Development and Safety Trial of the OstreaVent2™ Prototype for Mechanically Ventilated Adult Patients.

Background: With the surge of COVID-19 infections, there were concerns about shortage of mechanical ventilator in several countries including the Philippines. Objective: To transform a locally made, low-cost, neonatal ventilator into a volume- and pressure-controlled, adult ventilator and to determine its safe use among ventilated, adult patients at the Philippine General Hospital. Methods: The modification of the neonatal ventilator (OstreaVent1) to the adult OstreaVent2 was based on the critical need for adult ventilators, in volume or pressure mode, in the Philippines due to the COVID-19 pandemic. The adult ventilator settings were calibrated and tested for two days to check for consistency and tolerance and then submitted to a third party for certification. Once certified, a safety trial of 10 stable adult patients on mechanical ventilator was conducted. The patients were placed on the OstreaVent2 for four hours while ventilator parameters, patient's vital signs, and arterial blood gases were monitored at baseline, during, and after placement on the OstreaVent2. A post-study chest radiograph was also done to rule out pulmonary complications, particularly atelectasis and pneumothorax. Results: The prototype OstreaVent2 received an FDA Certification for Medical Listing after passing its third-party certification. Ten patients (60% male) recruited in the study had a mean age of 39.1 ± 11.6 years. Half of the patients had a diagnosis of non-COVID-19 pneumonia. During the 4-hour study period, the patients while on the OstreaVent2, had stable ventilator settings and most of the variabilities were within the acceptable tolerances. Vital signs were stable and arterial blood gases were within normal limits. One patient developed alar flaring which was relieved by endotracheal tube suctioning. No patient was withdrawn from the study. One patient who was already transferred out of the ICU subsequently deteriorated and died three days after transfer to the stepdown unit from a non-ventilator related cause. Conclusion: The new OstreaVent2 is safe to use among adults who need ventilator support. Variabilities in the ventilator's performance were within acceptable tolerances. Clinical and blood gas measurements of the patients were stable while on the ventilator.

Effect of docosahexaenoic acid and olive oil supplementation on pup weight in alcohol-exposed pregnant rats.

Background: Low birth weight has been observed in offspring of alcoholic mothers due likely to unresolved inflammation and oxidative injury. Dietary lipids play a role in inflammation and its resolution. The primary objective was to investigate the effect of DHA and olive oil on the birth weight of pups born to alcohol-exposed dams. Methods: Pregnant rats were randomized to the control or three treatment (alcohol) groups. From gestational days (GD) 8-19, the control group received daily olive oil and malto/dextrose, whereas groups 2 and 3 received olive oil and low-dose alcohol or high-dose alcohol, respectively. Group 4 received daily DHA and high-dose alcohol. The dam's blood was collected on GD 15 and 20 for cytokine analysis. Dams were sacrificed on GD 20. The mean birth weight of pups was compared by one-way ANOVA with post hoc Duncan's test. Results: There was a significant increase in the pups' mean birth weight in the high-dose alcohol/DHA and high-dose alcohol/olive oil. Higher pro-inflammatory cytokines (IL-1ß and IL-12p70) were noted in the alcohol-exposed dams. Conclusions: DHA and olive oil supplementation in alcohol-exposed pregnant rats significantly increased their pups' birth weight despite having high pro-inflammatory cytokines. The mechanism of this effect remains to be determined.

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.

Alluvial and riparian soils as major sources of lead exposure in young children in the Philippines: the role of floods.

The objective of this paper was to determine the prevalence and sources of high lead (Pb) exposure among children in Bulacan, Philippines. A total of 150 children (6-7 years old) and their caregivers were studied. Lead was analyzed in children hair and deciduous teeth. Sources of lead exposure were determined by caregiver interview and Pb analysis of house soil, drinking faucet water, air, and water from seven Bulacan rivers. Lead was positive in 91.3% of children's hair (MC or median concentration = 8.9 µg/g; range = 0-38.29), in 46.2% of the teeth (MC = 0.000 µg/mg in positive samples; range = 0.00-0.020), in 100% of soil (MC = 27.06 mg/kg; range = 3.05-1155.80), in 21.1% of air (MC = 0 µg/Ncm; range = 0-0.10), in 4% of house, faucet water (MC = 0.0 ppm; range = 0-40). There was a significant correlation (Spearman's rho) between Pb in children's hair and soil (r = 0.195; p = 0.017) and between Pb in house water and outdoor air (r = 0.616; p = 0.005). There is no significant correlation between Pb in children's hair and teeth. None of the potential sources of Pb from interview were related to lead exposure in the children. Water from seven Bulacan rivers was 100% positive for lead (MC = 70.00 ppb; range = 30-90). Widespread flooding with river overflow occurred in Bulacan in 2009 which likely caused lead contamination of the soil. There was no significant difference in the lead concentration of the soil whether near or far from the river (p = 0.205, Mann-Whitney U test). High lead exposure in children in Bulacan is likely from soil contaminated by lead-polluted rivers during flooding. In areas where flooding is common, alluvial and riparian soils from polluted rivers are important sources of lead exposure in children.

Trends in long term exposure to propoxur and pyrethroids in young children in the Philippines.

BACKGROUND/AIM: Pesticides are neurotoxic and can adversely affect children's neurobehavioral outcome. Ongoing pesticide exposure has to be monitored in the study of long term outcome of pesticide adverse effects since changes in the type and amount of exposure can influence outcome. The aim of this paper is to describe the trend in long term pesticide exposure in children through the analysis of pesticides in their hair. PATIENTS AND METHODS: As part of an NIH study on the long term effects of pesticide exposure in young children, ongoing exposure to pesticides was determined by the analysis of children's hair for propoxur and pyrethroids by gas chromatography/mass spectrometry at 2, 4 and 6 years of age. RESULTS: There were significant changes in the prevalence and concentration of propoxur and pyrethroids in children's hair at 2, 4 and 6 years of age. At ages 2 and 4 years, the prevalence of propoxur exposure increased from 12.4% to 24.1% (p<0.001) but dramatically decreased to 1.7% at 6 years (p<0.001). For bioallethrin, the prevalence of exposure steadily increased from 2 years (0.7%, p<0.001) to 4 years (12.4%, p<0.001) and to 6 years (18.4% p<0.001). Exposure to transfluthrin significantly increased from 4 years (1.0%) to 6 years (9.2%, p<0.001). There were also significantly higher median concentrations of bioallethrin at 2 compared to 4 years and for propoxur at 2 years compared to 6 years. Between 4 and 6 years, there was a higher median concentration of propoxur at 4 compared to 6 years and for transfluthrin and bioallethrin, at 6 compared to 4 years. CONCLUSION: Changes in the prevalence and concentration of exposure to propoxur and pyrethroids in children at 2, 4 and 6 years of age are related to the progress in ambulation of young children and to changes in the formulation of home spray pesticides. Thus, periodic monitoring of pesticide exposure is necessary when studying the long term effects of pesticide exposure in the neurodevelopment of young children.

Fetal exposure to propoxur and abnormal child neurodevelopment at 2 years of age.

OBJECTIVE: Our aim was to determine the effects of fetal exposure to propoxur and pyrethroids, on child neurodevelopment at 2 years of age. PATIENTS AND METHODS: Mothers were prospectively recruited during mid-pregnancy in Bulacan, Philippines where multiple pesticides including propoxur, cyfluthrin, chlorpyrifos, cypermethrin, pretilachlor, bioallethrin, malathion, diazinon and transfluthrin are used. To detect prenatal exposure to these pesticides, maternal hair and blood, infant's hair, cord blood, and meconium were analyzed for the pesticides by gas chromatography/mass spectrometry. Infants were examined at 2 years of age with 95.1% follow up rate and their neurodevelopment outcome was assessed by the Griffiths mental developmental scale (N=754). RESULTS: Meconium analysis was the most sensitive method to detect fetal exposure to pesticides and exposure was highest for propoxur (21.3%) and the grouped pyrethroids (2.5% - bioallethrin, transfluthrin, cyfluthrin and cypermethrin). Path analysis modeling was performed to determine the effects of fetal exposure to propoxur and pyrethroids on the child's neurodevelopment at 24 months of age while controlling for confounders. Only singletons and those with complete data for the path analysis were included (N=696). Using a path analysis model, there was a significant negative (ß=-0.14, p<0.001) relationship between prenatal pesticide exposure to propoxur and motor development at 2 years of age after controlling for confounders, e.g., infant gender, socioeconomic status, maternal intelligence, home stimulation (HOME), postnatal exposure to propoxur and blood lead level at 2 years of age. CONCLUSION: At 2 years of age, prenatal exposure to propoxur was associated with poorer motor development in children.

Auditory brainstem response latencies of infants and maternal eposure to environmental toxic product

OBJECTIVE: To explore the effects of pesticide exposure on the auditory system, specifically on hearing status based on auditory brainstem responses. METHODS: A cohort of pregnant women was identified in several communities in a rural area from April 2002 to February 2003 and followed up until delivery. Mother-infant dyads were assessed for exposure to pesticides. Maternal and fetal exposures to environmental toxic products were determined by measuring levels in maternal hair and blood, and infant cord blood, hair, and meconium, respectively. Hearing status was measured using otoacoustic emissions (OAE) and confirmed by diagnostic auditory brainstem responses (ABR) measured at 80, 60, and 40 decibels. Waves I, III, V were identified and absolute latencies measured, including inter-peak latencies from waves 11III, I-V, and III-V. Pesticide exposure was then correlated with latencies of Waves I, III, V, and interpeak latencies of waves I-III, IIV, and III-V. Hearing loss and pesticide exposures were correlated with Griffiths Mental Development Scores (GMDS). RESULTS: Significant delays in the ABR wave latencies were noted in the group with exposure to pesticides. Propoxur was the most common toxic product detected in infants and meconium the best substrate for its detection. There was a 1.4% risk of hearing loss with exposure to propoxur (RR=0.52 (0.12-2.30), p = 0.06), a 6.25% risk with cypermethrin exposure (RR= 4.53 (0.61133.64), P = 0.10) and 6.25% risk with pretilachlor exposure (3.13 (0.44-22.30), p = 0.07). Griffith's Mental Developmental Scale scores (GMDS- hearing and speech subscale and general quotient scores) were not significantly different between exposed and unexposed groups. However, three infants with positive exposures and hearing loss had below average, or low to average scores using this scale. CONCLUSION: Maternal exposure to environmental toxic products may affect the auditory pathway in infants at birth. Pregnant women should limit their exposure to such toxic products in order to avoid neurodevelopmental effects particularly on hearing because this is very important in the critical stage of language and speech development.

Analysis of House Dust and Children's Hair for Pesticides: A Comparison of Markers of Ongoing Pesticide Exposure in Children.

BACKGROUND/AIM: The long term study of the adverse effects of pesticides on child neuro development requires monitoring not only of initial, but ongoing pesticide exposure. Our aim was to compare house dust and children's hair as environmental and biological markers of ongoing pesticide exposure in children. DESIGN/METHODS: In a continuing NIH study on the adverse effects of prenatal pesticide exposure on child neurodevelopment, ongoing pesticide exposure after birth was measured in swept house dust and hair in the children at 4 years of age for propoxur and pyrethroids (transfluthrin, bioallethrin, cyfluthrin and cypermethrin) by gas chromatography/mass spectrometry. The prevalence and concentration of pesticides in the two matrices were compared. RESULTS: Prevalence of propoxur was higher in hair compared to house dust (p<0.001) whereas prevalence of the pyrethroids was higher (p<0.001) in house dust. The overall concentrations of the pyrethroids were also higher (p<0.007) in house dust compared to hair. There was a significant (p<0.001) correlation between dust and hair for bioallethrin and cypermethrin. CONCLUSIONS: Ongoing exposure of children to environmental pesticides is sensitively detected by analysis of children's hair and house dust. However, prevalence of propoxur was higher in hair compared to swept house dust, but the opposite was found for the pyrethroids. Thus, both matrices should be analyzed. There was a significant (p<0.001) correlation between house dust and hair for bioallethrin and cypermethrin.

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

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

An epidemiologic study comparing fetal exposure to tobacco smoke in three Southeast Asian countries.

The high prevalence of smoking in Southeast Asia (SEA) means pregnant women face exposure to tobacco smoke that may affect the health of their fetus. This study determined fetal exposure to tobacco smoke by meconium analysis for cotinine in 3 locations in SEA: Bulacan Province, Philippines (N=316), Bangkok, Thailand (N=106) and Singapore City (N=61). Maternal exposure to tobacco smoke was 71.1% (1.3% active; 69.8% passive) in Bulacan, 57.5% (0.9% active; 58.6% passive) in Bangkok and 54.1% (11.5% active; 42.0% passive) in Singapore. Fetal exposure to tobacco smoke (by meconium analysis) was 1.3% (Bulacan), 4.7% (Bangkok) and 13.1% (Singapore); however, a large proportion of infants who tested positive for cotinine (65%) were born to mothers who gave no history of either active or passive exposure to environmental tobacco smoke. Fetal exposure to tobacco smoke is a major health problem.

5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and the risk of acute lymphoblastic leukemia (ALL) in Filipino children.

BACKGROUND: 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism. Polymorphisms at the C677T and A1298C loci are associated with reduced activity; consequently more folate substrates are shunted toward thymidylate and DNA synthesis. Several studies have reported a reduced risk of developing ALL in children with MTHFR polymorphisms. The objective of this study was to determine the association between MTHFR polymorphisms and ALL in Filipino children. PROCEDURE: We conducted a case control study in children diagnosed with ALL at the Philippine General Hospital from 1/2001 through 12/2005. Bone marrow aspirate slides were reviewed by two expert hematologists to verify the morphologic diagnosis of ALL. DNA was isolated from the slides and MTHFR polymorphisms, C677T and A1298C, were determined using Taqman real-time PCR. Cord blood of healthy Filipino newborns served as control. RESULTS: There were a total of 191 ALL and 394 controls genotyped. The distribution of C677T polymorphisms was similar in the two groups (P = 1.0). However, for A1298C, there was significantly more AC and CC genotypes in the ALL compared to controls (P = 0.02; OR 1.57; CI: 1.08-2.28). The 1298C allele frequency for the control group was 36.8% and 677T allele frequency was 9.9%. CONCLUSION: A1298C polymorphisms is associated with an increased risk for ALL in Filipino children. This may be due to a difference in leukemia biology or to a high prevalence of folate deficiency in Filipinos. Our study reiterates the gene and environment interaction in leukemogenesis.

Adaptation of the Behavioral Assessment and Research System (BARS) for evaluating neurobehavioral performance in Filipino children.

Neurobehavioral tests have long been used to assess health effects in exposed working adult populations. The heightened concern over the potential impact of environmental exposures on neurological functioning in children has led to the development of test batteries for use with children. There is a need for reliable, easy-to-administer batteries to assess neurotoxic exposure in children. One such test battery previously validated with Spanish- and English-speaking children ages 4 and older, combines computerized tests from the Behavioral Assessment and Research System (BARS) with non-computerized tests. The goal of the present study was to determine the feasibility of using standardized neurobehavioral tests in preschool and school-aged Filipino children. Test instructions were translated into the vernacular, Tagalog or Tagalog-English ("Taglish") and some instructions and materials were modified to be appropriate for the target populations. The battery was administered to 4-6-year-old Filipino children (N=50). The performance of the Filipino children was compared to data previously collected from Spanish- and English-speaking children tested in the US. The majority of children had no difficulty completing the tests in the battery with the exception of the Symbol-Digit test and Digit Span-reverse. The three groups showed similar patterns of performance on the tests and the older children performed better than the younger children on all of the tests. The findings from this study demonstrate the utility of using this test battery to assess cognitive and motor performance in Filipino children. Tests in the battery assess a range of functions and the measures are sensitive to age differences. The current battery has been utilized in several cultures and socio-economic status classes, with only minor modifications needed. This study demonstrates the importance of pilot testing the methods before use in a new population, to ensure that the test is valid for that culture.

A comparison of infant hair, cord blood and meconium analysis to detect fetal exposure to environmental pesticides.

OBJECTIVE: The detection of fetal exposure to environmental pesticides is important because many of the pesticides are neurotoxicants and fetal exposure to these compounds can adversely affect prenatal and subsequent neurodevelopment. The aim of this study was to determine, by the comparative analysis of infant hair, cord blood and meconium, the most sensitive matrix to detect fetal exposure to pesticides. PATIENTS AND METHODS: Pregnant women were prospectively recruited from an agricultural site in the Philippines where a preliminary survey indicated a substantial use at home and in the farm of the following pesticides: propoxur, cyfluthrin, chlorpyrifos, cypermethrin, pretilachlor, bioallethrin, malathion, diazinon and transfluthrin. Infant hair, cord blood and meconium were obtained after birth and were analyzed by gas chromatography/mass spectrometry for the above compounds, including lindane and 1,1,1-trichloro-2,2-bis, p-chlorophenylethane (DDT) and some of their known metabolites. RESULTS: A total of 638 infants were included in the study. The highest exposure rate to pesticides was detected in meconium (23.8% to propoxur, 1.9% to pretilachlor, 1.9% to cypermethrin, 0.8% to cyfluthrin, 0.6% to DDT and 0.3% to malathion and bioallethrin). Cord blood was only positive for propoxur (1.9%) whereas infant hair was only positive for chlorpyrifos (0.2%). The highest exposure was to household pesticide (propoxur). The frequency and concentration of pesticides were compared in the three matrices and there was a significantly higher frequency and concentration of propoxur, pretilachlor, DDT, cyfluthrin and cypermethrin in meconium compared to cord blood and infant hair. Pesticide metabolites were not found in any of the matrices analyzed, except in one meconium sample which was positive for 4,4' dichlorodiphenyldichloro ethylene (DDE), a DDT metabolite. CONCLUSIONS: There is significant exposure of the pregnant woman and her fetus to pesticides, particularly to the home pesticide, propoxur. Our study has demonstrated that among cord blood, meconium or infant hair, meconium is the most sensitive matrix to analyze for fetal exposure to pesticides. The accumulation of pesticides in meconium, the ease of meconium collection and the large amount of meconium that could be collected are factors that contribute to the increased sensitivity of this matrix.

Quantitative determination of paraquat in meconium by sodium borohydride-nickel chloride chemical reduction and gas chromatography/mass spectrometry (GC/MS).

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 0.0156microg/g. Analysis of meconium samples from a study population in the Philippines (n=70) showed a 2.8% prevalence of fetal exposure to paraquat.

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

BACKGROUND: This study was designed to investigate the relationship between prenatal pesticide exposures and the generation of leukemia-associated t(8;21)(q22;q22), one of the most common cytogenetic abnormalities in childhood acute myeloid leukemia (AML). PROCEDURE: Gas chromatography/mass spectrometry (GC/MS) was used to quantitatively detect different pesticides (propoxur and cypermethrin) in meconium from 49 newborn babies from the Philippines. The generation of t(8;21) was determined in the corresponding umbilical cord blood samples by detection of the AML1-ETO fusion transcripts derived from t(8;21) using nested RT-PCR. Levels for the AML1-ETO fusion transcripts were quantitated by real-time RT-PCR in the t(8;21) positive cord blood samples. AML1-ETO fusion transcript forms were characterized by RT-PCR amplification and DNA sequencing. RESULTS: In the present study using umbilical cord blood samples obtained from infants whose prenatal exposure to the pesticide, propoxur, was determined by meconium analysis, we showed that (i) incidence of t(8;21) in the exposed group was two-fold higher than that in the unexposed group; and (ii) the levels for AML1-ETO fusion transcripts resulting from t(8;21) positively correlated with propoxur concentrations in meconium. Similar heterogeneity in the fusion transcripts was detected in the t(8;21) positive cord blood samples as in our previous study with t(8;21) AML patients. CONCLUSION: These results further confirm the prenatal origin of t(8;21) and establish a significant correlation between prenatal pesticide exposures and the generation of t(8;21). They suggest that prenatal pesticide exposures may be causal factors for the generation of leukemia-associated chromosomal translocations.

Fatty acid ethyl esters in meconium: are they biomarkers of fetal alcohol exposure and effect?

BACKGROUND: Biomarkers of fetal exposure to alcohol are important to establish so that early detection and intervention can be made on these infants to prevent undesirable outcomes. The aim of this study was to analyze long-chain fatty acid ethyl esters (FAEEs) in meconium as potential biomarkers of fetal alcohol exposure and effect. METHODS: Fatty acid ethyl esters were analyzed in the meconium of 124 singleton infants by positive chemical ionization gas chromatography/mass spectrometry (GC/MS) and correlated to maternal ethanol use. RESULTS: A total of 124 mother/infant dyads were enrolled in the study: 31 were in the control group and 93 were in the alcohol-exposed group. The incidence (28% vs 9.7%, p = 0.037) of ethyl linoleate detected in meconium was significantly higher in the alcohol-exposed groups than the control groups. Similarly, when the concentrations of ethyl linoleate in meconium were grouped (trichotomized), there was a significant linear by linear association between alcohol exposure and group concentrations of ethyl linoleate (p = 0.013). Furthermore, only alcohol-exposed infants were found in the group with the highest ethyl linoleate concentration. The sensitivity of ethyl linoleate in detecting prenatal alcohol exposure was only 26.9%, and its specificity and positive predictive value were 96.8 and 96.2%, respectively. There was no significant correlation between the concentration of ethyl linoleate in meconium and absolute alcohol consumed (oz) per drinking day across pregnancy, although a trend toward a positive correlation is seen at lower amounts of alcohol consumed. Among the polyunsaturated, long-chain FAEEs, there was weak evidence that the incidence (21.5% vs 6.5%, p = 0.057) and concentration (p = 0.064) of ethyl arachidonate (AA) were significantly higher in the alcohol-exposed groups than the control groups. Ethyl linolenate and ethyl docosahexanoate (DHA) in meconium were found only in the alcohol group, although not at statistically significant levels. Highly significant correlations were found among the concentrations of ethyl linoleate, ethyl linolenate, ethyl AA, and ethyl DHA in meconium (correlations ranged between rs = 0.203, p = 0.024; and rs = 0.594, p < 0.001). CONCLUSION: We conclude that FAEEs in meconium, particularly ethyl linoleate and ethyl AA, are biomarkers of high specificity for prenatal exposure to alcohol in newborn infants. We also propose that ethyl AA and DHA could be potential biomarkers of fetal alcohol effects on the developing fetal brain and should be investigated further.

Persistent pulmonary hypertension of the newborn: pathogenesis, etiology, and management.

Persistent pulmonary hypertension of the newborn (PPHN) is characterized by severe hypoxemia shortly after birth, absence of cyanotic congenital heart disease, marked pulmonary hypertension, and vasoreactivity with extrapulmonary right-to-left shunting of blood across the ductus arteriosus and/or foramen ovale. In utero, a number of factors determine the normally high vascular resistance in the fetal pulmonary circulation, which results in a higher pulmonary compared with systemic vascular pressure. However, abnormal conditions may arise antenatally, during, or soon after birth resulting in the failure of the pulmonary vascular resistance to normally decrease as the circulation evolves from a fetal to a postnatal state. This results in cyanosis due to right-to-left shunting of blood across normally existing cardiovascular channels (foramen ovale or ductus arteriosus) secondary to high pulmonary versus systemic pressure. The diagnosis is made by characteristic lability in oxygenation of the infant, echocardiographic evidence of increased pulmonary pressure, with demonstrable shunts across the ductus arteriosus or foramen ovale, and the absence of cyanotic heart disease lesions. Management of the disease includes treatment of underlying causes, sedation and analgesia, maintenance of adequate systemic blood pressure, and ventilator and pharmacologic measures to increase pulmonary vasodilatation, decrease pulmonary vascular resistance, increase blood and tissue oxygenation, and normalize blood pH. Inhaled nitric oxide has been one of the latest measures to successfully treat PPHN and significantly reduce the need for extracorporeal membrane oxygenation.

Maternal hair--an appropriate matrix for detecting maternal exposure to pesticides during pregnancy.

The detection of exposure of pregnant women to toxicants in the environment is important because these compounds can be harmful to the health of the woman and her fetus. The aim of this study was to analyze for pesticides/herbicides in paired maternal hair and blood samples to determine the most appropriate matrix for detecting maternal exposure to these compounds. A total of 449 pregnant women were prospectively recruited at midgestation from an agricultural site in the Philippines where a preliminary survey indicated significant use at home and on the farm of the following compounds: propoxur, cyfluthrin, chlorpyrifos, cypermethrin, pretilachlor, bioallethrin, malathion, diazinon, and transfluthrin. Paired maternal hair and blood samples were obtained from each subject upon recruitment into the study (midgestation) and at birth and were analyzed for the above compounds, as well as lindane and DDT [1,1,1-trichloro-2-2-bis(p-chlorophenyl) ethane], and some of their known metabolites by gas chromatography/mass spectrometry. The highest exposure rate was seen for propoxur and bioallethrin and maternal hair analysis provided the highest detection rate for these two compounds, compared to blood, at both time periods: (1) At midgestation, 10.5% positive for propoxur in hair compared to 0.7% in blood (P<0.001) and for bioallethrin, 11.9% positive in hair compared to 0% in blood (P < or = 0.001), and (2) at birth, 11.8% positive for propoxur in hair compared to 4% in blood (P < or = 0.001) and for bioallethrin, 7.8% in hair compared to 0% in blood (P < or = 0.001). A small number of maternal hair samples were also positive for malathion, chlorpyrifos, pretilachlor, and DDT. Only a few of the pesticide metabolites were detected, principally 3-phenoxybenzoic acid, malathion monocarboxylic acid, and DDE [1,1,dichloro-2-2-bis(p-chlorophenyl)ethylene], and they were mostly found in maternal blood. There was a significant association between the use of the home spray pesticide, Baygon, and propoxur in maternal hair at birth (P=0.001) and between the use of a slow-burning mosquito coil and the presence of bioallethrin in maternal hair at midgestation and at birth (P=0.001, P < or = 0.041, respectively). There is significant exposure of the pregnant woman to pesticides, particularly to pesticides that are used at home. Our study demonstrates the advantages of analyzing maternal hair as a readily available biologic matrix for studying maternal exposure to toxicants in the environment, compared to blood. For propoxur, there was a 3- to 15-fold higher detection rate of the pesticide in maternal hair as compared to blood. As for the other pesticides, bioallethrin, malathion, chlorpyrifos, and DDT were exclusively found in maternal hair compared to blood. On the other hand, pesticide metabolites were infrequently found in maternal hair or maternal blood. Pesticides in blood most likely represent acute exposure, whereas pesticides in hair represent past and/or concurrent exposure. The high sensitivity, wide window of exposure, availability, and ease of hair collection are distinct advantages in using hair to detect exposure to pesticides among pregnant women. However, pesticides in maternal hair may also be secondary to passive exposure and therefore not truly representative of the internal pesticide dose. Finally, the analysis of maternal hair for pesticides as an index of maternal exposure to pesticides in the environment allows the institution of measures to prevent further exposure during pregnancy.

Evaluation of a new transcutaneous bilirubinometer.

OBJECTIVE: The objective of this study was to evaluate the Minolta/Hill-Rom Air-Shields Transcutaneous Jaundice Meter model JM-103. METHODS: We studied a convenience sample of 849 newborns > or =35 weeks of gestation in 3 hospitals. These infants had total serum bilirubin (TSB) levels measured on clinical indication, and transcutaneous bilirubin (TcB) levels were obtained within 1 hour of the TSB levels. The population was 59.2% white, 29.8% black, 4.5% East Asian, 3.8% Middle Eastern, 1.6% Indian/Pakistani, and 1.1% Hispanic. RESULTS: There was a close correlation between TSB and TcB values in all of the population groups: white (n = 503, r =.949); black (n = 253, r =.822); and East Asian, Indian/Pakistani, and Hispanic (n = 93, r =.926). In the black population, the correlation was less close than in the other groups, and differences between the TcB and TSB measurements tended to increase with rising TSB values. JM-103 values differed from TSB values by 3 mg/dL or more in 2% of white, 3.2% of other, and 17.4% of black infants. In these black infants, the JM-103 value was always greater than the TSB value. CONCLUSIONS: We conclude that TcB measurements using the JM-103 jaundice meter correlate very closely with TSB levels over the range of TSB encountered in this study. Because only 3.3% of our infants had TSB values >15 mg/dL (257 micro mol/L), more data are needed in this range of TSB concentration. The correlation in black infants is not as close as in other groups, but because the tendency in blacks is for the JM-103 to overestimate serum bilirubin levels, dangerous clinical errors are unlikely to occur. The measurement technique is rapid and simple, and it is easy to perform repeated measurements over time, thus reducing the likelihood of error. TcB measurements with the JM-103 jaundice meter should obviate the need for most serum bilirubin levels in newborn infants > or =35 weeks of gestation, although serum bilirubin measurements are still required when treatment with phototherapy or exchange transfusion is being considered.

Drugs that affect the fetus and newborn infant via the placenta or breast milk.

In general, drugs that are taken by a mother during pregnancy or after birth may be transferred to the fetus or the infant (through breast milk). Many factors are involved that determine the amount of drugs that are transferred and their potential effects on the fetus or infant. A careful assessment of the risk versus benefit is necessary and should be individualized. In the breastfed infant, many measures can be undertaken further so that the amount of drug transferred to the infant is minimized.