Delay in the fine-tuning of locomotion in infants with meconium positive to biomarkers of alcohol exposure: a pilot study.

INTRODUCTION: Prenatal alcohol exposure causes a variety of impairments to the fetus called Fetal Alcohol Spectrum Disorders (FASD). Since it is very difficult to identify women that consume alcohol during pregnancy, different methods have been studied to evaluate alcohol exposure. Ethyl Glucuronide (EtG) and Fatty Acid Ethyl Esters (FAEEs) are commonly used to measure alcohol consumption in individuals at-risk for alcohol abuse, including pregnant women. MATERIALS AND METHODS: We conducted a study of two cohorts of 1.5 year-old infants (of mothers without a history of alcohol abuse) with or without meconium samples positive to both EtG and FAEEs and we evaluated their cognitive-behavioral development by the Griffiths Mental Developmental Scale (GMDS) method. Our protocol included 8 infants with meconium positive to alcohol metabolites (EtG and FAEEs) and 7 with meconium negative to alcohol metabolites. RESULTS: None of the 8 alcohol metabolites positive meconium infants exhibited distinctive facial features and growth retardation of severe FASD, showing that other factors may contribute to the FASD onset but elevations in EtG and FAEEs in the meconium were significantly associated with disrupted neurodevelopment and adaptive functions within the first year and a half of life. Indeed, we found out that infants with meconium positive for both EtG and FAEEs, although without displaying any FASD morphological features, had a delay in the fine regulation of their own locomotory capabilities. CONCLUSIONS: Further analyses and larger studies are needed to estimate the right link between prenatal alcohol exposure and the different range of disorders connected but this study provides an additional step in the field of FASD in order to suggest early treatments for at-risk newborns and infants.

First Insight into Fetal Exposure to Legacy and Emerging Plasticizers Revealed by Infant Hair and Meconium: Occurrence, Biotransformation, and Accumulation.

Epidemiological studies have demonstrated the embryonic and developmental toxicity of plasticizers. Thus, understanding the in utero biotransformation and accumulation of plasticizers is essential to assessing their fate and potential toxicity in early life. In the present study, 311 infant hair samples and 271 paired meconium samples were collected at birth in Guangzhou, China, to characterize fetal exposure to legacy and emerging plasticizers and their metabolites. Results showed that most of the target plasticizers were detected in infant hair, with medians of 9.30, 27.6, and 0.145 ng/g for phthalate esters (PAEs), organic phosphate ester (OPEs), and alternative plasticizers (APs), and 1.44, 0.313, and 0.066 ng/g for the metabolites of PAEs, OPEs, and APs, respectively. Positive correlations between plasticizers and their corresponding primary metabolites, as well as correlations among the oxidative metabolites of bis(2-ethylhexyl) phthalate (DEHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), were observed, indicating that infant hair retained the major phase-I metabolism of the target plasticizers. While no positive correlations were found in parent compounds or their primary metabolites between paired infant hair and meconium, significant positive correlations were observed among secondary oxidative metabolites of DEHP and DINCH in hair and meconium, suggesting that the primary metabolites in meconium come from hydrolysis of plasticizers in the fetus but most of the oxidative metabolites come from maternal-fetal transmission. The parent compound/metabolite ratios in infant hair showed a decreasing trend across pregnancy, suggesting in utero accumulation and deposition of plasticizers. To the best of our knowledge, this study is the first to report in utero exposure to both parent compounds and metabolites of plasticizers by using paired infant hair and meconium as noninvasive biomonitoring matrices and provides novel insights into the fetal biotransformation and accumulation of plasticizers across pregnancy.

Assessment of Fetal Exposure and Elimination of Perfluoroalkyl and Polyfluoroalkyl Substances: New Evidence from Paired Serum, Placenta, and Meconium Samples.

Multiple pieces of evidence have shown that prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is closely related to adverse birth outcomes for infants. However, difficult access to human samples limits our understanding of PFASs transport and metabolism across the human placental barrier, as well as the accurate assessment of fetal PFASs exposure. Herein, we assess fetal exposure to 28 PFASs based on paired serum, placenta, and meconium samples. Overall, 21 PFASs were identified first to be exposed to the fetus prenatally and to be metabolized and excreted by the fetus. In meconium samples, 25 PFASs were detected, with perfluorooctane sulfonate and perfluorohexane sulfonic acid being the dominant congeners, suggesting the metabolism and excretion of PFASs through meconium. Perfluoroalkyl sulfonic acids might be more easily eliminated through the meconium than perfluorinated carboxylic acids. Importantly, based on molecular docking, MRP1, OATP2B1, ASCT1, and P-gp were identified as crucial transporters in the dynamic placental transfer of PFASs between the mother and the fetus. ATSC5p and PubchemFP679 were recognized as critical structural features that affect the metabolism and secretion of PFASs through meconium. With increasing carbon chain length, both the transplacental transfer efficiency and meconium excretion efficiency of PFASs showed a structure-dependent manner. This study reports, for the first time, that meconium, which is a noninvasive and stable biological matrix, can be strong evidence of prenatal PFASs exposure.

Meconium Transferrin and Ferritin as Markers of Homeostasis in the Developing Fetus.

The molecular mechanisms regulating homeostasis in the developing fetus have not been satisfactorily elucidated. Meconium contains substances accumulated in the fetal intestines. Measurements of transferrin and ferritin concentrations in meconium and assessment of transferrin-ferritin relationships could enhance knowledge about specific processes of the intrauterine period involving the two proteins and their effects on the development and growth of the fetus. Transferrin and ferritin concentrations were measured by ELISA in the homogenates of first meconium portions from 125 neonates. Higher birth weight was associated with lower ferritin concentrations in meconium (r = -0.22, p = 0.015). In neonates with a birth weight of more than 3750 g, there was a positive correlation between transferrin and ferritin concentrations (r = 0.51, p = 0.003). With meconium transferrin concentrations above 43.52 µg/g, a negative correlation between transferrin and ferritin was established (r = -0.37, p = 0.036), while with transferrin concentrations below 43.52 µg/g, the correlations between the birth weight and the meconium transferrin and ferritin concentrations were negative (r = -0.61, p < 0.001 and r = -0.43, p = 0.017, respectively). Measurements of transferrin and ferritin in meconium specimens create a new use for these common biomarkers to improve our understanding of the effects of homeostasis in utero on the fetal development and growth. Establishing reference ranges of meconium transferrin and ferritin concentrations and their association with the clinical parameters during pregnancy could aid in the assessment of the impact of intrauterine life on the health status of the neonate and its adaptation to extrauterine life.

Links Between Vitamin D-Binding Protein, Alpha-1 Antitrypsin and Neutrophil Proteins in Meconium.

BACKGROUND/AIMS: Alpha-1 antitrypsin (AAT), vitamin-D binding protein (VDBP) and neutrophil granule proteins are specifically related to the neutrophil function and may be considered candidate biomarkers detected and measured in meconium (the first feces of newborn infants) as signals indicating abnormal processes in the fetal stage. Individual proteins found in meconium can be a source of information pertaining to the intrauterine metabolic processes. METHODS: Concentrations of AAT, VDBP, calprotectin, myeloperoxidase, lactoferrin and elastase were measured using ELISA tests in 80 meconium samples collected from 19 healthy, full-term neonates. RESULTS: The meconium concentrations of VDBP and AAT (mean±SD, [mg/g meconium]: 3.74±6.93, 3.72±1.79, respectively) were approximately 1000 times higher than those of the protein granule proteins calprotectin, myeloperoxidase, elastase and lactoferrin (mean ± SD, [µg/g meconium]: 285.7±215.8, 1.83±1.73, 1.72±2.70, 45.58±78.89, respectively). The correlation between VDBP and AAT was negative (r= - 0.40. p=0.000) and those between VDBP and calprotectin (r=0.38, p=0.000) and VDBP and myeloperoxidase (r=0.45, p=0.000) were positive. AAT was found to correlate positively with lactoferrin (r=0.38, p=0.000). CONCLUSION: The correlations between the concentrations of VDBP and AAT, and with neutrophil granule proteins observed in meconium indicate their functional relationship in the intrauterine environment of the developing fetus. Meconium can be seen as an apparently underutilized source of biomarkers for evaluation of metabolic processes specific to fetal development.

Drug testing in support of the diagnosis of neonatal abstinence syndrome: The current situation.

Illicit drug use during pregnancy is a concern worldwide, with many international studies describing attempted strategies to mitigate this problem. Drug misuse during pregnancy is associated with significant maternal as well as perinatal complications, which include a high incidence of stillbirths, fetal distress, neonatal abstinence syndrome (NAS) and increased neonatal mortality. Unfortunately, the identification of a drug-exposed mother or neonate is challenging. Maternal disclosure of drug use is often inaccurate, principally due to psychosocial factors including behavioral denial or the fear of the consequences resulting from such admissions. Likewise, many infants who have been exposed to drugs in utero may appear normal at birth and initially show no overt manifestations of drug effects. Thus, the identification of the drug-exposed infant requires a high index of clinical suspicion. Conversely, analytical testing is an objective means of determining drug exposure when it may be necessary to document proof of the infant's exposure to illicit drugs. The review will discuss the different matrices that are most commonly used for testing (e.g., maternal urine, neonatal urine, meconium, and umbilical cord), the strengths and limitations for each matrix, which drugs and metabolites are appropriate for testing, the various testing methods, and the advantages and disadvantages of each method.

The associations between prenatal phthalate exposure measured in child meconium and cognitive functioning of 12-month-old children in two cohorts at elevated risk for adverse neurodevelopment.

BACKGROUND: Phthalate metabolites in gestational-maternal urine represents short-term maternal exposure, but meconium, the newborn's first stool may better capture cumulative fetal exposure. We quantified phthalate metabolites in meconium from two cohorts of children at higher risk of adverse neurodevelopment and evaluated associations with their cognitive function at 12 months. METHODS: Meconium phthalate metabolites were quantified in the Safe Passage Study (SPS), N = 720, a pregnancy cohort with high community-levels of prenatal alcohol use, and the Early Autism Risk Longitudinal Investigation (EARLI), N = 236, a high familial autism risk pregnancy cohort. EARLI also had second and third trimester (T2/T3) maternal urine for exposure assessment. Molar sum of di (2-ethylhexyl) (∑DEHP) metabolites and an anti-androgenic score (AAS) using mono-isobutyl, mono-n-butyl, monobenzyl (MBZP), and DEHP metabolites were computed. Cognitive function was assessed at 12 months using the Mullen Scales of Early Learning-Composite (ELC). Multivariable linear regression assessed associations between loge-transformed metabolites and ELC. Quadratic terms explored nonlinearity and interaction terms of metabolite by child's sex examined effect modification. RESULTS: In SPS, MBzP (ßLinear = -6.73; 95% CI: 12.04, -1.42; ßquadratic = 1.95; 0.27, 3.62) and mono (2-ethyl-5-carboxypentyl), (ßLinear = -3.81; -7.53, -0.27; ßquadratic = 0.93; 0.09, 1.77) had U-shaped associations with ELC. In EARLI, T2 urine mono-carboxyisononyl was associated with linear decrease in ELC, indicating lower cognitive function. Interaction with sex was suggested (P < 0.2) for several urine metabolites, mostly indicating negative association between phthalates and ELC among girls but reversed among boys. Only mono-isononyl phthalate and ∑DEHP had consistent main effect associations across matrixes and cohorts, but similar interaction with sex was observed for meconium-measured ∑DEHP, AAS, MBzP, and mono (2-ethylhexyl) in both cohorts. CONCLUSIONS: Few phthalate metabolites were consistently associated with children's cognitive function, but a similar set of meconium metabolites from both cohorts displayed sex-specific associations. Gestational phthalate exposure may have sexually-dimorphic associations with early cognitive function in children at higher risk for adverse neurodevelopment.

Maternal anthropometric variables and clinical factors shape neonatal microbiome.

Recent studies indicate the existence of a complex microbiome in the meconium of newborns that plays a key role in regulating many host health-related conditions. However, a high variability between studies has been observed so far. In the present study, the meconium microbiome composition and the predicted microbial metabolic pathways were analysed in a consecutive cohort of 96 full-term newborns. The effect of maternal epidemiological variables on meconium diversity was analysed using regression analysis and PERMANOVA. Meconium microbiome composition mainly included Proteobacteria (30.95%), Bacteroidetes (23.17%) and Firmicutes (17.13%), while for predicted metabolic pathways, the most abundant genes belonged to the class "metabolism". We observed a significant effect of maternal Rh factor on Shannon and Inverse Simpson indexes (p = 0.045 and p = 0.049 respectively) and a significant effect of delivery mode and maternal antibiotic exposure on Jaccard and Bray-Curtis dissimilarities (p = 0.001 and 0.002 respectively), while gestational age was associated with observed richness and Shannon indexes (p = 0.018 and 0.037 respectively), and Jaccard and Bray-Curtis dissimilarities (p = 0.014 and 0.013 respectively). The association involving maternal Rh phenotype suggests a role for host genetics in shaping meconium microbiome prior to the exposition to the most well-known environmental variables, which will influence microbiome maturation in the newborn.

Paclitaxel use in pregnancy: neonatal follow-up of infants with positive detection of intact paclitaxel and metabolites in meconium at birth.

Paclitaxel is often excluded during pregnancy for women with breast cancer due to limited neonatal follow-up. We confirmed in utero fetal Paclitaxel exposure for 8 newborns. Birth details and follow-up to 36 months of age is reported. Meconium samples from newborns exposed to chemotherapy were screened by liquid chromatography-high resolution mass spectrometry while blinded to maternal treatment during pregnancy. Newborn information at birth and annually was obtained. Mean gestational age (GA) at cancer diagnosis and start of chemotherapy was 8.7 + 6.2 weeks and 17.1 ± 3.5 weeks. Paclitaxel was started at a mean GA of 27.0 ± 5.8 weeks. Paclitaxel followed Doxorubicin/Cyclophosphamide in 6 cases, 5-Fluouracil/Doxorubicin/Cyclophosphamide in 1, and was used alone in 1. Mean number of days between Paclitaxel and birth was 23 ± 15. Identification of Paclitaxel and/or metabolites was made in all meconium from paclitaxel-exposed fetuses. Birthweight was < 10% for GA in 3 infants. Three anomalies occurred: mild hip dysplasia without further treatment and mitral valve stenosis. The third child was diagnosed with Cleidocranial Dysostosis, a familial anomaly. Mean age at pediatric follow-up is 18.7 + 9.3 months. Pediatricians report eczema and recurrent otitis media in 1 child, iron deficiency anemia and upper respiratory infection in 2. One child is < 10% for height and weight at 15 months. All are meeting developmental milestones at median age of 18.7 months, range: 6-36 months. CONCLUSION: Up to 3 years of age, follow-up of neonates exposed to Paclitaxel in utero is reassuring. Continued observation of neonatal development is essential. WHAT IS KNOWN: • Chemotherapy during the second and third trimester of pregnancy does not result in an increase in congenital malformations or developmental delay. • In non-human primate studies by Van Calsteren et al., variable plasma and/or tissue concentrations of taxanes, carboplatin, and trastuzumab were encountered in the fetal compartment. • Pilot data reported by the current investigators proved that paclitaxel crosses the human placenta. WHAT IS NEW: • This current article provides medical and developmental follow up on the newborns from this exposure for 3 years after birth.

Ion Chromatography with Pulsed Amperometric Detection for Determining Cyanide in Urine and Meconium Samples.

The parents' addictions and eating habits have a significant influence on the child's growth. The first stool of a newborn baby provides a large amount of information about xenobiotics transmitted by the mother's body. The analytical technique used in the study is ion chromatography with pulsed amperometric detection (IC-PAD). The biological samples, which were obtained from women staying in a maternity ward and their partners, revealed cyanide concentrations in urine samples spanning 1.30-25.3 µg L-1. Meanwhile, the results of the meconium samples were in the range of 1.54 µg L-1 to 24.9 µg L-1. Under the optimized chromatographic conditions, the IC-PAD system exhibited satisfactory repeatability (R < 3%, n = 3) and good linearity in the range of 1-100 µg L-1. Thus, it proved to be an effective tool for monitoring trace cyanide concentration in a series of human body fluid matrices, including meconium. Based on the literature review, this is the first application of the IC-PAD analytical technique for the determination of cyanide ions in meconium samples.

Association of fatty acid ethyl esters in meconium with behavior during childhood.

OBJECTIVE: To examine associations between amounts of fatty acid ethyl esters (FAEEs) in meconium and behavior in school aged children exposed to alcohol and drugs in utero. METHODS: A secondary analysis of a prospective cohort of cocaine, polydrug exposed children, primarily African-American, low socioeconomic status, recruited at birth into a longitudinal study. FAEEs were quantified with gas chromatography via a flame ionization detector. Meconium was analyzed for FAEEs for 216 newborns of whom 194 were assessed with the Child Behavior Checklist (CBCL) at ages 4, 6, 9, 10, 11, and 12. Generalized estimating equation analyses were used to assess the relationship of quantity of FAEEs to outcomes, controlling for maternal psychological distress. RESULTS: Higher concentrations of FAEEs (ethyl myristate, ethyl palmitate, ethyl oleate, ethyl linoleate, and ethyl linolenate) were associated with caregiver reported aggressive and/or delinquent behavior at ages 10 and 12. After control for caregiver psychological distress, and age, significant (p < 0.05) FAEE by age interactions were found for ethyl myristate for aggression and for ethyl oleate, ethyl linoleate and ethyl linolenate for delinquency. Thus, higher concentrations of FAEE were related to more caregiver reported aggressive and delinquent behaviors of clinical significance at ages 10 and 12. CONCLUSION: Higher concentrations of FAEEs in meconium are potential markers for children at risk for aggressive and delinquent behaviors related to the effects of prenatal alcohol exposure.

Fatty acid ethyl esters in meconium and substance use in adolescence.

Prenatal alcohol exposure (PAE) continues to be a serious public health problem, yet no reliable clinical tools are available for assessing levels of drinking during pregnancy. Fatty acid ethyl esters (FAEEs), the nonoxidative metabolites of ethanol measured in meconium, are potential biomarkers to quantify the level of PAE. The association between the concentrations of FAEEs from meconium and adolescent substance use and related problems was examined in a prospective birth-cohort of adolescents exposed to alcohol and drugs in utero. FAEEs were quantified with gas chromatography via a flame ionization detector. Meconium was analyzed for FAEEs in 216 newborns; 183 of them (81 boys, 102 girls) were assessed at age 15 for alcohol, tobacco, and marijuana use using biologic assays and self-report. Substance use problems were assessed using the Problem Oriented Screening Instrument for Teenagers. Findings from multivariable logistic regression analyses indicated that, after controlling for other prenatal drug exposure and covariates, higher concentrations of FAEEs (ethyl myristate, ethyl palmitate, ethyl oleate, ethyl linoleate, ethyl linolenate, and ethyl arachidonate) were related to a greater likelihood of marijuana use and experiencing substance use problems, but not tobacco or alcohol use, at age 15. Elevated levels of FAEEs in meconium may be promising markers for PAE, identifying newborns at risk for early substance use and developing substance use problems.

Fatty acid ethyl esters in meconium: A biomarker of fetal alcohol exposure and effect.

To determine if meconium fatty acid ethyl esters (FAEE) in rat pups is a good biomarker of prenatal exposure and effect to alcohol, three groups of pregnant rats were studied: one control (pair fed) and two treatment groups given 25% alcohol at 2.2 or 5.5 g-1 kg-1 d-1. The pups were delivered on day 20 and, for each dam, were separated into a male and female group. The body, brain, intestines, and placenta of the pups were obtained, weighed, and stored at -20°C. The pups' intestines (as surrogate of meconium) from each group were pooled, and meconium was analyzed by gas chromatography/mass spectroscopy for FAEE. The meconium showed the following FAEE: ethyl palmitate, ethyl stearate, and ethyl linolenate and were only found in the alcohol-treated group and with high specificity but low sensitivity. Mean body weight of the pups was lower in the treatment groups compared to the control groups. Ethyl palmitate concentration correlated negatively to the pups' mean body and brain weights. Therefore, ethyl palmitate, stearate, and linolenate, in meconium of rat pups prenatally exposed to alcohol, are useful biomarkers of prenatal alcohol exposure, with ethyl palmitate a good biomarker of adverse effect on the pups' body and brain weight.

Meconium androgens are correlated with ASD-related phenotypic traits in early childhood in a familial enriched risk cohort.

BACKGROUND: Prenatal exposure to increased androgens has been suggested as a risk factor for autism spectrum disorder (ASD). This hypothesis has been examined by measurement of steroids in amniotic fluid, cord blood, saliva, and blood with mixed results. METHODS: To provide an orthogonal measure of fetal exposure, this study used meconium, the first stool of a newborn, to measure prenatal androgen exposure from infants in the Early Autism Risk Longitudinal Investigation (EARLI). EARLI is a familial-enriched risk cohort that enrolled pregnant mothers who already had a child with an ASD diagnosis. In the younger child, we investigated the association between meconium unconjugated (u) and total (t) concentrations of major androgens testosterone (T), dehydroepiandrosterone (DHEA), and androstenedione (A4), and ASD-related traits at 12 and 36 months of age. Traits were measured at 12 months with Autism Observation Scale for Infants (AOSI) and at 36 months with total score on the Social Responsiveness Scale (SRS). One hundred and seventy children had meconium and AOSI, 140 had meconium and SRS, and 137 had meconium and both AOSI and SRS. RESULTS: Separate robust linear regressions between each of the log-transformed androgens and log-transformed SRS scores revealed three-way interaction between sex of the child, sex of the proband, and testosterone concentration. In the adjusted analyses, t-T, u-A4, and u-DHEA (P ≤ 0.01) were positively associated with AOSI scores, while u-T (P = 0.004) and u-DHEA (P = 0.007) were positively associated with SRS total score among females with female probands (n = 10). Additionally, higher concentrations of u-T (P = 0.01) and t-T (P = 0.01) predicted higher SRS total score in males with male probands (n = 63). Limitations Since we explored three-way interactions, this resulted in a limited sample size for some analyses. This study was from an enriched-risk cohort which may limit generalizability, and this study used ASD-assessment scales as outcomes instead of diagnostic categories. Additionally, the novel use of meconium in this study limits the ability to compare the results in this cohort to others due to the paucity of research on meconium. CONCLUSIONS: This study supports the utility of meconium for studies of endogenous fetal metabolism and suggests the sex of older siblings with autism should be considered as a biological variable in relevant studies.

Assessment of Tobacco Exposure During Pregnancy by Meconium Analysis and Maternal Interview.

Smoking during pregnancy can have serious obstetric and fetal complications. Therefore, it is essential to identify in utero exposure to tobacco, being meconium the matrix of choice for this purpose. Meconium (n = 565) was analyzed for nicotine, cotinine and hydroxycotinine by LC-MS-MS. Then, tobacco meconium results were compared with smoking habits during pregnancy and neonatal outcomes measures (birth weight, length, head circumference, gestational age and Apgar scores). Although meconium analysis increased identification of in-utero exposure to tobacco (17.7% meconium positive specimens vs 13.5% mothers admitting tobacco use during pregnancy), there was a statistically significant relationship between meconium results and interview answers (P < 0.001). Birth weight was significantly lower for newborns with meconium positive results in males (P = 0.023) and females (P = 0.001), while for length significance was only observed in females (P = 0.001); however, when excluding meconium specimens positive for other drugs, a statistically significant difference was only found for female weight (P = 0.045). Meconium analysis proved to be more reliable for tobacco prenatal exposure detection than maternal interview. In addition, positive meconium results increased the probability for low birth weight, especially in females.

Screening for Opioid and Stimulant Exposure In Utero Through Targeted and Untargeted Metabolomics Analysis of Umbilical Cords.

BACKGROUND: Neonatal abstinence syndrome is an array of signs and symptoms experienced by a newborn due to abrupt discontinuation of intrauterine exposure to certain drugs, primarily opioids. In the United States, the incidence of neonatal abstinence syndrome has tripled over the past decade. The current standard of care for drug testing includes the analysis of infant urine and meconium. Sample collection is associated with several limitations, including diaper media interferences, limited sample amount, sample heterogeneity, and the need for professional staff for collection. Umbilical cord tissue has emerged as a convenient sample matrix for testing owing to its universal availability. The purpose of this study was to examine umbilical cords using an untargeted metabolomics approach to determine the detected drugs and validate an analytical method to confirm and quantify the identified drugs. METHODS: A metabolomics analysis was performed with 21 umbilical cords to screen for drugs and drug metabolites by liquid chromatography-mass spectrometry. Drugs were identified using the National Institute of Standards and Technology database, and an analytical method was developed and validated using secondary liquid chromatography-mass spectrometry instrument for positive confirmation and quantitative analysis. RESULTS: Twenty-one random umbilical cords from women were tested: 4 were positive for cocaine and the primary and secondary metabolites; one was positive for methadone, the primary metabolite; 3 were positive for cotinine, the metabolite of nicotine; and 5 were positive for acetyl norfentanyl. CONCLUSIONS: Our research is a prospective method development study using untargeted and targeted approaches to characterize steady-state drug metabolite levels in the umbilical cord matrix at the time of delivery. By characterizing drug type and concentration, this methodology can be used to develop a reliable complementary testing method for meconium toxicology screens.

The effect of meconium thickness level on neonatal outcome.

BACKGROUND: Despite its prevalence and potential maternal and neonatal implications, the literature on the thickness levels of meconium stained amniotic fluid (MSAF) and its impact on neonatal outcomes is relatively outdated and relies on relatively small sample sizes. AIMS: To study if different thickness levels of MSAF correlate with adverse neonatal outcome. STUDY DESIGN: A retrospective cohort study. SUBJECTS: The medical records and neonatal charts of all women with a singleton pregnancy, who underwent a trial of labor, at 37 + 0/7 weeks or beyond, between 10/2008 and 7/2018 were reviewed. OUTCOME MEASURES: The cohort was divided according to the level of meconium reported during labor into four groups: Clear (C group), Light meconium (LM group), Intermediate meconium (IM group), and Heavy meconium (HM group). Composite neonatal outcome included at least one of the following: umbilical artery pH ≤ 7.1, sepsis, need for blood transfusion, need for phototherapy, respiratory distress syndrome, meconium aspiration syndrome, need for mechanical ventilation support, necrotizing enterocolitis, intraventricular hemorrhage, hypoxic ischemic encephalopathy, periventricular leukomalacia, seizures, hypoglycemia, hypothermia, and death. Continuous parameters were compared with Anova's test or Kruskal Wallis, and categorical variables by chi-square test or Fisher exact test, as appropriate. Multivariant logistic regression was performed in order to eliminate possible cofounders. RESULTS: Overall, 24,445 deliveries were reviewed (C-20,185, LM-1074, IM-2736, HM-450). Composite adverse neonatal outcome was more common with increasing thickness of MSAF. On multivariable analysis, IM and HM were independently associated with composite adverse neonatal outcome. CONCLUSION: The degree of meconium thickness independently correlates with composite adverse neonatal outcome.

Quantifying fetal alcohol exposure by meconium fatty acid ethyl esters (FAEE); association with adverse fetal outcomes and population estimates of fetal alcohol exposure.

Fetal Alcohol Spectrum Disorder (FASD) describes the wide range of adverse physical, behavioral and cognitive effects resulting from ethanol exposure during embryonic and fetal development. Identification of children suffering from FASD is often difficult, as abuse of ethanol during pregnancy is a heavily stigmatized behavior that receives little prenatal screening attention in routine care. Over the last 3 decades, measurement of the ethanol metabolites fatty acid ethyl esters (FAEE) has emerged as a useful tool to detect in the neonatal period fetal alcohol exposure starting from mid gestation. This review aims at updating clinicians and researchers on the validity and utility of this biological marker in two aspects: The association with adverse fetal outcomes and in generating population estimates of fetal alcohol exposure.

Preliminary results of identification and quantification of paclitaxel and its metabolites in human meconium from newborns with gestational chemotherapeutic exposure.

OBJECTIVE: Cancer diagnosis during pregnancy occurs in 1 out of 1000 pregnancies with common malignancies including breast and hematological cancers. Fetal exposure to currently utilized agents is poorly described. We directly assessed fetal exposure by screening meconium from 23 newborns whose mothers had undergone treatment for cancer during pregnancy. STUDY DESIGN: Meconium was collected from newborns whose mothers were diagnosed with cancer during pregnancy and underwent chemotherapy in the second or third trimester as part of the Cancer and Pregnancy Registry. We conducted screening of 23 meconium samples for chemotherapeutics and known metabolites of chemotherapeutics by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Putative identification of paclitaxel and/or its metabolites was made in 8 screened samples. In positively screened samples, we quantified paclitaxel, 3'-p-hydroxypaclitaxel, and 6α-hydroxypaclitaxel by stable isotope dilution-LC-HRMS. RESULTS: Mean (standard deviation) levels of paclitaxel in positively screened samples were 399.9 (248.6) pg/mg in meconium samples from newborn born to mothers that underwent chemotherapy during pregnancy. 3'-p-hydroxypaclitaxel and 6α-hydroxypaclitaxel mean levels were 105.2 (54.6) and 113.4 (48.9) pg/mg meconium, respectively. CONCLUSION: Intact paclitaxel, 3'-p-hydroxypaclitaxel, and 6α-hydroxypaclitaxel were detected in meconium, providing unambiguous confirmation of human fetal exposure. Variability in meconium levels between individuals may indicate a potential for reducing fetal exposure based on timing, dosing, and individual characteristics. This preliminary study may provide an approach for examining the effects of cancer diagnosis during pregnancy on other outcomes by providing a measure of direct fetal exposure.

Monitoring of prenatal exposure to organic and inorganic contaminants using meconium from an Eastern Canada cohort.

Evaluating in utero exposure to inorganic and multiclass organic contaminants is critical to better evaluate potential harmful effects on prenatal and postnatal development. The analysis of meconium, the first bowel discharge of the newborn, has been proposed as a non-invasive way to assess cumulative prenatal exposure. The aim of this study was to implement an analytical method for quantifying 72 targeted organic compounds, including pesticides, pharmaceutical compounds and daily life xenobiotics, in meconium in addition to selected elements (17 elements). We report initial monitoring results based on the analysis of 396 meconium samples from an Eastern Canada cohort (Quebec, Canada). Element contents in meconium were analysed by mass spectrometry after digestion in nitric acid and peroxide. Targeted organic compounds were extracted and purified from meconium samples by a solid-liquid extraction followed by a dispersive-SPE purification before tandem mass spectrometry analysis. Concentrations of targeted elements were within the range of concentration reported in European and US studies but were lower than concentrations found in a developing country cohort (i.e., Pb, Cd). Out of the 72 targeted organic compounds, 31 were detected at least once and 30 were quantified. Compounds with the highest frequency of detection were caffeine, detected in all samples (from 2.80 to 6186 ng g-1), followed by acetaminophen detected in 53% of the samples (up to ~402 µg g-1) and methyl paraben detected in 20% of the samples (up to ~10 µg g-1). Pesticides were detected in low frequencies (< 2%) and low concentration (< 35 ng g-1). Results show that meconium can be used to monitor prenatal exposure of foetus to a wide array of inorganic and organic contaminants.