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.

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.

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.

Meconium analysis to assess fetal exposure to nicotine by active and passive maternal smoking.

We measured nicotine metabolites (cotinine and trans-3'-hydroxycotinine) in meconium of infants of passive or active smokers as a direct marker of fetal exposure to tobacco smoke. Meconium was collected from 55 infants whose mothers were nonsmokers, passive smokers, or light or heavy active smokers. Nicotine metabolite concentration (NMC) in meconium was analyzed by radioimmunoassay and gas chromatography-mass spectrometry. Radioimmunoassay showed the following mean meconium NMCs (in nanograms per milliliter); nonsmoker, 10.9; passive smoker, 31.6; light active smoker; 34.7, and heavy active smoker, 54.6. Analysis of available samples by gas chromatography-mass spectrometry confirmed the presence of cotinine. Correlation between meconium NMC and the degree of maternal smoking was 0.54 (p < 0.001). Meconium NMCs in infants of passive and active smokers were significantly higher than in those of nonsmokers (p < 0.05). Meconium NMC in passive smokers was not significantly different from that in light active smokers (p > 0.05). Thus exposure of the fetus to tobacco smoke is substantial, even by passive maternal smoking. Meconium analysis for nicotine metabolites may be useful for clinical and research purposes.

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

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.

Adaptation of the meconium drug test for mass screening.

For purposes of mass drug screening, the procedure for analysis of meconium for drugs was modified into a one-step extraction and analysis by enzyme immunoassay. The accuracy of this modified method was tested by comparing the results of simultaneous analysis of 61 meconium samples for cocaine opiate and cannabinoid metabolites by both the original and the modified methods. In 61 samples analyzed, opiate was detected in 8 (13%) samples by the original method and in 9 (15%) by the modified method; cocaine was detected in 39 (64%) samples by the original method and in 39 (64%) by the modified method. The concordance between the negative and positive results of the modified versus the original methods was 98% and 100%, respectively, for opiate and 95% and 98%, respectively, for cocaine. Only one sample was positive for cannabinoid. Thus a comparison of positive results for cannabinoid was not done; however, all the negative results obtained by the modified method were confirmed by the original method. The clinical experience of mass meconium drug testing using the modified method in 1991 is also reported. In four centers tested (total tests = 4409), the prevalence of presence of drug was consistent with the high- or low-risk status of the population. This simplified, rapid procedure can be performed in most clinical laboratories. This adaptation has made the meconium drug test feasible for large-scale clinical and research use.

Drug screening of meconium in infants of drug-dependent mothers: an alternative to urine testing.

Meconium specimens (first 3 days' stool) obtained from 20 infants of drug-dependent mothers and five control infants were analyzed by radioimmunoassay for the metabolites of three commonly abused drugs, heroin, cocaine, and cannabinoids. Control stools contained no drug. Meconium from the infants of drug-dependent mothers showed the presence of at least one drug metabolite: 80% of the infants of drug-dependent mothers showed cocaine (range 0.14 to 19.91 micrograms/gm stool), 55% showed morphine (range 0.41 to 14.97 micrograms/gm stool), and 60% showed cannabinoid (range 0.05 to 0.67 micrograms/gm stool). The concentrations of metabolites were highest during the first 2 days; some stools tested positive up to the third day. In contrast, only 37% of the infants had positive results on a urine screen (fluorescent polarization immunoassay method). Paired urine and meconium specimens, both analyzed by radioimmunoassay, showed a higher concentration of drug metabolites in the latter; eight urine samples had no detectable drugs despite a corresponding positive stool test result. We conclude that meconium is useful for drug screening in the neonate.

Influence of free fatty acids and glucose infusion on serum bilirubin and bilirubin binding to albumin: clinical implications.

We studied the risk of a large group of jaundiced neonates for bilirubin encephalopathy by serial assessment of their reserve serum albumin binding capacity as measured by the saturation index test. In 1271 infants with serum bilirubin concentration greater than 10 mg/dl, 12% had a saturation index (SI) of 7% or greater and therefore were clinically at or near risk for bilirubin encephalopathy. Treatment with glucose infusion (1 gm/kg over one hour) was highly effective in lowering the SI (delta = -3.7%. P less than 0.001). In none of the infants did SI rebound to 7% or greater within 24 hours after the infusion. In a detailed study of 19 infants who received glucose, the highly significant (P less than 0.001) fall in SI (delta = -3.7%) was accompanied by an equally significant rise in serum values for insulin (delta = +21.6 mcu/ml) and fall in serum free fatty acids (delta = -0.51 mEq/L). Many factors in the study, such as prematurity, hemolysis, acidosis, and hypoxemia, could have predisposed the infants to the risk of bilirubin encephalopathy. However, the facility by which most (93%) of the infants with high SI, including those who were premature or had evidence of hemolysis or respiratory insufficiency, responded to infusion of glucose indicates that serum free fatty acids may be the principal factor contributing to the high saturation index and therefore an underestimated factor in bilirubin binding to albumin.

Behavioural concomitants of prenatal addiction to narcotics.

Behavioral characteristics of infants of methadone-treated and nonaddicted women were studied during the neonatal period and at three, six, and 12 months of age. Several Brazelton Neonatal Behavioral Assment Scale measures differentiated between groups. Major differences occurred in irritability of the central nervous system, and these measures appeared able to predict severity of withdrawal. The increased tremulousness of addicted infants remained through at least the first month of life. Mental and motor development was within normal limits in both groups throughout the year. However, the addicted infants showed a progressive decline in psychomotor performance whereas nonaddicted infants' scores remained stable.

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

A prospective study of 196 drug-addicted mothers and their infants was conducted to determine the maternal, fetal, or environmental factors that may affect the severity of narcotic withdrawal in the infants. The severity of neonatal withdrawal did not correlate with the infant's gestational age, sex, race, or Apgar score, not to maternal age, parity, duration of heroin intake, or the level of morphine measured in the infant's urine or blood. Reduction in the amount of illumination and noise in a study nursery also did not lower the incidence of severe withdrawal in the infants. There was, however, significant correlation between the severity of withdrawal in the infant and the maternal methadone dose (p less than 0.025). It is therefore recommended that mothers on methadone treatment be put on a low dose of the drug (less than 20 mg/day) as soon as is safely possible to prevent serious withdrawal in her infant.

The role of the pediatric nurse practitioner in a neonatal unit.

A pediatric nurse practitioner was given responsibility for a nursery. Her major responsibilities included: (1) daily chart and infant rounds, (2) initial physical examinations, (3) rounds with mothers, and (4) daily report to the physician on the condition and problems in her nursery. Over a one-year period of time, the PNP detected 20 serious problems, such as significant jaundice, sepsis, tachypnea, hypoglycemia, and two major congenital anomalies. The accuracy of the physical examination by the PNP was compared with that of the physician. In 72 percent of cases, the assessment of the PNP was essentially the same as that of the physician; in the remaining 28 percent the differences in diagnosis were minor and related to the timing of the examination. A telephone interview of a random sample of mothers showed that mothers under the care of the PNP had received more instructions on infant care; an 81 percent return of the infants to the clinic was achieved. The pediatric residents approved the participation of the PNP in the nursery. It is concluded that there is a useful role for the PNP in a neonatal unit.