Search

Using the pharmacodynamic model without plasma concentrations described by Bragg et al, an individual approach resulted in highly variable parameters for rocuronium. Using a population approach of the model, the time course of the effect of an IV bolus dose of 400, 600, and 800 microg/kg of rocuronium was studied. Response was measured by accelerometry (TOF-Guard) in 45 low-risk surgical children, ages 2 to 14 years, who were receiving general anesthesia with isoflurane. Using a Bayesian approach and the software P-PHARM, response (the first twitch of the TOF) was modeled. The apparent rate constant of elimination, the rate constant for equilibrium between plasma and the effect compartment, the sigmoidicity factor of the relationship between drug concentration in the effect compartment and the effect, and the infusion rate that produces 50% of the effect at steady state were obtained. Population and individual post hoc parameters were similar among groups and variability was reduced. [ABSTRACT FROM AUTHOR]

Background: Nausea and of pregnancy (NVP) affects up to 80% of pregnant women. In many cases NVP causes changes in family, social, or occupational functioning. Several studies have linked NVP with depression; however, whether depression preceded or resulted from NVP, has not been established. Objective: To examine whether pregnant women, diagnosed with depression pre-conceptionally, treated with an antidepressant, reported a higher incidence of NVP when compared with pregnant women without depression. Method: In this pilot study, two groups of pregnant women who called the Motherisk Program in Toronto, Canada, were compared. Group 1 was comprised of 179 pregnant women who reported taking an antidepressant for the treatment of depression prior to pregnancy and in the first trimester. Group 2 was comprised of 179 pregnant women with no history of depression. The incidence of NVP in both groups was recorded and compared. Results: In the depressed group 109/179 (61%) women reported suffering from NVP vs. 121/179 (68%) in the non-depressed group (P=0.1). The logistic regression analysis did not identify any independent variable as significantly explaining NVP. Conclusion: Depression and treatment with anti-depressants prior to and in early pregnancy, does not appear to affect the incidence of NVP. [ABSTRACT FROM AUTHOR]

It is accepted that blood phosphatidylethanol (PEth) concentrations are reliable biomarkers of ethanol (alcohol) exposure. We therefore conducted a preliminary study to test the hypothesis that elevated blood PEth concentrations can help to identifying women with prenatal alcohol exposure who are at higher risk of adverse pregnancy outcomes. The study included 35 first-trimester pregnant women who self-reported alcohol ingestion and had PEth blood concentration ⩾4 nM at recruitment. As a control group, 233 first-trimester pregnant women who self-reported as being either abstainers or light alcohol drinkers and had blood PEth concentrations <4 nM, were also included. All participants were followed up until completion of their pregnancies. Women with prenatal alcohol exposure and PEth concentrations ⩾4 nM had a risk ratio of spontaneous abortions of 3.21 (95%CI 0.93-11.06; P=0.074). Because of the potential implications in the prenatal care of women reporting risky alcohol exposure, the preliminary results from the present study indicate the need for testing the hypothesis in a more definitive approach., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Since the urinary concentration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a reliable biomarker of exposure to tobacco smoke, we developed a relatively simple high-throughput chromatographic method to quantify total urinary NNAL concentrations in the general population., Methods: The high-throughput analytical method was developed using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) to identify and quantify total urinary NNAL concentrations in 10 non-smokers and 15 otherwise healthy smokers., Results: Loss of nitric oxide at m/z 30 was found to be the predominant mass transitioned, and therefore was used as the SIM transition to quantify both NNAL and NNAL-methyl-d3 in urine. The analytical method did not require sample derivatization. Standard curves for total NNAL concentrations were linear between 20 and 1500 pg/mL, with coefficients of determination >0.95. Precision and accuracy ranged from 2.2% to 8.6% (CV) and from -5.6% to 10.9% (percent error), respectively. The lowest limit of quantification was 6.7 pg/mL, and 2.0 pg/mL the lowest limit of detection (LLOD). Total urinary NNAL concentrations in non-smoker subjects were

Presence of individual fatty acid ethyl esters (FAEEs) in meconium is considered to be a reliable biomarker of prenatal alcohol exposure, and their concentration has been found to be linearly associated with poor postnatal development, supporting the widely extended idea that ethanol is a non-threshold teratogen. However, a growing number of epidemiological studies have consistently found a lack of adverse short- and long-term fetal outcomes at low exposure levels. We therefore aimed to investigate the relationship between the concentration of individual FAEEs and prenatal alcohol exposure in meconium samples collected within the first 6 to 12?h after birth from 182 babies born to abstainer mothers and from 54 babies born to women who self-reported either light or moderate alcohol ingestion in the second or third trimester of pregnancy. In most cases, the individual FAEE concentrations were negligible and not significantly different (P >0.05) between exposed and control babies. The concentrations appeared to increase linearly with the dose only in the few babies born to mothers who reported >3 drinks/week. These results provide evidence that the correlation between prenatal alcohol exposure and individual FAEE concentrations in meconium is non-linear shape, with a threshold probably at 3 drinks/week.

The present study was designed to investigate if exposure to dried ginger during pregnancy would increase the risk of adverse fetal and neonatal outcomes. Participants consisted of 159 singleton pregnant women who received dried ginger as a herbal medication. We also included a control group of 306 pregnant women who had not been exposed to any herbal medication or any known teratogen. No increased risk of major malformations was detected in exposed women (OR = 4.9; 95% CI 0.9-25.5; p = 0.051). The incidence of stillbirths in the exposed group was marginally higher than in the controls (OR = 7.8; 95% CI 0.9-70.3; p = 0.05). The risk was more evident when the exposed group was compared with the general population in the Republic of Korea (OR = 7.9; 95% CI 2.9-21.4; p < 0.0001). Other fetal and neonatal study outcomes investigated in the exposed group were similar (p > 0.05) to the controls. In conclusion, dried ginger does not appear to be a major teratogen. However, due to the limitations of the study, e.g. the large variability in the dose of dried ginger in the exposed group, as well as the concomitant exposure to other herbal medications, the increased incidence of stillbirths requires confirmation in larger cohort studies.

Information on the safety of first-trimester exposure to diagnostic magnetic resonance imaging (MRI) remains scarce. We are reporting a case series of 15 consecutive pregnant women who underwent an MRI scan with a 1.5-Tesla scanner of either the head (n = 5), cervical spine (n = 4), lumbar spine (n = 4), pelvis (n = 1) or knee (n = 1) in their first trimester of pregnancy (mean gestational age at exposure: 3.8 weeks). Patients were prospectively followed up until the completion of their pregnancy. Two cases received gadolinium as a contrast agent. There were 15 babies born alive. Of them, one baby was born with the left kidney not visualised by ultrasound examination, and another one with an overlapping toe in the right foot. None of these abnormalities were considered by the authors related to the MRI exposure. In conclusion, our study provides support to published preliminary evidence regarding the safety of MRI in the first-trimester pregnant women.

Objectives: Little is known on how the dose and timing of exposure co-influence the cumulative concentration of fatty acid ethyl esters (FAEEs) in meconium. The objective of the study was to assess the cumulative concentration of FAEEs in meconium as a biomarker of light, moderate, or heavy prenatal alcohol exposure occurring at either first, second, or third trimesters of pregnancy., Methods: History of prenatal alcohol exposure was obtained in the 34th week of gestation from 294 pregnant women. Meconium was collected from their babies within the first 6 to 12 h after birth and examined for the presence of nine FAEEs., Results: No significant differences were identified between the cumulative levels of FAEEs in the meconium from the babies born to abstainers and those born to mothers with history of light-to-moderate prenatal alcohol exposure during their pregnancy., Conclusions: Light-to-moderate prenatal alcohol exposure cannot be reliably predicted by the cumulative FAEE concentrations in meconium of exposed babies. A cumulative FAEE level of >10 nmol/g would be required to consider that prenatal alcohol exposure during the second to third trimesters occurred at risky levels in the absence of reliable maternal history of ethanol exposure., (© 2014 John Wiley & Sons, Ltd.)

Although there is accumulating evidence regarding the additional protective effect of folic acid against adverse pregnancy outcomes other than neural tube defects, these effects have not been elucidated in detail. We evaluated whether folic acid supplementation is associated with favorable maternal and fetal outcomes. This was a secondary analysis of 215 pregnant women who were enrolled in our prior study. With additional data from telephone interviews regarding prenatal folic acid supplementation, existing demographic, maternal and fetal data were statistically analyzed. The concentration of folic acid in maternal blood was significantly higher following folic acid supplementation (24.6 ng/mL vs.11.8 ng/mL). In contrast, homocysteine level in maternal blood decreased with folic acid supplementation (5.5 µmol/mL vs. 6.8 µmol/mL). The rates of both preeclampsia (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.09-0.76) and small for gestational age (SGA; 9.2% vs. 20.0%; OR, 0.42; 95% CI, 0.18-0.99) were lower in the folic acid supplementation group than those in the control group. Other pregnancy outcomes had no association with folic acid supplementation. The findings indicate that folic acid supplementation may help to prevent preeclampsia and SGA. Further studies are warranted to elucidate the favorable effects of folic acid supplementation on pregnancy outcomes.

Objective: Phosphatidylethanol (PEth) is formed endogenously by the direct action of ethanol, and has a half-life long enough to make it a reliable biomarker of alcohol exposure in early pregnancy. In this study, we aimed to characterize PEth blood concentrations to differentiate different levels of alcohol exposure in pregnant women., Methods: The study consisted of 305 consecutive pregnant women who had been referred to our hospital for antenatal care. Of them, 117 self-reported alcohol ingestion in the first trimester of pregnancy and 188 were abstainers. Total PEth concentration in whole blood was quantified by liquid chromatography-mass spectrometry (LC-MS/MS). Alcohol ingestion was classified according to the United States National Institute on Alcohol Abuse and Alcoholism into light drinkers: ≤ 3 drinks/week, moderate drinkers: 3-7 drinks/week, and heavier drinkers: > 7 drinks/week (a standard drink = 14 g of ethanol)., Results: Participants had quantifiable PEth blood levels 3-4 weeks after the last drink. There were 4.8% abstainers who had positive PEth concentrations; all of them reported a positive history of alcohol consumption before conception. PEth blood concentrations were significantly correlated to drinks per occasion (r = 0.44; P < 0.001) and days drinking per week (r = 0.34; P < 0.001). However, almost 74% of participants with ≤ 3 drinks/week of alcohol, and 46% with 3-7 drinks/week, had PEth blood concentrations below the lower limit of quantification (LLOQ). The area under the curve (AUC) generated by a receiver operation characteristic curve (ROC) analysis increased as the cutoff value of PEth blood concentration increased. However, the cutoff values were below or close to the LLOQ., Conclusions: Our study presents a formal characterization of PEth blood concentrations for screening alcohol ingestion in first-trimester pregnant women. However, caution is recommended for overrepresenting either negative or positive results.

Background/aim: Little is known about exposures to low radiation doses in the first trimester of pregnancy and deterministic adverse effects in the offspring, and risks are extrapolated from catastrophic events or from exposures to radiotherapy. The study aimed to assess the foetal and neonatal outcomes of pregnant women exposed to radiodiagnostic procedures with abdominal or lumbar irradiation., Methods: In a prospective cohort design, we studied the foetal and neonatal outcomes in 115 singleton pregnant women who required abdominal or lumbar radiodiagnostic procedures without the administration of radionucleotides, and in 527 age-matched (± 2 years) control pregnant women., Results: In the exposed group, lumbar spine radiography (33.9%), plain abdominal radiography (16.5%) and upper gastrointestinal tract radiography with abdominal irradiation (15.7%) were the most common radiodiagnostic procedures. Major congenital malformations were identified in two (1.9%) babies born in the exposed group and in two (0.4%) babies born in the control group (odds ratio = 4.7; 95% confidence interval 0.7-33.6; P = 0.15). The rest of the foetal and neonatal outcomes was similar in the two groups except by a marginally higher rate of admissions to the neonatal intensive care unit among babies born to exposed women (odds ratio = 2.9; 95% confidence interval 1.0-9.4; P = 0.06)., Conclusion: Our results indicate that X-ray and computed tomography scan exposure involving abdominal irradiation without the administration of radionucleotides is not associated with adverse foetal and neonatal deterministic outcomes. Efforts are required to reduce the use of radiodiagnostic procedures for general check-ups in childbearing age women., (© 2012 The Authors; Internal Medicine Journal © 2012 Royal Australasian College of Physicians.)

The safety of domperidone in pregnancy remains unknown. Therefore, the study aimed to prospectively evaluate the fetal outcomes of women who were taking domperidone during pregnancy. In a prospective cohort study design, 120 1st- trimester pregnant women who were taking domperidone for controlling gastrointestinal tract symptoms and 212 age-matched pregnant women not exposed to any potential teratogenic agent, were followed-up until delivery. In the case group, domperidone was indicated for control of functional gastrointestinal disorders in 59.2%, the maximum dose was 30 mg/day and exposure occurred between 2(+4) and 20 weeks' gestation. Fetal outcomes including gestational age at birth, birth weight and length, head circumference at birth, and 1- and 5-min Apgar score were similar in the two study groups. There were three babies born with malformations in each group (OR = 0.6; 95% CI 0.1, 2.8). In conclusion, domperidone does not appear to be a major human teratogen. However, our findings require further confirmation in larger studies.

Maternal intake of licorice from dietary sources has been associated with adverse maternal and fetal outcomes. We prospectively studied the outcome of 185 singleton pregnancies who took over-the-counter or naturopathic formulations containing licorice during their pregnancy, and 370 age-matched singleton pregnant controls that were not exposed to any potential teratogen. The indication in 56.8% of the women taking licorice was for cough and cold control, with the maximum dose of 2104 mg/day and exposure occurring between the 4th day and 25th week of gestation. The rate of stillbirths was marginally higher among women who took licorice than those who did not (OR = 7.9; 95% CI 0.9-71.5; p = 0.048), and significantly higher when compared to the general population in the Republic of Korea (OR = 13.3; 95% CI 4.9-35.8; p < 0.001). Other fetal outcomes assessed in the study were similar between the two study groups, e.g., the OR of major malformations was 3.9 (95% CI 0.4-43.5; p = 0.27). In conclusion, the present study suggests that licorice is not a major teratogen. However, whether licorice may increase the risk of stillbirths requires careful consideration in further studies with a larger sample size., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: We aimed to study the pregnancy outcomes of women exposed to isotretinoin and to identify the factors influencing their decision to request an abortion., Methods: The study prospectively identified 79 women who had been treated for acne with isotretinoin during the periconceptional period, and who were followed up until completion of their pregnancy. Characteristics of exposure and doses were self-reported by participants., Results: Of the 56 participants who decided to continue their pregnancy, there were 11 spontaneous abortions and 44 women who delivered healthy full-term babies of which 19 had been exposed to isotretinoin <1 month before conception or during pregnancy. In a nominal logistic regression analysis including 68 patients who provided adequate information for analysis, exposure to isotretinoin >2 weeks post-conception and pregnancy termination recommended by the first-contact physician were found to be significantly associated with patients' decision to undergo elective abortion: adjusted OR = 9.87 (95% CI 1.18-82.34) and 12.51 (95% CI 2.36-66.29), respectively., Conclusions: Our study reports an elevated rate of babies born without evidence of gross malformation or neurofunctional abnormality even tough exposure occurred during the teratogenic risk period. However, caution is recommended since a substantial risk of congenital malformations has been reported with low doses of isotretinoin and at exposures limited to early pregnancy. We also found that primary-care physicians may influence patients' decision to request pregnancy termination independently of their timing of exposure to isotretinoin.

Objective: A reliable biomarker of low alcohol exposure during pregnancy is needed to clarify the controversy on the teratogenicity of low-to-moderate alcohol levels., Methods: Blood samples were obtained from 13 pregnant women who self-reported alcohol ingestion between 2.5 and 20 drinks/week, and from 26 controls. Total lipids were extracted, and phosphatidylethanol (PEth) species 16:0/16:0, 16:0/18:1, and 16:0/18:1 were separated by high-performance liquid chromatography (HPLC) on a reverse-phase phenyl column. These PEth species were quantified by MS/MS using phosphatidylpropanol as internal standard, with electrospray ionization and MRM., Results: PEth species were not detected in women who abstained from alcohol ingestion during pregnancy, whereas PEth-16:0/18:1 was > 5 nmol/L in those with positive alcohol ingestion. PEth species were detected for up to 4 weeks after cessation of exposure., Conclusions: PEth-16:0/18:1 was detected in pregnant women at 4-6 weeks after their last low-to-moderate alcohol ingestion, and therefore appears to be a reliable biomarker of prenatal alcohol exposure to study the teratogenicity of alcohol at these exposure levels.

Objective: This study aimed to assess the pregnancy outcomes of women who reported social intake of low or very low alcohol levels during pregnancy., Methods: Obstetric and foetal outcomes were assessed in a prospective cohort of 1667 pregnant women who reported low or very low alcohol consumption during pregnancy (cases) and 1840 alcohol-abstainer women (controls)., Results: Among cases, alcohol consumption occurred during the first 4.4 (median) weeks of pregnancy, with a median ingestion of 1.0 (0.01-6.0) drinks/week, equivalent to 7.6 (0.09-47.5) g/week. Cigarette smoking was reported approximately four times more often in the exposed group than in the controls (p < 0.001). Pregnancy outcomes were similar between groups. There were 37 (2.4%) babies born with malformations in the exposed group and 41 (2.4%) in the control group (p = 0.9)., Conclusions: Low-to-very low levels of alcohol ingestion during pregnancy do not appear to be associated with adverse maternal or foetal outcomes.

Objective. To evaluate the ethics of performing research in the field of maternal-fetal medicine involving women undergoing pregnancy termination. Methods. We identified published pharmacological studies performed during elective pregnancy termination. In addition, a questionnaire was administered to investigate whether this research would be acceptable to professionals performing research in the field of maternal-fetal pharmacology. Results. The majority of participants believe that this form of research is necessary to furthering our understanding of drug use in pregnancy. Twenty studies were identified in women undergoing a pregnancy termination where exogenous drug was administered and drug measurement conducted during an abortion. The majority of studies were completed by international groups and not in North America or Western Europe. Conclusions. While a majority of respondents to the survey felt that, although research in women undergoing a pregnancy termination is ethically acceptable, 40% stated that it is not likely to be approved by institutional review boards of most North American medical institutions.

Despite barium being used as a contrast media for decades, the specific assessment of its safety in pregnant women is scarce. We are reporting the favourable pregnancy outcome in women who were inadvertently exposed to barium swallow and associated ionising radiation, early in pregnancy. A control group of age- and gravidity-matched unexposed pregnant women was also included. There were 32 live-born babies in the exposed group and 94 in the control group. Women had undergone diagnostic upper gastrointestinal tract (UGT) fluoroscopic examination at 3.3 ± 1.5 weeks' gestation. Estimated maternal radiation dose secondary to barium swallow varied widely, the maximum dose was estimated to be 2.45 mSv. Similar pregnancy outcomes were observed between the groups. The number of babies born with major malformations was not significantly different (p = 1.0) between cases and controls: one (3.1%) vs three (3.2%), respectively. In conclusion, our small prospective cohort study of women suggests no association between inadvertent exposure to ionising radiation and barium sulphate during fluoroscopic barium swallow and adverse fetal outcomes.

Background: Ondansetron is increasingly used to prevent emesis in children with acute gastroenteritis; however, the optimal dose is unknown., Objective: To determine if higher doses of oral ondansetron are associated with greater efficacy or side effects., Methods: We analyzed data from a prospective clinical trial performed between January 2004 and April 2005. Data were collected on 105 children with dehydration due to gastroenteritis who received an ondansetron oral disintegrating formulation. The following outcomes of efficacy were analyzed: number of vomiting episodes, volume of oral rehydration fluids consumed, percent weight gain, and the proportions of children who had ongoing vomiting, received intravenous rehydration, and were hospitalized. In addition, the number of episodes of diarrhea was evaluated to measure whether there were dose-dependent side effects., Results: Participants were aged 0.5-8.2 years and the dose ranged between 0.13 and 0.26 mg/kg. There was no significant association between the dose of ondansetron and the outcomes of number of vomiting episodes, volume of fluids consumed, increase in bodyweight, or number of diarrhea episodes/hour. The mean dose of ondansetron (mg/kg) administered was not different amongst those who did and did not have ongoing vomiting, undergo hospitalization, and receive intravenous rehydration., Conclusions: Within the dose range of 0.13-0.26 mg/kg, higher doses of ondansetron were not superior to lower doses, nor were they associated with increased side effects. Thus, ondansetron in this dose range was shown to result in a similar reduction in emesis in children with acute gastroenteritis.

This paper reports the development and validation of an improved assay for quantitation of fatty acid ethyl esters (FAEEs) in human meconium using liquid chromatography/tandem mass spectrometry (LC-MS/MS). FAAEs (ethyl laurate, ethyl myristate, ethyl palmitate, ethyl palmitoleate, ethyl stearate, ethyl oleate, ethyl linoleate, ethyl linolenate, and ethyl arachidonate) and the internal standard (I.S.), ethyl heptadecanoate, were separated by reverse phase HPLC and quantified by MS/MS using electrospray ionization (ESI) and multiple reaction monitoring (MRM) in the positive ionization mode. The absolute recovery of FAEEs varied from 55+/-10% for 0.33 nmol/g (100 ng/g) of ethyl linoleate up to 86+/-8% for 1.55 nmol/g (500 ng/g) of ethyl miristate. The LODs and LOQs varied from 0.01 to 0.08 nmol/g and from 0.02 to 0.27 nmol/g, respectively. The assay has been successfully applied to examine the FAEE levels in 81 meconium samples from babies born to mothers reporting alcohol consumption, to varying degrees, during pregnancy., (Copyright 2010 Elsevier B.V. All rights reserved.)

No information is currently available on the safety of methylephedrine, a component of various cold medications available in South Korea. With previous approval by an Institutional Review Board, 349 women inadvertently exposed to methylephedrine during the 1st trimester of pregnancy and an age- and gravidity-matched control group, were enrolled in a prospective cohort study. Study outcomes, for example gestational age at birth, birth weight and major and minor malformations were evaluated in 282 cases and 280 controls. Exposure to methylephedrine was at a gestational age of 4.0 weeks (median), at doses ranging from 52.5 to 1,575 mg/day, for a median duration of 3 (range: 1-30) days. No differences were observed between cases and controls in any of the pregnancy outcomes studied. There were 4/265 (1.5%) babies born with major malformations in the case group and 4/260 (1.5%) in the control group. In conclusion, inadvertent exposure to methylephedrine as a component of over-the counter oral cold remedies in early pregnancy was not associated with an increased rate of adverse pregnancy outcomes. Co-exposure with acetaminophen, cigarette smoking or alcohol did not appear to modify the outcomes.

X-ray exposure, especially if directed to the abdominal region, is of major concern for pregnant women and their physicians. In this study, favourable long-term outcomes are reported in a series of babies born to women inadvertently exposed to barium enema, and associated ionising radiation, early in pregnancy. Six singleton babies were vaginally delivered without any evidence of gross malformations. There was one voluntary abortion. Follow-up on five of the babies was performed over the course of at least 4 years. All the children were deemed healthy and had developed milestones according to their age. Our findings support larger studies suggesting barium enema is not a teratogenic agent. Collectively, this research can be used to counsel women undergoing radiological procedures early in pregnancy.

Sixty hybrid Yorkshire-Landrace penned sows, 30 with eutocic farrowing and 30 experiencing a dystocic parturition, were studied to evaluate the obstetric and neonatal outcomes to low doses of oxytocin administered at advanced stages of parturition. Animals in each group were randomly subdivided into 2 subgroups: 15 eutocic and 15 dystocic sows received oxytocin 0.083 IU/kg (equivalent to 1 IU/12 kg body weight), administered intramuscularly after the delivery of the 5th piglet; the other 15 eutocic and 15 dystocic sows received saline solution intramuscularly at the same time. Oxytocin decreased the number of intrapartum deaths by approximately 50% (P = 0.002). No piglet was born dead from the saline- and oxytocin-treated eutocic sows. The highest viability score was observed among piglets born to eutocic sows treated with oxytocin. In summary, this dose schedule would help to decrease the number of stillbirths in both eutocic and dystocic farrowing sows.

We assessed the pregnancy outcome of nine women inadvertently transfused with acitretin-contaminated blood products in South Korea. A total of 18 women matched to cases by age, gravidity, and singleton- or twin-pregnancy, and who were transfused with blood products not contaminated with acitretin, was also recruited. There were nine babies born in the case group. No differences (p > 0.05) were observed between cases and controls in the gestational age at delivery (38.3 +/- 1.6 weeks vs 37.8 +/- 2.2 weeks), birth weight (3,146 +/- 874 g vs 3,106 +/- 568 g), rate of pre-term deliveries (22.2% vs 11.1%) and rate of low birth weight (<2,500 g) (33.3% vs 16.7%). There was no case of malformation or neurological abnormalities born in either group. In conclusion, inadvertent exposure to acitretin-contaminated blood products was not associated with adverse pregnancy outcomes, probably because of the removal of acitretin and etretinate during the manufacturing process of blood products.

Nalbuphine and tramadol are potent analgesic drugs. Our aim was to preliminarily assess and compare the efficacy and safety of nalbuphine and tramadol for postoperative analgesia in children. In a double-blind design, 24 ASA 1-3 children aged 1 to 10 years undergoing a scheduled surgical procedure were randomly allocated to receive either an intravenous bolus dose of nalbuphine 100 microg/kg immediately before the end of surgery followed by an infusion of 0.2 microg/kg/min for 72 hrs., or an intravenous bolus dose of tramadol 1000 microg/kg followed by an infusion of 2.0 microg/kg/min for 72 hrs. Postoperative pain control and drug-related adverse events were recorded. Three children who received nalbuphine required an extra bolus dose within the 12 hrs. of post-surgery versus one child in the tramadol group. A similar number of patients in both groups required an increment in the infusion rate within the 72 post-surgery hours. Sedation was observed in 2 children in the nalbuphine group and in 1 child in the tramadol group. Four children presented vomiting with tramadol and two with nalbuphine. Cardiovascular parameters remained within the normal ranges in both groups. In conclusion, the bolus/infusion regimen of tramadol evaluated in this study appears to have better postoperative analgesic efficacy than the bolus/infusion regimen of nalbuphine. These preliminary results require further confirmation by studies with a sample size enough to clearly identify differences in their efficacy as well as in the rate of adverse events secondary to the administration of each of them.

No information is currently available on the safety of the aminoglycoside ribostamycin in pregnancy. We aimed to study the pregnancy outcome of women inadvertently exposed to ribostamycin during the first trimester of pregnancy. In a prospective cohort study, 102 women inadvertently exposed to ribostamycin during the first trimester of pregnancy and an age- and gravidity-matched control group, were enrolled. Study outcomes were gestational age at birth, major and minor malformations, and birth weight. Fetal outcomes were evaluated in 85 women inadvertently exposed to ribostamycin during the first-trimester of pregnancy and in 170 control subjects. Newborns were clinically examined at birth by a neonatologist and by imaging studies if any suspicious abnormalities were noted. There were 4/85 (4.9%) babies born with major malformations in the exposed group and 3/170 (1.8%) in the control group (P=0.7). Gestational age at delivery, rate of minor anomalies, rate of preterm births, and birth weight were not different between groups. In conclusion, similar to what is reported for other aminoglycoside, exposure to ribostamycin during the first-trimester of pregnancy does not appear to increase the risk of adverse fetal outcomes.

Objective: We aimed to investigate the factors associated with a positive intake of folic acid (FA) during the periconceptional period among Korean women., Design: In a cross-sectional study of demographic, obstetric and socio-economic data, history of periconceptional intake of FA and awareness of the benefits of FA supplementation in pregnancy were obtained and analysed using the chi2 test, followed by multiple logistic regression analysis., Setting: The Maternity School, Cheil General Hospital and Women's Healthcare Center, Seoul, South Korea, between October 2005 and March 2006., Subjects: In total 1313 pregnant women participating in a two-day training course available every month., Results: After excluding subjects with incomplete or inconsistent data, there were 1277 women included in the analysis. Participants were aged 29.4 (sd 2.9) years and had a mean gestational age of 27.9 (sd 7.1) weeks. Only 131 (10.3 %) women took FA during the periconceptional period. According to multiple logistic regression analyses, the adjusted OR for FA supplementation was 1.79 (95 % CI 1.10, 2.91) in women who had previous spontaneous abortions, 4.10 (95 % CI 2.43, 6.78) in women who planned their pregnancy and 6.63 (95 % CI 2.08, 21.12) in those who were aware of the protective effects of FA., Conclusions: Periconceptional intake of FA was more likely among Korean women with a history of previous spontaneous abortion, who planned their pregnancy or who were aware of the protective effects of FA during pregnancy. However, the proportion of women who took FA in the periconceptional period was low.

Multiple standard software packages for population pharmacokinetics (PK) modeling are currently available. These programs may significantly vary in the algorithms used for modeling plasma concentrations as a function of time course. We compared the population PK parameters obtained by using two standard software packages, p-pharm and saam ii, for analysis of a similar data set of serum samples of doxorubicin obtained from 11 infants and children with malignant diseases. Plasma drug concentrations were fitted to time by a two-compartment intra-vascular PK model by saam ii and p-pharm programs. The population parameters obtained from the analysis by the two software programs were substantially different. For example, Vd was almost five times larger when using saam ii compared with p-pharm (9.6 L/kg vs. 2.0 L/kg, respectively), whereas t((1/2)beta) was about 30 times larger in the latter (7.7 h vs. 206.9 h, respectively). When considering the results reported from a population PK analysis, validation of the results by different software should be considered, especially when extreme, unexpected values are obtained.

Piglets appear to be neurologically sensitive to intrapartum asphyxia. Our aim was to investigate the short-term neurophysiologic consequences of intrapartum asphyxia in piglets. We studied 10 piglets suffering intrapartum asphyxia and 10 control piglets. Glucose and blood gas levels, tympanic membrane temperature, and body weight were measured within the first 2 min after birth. Animals were followed up for a 5-day period. As surrogated markers of piglets' neurological function, a viability score and the time elapsed from birth to the first contact with the maternal udder were recorded. In the control group, temperature and blood pH levels at birth were significantly higher (p < or = .001), whereas calcium, lactate and PCO2 levels were statistically lower (p < or = .05) than in the piglets experiencing intrapartum asphyxia. Lower temperature and blood pH levels as well as higher blood PCO2 and lactate levels were observed in piglets with lower viability scores and in piglets with prolonged times until first udder contact. At the end of the study, asphyxiated piglets weighed on average 200 g less (p = .023) than control piglets. In conclusion, intrapartum asphyxia in spontaneously born piglets was associated with signs of acute neurological dysfunction and lower weight gain, supporting the hypothesis that they may be used as a naturalistic model for the study of asphyxia in newborns.

Different antimicrobial treatments have proved to be effective in patients with aspiration pneumonia. However, resistant bacterial strains are commonly observed in hospital settings challenging the empirical treatment of these patients. In this study, we aimed to compare the efficacy of cefepime/clindamycin and ceftriaxone/clindamycin for empiric therapy of poisoned patients with aspiration pneumonia. In an open, randomized, prospective design, 140 consecutive patients aged more than 13 years, with radiographic signs of infiltration in chest radiography and dullness on percussion or pulmonary rales or ronchi in combination with at least two of the following clinical criteria were considered as eligible: fever > or = 37 degrees C (axillary), or hypothermia < 35 degrees C (axillary) and leukocytosis (> 10 cells/mm3), or leukopenia (< 3,000 cells/mm3), a left-shift of > 10%, or purulent sputum or secretion from trachea or bronchi. Participants received intravenously either ceftriaxone 1 g q12 h and clindamycin 900 mg q8 h (group 1) or cefepime 1 g q12 h and clindamycin 900 mg q8 h (group 2). On day 5 of treatment, the number of improved/cured patients was not different between groups (OR 0.86; 95% CI 0.24 to 2.90) nor at 14 days of the study (OR 0.66; 95% CI 0.12 to 3.29). Six patients died in group 1 and 5 in group 2 (RR 0.83; 95% CI 0.28 to 2.46). In conclusion, efficacy of empiric treatment of poisoned patients with aspiration pneumonia with ceftriaxone/clindamycin was comparable to treatment with cefepime/clindamycin.

Several studies have reported an association between depression and folic acid deficiency. We investigated whether intake of prenatal multivitamins containing folic acid (MVandFA) was associated with decreased rates of depression among pregnant women. A questionnaire was given to 1,314 low-risk pregnant women. Of them, 1,277 (97.2%) women completed the questionnaire. The overall prevalence of depression was 8.1%. Of 652 participants who did not take MVandFA, 9.4% had depression, whereas 6.9% of 624 women who had MVandFA had depression (p = 0.11). In a multivariate logistic regression analysis, family history of depression (adjusted OR 3.7; 95% CI 1.9-7.3) and premenstrual syndrome (adjusted OR 3.0, 95% CI 1.8-4.8) were identified as risk factors for depression during pregnancy. In conclusion, intake of MVandFA was not associated with lower rates of depression during pregnancy whereas family history of depression and personal history of premenstrual syndrome were significant risk factors.

We present a 1.5-year old, 11 kg, female infant with a history of bronchial hyper-responsiveness who accidentally ingested half of a "Chinese chalk". A day later, the infant showed vomiting, cough, fever, drowsiness, and irritability and her clinical conditions progressively worsened. She was admitted to the emergency department with cough, respiratory distress, and hepatomegaly. It has been reported that the chalk may contain deltamethrin and cypermethrin. The patient was successfully treated with supportive therapy. This report identifies "Chinese chalk" as a potential source of accidental poisoning in children and should be considered as part of the differential diagnoses in the emergency rooms since poisoning with these compounds may be misdiagnosed as organophosphate poisoning due to the presentation of similar symptoms.

Sophrology, based on a combination of Western relaxation therapy and Eastern yoga and meditation might decrease maternal stress during labor. This study aimed to evaluate whether prenatal sophrologic childbirth preparation may decrease maternal and neonatal adverse response associated with delivery. In a nested case-control study, 69 nulliparous, singleton pregnant women who underwent an educational course of sophrologic childbirth preparation were compared to 69 nulliparous, singleton, age- and gestational age-matched pregnant women who did not receive any childbirth preparation. All babies were vaginally delivered. Groups were not different (P > 0.05) in the number of neonates born with meconium-stained amniotic fluid as well as in the number of babies with Apgar score < or = 7 at 1 and 5 minutes after birth. Duration of labor was not different between groups. The number of women requiring oxytocin and delivering babies with low pH blood levels tended to be lower in the group undergoing sophrologic childbirth preparation, i.e. 58.0% vs 72.5% (P = 0.07) and 1.4% vs 10.9% (P = 0.06), respectively. In conclusion, we were unable to confirm that prenatal sophrologic childbirth preparation has a definitive role in decreasing adverse maternal and fetal response to pain or in shortening labor. Prospective cohort studies with a larger sample size or randomized trials may help to clarify this gap.

Question: One of my patients is in the third trimester of her first pregnancy. She has recently experienced spotting during her bowel movements. She has hemorrhoids. What medications are safe?, Answer: The treatment is mainly symptomatic for most patients. Most forms of the condition can be treated by increasing fibre content in the diet, administering stool softeners, increasing liquid intake, and training in toilet habits. Although none of the topical antihemorrhoidal agents commonly used have been assessed for safety in pregnancy, it is unlikely that the constituent parts (anesthetic, corticosteroids, and anti-inflammatory agents) will harm the third-trimester infant. In most women, most symptoms of the condition will resolve spontaneously soon after giving birth.

We describe a 20-month-old girl with hypereosinophilia, hyper-immunoglobulin (Ig) E syndrome, and atopic dermatitis. Her peripheral eosinophil count and IgE plasma levels were 2.65 x 10(9)/L and 6702 IU/mL, respectively. Specific IgE levels for a variety of foods and inhalants were high and single-blind food challenges were positive for cow's milk, hen's egg, oat, wheat, and soy. When the patient received an extensively hydrolyzed milk formula, an exclusion diet, and 2 mg/kg of prednisone daily, the atopic dermatitis partially improved. Further improvement was observed with 1 mg/kg of azathioprine daily. Long-term clinical response was satisfactory. We suggest that food hypersensitivity should be ruled out in patients with hypereosinophilia, hyper-IgE syndrome, and atopic dermatitis. Azathioprine may be a good therapeutic alternative for treatment in such cases.

Objective: Our goal was to determine whether sildenafil increased fetal weight and favored fetal tolerance to induced asphyxia at birth in guinea pigs., Study Design: Twenty guinea pigs were randomly allocated to placebo (n = 10) or sildenafil 50 microg/kg (n = 5) or 500 microg/kg (n = 5), starting from day 35 of gestation to delivery. Fetuses were delivered by cesarean section. Fetal asphyxia was induced by clamping the umbilical cord at birth for 5 minutes., Results: Sildenafil protected the pups against induced asphyxia at birth in a dose-dependent manner (eg, partial pressure (tension) of carbon dioxide levels were 75.9 +/- 19.3, 66.9 +/- 18.8, and 54.8 +/- 13.0 in the control and low- and high-dose sildenafil groups, respectively). The high-dose sildenafil group of piglets gained 1.5 times more body weight., Conclusion: In guinea pigs, low doses of sildenafil administered from day 35 to the end of gestation favored fetal tolerability to induced intrapartum asphyxia. High doses of sildenafil increased fetal weight.

Background: The aim of the study was to report the maternal and fetal outcomes of women with respiratory illnesses who were treated with inhaled fluticasone during pregnancy., Material and Methods: We identified 12 cases treated with inhaled fluticasone during pregnancy out of women who received obstetric and teratogen-risk evaluation at the Korean Motherisk Program. A detailed medical and obstetric history was obtained and cases were followed-up until either spontaneous or voluntary pregnancy termination or delivery occurred., Results: None of the participants had any obstetric complication. However, in addition to fluticasone, most of the 12 cases were simultaneously exposed to a variety of medications. There were 3 abortions (one spontaneous and 2 requested by the patients arguing personal reasons). Live born babies without any evidence of major congenital malformations included 8 singleton babies and 2 twins. Of them, 3 babies were born prematurely., Conclusions: Our results are in agreement with previous large studies where no increased rate of adverse outcomes was reported with the use of inhaled corticosteroids during pregnancy.

Background: The aim of this study was to investigate the relationship between food hypersensitivity and atopic dermatitis (AD) in young children., Material and Methods: In a case-control design, 28 patients < 3 years old, with AD and 28 age-matched healthy children were included in the study. A detailed medical history of allergies and timing of weaning was obtained. Children underwent skin tests (prick and patch) to evaluate food hypersensitivity. The status of DA and food allergies in the study participants was investigated 4 years later., Results: There were more children with positive skin tests for food hypersensitivity among cases than controls, OR 4.2 (95%CI 1.3 to 13.4). In contrast, there were no differences in the number of children with positive family history of allergic diseases or weaned at < or = 6 months of age between groups. Four years later, out of the 28 original cases, the state of AD was investigated in 13 (46.4%) infants. Of them, 11 followed an exclusion diet; 6 (46.1%) remained with AD. Of 28 original controls, 15 (51.7%) infants were investigated 4 years later; only one case developed AD., Conclusions: Young children who had hypersensitivity to cow's milk, hen egg, wheat, fish, soy, or legumes were found to have a higher risk of AD. Positive family history of allergies and early weaning were not found to be relevant risk factors.

Sildenafil could be an alternative in the treatment of intrauterine growth retardation (IUGR) and premature delivery. In order to systematically review the reproductive-related effects of sildenafil, a search was made on PubMed and the Science Citation Index for studies evaluating the effects of sildenafil on uterine vessels or myometrium either in vitro or in experimental animal models as well as for any clinical trial or case reporting the outcome of pregnant women treated with sildenafil. The information was obtained from: three in vitro studies, five studies performed in experimental animal models, four studies on women with fertility and sterility disorders receiving 100 mg/day of sildenafil intravaginally, and two case reports of pregnant women who received sildenafil for the treatment of pulmonary hypertension. Incubation with sildenafil of different in vitro preparations resulted in vasodilator and uterine relaxant effects. No evidence of teratogenicity was observed in the studies performed in mice, rats and dogs. Sildenafil increased fetal weight in rats. In women, contradictory results on uterine blood flow and endometrial development were reported after the intravaginal administration of sildenafil. No adverse fetal outcomes were reported in the two pregnant women with pulmonary hypertension receiving sildenafil late in their pregnancy. In conclusion, there is still limited information about the efficacy of sildenafil for the treatment of IUGR and premature delivery. However, studies in experimental animal models and two human case reports have reported no deleterious effects on the mother or offspring.

This study investigated the effect of an acute bout of exercise (>85% VO2Max) on biochemical, hemodynamic and oxidative stress variables in sedentary and physically active subjects with type 2 diabetes (T2D). Blood measurements were taken before and after a treadmill test on 12 sedentary non-diabetes subjects (ND), 12 sedentary type 2 diabetes (T2S) and 9 physically active T2D subjects (T2DA). T2DS subjects before and after the treadmill test showed a higher plasma glucose (123.2 +/- 19.0 mg/dL versus 108.9 +/- 16.8 mg/dL, p < 0.001), HbA1C (8.7 +/- 2.4% versus 7.3 +/- 1.2%, p < 0.001) and body fat% (21.3 +/- 5.7% versus 34.6 +/- 4.5%, p < 0.001) than T2DA subjects. T2DA had higher VO2Max (37.7 +/- 3.5 versus 29.5 +/- 3.2, p < 0.05), time on treadmill (22.3 +/- 2.1 min versus 16.1 +/- 2.1 min, p < 0.05), hemoglobin (17.9 +/- 0.9 g/dL, p < 0.05) and lower blood pressure levels in comparison to ND and T2DS subjects. Thiobarbituric acid substances (TBARS) in T2DS were higher than in T2DA subjects (0.27 +/- 0.1 nmol/mL versus 0.21 +/- 0.1 nmol/mL, p < 0.05). Glutathione (GSH) levels were similar among the groups. Physically active type 2 diabetes subjects had a more favorable biochemical, hemodynamic and oxidative stress profile than sedentary subjects. The coexistence of a poor cardiopulmonary performance and high oxidative stress environment can determine a profile of high risk for serious cardiovascular events in patients with diabetes.

There are only a limited number of drugs proven to be human teratogens including thalidomide, isotretinoin, coumarin derivates, valproic acid, and folate antagonists. In some cases, the combination of 2 drugs may increase the teratogenic risk. The risk of birth defects may also vary with the time at which the drug is administered during pregnancy and the dose. There are some examples of drugs in which the dose has proven to be a major determinant of their teratogenicity in humans. There is more safety information for older than for newer drugs. Proactive teratogen risk counseling should include a critical appraisal of all available data including the consequences of the untreated maternal condition.

Objective: To assess the fetal outcome of three hypertensive women exposed to amlodipine. 5 mg/day, in the first trimester of pregnancy. CASE 1: The patient was treated with amlodipine until 7 weeks of gestation. She was also exposed to levosulpiride, aluminum hydroxide gel, magnesium carbonate, and Ginkgo biloba. At 38(+3) weeks of pregnancy, she delivered a 3750 g healthy female baby, and restarted taking amlodipine, 5 mg/day, while exclusively breastfeeding her daughter. At three months of age, the infant was healthy. CASE 2: The patient was treated with amlodipine from 2(+2) to 3(+4) weeks of pregnancy. Her treatment was modified to atenolol until the week 6(+4 weeks), when she declined any antihypertensive treatment. At 39(+4) weeks of pregnancy, the patient delivered a 2600 g baby. At 20 months old, the baby presented with intellectual delay and weakness in the left arm and hand grasp. These neurological alterations were not attributed to her exposure to amlodipine early in utero. CASE 3: The patient was treated with amlodipine from 7(+6) to 12 weeks of pregnancy. She was also taking sucralfate and lorazepam. At 12 weeks of amenorrhea, ultrasound revealed a 15.3 mm, single fetal pole in the gestational sac without cardiac activity. She underwent dilatation and evacuation of a dead embryo., Conclusion: As reported with other calcium-channel blockers, amlodipine does not appear to be teratogenic and it appears to be compatible with breastfeeding.

Oxytocin is extensively used to induce or augment uterine contractions, especially to facilitate the third stage of labor in humans. Administration of oxytocin to parturient sows reduces duration of labor whereas mortality of the offspring may remain unchanged. This study aimed to evaluate whether time of administration of oxytocin during parturition may alter the uterine response and fetal outcomes. Two hundred parturient sows were randomly assigned to intramuscularly receive either saline solution (control group) or oxytocin 0.083 IU/kg immediately after the delivery of the 1st, 4th or 8th piglet (groups O-1, 0-4 and 0-8, respectively). Uterine effects and fetal outcomes were registered in all groups. The duration of labor was 20-40 min shorter (P < 0.0001) and time interval between babies was reduced by 3-5 min (P < 0.0001) in the three groups receiving oxytocin. The duration and intensity of contractions, meconium-stained piglets and intrapartum deaths decreased as time at which oxytocin administered during labor was increased. In group 0-8, we observed approximately 70% less meconium-stained piglets and intrapartum deaths than in the control group. In conclusion, oxytocin administered at early phases of parturition to sows may increase duration and intensity of uterine contractions as well as adverse fetal outcomes.

In order to evaluate how spontaneously born piglets could be a suitable model for the study of intrapartum hypoxia, 230 newborn piglets were studied. Out them, 8.3% (n = 19) died intrapartum, 21.7% (n = 50) were born with moderate-to-severe intrapartum hypoxia, and 70% (n = 161) were born with mild or no evidence of intrapartum distress. Piglets born without any evidence of intrapartum asphyxia weighed approximately 240 g lower than those born with intrapartum hypoxia and intrapartum-dead piglets (P<0.0001). The viability score was approximately 3 units lower and the latency to contact the udder was two times longer in the piglets surviving intrapartum hypoxia than in controls (P <0.0001). In comparison with the control group, metabolic acidosis was most severe among intrapartum-dead piglets followed by piglets surviving intrapartum asphyxia (P =0.002). According to a multiple linear regression analysis, pCO2 and lactate blood levels, and birth weight were identified as explanatory variables of viability score (r: 0.78; P <0.001). Viability score, K+ and lactate blood levels, and birth weight were identified as explanatory variables of latency to contact the udder (r: 0.80; P <0.001). In conclusion, the spontaneously-born asphyxiated piglet could be considered as a naturalistic model for the study of intrapartum asphyxia. Histopathologic and more rigorous functional and behavioral evaluations are still required to further characterize the model. (www.actabiomedica.it)