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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 12h 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 >10nmol/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.

Slaughtered cattle (n = 582) from Mexico State were bled for a serological screening of clenbuterol residues, using a commercial enzyme-linked immunosorbent assay (ELISA). Clenbuterol residues were found in a total of 153/582 (26.2%) sera analysed. These results reinforced the assumption of the illegal use of clenbuterol in cattle production in Mexico; therefore, routine screening examinations in slaughtered cattle were strongly advised considering the toxic potential for humans.

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.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).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; P0.001) and days drinking per week (r = 0.34; P0.001). 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.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.

Despite its frequent use, the optimal dosing regimen of intravenous vancomycin remains controversial. Achievement of therapeutic trough early in the course of illness may be beneficial. Our objective was to assess whether a loading dose of vancomycin would increase the proportion of children reaching target trough concentrations 8 hours after initiation of therapy.We enrolled hospitalized children aged 2-18 years prescribed vancomycin at Boston Children's Hospital between February 2011 and January 2012. Participants were randomized to receive a loading dose (30 mg/kg) or a conventional initial dose (20 mg/kg). These were followed by a 20 mg/kg/dose every 8 hours in both groups. Serum vancomycin concentrations were measured before the second and third doses. Pharmacokinetic parameters were calculated using individual and population pharmacokinetic models.Two of nineteen (11%) loading dose recipients had a trough 15-20 mg/L before the second dose, compared with 0 of 27 in the conventional dose group (P=0.17). However, the median area under the curve/minimum inhibitory concentration estimates (for a hypothetical minimum inhibitory concentration=1 mg/L) were above 400 in both groups. Red man syndrome incidence was higher in loading dose recipients (48% vs. 24%, P=0.06).A vancomycin loading dose did not result in earlier achievement of therapeutic trough concentrations in this study. However, the systemic exposure to vancomycin in children administered 60 mg/kg/day was adequate, despite lower than recommended measured trough levels. Therefore, the need for higher target trough concentrations should be questioned.

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.

A reliable biomarker of low alcohol exposure during pregnancy is needed to clarify the controversy on the teratogenicity of low-to-moderate alcohol levels.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.PEth species were not detected in women who abstained from alcohol ingestion during pregnancy, whereas PEth-16:0/18:1 was5 nmol/L in those with positive alcohol ingestion. PEth species were detected for up to 4 weeks after cessation of exposure.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.

Ondansetron is increasingly used to prevent emesis in children with acute gastroenteritis; however, the optimal dose is unknown. To determine if higher doses of oral ondansetron are associated with greater efficacy or side effects. 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. Participants were aged 0.5–8.2 years and the dose ranged between 0.13 and 0.26mg/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. 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.

Ifosfamide (IF), a potent chemotherapeutic agent for solid tumors, is known to cause high rates of nephrotoxicity in children with cancer, which is most likely due to the renal production of the metabolite chloroacetaldehyde. Using plasma samples obtained from pediatric oncology patients, we developed a simple nonderivatizing enantioselective liquid chromatography mass spectrometry method to detect the (R) and (S)-2- and 3-dechloroethylifosfamide metabolites. The (R) and (S)-enantiomers of the 2- and 3-DCEIF (N-3-dechlroethylifosfamide) were detectable in all 22 patients' samples with levels ranging from 9.9 to 238.7 ng/ml for (R)-2-DCEIF, 15.8 to 663.0 ng/ml for (S)-2-DCEIF, 20.8 to 852.8 ng/l for (R)-3-DCEIF and 28.0 to 862.0 ng/ml for (S)-3-DCEIF. In addition, the lower limit of quantification for this method is 1 ng/ml. Future studies should concentrate on (R) or (S) production of the 2-DCEIF and 3-DCEIF and subsequently chloroacetaldehyde formation with the aim of considering the administration of only the (R)-IF as its metabolism results in a lower production of chloroacetaldehyde.

To evaluate whether periconceptional exposure to oral contraceptives (OCs) increased adverse pregnancy outcomes, 136 pregnant women taking OCs within the periconceptional period were identified at the Korean Motherisk Program. Of them, 120 pregnant women accepted to participate in their study and were followed up until completion of the pregnancy. A control group of 240 age- and gravidity-matched pregnant women exposed to non-teratogen drugs for at least 1 month before pregnancy was also included. The median gestational age at delivery was 39.1 (27.0–41.0) weeks in the exposed group and 39.3 (27.4–42.0) weeks in the control group ( P = 0.19). In the exposed group, 7.1% of babies were born with low birth weight versus 2.6% in the control group ( P = 0.068). The number of preterm deliveries or babies born large for gestational age did not differ between the two groups. In the exposed group, the rate of birth defects was 3.2% ( n = 3/99) versus 3.6% ( n = 7/193) in the control group ( P = 1.0). There were 15 women who took high doses of progesterone (emergency contraception) and no adverse fetal outcomes were observed. In conclusion, periconceptional exposure to OCs does not appear to increase the risk for adverse pregnancy outcomes.

The aim of this study was to investigate the relationship between food hypersensitivity and atopic dermatitis (AD) in young children.In a case-control design, 28 patients3 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.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 ator = 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.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.

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.

Because very little information exists on the fetal safety of roxithromycin, we aimed to extend the knowledge on fetal outcome in pregnant women who were exposed to roxithromycin in early pregnancy.Twenty pregnant women inadvertently exposed to roxithromycin during early pregnancy were identified and prospectively followed-up. For comparison, 170 pregnant women matched by age and gravidity, not being exposed to any potential teratogenic agent during pregnancy, were recruited as controls. All gestations were confirmed by ultrasound examination, and participants were followed-up until delivery. Newborns were examined by a neonatologist.Of 20 pregnant women exposed to roxithromycin during early pregnancy, information was obtained from 17 cases. The median dose of roxithromycin to which pregnant women were exposed was 300 mg/day (range 300-450 mg/day) and exposure occurred at a mean of 4.0 (range 2.8-17.6) weeks. Mean gestational age at delivery was 39.2 weeks in the exposed group and 39.4 in the controls (p = 0.6). Birth weight of babies exposed in utero to roxithromycin was not different to controls. We did not observe any major malformation in the exposed group whereas three (1.8%) occurred in the control group.. Despite the limitations of the study due to the small sample size, roxithromycin appears not to be a major teratogen.

This study aimed to compare the efficacy of nebulized therapy with salbutamol alone or in combination with fluticasone. In a randomized, double-blind clinical trial, 150 children with moderate acute asthma were randomly assigned to receive by nebulizations either (i) three doses of salbutamol 30 microl/kg per dose, each dose administered every 15 min, (ii) three doses of salbutamol plus two doses of fluticasone 500 microg/dose at 15 and 30 min after first dose of salbutamol, or (iii) three doses of salbutamol/fluticasone 500 microg/dose, each combined dose administered every 15 min. Pulse oxymetry (SaO2), peak expiratory flow (PEF) and Wood et al. (Am J Dis Child, 123, 1972, 123) clinical scale were evaluated at baseline, 15, 30, 45, 60, 90 and 120 min after the first nebulization. Patients in the three groups significantly improved since 15 min after the first nebulization. We did not observe differences in the recovery of SaO2 and PEF among the three groups of treatment (p > 0.10). In group 3, children showed better clinical response at 120 min than the other two groups (p < 0.05). No significant adverse effects were observed with any treatment. To summarize, in children with acute moderate asthma, nebulized salbutamol at an accumulated dose of 90 mul/kg plus fluticasone at an accumulated dose of 1500 microg produced better clinical relief after 2 h. However, similar PEF and SaO2 responses were observed with salbutamol alone or in combination with different doses of fluticasone.

Summary Background : We aimed to evaluate the efficacy of clear liquids orally administered at 06:00–06:30 am on the morning of surgery to reduce prolonged preoperative fasting periods. Methods : After obtaining informed parental consent, 100 children undergoing scheduled orthopedic surgical procedures, ASA I–II, were randomly allocated to two groups. In group 1, children underwent the typical overnight preoperative period and patients in group 2 received a commercial brand of apple juice (glucose 28 g in 250 ml) at 06:00–06:30 am on the day of surgery. Patients

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

Although the internet may play a role in providing proper teratogen-risk counselling for pregnant women, the experience with this type of service has not been reported. We aimed to compare the pregnancy outcome of women counselled by the internet to women that received typically in-clinic teratogen risk counselling in the clinic. In a prospective cohort design, 1,011 patients were counselled in the clinic and 235 patients were counselled via the internet. Teratogen risk counselling was provided according with the information obtained from medical literature and specialised software. Information about pregnancy outcome (delivery, spontaneous abortion, or termination of pregnancy and major malformations) was obtained from 903 (89.3%) patients from the clinic group and 141 (60%) from the internet group. The amount of alcohol, cigarettes smoked, and millirads of X-ray were greater ( p < 0.05) in patients counselled by internet than in clinic. The rate of deliveries, ongoing pregnancies, pregnancy terminations, and spontaneous abortions were similar between clinic and internet (chi2 = 1.32; p = 0.7). Of 498 babies born to mothers counselled in the clinic, major malformations were identified in 3.6%. Of 67 babies born to mothers counselled by internet, major malformations were present in 1.5% ( p = 0.6). Teratogen-risk counselling by internet and clinic seems to have a similar efficacy in pregnancy outcome.

Bleomycin plus etoposide and cisplatin seem to be a promising alternative for women with ovarian cancer. We are reporting two cases with favorable pregnancy outcome after exposure to these chemotherapeutic agents at the second and third trimesters of pregnancy. A pregnant woman with a stage Ic yolk-sac tumor underwent a right oophorectomy with omentectomy, and received five cycles of bleomycin, etoposide and cisplatin from the 22nd week of pregnancy until delivery. The second case was a pregnant woman with a stage Ia immature teratoma who underwent right salpingo-oophorectomy and received two cycles of bleomycin, etoposide and cisplatin starting at 30th week of pregnancy. The two patients did not have any evidence of recurrence of ovarian cancer for 6 and 2 years, respectively. Their babies did not have any evidence of minor or major malformations, and showed normal neurological development at 6 and 2 years of follow-up, respectively.

BACKGROUND: We aimed to investigate the risk factors associated with unintended pregnancies as well as the association between unintended pregnancies and potential teratogenic exposures. METHODS: A cross-sectional survey was performed among women attending the Maternity School of the Samsung Cheil Hospital and Women's Health Care Center in Seoul, Korea. Demographic data, obstetric history, socioeconomic status, intention to become pregnant, and exposure to potential teratogens were obtained. RESULTS: A total of 1354 women with median age of 29 years and median gestational age of 29 weeks were included. Of these, an educational level above high school was 74.2%, primigravida was 77.3% and unintended pregnancy was 48%. In the logistic regression analysis, women younger than 24 years of age had a relative risk (RR) of 2.5 (95% confidence interval [CI], 1.3-4.7) of having an unintended pregnancy and women with lower household monthly income level had a RR of 1.3 (95% CI, 1.0-1.6). Women with unintended pregnancies had an RR of 1.9 (95% CI, 1.5-2.5), 3.0 (95% CI, 2.0-4.5), 1.5 (95% CI, 1.0-2.3), 2.9 (95% CI, 1.1-7.2), and 2.0 (95% CI, 1.62.4) of being exposed to alcohol, medications, cigarette smoking, X-rays, or to any of these, respectively, during the first trimester of pregnancy. CONCLUSIONS: Unintended pregnancies are more likely to occur among young women with a lower household monthly income level. Prenatal counseling should be especially recommended for women with unintended pregnancies in order to evaluate whether they have been exposed to potential teratogenic agents.

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.

To evaluate the pharmacokinetics of ethanol in the early second trimester of pregnancy, ethanol concentrations simultaneously measured in the maternal blood (EtOH-MB) and in the amniotic fluid (EtOH-AF) of six pregnant women were obtained from a previous study in which a single ethanol dose of 300mgkg(-1) body weight was administered orally. For maternal blood ethanol concentration, the kinetic equation was: [Formula: see text] where k(12) and k(21) are, respectively, the rate constant of ethanol transfer from either the central compartment to the peripheral compartment or vice versa; V(max)(EtOH)is the maximal velocity for ethanol oxidation; and K(m)(EtOH) is the concentration at which half of the maximal rate of ethanol elimination is reached. The maximum concentration of EtOH in AF was 60% lower than in MB (P=0.36). However, the AUC(0-3.5h) in AF was only 16% lower than the value for MB (P=0.059). The k(12) (0.20 =/- 0.26 h(-1)) was almost twice faster than k(21) (0, h(-1)). The V(max)(EtOH) was 237.6 +/- 71.5 microgml(-1)h(-1) and K(m)(EtOH) was 3.7 +/- 4.7 microgml(-1). Our results imply that in the early second trimester, ethanol metabolism is fast. However, ethanol clearance from the AF is slower than ethanol clearance in MB. This process is widely variable, and our findings may partially explain the wide variability of ethanol's toxic effects on the fetus.

Aconitum roots are traditionally prescribed for the management of different types of painful affections in Asiatic countries. A quantitative structure-activity relationship (QSAR) analysis was performed to study the effect of chemical substitutes in the analgesic potency of alkaloids available in Chinese Aconitum roots. Using the CAChe program package for biomolecules, molecular modelling was performed in 12 alkaloids previously tested in a model of acetic acid-induced writhing in rats. The ED50 (micromol/kg) was used as the activity parameter. Structural parameters were compared between alkaloids with an aroyl/aroyloxy group at R14 and alkaloids with the aroyloxy group at R4. Single linear regression analyses were performed in order to find the parameters explaining activity. Alkaloids with an aroyl/aroyloxy group at R14 exhibited the highest potency (significantly less ED50). The stability parameters were different between groups, e.g. total energy was -8.0 +/- 0.4 in the potent analgesic alkaloids and -6.7 +/- 0.3 in the weak analgesic alkaloids (P = 0.001). The reactivity index of C2', C3' and C5' of the aromatic ring was also different between groups, e.g. the reactivity index of C5' was 40.8 +/- 0.6 in potent analgesic alkaloids and 48.1 +/- 0.6 in weaker analgesic alkaloids (P < 0.001). Several structural parameters explained analgesic activity of alkaloids, being the reactivity index of C5' on the aromatic group the most important factor (r = 0.89; P < 0.001).

The present study prospectively assessed pregnancy outcome of women taking probiotics during the periconceptional period. A group of 104 women who had taken Lactobacillus in early pregnancy and 200 age- and parity-matched control pregnant women exposed to non-teratogenic agents were also recruited into the study and followed-up prospectively. Median gestational age of women exposed to Lactobacillus was 5.2 (range: 1.9-17.6) weeks. Exposure was at a mean dose of 510 mg/day for a median of 4.0 days (range: 1-90 days). In the exposed group, pregnancy outcomes included 96 live births and eight spontaneous abortions versus 187 live births and 21 spontaneous abortions in the non-exposed group. There was no statistical difference in adverse pregnancy outcomes, including the number of spontaneous abortions, pre-term births as well as a low birth weight between the two groups (p > 0.05). In the exposed group, there were two (2.1%) major congenital malformations in comparison with five (2.7%) in the comparison group (p = 0.7). In conclusion, no association was identified between ingestion of Lactobacillus in early pregnancy for a limited period of time and adverse pregnancy outcomes. However, rare pregnancy outcomes may have been missed due to the limited sample size included in the study.

Background: Since 1970, bupivacaine 0.25% in a dose of 4 mg·kg−1 (1.6 ml·kg−1) has been used at the Hospital Infantil de Mexico for caudal block in children undergoing surgical correction of congenital pyloric stenosis (CPS). Although this dose is considered unsafe, in our experience, it has been associated with a high success rate and a low incidence of adverse events. This experience has not been previously documented. Methods: A retrospective cohort of patients undergoing surgical correction of CPS was studied. Nineteen patients received general anaesthesia while 223 received caudal block. The latter were then grouped according to the sedation technique. The rate of successful caudal blocks and complications were considered the major outcomes of the study, whereas the postsurgical fasting period and hospital stay were considered secondary outcomes. Results: The rate of success of caudal block was 96%. Anaesthetic complications related to bupivacaine were present in 1.3%. Mortality occurred in the postoperatory period in one septic patient who also was suffering from gastroschisis that required general anaesthesia. Postoperatory fasting period and hospital stay tended to be higher with general anaesthesia than caudal block. However, of the 19 patients receiving general anaesthesia, five suffered serious comorbidity and nine were failed caudal blocks. Conclusions: Caudal block with bupivacaine 0.25% (4 mg·kg−1) was associated with a low rate of anaesthetic complications. Further prospective studies to clarify the risks and benefits are required.

Summary: Purpose: Differences in potency among valproate (VPA) metabolites could be explained by structural properties. Therefore, a quantitative structure–activity relation (QSAR) analysis was performed to study the relation between structural parameters and the effect of the following VPA metabolites: 4-en-VPA, 2-en-VPA, 3-en-VPA, 2,4'-dien-VPA, 4,4'-dien-VPA, 4-hydroxy-VPA, 3-ceto-VPA, 3-hydroxy-VPA, 5-hydroxy-VPA, and propylglutaric acid. Methods: By using the CAChe program package for biomolecules (Oxford Molecular, Ltd), we performed molecular modeling. The anticonvulsant activity determined on the threshold for maximal electroconvulsions in mice was obtained from a study of Loscher and Nau. Structural parameters were compared between metabolites with a double bond and metabolites with oxygen at either side chain (unpaired Student's t test). A single linear regression analysis between each structural parameter and the relative anticonvulsant potency was also performed. Results: Similar parameters were found between the cis and trans and R and S isomers. Biologic activity and most of the structural parameters were significantly different between metabolites with a double bond and metabolites with oxygen at either side chain. Activity was directly related to log Poct (r2 = 0.77) and to reactivity parameters and was inversely related to stability parameters and to molecular weight and surface. The most potent metabolites had a log Poct value of higher than 2 units. Conclusions: Similar data were identified between cis and trans, and R and S isomers of VPA metabolites. Anticonvulsant activity was mainly related to log Poct, probably reflecting the ability of VPA metabolites to cross the blood–brain barrier.

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.

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.

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

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

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; p0.0001). Other fetal and neonatal study outcomes investigated in the exposed group were similar (p0.05) 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.

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.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.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.Light-to-moderate prenatal alcohol exposure cannot be reliably predicted by the cumulative FAEE concentrations in meconium of exposed babies. A cumulative FAEE level of10 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.

The complex process to develop a successful therapeutic drug is lengthy and costly. In order to accelerate this process, molecular modeling has become a key component of drug design. Methods used in computational chemistry vary from Ab initio quantum chemistry methods, to semi-empirical calculations and molecular mechanics. A study of the anticancer activity of a series of 7-aryl- and 7-hetaryl-7-deazaadenosines published by Bourderioux (2011) showed that nucleosides with 5-member heterocycles at the position 7 were more potent in vitro cytostatic agents against hematological and solid tumor cell lines than molecules with 6-member heterocycles. We decided to conduct a quantitative structure–activity relationship (QSAR) analysis of these chemical moieties in order to have a better understanding of their structural properties and identify their molecular descriptors explaining their biological activities. We found that 5-member cyclic structures have three energy molecular descriptors that were negatively correlated to their biological activity, in particular, compounds with higher energies had higher biological potency represented by lower IC50 values. CLogP, a parameter of lipophilicity, was also found to be positively correlated to their biological activity, i.e. compounds with lower CLogP values had higher biological potency represented by lower concentrations inhibiting the growth of cancer cells by 50 %. Qualitatively, 5-member-ring heterocycles of 7-deazaadenosine had lower steric hindrance, i.e. were structurally smaller, than their 6-member counterparts. In this context, a QSAR analysis could be extraordinarily helpful in studying the mode of action of molecules with potential pharmacological relevance.

Organophosphorus pesticides are the most common classes involved in poisonings related to pesticides. We used enzymatic activity of chloroperoxidase on the metabolism of some phosphorothioate pesticides published previously and molecular mechanics methods to perform a theoretical approach of the mechanism of biological oxidation of this class of pesticides. The molecular structure of eight pesticides were optimized by molecular mechanics methods using the CAChe program package for biomolecules, ver. 3.11 (Oxford Molecular Ltd., Campbell, CA). Total energy resulted from the structure optimization process and the partial charges of both phosphorus and sulfur were computed for every pesticide. Phosphorus partial charge and enzymatic activity were significantly related by linear regression analysis (r=0.82, P

Background Malignancies are among the most common causes of death in children. The present study was undertaken to evaluate and compare bone marrow aspiration and unilateral biopsy to detect bone marrow metastases in pediatric patients, using bilateral biopsy as the gold standard. Methods During a 6-month period, 63 consecutive newly diagnosed children with confirmed malignant diseases other than leukemia were evaluated for bone marrow metastases or infiltration. Biopsies were obtained from both right and left posterior iliac crests whereas aspiration was performed only at the right crest. Interpretation to the right-side biopsy was considered as the unilateral biopsy result, whereas the bilateral biopsy result was as follows: positively was accepted if one or both of the two-side samples were qualified as positive, while a negative result was considered only if both sides were negative. The bilateral biopsy was considered the gold standard, and sensitivity, specificity, positive and negative predictive value, and false positive and negative rates were computed for the unilateral biopsy and aspiration procedure. Results We identified bone marrow metastases in 11 (17.5%) patients. The sensitivity was the only significant difference ( p Conclusions Unilateral biopsy was better than bone marrow aspiration. However, because bilateral biopsy is the gold standard, we recommend using this and bone marrow aspiration simultaneously to evaluate a pediatric patient with any malignancy potentially infiltrating bone marrow.

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.

Background The time-course of the effect of rocuronium during isoflurane anesthesia in children has rarely been evaluated. Forty-five children, aged 2–14 years, ASA 1, undergoing elective surgery and receiving isoflurane anesthesia, were studied. Methods Patients randomly received a dose of 400, 600, or 800 μg/kg of rocuronium. The first response to the control height (T1:T0) was fitted to time in order to obtain times to onset of action (TOA) including time to 90 (B 90 ) and 99.9% (B 100 ) of relaxation and to spontaneous recovery of 10 (T 10 ), 25 (T 25 ), 50 (T 50 ), 75 (T 75 ), and 90% (T 90 ) of neuromuscular function (NMF). Each time was compared among groups. Linear regression analysis between the TOA or the times to spontaneous recovery of NMF (TSRNMF) and age or weight were also performed. Results The TOA were similar among the three groups while TSRNF in children receiving 600 or 800 μg/kg were longer ( p 10 and T 25 were related to age ( p = 0.05), whereas T 10 , T 50 , T 75, and T 90 were related to weight ( p Conclusions Maximal relaxation was reached in all children receiving 600 or 800 μg/kg of rocuronium. The TSRNMF were mainly related to the weight of the children, and gender affected each relationship. Widely variable responses were observed with all three doses.

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.

The primary objective of this study was to evaluate in a random double-blind design, the sedative and behavioural responses of children undergoing outpatient paediatric dental procedures receiving either chloral hydrate (CH) alone or in combination with hydroxyzine. Forty American Society of Anaesthesiologists class I children (21 to 36 months of age) were randomly allocated to receive either 70 mg/kg CH alone or with 2 mg/kg hydroxyzine. The degree of crying, movement and overall behaviour was evaluated during treatment at different times. The combination of chloral hydrate/hydroxyzine (CH/H) significantly decreased crying and movement in relation to the effect induced by CH alone (p0.05) only at 45-60 min following the insertion of a rubber dam, whereas the overall behavior in both groups was no different throughout the dental procedures. In conclusion, our study demonstrated that hydroxyzine increased the effect of CH. However, because of the presence of high rates of oxygen desaturations and of deep sedation, careful use of this drug combination should be stressed.

Background. The study aimed to evaluate the household smoking habits as risk factors for wheezing in adolescents. Methods. During a 2-month period, the study was performed by applying the standardized ISAAC phase 1 questionnaire to 3474 adolescents attending a random sample of secondary public schools located at the southeast of Mexico City. Adolescents were grouped as “cases” if they had at least one episode of wheezing in the year prior to the study, or as “controls” if they did not. Positive individual and family (father, mother or other persons living in the home) smoking habits at home were evaluated as potential risk factors. Results. More than 98% of respondents in the two groups reported that the father smoked in the house. More mothers who smoked were reported among cases than controls (OR 2.42; 95% CI 1.60–3.68). More adolescents in the group of cases had history of ever having rhinitis, rash or wheezing. Fifty-four percent of adolescents in the group of cases had ever smoked versus 38.8% of controls (OR 1.89; 95% CI 1.33–2.67). Sex-adjusted logistic regression analysis identified a “protective” role for wheezing when the number of smokers at home was ≤ 2 (OR 0.44; 95% CI 0.27–0.71). Conclusion. Individual, maternal and other family members' indoor smoking habits may increase the risk of wheezing among adolescents.

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; p0.001). 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.

1. Drugs administered into the epidural space by caudal block are cleared by means of a process potentially affected by the lipophilic character of the compounds. 2. In the present study, we examined the relationship between the octanol-water partition coefficient (log Poct) and the time to reach the maximum plasma drug concentration (tmax) of lignocaine, bupivacaine and ropivacaine administered by caudal block in paediatric patients. We also examined the relationship between log Poct and the toxicity of these local anaesthetic agents in experimental models. The tmax and toxicity data were obtained from the literature. 3. Ropivacaine, with a log Poct of 2.9, exhibited a tmax of 61.6 min. The tmax of lignocaine, with a log Poct of 2.4, and bupivacaine, with a log Poct of with 3.4, were approximately 50% shorter than ropivacaine. At log Poct of approximately 3.0, the toxicity of these local anaesthetic agents was substantially increased. The relationship between log Poct and the convulsive effect in dogs was similar to the relationship between log Poct and the lethal dose in sheep. 4. With local anaesthetic agents, it appears that the relationship between log Poct and drug transfer from the epidural space to the blood stream is parabolic, being the slowest rate of transference at log Poct 3.0. Toxicity, due to plasma availability of these local anaesthetic agents, seems to be increased at log Poct equal or higher than 3.0 secondary to the highest transfer from plasma into the central nervous system.

We aimed to study the pregnancy outcomes of women exposed to isotretinoin and to identify the factors influencing their decision to request an abortion.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.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 isotretinoin1 month before conception or during pregnancy. In a nominal logistic regression analysis including 68 patients who provided adequate information for analysis, exposure to isotretinoin2 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.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.

The purpose of this study is to evaluate the relationship between maternal and/or cord blood folate/homocysteine concentrations and adverse pregnancy outcomes. The study population included a random sample of singleton pregnant women in whom we measured total homocysteine and folic acid in maternal or cord blood at deliveries. A total of 227 pregnant women were enrolled. The concentration of folate in maternal blood tended to be significantly lower in pre-term birth than in full-term delivery group (median (95% CI), 14.4 (3.6-73) vs 25 (7.3-105.5) p < 0.01). The total homocysteine in maternal and cord blood was significantly higher in the pre-eclampsia than in the normotensive group (7.9 (1.7-28.2) vs 5.9 (1.8-14.6) μmol/ml, p < 0.05; and 5.8 (2.6-14.4) vs 4.2 (0.7-7.9) ng/ml, p < 0.05, respectively). Lower maternal serum folate concentration is associated with pre-term delivery and higher maternal plasma homocysteine concentration with pre-eclampsia.