed using gas chromatography. Charts were reviewed. RESULTS: Of the 30 specimens obtained, 26 were below the optimal amount needed (0.5 g). Regardless, all samples were analyzed and three were positive for cocaine (10%), none for opiates. Two of the 3 positive samples were of 'insufficient quantity'. In one, the presumptive cause of fetal demise was diabetes, with no additional factors suggesting substance abuse. The other fetal loss was due to idiopathic preterm labor at 21.5 weeks, with a positive UDS. CONCLUSION: In this pilot study, inability to obtain an optimal volume of meconium occurred frequently. However, important and unexpected laboratory data were generated even with 'insufficient quantity'. This highlights the need to develop more refined methodologies for this screening tool in stillborn fetuses.

Mortality within the first 2 years in infants exposed to cocaine, opiate, or cannabinoid during gestation.

OBJECTIVE: To determine the mortality rate, during the first 2 years of life, in infants who were exposed to cocaine, opiate, or cannabinoid during gestation. METHODS: For a period of 11 months, a large group of infants were enrolled and screened at birth for exposure to cocaine, opiate, or cannabinoid by meconium analysis. Death outcome, within the first 2 years after birth, was determined in this group of infants using the death registry of the Michigan Department of Public Health. RESULTS: A total of 2964 infants was studied. At birth, 44% of the infants tested positive for drugs: 30. 5% positive for cocaine, 20.2% for opiate, and 11.4% for cannabinoids. Compared to the drug negative group, a significantly higher percentage (P < .05) of the drug positive infants had lower weight and smaller head circumference and length at birth and a higher percent of their mothers were single, multigravid, multiparous, and had little to no prenatal care. Within the first 2 years of life, 44 infants died: 26 were drug negative (15.7 deaths per 1000 live births) and 18 were drug positive (13.7 deaths per 1000 live births). The mortality rate among cocaine, opiate, or cannabinoid positive infants were 17.7, 18.4, and 8.9 per 1000 live births, respectively. Among infants with birth weight

The resurgence of congenital syphilis: a cocaine-related problem.

The relationship of maternal illicit drug use to congenital syphilis was studied in a population of newborn infants (N = 1012) who were screened for intrauterine exposure to illicit drugs by meconium analysis and whose mothers were screened for syphilis by the rapid plasmin reagin fluorescent treponemal antibody, absorbed (RPR/FTA-ABS) test. The result of the meconium drug screening was positive in 449 (44.3%) infants: 401 (39.6%) screening results were positive for cocaine, 71 (7%) positive for opiate, and 31 (3.1%) positive for cannabinoid. The maternal RPR/FTA-ABS result was positive in 72 (7.1%) women, and congenital syphilis was diagnosed in 46 (4.5%) infants on the basis of Centers for Disease Control and Prevention definitions. The incidence of positive RPR/FTA-ABS result (10.5% vs 4.4%) and congenital syphilis (7% vs 2.5%) was significantly higher (p < 0.01) among infants with positive results compared with those with negative drug screening results. Similarly, the incidence of positive RPR/FTA-ABS (11% vs 4.6%) and congenital syphilis (8% vs 2.3%) was significantly (p < 0.01) higher among infants with cocaine-positive results compared with those with cocaine-negative results. We conclude that maternal illicit drug use, specifically cocaine, is significantly related to the resurgence of congenital syphilis among newborn infants.

Effects of timing, dosage, and duration of morphine intake during pregnancy on the amount of morphine in meconium in a rat model.

Meconium drug analysis is a new and sensitive test for detecting the intrauterine exposure of infants to drugs of abuse. To explore other potential, diagnostic use of the test, we studied, in timed pregnant rats, the relationship between timing, dosage, and duration of morphine administration to the dam and the concentration of morphine, analyzed by radioimmunoassay, in their pups' meconium. The term 'meconium' refers to both the intestine and its contents. Due to the minute size of the pups' intestines, the intestinal contents were not separated from the intestines. The mean morphine concentration in meconium was found to be significantly (p < 0.05) higher in the groups treated with a higher morphine dose (10 vs. 5 mg/ kg/day), longer duration of treatment (7-20 vs. 18-20 days), or treated during the last week of gestation (14-20 vs. 1-6 or 7-13 days). We conclude that the concentration of a drug in the meconium is related to amount, timing, or duration of the drug exposure of the fetus, in utero. The quantitative analysis of drugs in the meconium, therefore, provides added information which enhances the diagnostic use of the test.

Prenatal cocaine and neonatal outcome: evaluation of dose-response relationship.

OBJECTIVE: The aim of this study was to evaluate the hypothesis that prenatal cocaine exposure would negatively affect newborn behavior. METHODS: A prospective observational study of term infants recruited from the low-risk nursery used a structured, standardized interview to obtain maternal data. Cocaine exposure was determined by radioimmunoassay of the infant's meconium stool. An examiner blinded to the infant's cocaine status administered the Brazelton Neonatal Behavioral Assessment Scales. RESULTS: The sample was composed of 23 exposed and 29 nonexposed infants. On six of the seven Brazelton Neonatal Behavioral Assessment Scale clusters, cocaine-exposed infants performed less well than control infants, with significant differences observed for autonomic stability. In addition, a dose-response relationship was suggested. Significant negative, within-group relationships were evident in the exposed group, indicating poorer performance with increasing meconium cocaine concentration for orientation (r = -.40) and regulation of state (r = -.40). Regression model testing of the influence of meconium cocaine concentration on neurobehavioral outcomes, after controlling for significant confounders, identified a significant independent, negative effect of meconium cocaine concentration on two clusters-motor and regulation of state. CONCLUSION: In otherwise healthy full-term infants, prenatal cocaine exposure identified by quantitative analysis of cocaine concentration in meconium had a significant, independent negative association with motor and regulation of state that remained after controlling for other significant confounders. A dose-response relationship was evident.