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Prenatal psychoactive substance exposure has significant impact on neonatal health and child development and the development of reliable biomarkers is critical. Meconium presents several advantages for detecting prenatal exposure to psychoactive substances, as it is easy to collect and provides a broad time frame of exposure (third trimester). The aim of our study was to compare the prevalence of alcohol, tobacco and/or cannabis use during the third trimester of pregnancy (using maternal self-reports) with the results of meconium testing of their metabolites in newborns (cotinine, ethyl-glucuronide (EtG) and cannabinoid metabolites). Among all deliveries (993) that occurred in all maternities in Rouen (Normandy) during a defined time period (5 consecutive weeks in August, 2010 and August, 2011), 724 mothers were included and 645 meconium samples were collected. Maternal self-reports, using the Addiction Severity Index (5th edition), and meconium samples were collected within 72 h of delivery. Cotinine detection appears highly correlated to maternal self-reports (Kappa value: 0.79; [95%CI: 0.73–0.85]). Moreover, detection in meconium seems more accurate in the prediction of neonatal consequences of prenatal tobacco exposure as compared to maternal self-reports. In contrast, we have found a lower concordance between maternal self-reports and meconium testing for EtG and cannabinoid metabolites (Kappa value: 0.13; [95%CI: 0.04–0.22] and: 0.30; [95%CI: −0.03–0.63], respectively); however the total number of EtG- and cannabinoid-positive meconium samples was small. Interestingly, meconium samples with the highest levels of EtG mainly corresponded to negative maternal self-reports. Fetal exposure to alcohol, tobacco or cannabis may also considerably differ as displayed in our pairs of dizygotic twins. Finally, a polyconsumption of these psychoactive substances was not frequently observed according to meconium testing. In conclusion, cotinine detection appears as a valuable meconium biomarker. EtG measurement in meconium samples seems interesting if there is any risk of high fetal exposure, whereas assessment of prenatal cannabis exposure, using meconium testing, needs to be improved. [ABSTRACT FROM AUTHOR]

Abstract: The objective of this study was to develop a procedure for the GC/MS assay of paraquat in meconium as a biomarker of fetal exposure to paraquat. The method involved a sodium borohydride-nickel chloride reduction procedure, liquid–liquid extraction of the perhydrogenated product, concentration, and GC/MS assay. The method demonstrated good overall recovery (102.56%) with %CV (inter-assay) of less than 13%, and a limit of detection of 0.0156μg/g. Analysis of meconium samples from a study population in the Philippines (n =70) showed a 2.8% prevalence of fetal exposure to paraquat. [Copyright &y& Elsevier]

Aim: To investigate the prevalence of in utero exposure to cannabis in a cohort of 974 mother-infants dyads from Barcelona (Spain). Methods: A validated gas chromatographic-mass spectrometric assay was used for meconium analysis. Results: Prenatal exposure to cannabis was detected in 5.3% newborns; however, only 1.7% of the participating mothers disclosed gestational drug use. Ethnicity was not associated with cannabis use, nor were the maternal features or newborns somatometry. A significantly higher percentage of cannabis using mothers had a managerial professional job versus nonusers. Conclusions: Meconium analysis is especially important to identify neonates who have been exposed to cannabis in utero, which appear normal at birth and therefore may not be recognized. Timely detection of these newborns at risk provides the basis for appropriate treatment and adequate medical and social follow-up. [ABSTRACT FROM AUTHOR]

• HPLC-DAD method can be used to determine short-chain organic acids in neonatal meconium. • Meconium samples were collected from healthy children born either via cesarian section or through vaginal delivery. • The concentrations of organic acids in meconium varied in wide ranges. The purpose of this study was to develop and validate a high-performance liquid chromatography with a diode-array detector (HPLC-DAD) method for the determination of short-chain fatty acids (SCFAs) such as: acetic, propionic, butyric, valeric and isovaleric acids in meconium. Additionally, the proposed analytical procedure was used to determine SCFAs in meconium obtained from 17 neonates. All determined organic acids in meconium samples were separated with good resolution. The HPLC system was characterized by high precision (the coefficient of variance ≤ 2.5%), high determination coefficients of calibration curves (R2>0.997) and low limits of detection (LOD) and quantification (LOQ). For all investigated organic acids, LOD ranged from 0.01 to 0.80 mmol/ kg and LOQ values ranged between 0.04 and 2.64 mmol/ kg. Recovery of the HPLC assay for individual analytes comprised the range of 90±2 - 106±2%. Concentrations of acids in meconium collected from healthy children varied in wide ranges (CV within the range 0.79–2.47%) and no regularity was found in the molar ratios of the individual acids. The validation parameters obtained in this study, made the HPLC-DAD method reliable and useful tool for the determination of short-chain fatty acids in meconium samples. [ABSTRACT FROM AUTHOR]

The determination of fetal drug exposure is of great importance for the future development of the neonate. Meconium, the first fecal material excreted by the newborn is an excellent depository for drugs to which the fetus has been exposed. Correct diagnosis of drug use during pregnancy allows the child to receive specialized treatment and care, which will aid in learning behavioral development. Meconium analysis is gaining significant credibility as an alternative or an additional sample to neonatal or maternal urine, because meconium provides a longer history of drug use than urine and drug concentrations are higher. Therefore, number of false negative results is decreased. Meconium analysis is a relatively new scientific development. Reported analytical procedures and techniques for drugs and metabolites in meconium are predominantly cocaine-related, although other compounds have been studied. Meconium, a complex matrix, requires pre-treatment and the extraction of drugs using organic solvents and solid-phases is discussed. Preliminary drug screening using predominantly immunoassays and quantitative confirmatory analytical chromatographic methods, are reviewed. Drugs of abuse described include cocaine, amphetamines, phencyclidine, marijuana, opiates, nicotine, benzodiazepines and barbiturates., (Copyright © 1995 Central Police University.)

Eighty-eight neonates born to mothers with a history of cocaine use during pregnancy were divided into two groups based upon the detection of cocaine metabolites in the first neonatal urine. Forty neonatal urine samples were positive for cocaine and 46 were negative. Preterm labor, premature rupture of membranes, and meconium-stained amniotic fluid were significantly more frequent in those mothers whose neonates tested positive for cocaine metabolites than in those whose infants were negative (P less than .05). Neonates testing positive were more likely to exhibit signs and symptoms of acute cocaine intoxication. Low birth weight, growth retardation, and abruptio placentae were also more frequent than would be expected in the general population, but were not statistically different between the groups. These findings suggest that the differences noted in the cocaine-positive group may represent acute and chronic exposure, whereas the negative group reflects the problems associated with chronic usage alone.

In the course of characterising neoglycolipid products derived from mucin oligosaccharide alditols after periodate oxidation and coupling by reductive amination to the aminolipid dipalmitoylglycerophosphoethanolamine, we have obtained evidence that oxidative cleavage occurs specifically at the C4-C5 bond of core N-acetylgalactosaminitol. Two lipid-linked fragments thus obtained from each oligosaccharide alditol are well resolved on thin-layer chromatography and can be sensitively analysed by liquid-secondary-ion mass spectrometry to assign the sequence and branching patterns of oligosaccharides linked at C6 and C3 to the N-acetylgalactosamitol. These conclusions have been reached from detailed studies of the neoglycolipid derivatives of several oligosaccharides (di- to hexasaccharides) which were isolated from human meconium and characterised previously by MS and NMR studies as the free alditols.

A report is presented of a newborn baby who developed a pneumothorax and extensive surgical emphysema after being delivered by Caesarean section for fetal distress soon after the mother had an amniocentesis.

Sisomicin is an aminoglycoside effective against gramnegative germs. The sensitiveness of coli, proteus, pseudomonas and klebsiella ranges from 0,1 to 0,4 mcg/ml. Germs with inhibition-values of up to 1 mcg/ml are certainly Sisomicin-sensitive. The side-effects of Sisomicin resemble those of other aminoglycosides, as for instance lesions of the VIIth cranial nerve and the kidney. Since aminoglycosides have a relatively small therapeutic range between toxicity and effective minimal-concentration, investigations are important especially in children. 66 children of different age groups received Sisomicin in doses of 3 mg/kg, 2 mg/kg and 1 mg/kg, and examined pharmacokineticly. Serum-levels were measured after 30 min 1, 2, and 4h, in some cases also after 6 and 8 h. In a separate group we determined the values after 5, 10, 15, 20, 30 and 40 min. The urinary output was controlled and the content of Sisomicin in meconium determined. Based on these results we recommend an individual, Sisomicin dosage for each age group. Clinically the Sisomicin proved to be well tolerated and effective antibioticum.

During a study on the influence of different amounts of fluid intake on water and electrolyte metabolism in the first 3 days of life, a high incidence of hyperbilirubinemia was observed in infants receiving a large water load (150 ml/kg/24 h) intravenously. The amount of meconium excreted during the 3-day period in newborns with total parenteral alimentation was significantly lower than in controls. Hyperbilirubinemia is considered to be due to the enterohepatic circulation of bilirubin present in the retained meconium. The role of slight hemolysis and insufficient stimulation of choleresis is discussed.

The first urine passed by a newborn infant who has inhaled meconium or meconium-stained amniotic fluid often contains a dark-coloured water-soluble substance, recognisable spectrophotometrically by an absorption band at about 405 nm. Spectrophotometric analysis of the first urine can in this way be used to diagnose preceding meconium aspiration.

In order to show that for a possible application in medical diagnosis NMR-relaxation experiments at low Larmor frequencies (v0 less than or equal to 20 kHz) are more sensitive than the up to now done high field measurements in the MHz-range, we present dispersion curves (v0 = 50 Hz to 50 MHz) of the proton longitudinal relaxation time T1 and values of the transversal relaxation time T2 for the example of amniotic fluids. Only for Larmor frequencies below congruent to 100 kHz the relaxation times for healthy amniotic fluid and pathological meconium solutions are significantly different, whereas at high Larmor frequencies, i.e. in the conventional MHz-range, the observed changes are rather small.

Till now there is no unequivocal diagnostic tool for the discovery of prolonged pregnancy. Therefore the present study was performed to evaluate whether HPL-values correlate with the presence of postmaturity syndrome in coherence with other known symptoms. 86 cases, partly with signs of postmaturity (n = 12), partly without such signs (n = 74), were compared with a non-postmature group. In prolonged pregnancy HPL-values were distinctly lower than at term. The more severe the condition, the lower were the HPL-values. There was a significant incidence of higher rates of meconium stained amniotic fluid beyond 42 weeks of gestation. After careful delivery the babies were generally in good condition. There was a slight shift to lower Apgar-values, but base excess and actual pH were found to be normal in umbilical artery. Birth-weights of the postmature infants did not show any differences to those born at term.

Ninety neonates who presented variable decelerations during labor were divided into two groups, according to the one-minute Apgar scores of greater than or equal to 8 and 7 less than or equal to. Only neonates of singleton pregnancies and cephalic presentations of 34 weeks gestation or more were included in the study. Several parameters of this fetal heart rate (FHR) pattern and the presence or absence of meconium staining were compared. Followings were found to be statistically significant. 1) The duration of the variable deceleration (less than 2 hours). 2) The FHR deceleration/uterine contraction ratio (less than 80%). 3) The absence of meconium staining. An effort was made to establish safe limits of variable decelerations. These are shown in parentheses. Based on both these data and findings of others, a multifactorial scoring system named a variable deceleration score was proposed for the proper management of this FHR pattern. Five variables were selected for the system. These were: The duration of variable decelerations, the FHR deceleration/uterine contraction ratio, the duration and amplitude of dips, and the presence or absence of meconium staining. The system scores from 0 to 2 for each of five factors, and was designed to be able to predict depressed neonates with the numerical increase of the score.

The structure of the major O-glycosidically linked neutral and acidic oligosaccharides isolated from human meconium glycoproteins were established. Neutral and acidic oligosaccharides were released by alkaline borohydride treatment, purified by Biogel P-6 and fractionated by high-performance liquid chromatography. This approach resulted in 50 neutral and 30 acidic oligosaccharides. The present study reports the primary structural analysis of five neutral oligosaccharides, ten monosialylated oligosaccharides, one monosialylated monosulfated oligosaccharide and three disialylated oligosaccharides, by permethylation, fast-atom-bombardment mass spectrometry analysis and 400-MHz 1H-NMR spectroscopy. The following structure have not been described previously: (formula; see text) The intestinal glycoproteins of human meconium are characterized as high molecular mass compounds with numerous carbohydrate chains of the mucin type. These mucins are a rich source of carbohydrate structures which express multiple blood group activities and occur as membrane-associated antigens, recognized by hybridoma antibodies [1-4]. A previous study [5] described the structure of fifteen free oligosaccharides derived from catabolism of O- and N-glycans accumulating in new born meconium. In the same group [6] the research has been extended to glycoasparagines with the description of thirteen of them by high resolution 1H-NMR spectroscopy analysis. From O-glycosidically linked glycoproteins, further studies [7] established the structures of nine major monosaccharides to tetrasaccharides obtained after mild acid hydrolysis and base-borohydride degradation from meconium samples of group O secretors. These oligosaccharides were derived from meconium glycopeptides which had been depleted of I- and i-antigen activities. Recently [8], neutral and acidic oligosaccharide-alditols obtained by alkaline borohydride degradation of human meconium glycoproteins have been separated by HPLC on an anion-exchange column. The neutral fraction was further purified by normal-phase and reversed-phase chromatography while acidic fractions were fractionated only by normal-phase chromatography. Thus, we have isolated several low molecular mass oligosaccharides of different size and composition and also isomers which vary in linkage position or anomer configuration. Using methylation analysis, 1H-NMR spectroscopy and fast-atom-bombardment mass spectrometry (FAB-MS), we propose the primary structure for 19 major oligosaccharides.

Patients with perinatal asphyxia from a total population of 15,216 births were studied prospectively. A total of 76 newborn infants achieved the criteria for inclusion. These were distributed in three populations: 53 (73%) without acute renal failure (ARF); 17 (22%) with ARF of prerenal type; 6, (8%) with ARF of renal type. Incidence of several perinatal factors were compared (gestational age, birth weight, meconial amniotic fluid, cord and/or placental disturbances, type of delivery, APGAR Score, and resuscitation). Authors observed that in the group of preterm infants, ARF is present, always was of renal type. In the population with ARF of renal type perinatal asphyxia was clinically worse: greatest frequency of meconial amniotic fluid (p less than 0,025) and worse response to resuscitation with a lower increment in the APGAR Score between one and five minutes (p less than 0.005).

In this prospective study we evaluate the role of serum bile acids in the investigation and management of cholestasis of pregnancy in a detailed study of 18 patients. Bile acids were the most sensitive diagnostic test. The increased incidence of fetal distress (33.3% in this series) and meconium-stained fluid (58.3%) did not correlate with very high values of bile acids in maternal serum, umbilical cord serum, or amniotic fluid. Treatment of pruritus with cholestyramine and/or phenobarbital is ineffective in this condition, induction of labor is suggested once fetal lung maturity is established.

Sixty-seven patients with a history of no fetal movements for at least 12 hours and a live fetus were managed according to a fixed protocol. Twelve of these patients were found to have meconium-stained amniotic fluid and/or abnormal unstressed or oxytocin-stressed cardiotocograms; all of them were delivered within 24 hours of a live infant. The remaining 55 patients had no meconium and normal unstressed and stressed cardiotocograms, and their pregnancy, was allowed to continue. All felt fetal movements again and were delivered of live babies one to ten weeks later.

A survey is given of the morphological and biochemical lesions of the small intestine that can be found in cystic fibrosis patients. The available data on the structure and function of the small intestine in CF patients favour the hypothesis that the small intestine itself might contribute to the malabsorption of nutrients in this disease. The most pronounced lesions, i.e. meconium ileus and absent active transport of bile salts are found in the ileum. It might be remembered that the ileum is also the site of intensive exchange of chloride and bicarbonate, a function that is heavily disturbed in the pancreas of CF patients. For this reason, further studies on the ileal function in cystic fibrosis are warranted.

The glycosphingolipids of meconium of a human O Le(a--b+) secretor have been subjected to structural and immunological characterization. Mass spectrometry, proton NMR spectroscopy, and gas-liquid chromatography were used for chemical analyses, and haemagglutination-inhibition for immunological characterization. The great amounts of glycolipids present also facilitated the analyses of minor species constituting only 1% or less of the total weight of the non-acid glycolipids. Glucosylceramide and galactosylceramide were the dominating glycolipids comprising 15 and 30%, respectively, of the total weight. The diglycosylceramides found were lactosylceramide and digalactosylceramide. The globo series was represented by globotriaosylceramide, small amounts of globotetraosylceramide, part of which had ceramide of phytosphingosine and hydroxy fatty acid, and a minor species of monofucosyl hexaglycosylceramide with an inner globotetraose oligosaccharide. No Forssman or Forssman-like antigen was found. The lacto series, quantitatively approximately 30% of the total weight, was mainly represented by lactotetraosylceramide and H-active, Lea-active, and Leb-active glycolipids with 5-6 sugars based on lactotetraosylceramide. Minor species having 0-3 fucoses in their carbohydrate chains and carrying up to 11 sugar residues were also identified. Great amounts of free ceramides were also found to be typical for this tissue.

The Authors examined perinatal outcome and presence of accelerations in cardiotocographic records in a group of patients showing meconium staining of amniotic fluid in labor, in comparison with the data of a control group. The first group showed an average Apgar between 1' and 5' and an average number of accelerations every 30' significantly lower than those of the control group. Moreover the study of accelerations confirmed that an average of more than 5 accelerations every 30' is a clear indicator of fetal well-being.

The bile acids found in the fetus and newborn are more numerous and diverse than has generally been appreciated. The four conventional bile acids, cholic, chenodeoxycholic, deoxycholic, and lithocholic acids, are found. In addition, however, stereoisomers of the conventional bile acids, bile acids with functional groups at different positions or in greater number than found in conventional bile acids, and "short-chain" and "long-chain" bile acids are found. The site of origin, pathways of synthesis, metabolism, and excretory routes of these unconventional bile acids are largely unknown. Their effects on the function of the liver and other tissues have not yet been established. It is uncertain which of these compounds is peculiar to the fetus and newborn, and which will be found in normal or abnormal adults. This review is an early look at a field bound to advance rapidly in the next several years.

Monohydroxylated acid fraction isolated from human meconium was found to contain, in addition to C20 and C24 acids identified previously, three C22 bile acids-(20S)-3 alpha-hydroxy-23,24-bisnor-5 beta-cholan-22-oic, (20S)- and (20R)-3 beta-hydroxy-23,24-bisnor-chol-5-en-22-oic, and one C21 acid-3 beta-hydroxypregn-5-en-21-oic. These compounds were identified by capillary gas chromatography-mass spectrometry and by comparison with standards. It is postulated that these C22 acids, as well as the two monohydroxylated C24 bile acids (lithocholic and 3 beta-hydroxychol-5-enoic) are produced in the maternal intestine by microbial flora and transferred to the fetus through the placenta.

Seven 3,20-dihydroxypregnan-21-oic acids (C21) were detected by capillary gas chromatography-mass spectrometry in the acid fraction isolated from human meconium after solvolysis and mild alkaline hydrolysis. The two major acids were isolated and identified by nmr as 3 alpha, 20 alpha-dihydroxy-5 alpha-and 3 alpha, 20 alpha-dihydroxy-5 beta-pregnan-21-oic acids. Two minor C21 components were identified as 3 alpha, 20 beta-dihydroxy-5 beta-pregnan-21-oic and 3 beta, 20 alpha-dihydroxypregn-5-en-21-oic acids. A trace amount of 3 alpha, 20 beta-dihydroxy-5 alpha-, 3 beta, 20 alpha-dihydroxy-5 alpha-pregnan-21-oic, and 3 beta, 20 beta-dihydroxypregn-5-en-21-oic acids were also detected. The identification of these C21 acids was confirmed by mass spectral and chromatographic comparison with standards of eight saturated and two 5-unsaturated 3, 20-dihydroxylated C21 acids. The decisive predominance of 20 alpha isomers confirmed the native presence of C21 acids in meconium. Six acids, with an exception of 3 beta, 20 beta-dihydroxy-pregn-5-en-21-oic acid, were detected in the extract of meconium prepared in the presence of large excess of sodium borohydride; this minor acid, together with a part of its 20-epimer, was evidently formed as result of the artefactual oxidation of 21-hydroxypregnenolone, the known constituent of meconium. The co-occurrence of relatively high concentrations of C21 acids and monohydroxylated C20 acids, previously detected in human meconium, pointed to the significance of the oxidative catabolism of neutral C21 steroids in the case of feto-placental-maternal unit.

The results of more than eight years of screening for cystic fibrosis (CF), utilizing the albumin concentration in meconium, are reported. Over 28 000 meconium samples were tested, over 24 000 of them by the Boehringer-Mannheim strip test, and all samples considered as showing a trace or positive result were followed up by an immunological technique. Eight-three meconium samples contained more than 20 g albumin/kg dry weight meconium and five of these were from children who were found to have CF. One child with CF was missed in the screening. From these figures the sensitivity of the method for detecting CF children at birth was calculated to be 75%, the specificity 99.7%, the negative predictive value 100%, the positive predictive value 4.0% and the incidence of CF in Sweden about 1:4,500. The incidence of pathologically elevated meconium albumin concentrations was found to be 25 times higher in premature than in full-term infants. Since the number of false positive results creates a problem, we suggest that premature children (birth weight less than 2500 g) and newborns with melaena should be excluded from further follow-up studies.

High level of maternal serum alkaline phosphatase (AP) (above 4 Bessey-Lowry units) was found to be indicative of meconium-stained amniotic fluid (AF). Simultaneous maternal serum AP and AF AP were measured in two groups: group A, the study group (78 cases), parturients with meconium-stained AF, and group B (29 cases), the control group, parturients with clear AF. A positive significant correlation was found between the level of AP in the AF and the level of AP in the parturient's serum, when meconium was present. It is our feeling that the high level of AP in the maternal serum is due to transfer of heat-labile AP from the meconium-stained AF, meconium being rich in AP. The mechanism has as yet to be elucidated.

The developmental metabolism of bile acids can be partly studied by the analysis of bile acid patterns in meconium. Employing modern analytical techniques, it has been found that besides the main bile acids of humans (cholic, chenodexoycholic, deoxycholic, and lithocholic acids) several "atypical" bile acids occur in meconium. It is unlikely that these "atypical+ bile acids are derived from materno--fetal transfer, and they therefore probably reflect a special fetal bile acid metabolism. Hydroxylations at positions 1 and 6 of the steroid skeleton are regularly encountered. These hydroxylations, as well as the occurrence of 3 beta-hydroxy-delta 5 compounds and of bile acids of the 5 alpha series, suggest that fetal bile acid synthesis differs markedly from that of the adult. These observations are of interest in relation to the origin of unusual bile acids found in the cholestatic condition of the adult. It appears that a resurgence of the fetal biosynthetic patterns takes place under the conditions of cholestatic liver disease.

In the Federal Republic of Germany screening for cystic fibrosis by the albumin content of meconium (BM-test) is performed on most newborns. In this paper arguments for and against this test are discussed. Arguments in favour of BM-test-screening are the possibility of early diagnosis, early treatment and genetic counseling. Drawbacks of the test are false positive and false negative results. The authors conclude that this screening test should not be performed.

A total of 2702 transabdominal amniocenteses performed at the Los Angeles County--University of Southern California Medical Center were reviewed, with particular emphasis on 392 samples performed beyong 41 weeks' gestation. A significant rise in the percent of amniocenteses with meconium staining was found to occur at an beyond 39 weeks. Meconium-stained fluid at amniocentesis was found to be associated with an increased incidence of babies weighing greater than 4000 g, maternal diabetes mellitus, and cesarean deliveries, in comparison to samples with clear amniotic fluid. Infants with meconium-stained fluid had an increased incidence of low 1-minute Apgar scores, but all 5-minute Apgar scores were 7 or greater. Ten perinatal deaths occurred after an amniocentesis with clear fluid in prolonged pregnancy, with four of these occurring within 7 days of amniocentesis. Lecithin/sphingomyelin (L/S) ratios less than 2.0 were found in 6% of amniocenteses performed beyond 41 weeks. However, none of the newborns with low L/S ratios develop subsequent neonatal respiratory distress syndrome. Amniotic fluid creatine values or blood-contaminated fluid were not found to be correlated with fetal outcome. No fetal mortality was attributable to amniocentesis. In view of the significant amount of false-positive and false-negative results, and the rare inherent danger associated with amniocentesis, its use solely to demonstrate the presence or absence of meconium staining appears to be of questionable value in the management of prolonged pregnancy.