Association of Prenatal Acetaminophen Exposure Measured in Meconium With Risk of Attention-Deficit/Hyperactivity Disorder Mediated by Frontoparietal Network Brain Connectivity.

Importance: Despite evidence of an association between prenatal acetaminophen exposure and attention-deficit/hyperactivity disorder (ADHD) in offspring, the drug is not contraindicated during pregnancy, possibly because prior studies have relied on maternal self-report, failed to quantify acetaminophen dose, and lacked mechanistic insight. Objective: To examine the association between prenatal acetaminophen exposure measured in meconium (hereinafter referred to as meconium acetaminophen) and ADHD in children aged 6 to 7 years, along with the potential for mediation by functional brain connectivity. Design, Setting, and Participants: This prospective birth cohort study from the Centre Hospitalier Université de Sherbrooke in Sherbrooke, Québec, Canada, included 394 eligible children, of whom 345 had meconium samples collected at delivery and information on ADHD diagnosis. Mothers were enrolled from September 25, 2007, to September 10, 2009, at their first prenatal care visit or delivery and were followed up when children were aged 6 to 7 years. When children were aged 9 to 11 years, resting-state brain connectivity was assessed with magnetic resonance imaging. Data for the present study were collected from September 25, 2007, to January 18, 2020, and analyzed from January 7, 2019, to January 22, 2020. Exposures: Acetaminophen levels measured in meconium. Main Outcomes and Measures: Physician diagnosis of ADHD was determined at follow-up when children were aged 6 to 7 years or from medical records. Resting-state brain connectivity was assessed with magnetic resonance imaging; attention problems and hyperactivity were assessed with the Behavioral Assessment System for Children Parent Report Scale. Associations between meconium acetaminophen levels and outcomes were estimated with linear and logistic regressions weighted on the inverse probability of treatment to account for potential confounders. Causal mediation analysis was used to test for mediation of the association between prenatal acetaminophen exposure and hyperactivity by resting-state brain connectivity. Results: Among the 345 children included in the analysis (177 boys [51.3%]; mean [SD] age, 6.58 [0.54] years), acetaminophen was detected in 199 meconium samples (57.7%), and ADHD was diagnosed in 33 children (9.6%). Compared with no acetaminophen, detection of acetaminophen in meconium was associated with increased odds of ADHD (odds ratio [OR], 2.43; 95% CI, 1.41-4.21). A dose-response association was detected; each doubling of exposure increased the odds of ADHD by 10% (OR, 1.10; 95% CI, 1.02-1.19). Children with acetaminophen detected in meconium showed increased negative connectivity between frontoparietal and default mode network nodes to clusters in the sensorimotor cortices, which mediated an indirect effect on increased child hyperactivity (14%; 95% CI, 1%-26%). Conclusions and Relevance: Together with the multitude of other cohort studies showing adverse neurodevelopment associated with prenatal acetaminophen exposure, this work suggests caution should be used in administering acetaminophen during pregnancy. Research into alternative pain management strategies for pregnant women could be beneficial.

Ultra-high-pressure liquid chromatography tandem mass spectrometry determination of antidepressant and anxiolytic drugs in neonatal meconium and maternal hair.

A procedure based on ultra-high-pressure liquid chromatography tandem mass spectrometry has been developed for the determination of 22 antidepressant and anxiolytic drugs ad metabolites in the three consecutive maternal hair segments representing the pregnancy trimesters and paired neonatal meconium samples. After hair washing with methyl alcohol and diethyl ether and subsequent addition of internal standards, hair samples were treated with 500 µl VMA-T M3 reagent for 1h at 100 °C. After cooling, 100 µl M3 extract were diluted with 400 µl water and a volume of 10 µl was injected into chromatographic system. Meconium samples were firstly treated with 1 ml methyl alcohol and the organic layer back-extracted twice with 1.5 ml of a mixture of ethylacetate:hexane (80:20, v/v). Chromatographic separation was achieved at ambient temperature using a reverse-phase column and a linear gradient elution with two solvents: 0.3% formic acid in acetonitrile and 5mM ammonium formate pH 3. The mass spectrometer was operated in positive ion mode, using multiple reaction monitoring via positive electrospray ionization. The method was linear from the limit of quantification (0.05-1 ng/mg hair and 5-25 ng/g meconium depending on analyte under investigation;) to 10 ng/mg hair and 1000 ng/g meconium, with an intra- and inter-assay imprecision and inaccuracy always less than 20% and an analytical recovery between 66.6% and 95.3%, depending on the considered analyte and biological matrix. Using the validated method, 7 mothers were found positive to one or more hair segments and 5 meconium samples were found positive to one or more antidepressant and anxiolytic drugs, assessing prenatal exposure to these drugs following maternal consumption in one or more pregnancy trimesters.

The effect of labour on the coagulation system in the term neonate.

The coagulation system of the foetus is markedly different from that of adults. To assess the influence of maternal age, mode of delivery and intrapartum events, and foetal gender and weight on the foetal coagulation system. Cord blood was collected from 154 healthy pregnant women, with gestational age 37 - 42 weeks at birth. Mann-Whitney test was used for analysis of binary data and continuous variables were analysed using Pearson's correlation coefficient. Mean cord blood levels of FVIII:C, VWF:Ag, VWF:CB, FIX, FXI, FXII and plasminogen were significantly higher in babies delivered after labour, compared to those delivered after an elective caesarean. Mean cord blood levels of FII (P = 0.003), FV (P = 0.009), FVII (P = 0.0004) and FX (P = 0.0009) were significantly lower in the babies with meconium stained liquor in labour, compared with those with clear liquor. Augmentation with oxytocin, instrumental delivery, did not affect any of the factor levels and duration of labour did not have an effect on the level of coagulation proteins in cord blood. This study provides valuable information about effect of labour on the coagulation system of the foetus. It is concluded that, in cord blood, the results of coagulation parameters in the newborn baby should be considered in light of mode of delivery and events of labour.

Development and validation of the first liquid chromatography-tandem mass spectrometry assay for simultaneous quantification of multiple antiretrovirals in meconium.

A novel method for the simultaneous quantification of 16 antiretroviral (ARV) drugs and 4 metabolites in meconium was developed and validated. Quantification of 6 nucleoside/nucleotide reverse transcriptase inhibitors, 2 non-nucleoside reverse transcriptase inhibitors, 7 protease inhibitors, and 1 integrase inhibitor was achieved in 0.25 g of meconium. Specimen preparation included methanol homogenization and solid-phase extraction. Separate positive and negative polarity multiple reaction monitoring mode injections were required to achieve sufficient sensitivity. Linearity ranged from 10 to 75 ng/g up to 2500 ng/g for most analytes and 100-500 ng/g up to 25,000 ng/g for some; all correlation coefficients were ≥0.99. Extraction efficiencies from meconium were 32.8-119.5% with analytical recovery of 80.3-108.3% and total imprecision of 2.2-11.0% for all quantitative analytes. Two analytes with analytical recovery (70.0-138.5%) falling outside the 80-120% criteria range were considered semiquantitative. Matrix effects were -98.3-47.0% and -98.0-67.2% for analytes and internal standards, respectively. Analytes were stable (>75%) at room temperature for 24 h, 4 °C for 3 days, -20 °C for 3 freeze-thaw cycles over 3 days, and on the autosampler. Method applicability was demonstrated by analyzing meconium from HIV-uninfected infants born to HIV-positive mothers on ARV therapy. This method can be used as a tool to investigate the potential effects of in utero ARV exposure on childhood health and neurodevelopmental outcomes.

Auditory evoked arousal responses of 3-month-old infants exposed to methamphetamine in utero: a nap study.

AIM: To investigate whether or not infants exposed to methamphetamine prenatally have impaired arousal responses from sleep. METHODS: The polygraphic nap studies involved 42 infants aged 3 months exposed to methamphetamine in utero and a comparison group of 57 infants. A proportion of mothers in both groups smoked cigarettes and/or marijuana and drank alcohol during pregnancy. White noise from 50 to 100 decibels (dB) was administered at 10 dB intervals twice within non-rapid eye movement (NREM) and rapid eye movement (REM) sleep states and arousal thresholds measured. RESULTS: Combining groups, 306 tests were completed (128 and 178 within REM and NREM sleep, respectively) and infants were more likely to wake at lower thresholds in REM than NREM sleep (hazard ratio 5.58; 95% CI, 3.78-8.23 p < 0.0001). No significant differences in arousal threshold were found between methamphetamine and comparison groups, before or after controlling for other substance use (NREM sleep; 0.98, 95% CI, 0.60-1.59 and REM sleep; 1.03, 95% CI, 0.56-1.89). CONCLUSIONS: These findings suggest that arousal responses of methamphetamine-exposed infants remain intact, providing no support for the hypothesis that prenatal exposure could increase their vulnerability to sudden infant death syndrome (SIDS) through arousal deficits.

The effect of an osmotic contrast agent on complete meconium evacuation in preterm infants.

OBJECTIVE: To determine whether enteral application of the osmotic contrast agent Gastrografin accelerates complete meconium excretion and improves feeding tolerance in very low birth weight infants. METHODS: This study was a stratified, randomized, placebo-controlled trial in premature infants with a birth weight <1500 g and a gestational age <32 weeks who received 3 mL/kg Gastrografin diluted 1:3 with water within their first 24 hours of life, or placebo. RESULTS: Passage of last meconium occurred after a median of 7 days (95% confidence interval: 6-9 days, n = 39) in the intervention group and after 8 days (95% confidence interval: 7-10 days, n = 39) in the control group (P = .61); however, Gastrografin application was associated with a 7.5-day shorter time to full enteral feedings, a 24-day shorter stay in the NICU, and a 17-day reduction in the overall hospital stay in the intervention group compared with the control group. A numerically higher incidence of necrotizing enterocolitis (21%) was observed in the intervention group, however. CONCLUSIONS: Gastrografin application did not accelerate meconium evacuation, but the higher stool frequency during the first week of life had a beneficial effect on the time to full enteral feedings and later hospital stay; however, it may increase the necrotizing enterocolitis risk. Further investigations are needed with modified protocols, and the prophylactic use of Gastrografin cannot currently be recommended without further clinical trials.

Stability of extemporaneously prepared acetylcysteine 1% and 10% solutions for treatment of meconium ileus.

PURPOSE: The stability of extemporaneously prepared acetylcysteine 1% and 10% solutions for treatment of meconium ileus was evaluated. METHODS: Acetylcysteine 1% (10-mg/mL) and 10% (100-mg/mL) solutions were prepared by mixing 3 and 10 mL, respectively, of commercially available 20% acetylcysteine solution with a sufficient quantity of bacteriostatic 0.9% sodium chloride for injection to make a final volume of 60 mL. Three identical samples of each concentration were prepared, placed in 2-oz amber plastic prescription bottles, and stored at 20-25 °C. Samples were assayed in duplicate using high-performance liquid chromatography and inspected for changes in color, odor, and pH immediately after preparation and at 7, 14, 30, 60, and 90 days. Stability was defined as retention of at least 90% of the initial concentration. RESULTS: At least 90% of the initial concentration of acetylcysteine was retained in both formulations for 60 days. No appreciable change from the initial pH occurred in the acetylcysteine 1% or 10% solution during the first 60 days, but there was a notable change in pH after 90 days in both formulations. Neither solution was stable at day 90. There was no detectable change in color at 90 days; however, the odor of hydrogen sulfide was more pungent than on previous study days. CONCLUSION: Extemporaneously prepared solutions of acetylcysteine 1% (10 mg/mL) and 10% (100 mg/mL) prepared with bacteriostatic 0.9% sodium chloride for injection were stable for at least 60 days when stored in plastic amber bottles at room temperature.

Nicotine and its metabolites in amniotic fluid at birth--assessment of prenatal tobacco smoke exposure.

Amniotic fluid was collected from 78 pregnant women at birth additionally with their urine prior to delivery as well as neonatal urine and meconium. The smoking markers, nicotine and its metabolites cotinine and trans-3'-hydroxycotinine (OH-cotinine), were determined using high-performance liquid chromatography (HPLC). The self-reported smoking status during pregnancy determined by means of a questionnaire was verified by measurement of maternal urine. In all smokers, nicotine metabolites were detected in amniotic fluid and in 80% of them nicotine as well. However, the sum of the nicotine metabolites (Sum(met)) was significantly lower (p < .001) in amniotic fluid (704 +/- 464 nmol/L) than in meconium (921 +/- 588 nmol/L), neonatal urine (1139 +/- 813 nmol/L) and maternal urine (4496 +/- 3535 nmol/L). Concentrations of nicotine metabolites in amniotic fluid correlated well (p < .001) with that in the other specimen types. After environmental tobacco smoke (ETS) exposure, no nicotine or nicotine metabolites were detectable in amniotic fluid but only in maternal and neonatal urine. Analysis of amniotic fluid at birth lends itself to verifying smoking habits during pregnancy and clearly discriminating from ETS exposure, but it is not a suitable approach to differentiating between ETS exposure and non-exposure.

Meconium-induced release of cytokines is mediated by the TRL4/MD-2 complex in a CD14-dependent manner.

OBJECTIVE: Meconium, the first intestinal discharge of the newborn, contains material accumulated during fetal life. Meconium activates complement and CD14 and may induce a systemic inflammatory response. Toll-like receptors are classical pattern-recognition receptors recognizing both exogenous and host-derived ligands. The cyanobacterial product CyP is a potent LPS antagonist binding to the TLR4/MD-2 complex. The aim of the present study was to investigate the role of the CD14/TLR4/MD-2 complex in meconium-induced inflammation. METHODS: Whole blood from six donors was preincubated with anti-CD14 or CyP. Meconium was added and the samples were incubated for 4h. Twenty-seven inflammatory mediators were measured in a Bioplex Array Reader. Human embryonic kidney cells transfected with plasmids containing NF-kappaB dependent luciferase reporter, human MD-2, TLR4, TLR2 and/or CD14, were incubated with meconium or LPS for 18 h. Luciferase activity in cytoplasmic extracts was measured using a Luciferase Assay System kit. RESULTS: Meconium induced formation of a broad panel of inflammatory mediators. CyP and anti-CD14 significantly (p<0.001) inhibited meconium-induced formation of (a) proinflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IFN-gamma) by 60-80% and 72-94%, respectively, (b) anti-inflammatory cytokines (IL-10, IL-1Ra) by 58-59% and 50-65%, respectively, (c) chemokines (IL-8, MCP-1, MIP-1alpha, MIP-1beta, eotaxin, IP-10) by 43-77% and 57-87%, respectively, and (d) growth factors (G-CSF, GM-CSF, basic FGF, PDGFbb) by 53-71% and 40-78%, respectively, with no statistical significant difference between Cyp and anti-CD14. The inflammatory response could only partly be explained by LPS, suggesting that endogenous components of meconium contribute to the inflammatory response. Meconium activated NF-kappaB dose-dependently in cells expressing TLR4/MD-2 together with CD14, while no effect was seen in cells expressing TLR4/MD-2 alone or in TLR2/CD14 transfected cells. CONCLUSIONS: The results indicate that the CD14-dependent meconium-induced inflammatory reaction is mediated through the TLR4/MD2 complex. These data may have implications for future therapeutic strategies for meconium aspiration syndrome.

Hepatic derangement following N-Acetylcysteine enemas in an infant with cystic fibrosis.

We discuss an infant with MI secondary to cystic fibrosis, who was managed surgically by a double barrel ileostomy for mid - small bowel atresia and developed severe faecal impaction in the post - operative period. The faecal impaction was treated successfully with oral NAC and 0.2% NAC contrast enemas. The patient's liver function tests revealed a dramatic increase in transaminases and bilirubin contemporaneous with the administration of the enemas. The levels showed a spontaneous improvement after discontinuation. This is only the second reported case of hepatotoxicity secondary to NAC enemas in the literature. While our experience offers modest support for the use of NAC, its efficacy is not yet proven and paediatric surgeons using NAC in the enema form need to closely monitor liver function contemporaneous with this agent's administration and adjust their treatment accordingly.

Duration of meconium passage in preterm and term infants.

BACKGROUND: First passage of stool after birth, meconium, is delayed in preterm infants compared to term infants. The difference in duration of meconium passage until transition to normal stools has however never been assessed in preterm and term infants. HYPOTHESIS: Preterm infants have prolonged duration of passage of meconium (PoM) compared to term infants. METHODS: Between August and November 2006, all infants born in an academic and non-academic hospital with gestational age (GA) 25-42 weeks and without metabolical, congenital diseases or gastrointestinal disorders, were included. Infants were divided into four groups: (A) GA < or =30 weeks; (B) GA between 31 and 34 weeks; (C) GA between 35 and 36 weeks; (D) GA > or = 37 weeks (term born). RESULTS: A total of 198 infants (102 males); 32, 62, 33 and 71 infants in groups A, B, C and D, respectively, were included. With decreasing gestation a trend was found for delayed first PoM (p<0.001). Compared to term infants 79% (56/71), less preterm infants passed their first stool within 24 h after birth--group A: 44% (14/32); group B: 68% (42/62); and group C: 73% (24/33). With decreasing gestation a trend for prolonged PoM was found (p<0.001). The mean (SD) PoM duration was prolonged in group A: 7.8 days (2.5); group B: 4.3 days (2.4); and group C: 2.9 days (1.3) compared to term infants. Furthermore, PoM was associated with birth weights < or =2500 g (p = 0.03) and morphine therapy (p = 0.03). Duration of PoM was not associated with type of feeding, small for gestational age, large for gestational age or need for respiratory support. CONCLUSION: PoM was not only delayed but also prolonged in preterm infants. Duration of PoM was associated with GA, birth weight and morphine therapy.

Assessment of prenatal tobacco smoke exposure by determining nicotine and its metabolites in meconium.

Meconium samples collected from 115 neonates were analysed for nicotine, cotinine and trans -3-hydroxycotinine (OH-cotinine) by means of high-performance liquid chromatography (HPLC) to identify prenatal smoke exposure. The self-reported maternal smoking status during pregnancy was determined by means of a questionnaire and verified by measurements in urine prior to childbirth. The total sum of nicotine and its metabolites (Sum(tot)) of the first passed meconium samples was 1560 +/- 1024 pmol/g in newborns of smoking mothers. Smoking of less than five cigarettes was clearly detected. Sum(tot) remained constant in all meconium samples passed by a neonate in succession. However, the proportion of nicotine decreased with the time of passage after birth and the OH-cotinine proportion increased, whereas cotinine hardly changed. Nicotine or its metabolites were not detectable in meconium (detection limit < 20 pmol/g), when the mothers were only exposed to environmental tobacco smoke (ETS) using the HPLC method. The hypothesis that the content of nicotine metabolites in meconium reflects long-term smoke exposure could not be confirmed in newborns whose mothers had quit smoking during the latter half of pregnancy. Determining Sum(tot) enables the intensity of continuous smoking during pregnancy to be estimated in all meconium samples passed by a newborn.

Corticotropin-releasing factor inhibition of sheep fetal colonic contractility: mechanisms to prevent meconium passage in utero.

OBJECTIVE: In humans, fetal in utero meconium (MEC) passage rarely occurs before term gestation. We hypothesized the existence of inhibitory mechanism(s) preventing colonic motility and MEC passage prior to term. STUDY DESIGN: Longitudinal smooth muscle strips prepared from distal colon of preterm ovine fetuses (130-132 d; term = 148-152 d) were examined for their contractile responses to muscarinic receptor agonist (bethanechol) and both nonspecific (atropine) and receptor subtype specific antagonists (M1: pirenzepine dihydrochloride, M2 methoctramine, M3: 4-diphenylacetoxy-N-methlpiperidine methiodide [4-DAMP] and M4: tropicamide) in an in vitro organ bath system. Effects of corticotrophin releasing factor (CRF) and Urocortin I (URO-I), known modulators of colonic motility and smooth muscle contractility, were studied on bethanechol-induced contractility. Immunohistochemical analysis was performed to confirm the expression of CRF and URO-I, and muscarinic and CRF R2 receptors in distal colon. RESULTS: Bethanechol induced smooth muscle contractions via muscarinic receptor subtype M3. CRF and URO-I elicited a significant inhibition of bethanechol induced contraction. Immunohistochemical analysis verified the expression of muscarinic receptor subtype M3, CRF, URO-I and CRF-receptor-R2 in distal colon. CONCLUSION: Inhibition of M3 dependent distal colonic motility by CRF system may prevent the passage of MEC in the preterm ovine fetus.

Dose minimization study of oxytocin in early labor in sows: uterine activity and fetal outcome.

Two hundred sows were randomly assigned to intramuscularly receive 0.9% NaCl (group 1) or oxytocin 0.083, 0.11 or 0.17 IU/kg (groups 2, 3 and 4, respectively) immediately after the expulsion of the first piglet. The overall duration of labor was decreased in a dose-dependent relationship. Time interval between piglets was decreased approximately 5 min in groups 3 and 4 while sows in these groups exhibited approximately 10-20 contractions x 10 births more than controls (P<0.005). Duration and intensity of uterine contractions also showed a positive dose-response relationship. As an indicative of fetal distress, approximately 2.5 times more meconium-stained piglets were born to sows receiving the higher doses of oxytocin, but in the lowest dose significantly decreased. Oxytocin 0.083 IU/kg significant decreased the mortality rate of piglets [OR 0.49 (95%CI, 0.26-0.92)]. In conclusion, we recommend the intramuscular administration of the lowest possible dose of oxytocin, which still decreases the duration of labor in sows.

Marijuana impairs growth in mid-gestation fetuses.

Marijuana (Cannabis sativa) is the most commonly used illicit drug by pregnant women, but information is limited about the effects of prenatal cannabis exposure on fetal development. The present study evaluated the influence of early maternal marijuana use on fetal growth. Women electing voluntary saline-induced abortions were recruited at a mid-gestational stage of pregnancy (weeks 17-22), and detailed drug use and medical histories were obtained. Toxicological assays (maternal urine and fetal meconium) were used in conjunction with the maternal report to assign groups. Subjects with documented cocaine and opiate use were excluded. Main developmental outcome variables were fetal weight, foot length, body length, and head circumference; ponderal index was also examined. Analyses were adjusted for maternal alcohol and cigarette use. Marijuana (n=44)- and nonmarijuana (n=95)-exposed fetuses had similar rates of growth with increased age. However, there was a 0.08-cm (95% CI -0.15 to -0.01) and 14.53-g (95% CI -28.21 to 0.86) significant reduction of foot length and body weight, respectively, for marijuana-exposed fetuses. Moreover, fetal foot length development was negatively correlated with the amount and frequency of marijuana use reported by the mothers. These findings provide evidence of a negative impact of prenatal marijuana exposure on the mid-gestational fetal growth even when adjusting for maternal use of other substances well known to impair fetal development.

Is induction of fetal diuresis with intraamniotic furosemide effective for the removal of intestinal waste products from amniotic fluid?

AIM: In gastroschisis, contact with amniotic fluid (AF) causes intestinal damage. Intraamniotic meconium has been shown to be responsible for the intestinal damage, and intestinal damage has been shown to correlate with intraamniotic meconium concentrations. Intraamniotic meconium below a threshold level does not cause intestinal damage. Intraamniotic meconium concentrations can be lowered by AF exchange. Can induction of foetal diuresis by an intraamniotic injection of furosemide be used as an alternative method for the same purpose? METHOD: Pregnant rabbits on the 23rd - 25th gestational days (normal gestation time: 31 - 33 days) were divided into two groups, the control group and the furosemide group. Initial AF samples were taken, then either 5 mg/kg furosemide or a placebo was injected into the amniotic cavity. Final AF samples were obtained 6 hours later. AF urea nitrogen, creatinine, amylase, alkaline phosphatase and bilirubin levels were determined. RESULTS: There was no significant difference between the initial and final levels of AF urea nitrogen, creatinine, bilirubin, amylase, and alkaline phosphatase in the control group, while the final AF urea nitrogen and creatinine levels of the furosemide group were not significantly different from the initial levels (p > 0.05). Final AF bilirubin, amylase and alkaline phosphatase levels of the furosemide group were significantly decreased compared with initial levels (p < 0.01). CONCLUSION: Induction of foetal diuresis with intraamniotic furosemide is effective for the removal of intestinal waste products from amniotic fluid.

Effect of oxytocin treatment in sows on umbilical cord morphology, meconium staining, and neonatal mortality of piglets.

OBJECTIVE: To evaluate the effect of 2 oxytocin products administered to sows at the onset of fetal expulsion on the integrity of umbilical cords, meconium staining, and piglet mortality. ANIMALS: 2099 neonatal pigs. PROCEDURE: 180 parturient sows were randomly assigned to 3 stratified groups of 60 sows each. Two groups of sows were injected IM at the onset of fetal expulsion with 1 of 2 oxytocin commercial products (20, 40, or 50 U for sows weighing 120 to 150 kg, 151 to 250 kg, or > or = 251 kg, respectively). Control sows were treated IM with saline (0.9% NaCI) solution. Farrowing time, expulsion intervals, and numbers of stillborn and liveborn piglets were recorded for each sow. Piglets were evaluated for inspiratory effort, heart rates, and degree of meconium staining of skin (nonstained, and moderately or severely stained). Umbilical cords were classified as normal in appearance, edematous, congested, hemorrhagic, or ruptured. RESULTS: Oxytocin-treated sows had a significant decrease in farrowing time and expulsion intervals and also had a significantly higher number of stillborn piglets per litter, compared with control sows. The number of piglets per litter with ruptured and hemorrhagic umbilical cords was significantly greater in oxytocin-treated sows, compared with control sows. In near-death stillborn piglets, oxytocin treatment significantly decreased inspiratory efforts at birth and increased the rate and severity of meconium staining, compared with saline treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Oxytocin given to sows at the onset of fetal expulsion significantly increases the rate of fetal distress, anoxia, and intrapartum death in piglets.

Dextran reduces surfactant inhibition by meconium.

We have previously shown that an addition of dextran to surfactant increases resistance to inactivation by albumin. The present study was designed to investigate whether dextran has a protective effect against inactivation of surfactant by meconium. The dynamic surface properties of various mixtures of modified natural surfactant (Curosurf), meconium and dextran were evaluated with the pulsating bubble technique. In the absence of meconium, an addition of dextran at 10 mg ml(-1) significantly shortened the surface adsorption time of Curosurf suspended in normal saline at a concentration of 5 mg ml(-1) from 1.6+/-1.3 (mean +/- SD) sec to 0.4+/-0.4 sec (p < 0.05). Meconium at 5 mg ml(-1) increased the mean minimum surface tension (gammamin) after 3 min of pulsation from 2.1 mN m(-1) to 24 mN m(-1) (p < 0.05). An addition of dextran at 5 and 10 mg ml(-1) to the meconium-surfactant mixture significantly reduced the gammamin to 6.4+/-4.5 mN m(-1) and 2.6+/-5.6 mN m(-1), respectively (p < 0.05 vs dextran 0 mg ml(-1)). Meconium also increased the maximum surface tension (gammamax) of Curosurf from about 33 mN m(-1) to 53 mN m(-1). An addition of dextran at 5 and 10 mg ml(-1) to the meconium-surfactant mixture reduced the gammamax to 41 and 39 mN m(-1), respectively (p < 0.05 vs dextran 0 mg ml(-1)). There were significant negative correlations between dextran concentration and both gammamin and gammamax. We conclude that dextran reduces surfactant inhibition by meconium in a dose-dependent manner.