Prenatal iodine supplementation and early childhood neurodevelopment: the PoppiE trial - study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Observational studies suggest both low and high iodine intakes in pregnancy are associated with poorer neurodevelopmental outcomes in children. This raises concern that current universal iodine supplement recommendations for pregnant women in populations considered to be iodine sufficient may negatively impact child neurodevelopment. We aim to determine the effect of reducing iodine intake from supplements for women who have adequate iodine intake from food on the cognitive development of children at 24 months of age. METHODS AND ANALYSIS: A multicentre, randomised, controlled, clinician, researcher and participant blinded trial with two parallel groups. Using a hybrid decentralised clinical trial model, 754 women (377 per group) less than 13 weeks' gestation with an iodine intake of ≥165 µg/day from food will be randomised to receive either a low iodine (20 µg/day) multivitamin and mineral supplement or an identical supplement containing 200) µg/day (amount commonly used in prenatal supplements in Australia), from enrolment until delivery. The primary outcome is the developmental quotient of infants at 24 months of age assessed with the Cognitive Scale of the Bayley Scales of Infant Development, fourth edition. Secondary outcomes include infant language and motor development; behavioural and emotional development; maternal and infant clinical outcomes and health service utilisation of children. Cognitive scores will be compared between groups using linear regression, with adjustment for location of enrolment and the treatment effect described as a mean difference with 95% CI. ETHICS AND DISSEMINATION: Ethical approval has been granted from the Women's and Children's Health Network Research Ethics Committee (HREC/17/WCHN/187). The results of this trial will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04586348.

Gas chromatographic/mass spectrometric detection of narcotine, papaverine, and thebaine in seeds of Papaver somniferum.

In addition to codeine and morphine, three more compounds: narcotine (noscapine), papaverine, and thebaine were found in Indian and Netherlands poppy seeds (Papaver somniferum L). The compounds were detected by a GC/MS technique and the identities were confirmed by comparing retention times and ion ratios with the known references. The concentrations of codeine, morphine, thebaine, papaverine, and narcotine were 44, 167, 41, 67, and 230 micrograms/g in Indian poppy seeds, and were 1.8, 39, 1.0, 0.17, 0.84 micrograms/g in Netherlands poppy seeds, respectively. Because these compounds may be urinary products after poppy seed consumption, the lowest detectable concentrations of codeine, morphine, thebaine, papaverine, and narcotine in urine are of interest and were found to be 4, 4, 5, 0.4, and 4 ng/ml, respectively. The detection of urinary narcotine, papaverine, or thebaine may be utilized to differentiate poppy seed consumption from illicit codeine, morphine, or heroin use.

Preclinical toxicity evaluation of tepoxalin, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, in Sprague-Dawley rats and beagle dogs.

Tepoxalin [5- (4-chlorophenyl)-N-hydroxy-1-(4-methoxyphenyl)-N-methyl-1H-pyrazole -3-propanamide] is an orally active anti-inflammatory agent, which inhibits both cyclooxygenase and 5-lipoxygenase activities. The oral toxicity of tepoxalin was evaluated in 1- and 6-month rat (up to 50 mg/kg/day) and dog (up to 150 mg/kg bid) studies. In rats, increased liver weight, centrilobular hypertrophy, and hepatic necrosis were observed at dosages >/=20 mg/kg/day. Renal changes indicative of analgesic nephropathy syndrome (i.e., papillary edema or necrosis, cortical tubular dilatation) were seen at >/=15 mg/kg. In rats treated for 1 month, these hepatic and renal effects were largely reversible after a 1-month recovery period. Gastrointestinal erosions and ulcers were seen in female rats given 40 mg/kg/day for 6 months. Changes in clinical pathology parameters included decreases in red blood cell count, hemoglobin, and hematocrit mean values; elevation in platelet counts; and an increase in prothrombin and activated partial thromboplastin times. Mild increases in alanine aminotransferase, aspartate aminotransferase, and cholesterol were also noted in rats. Decreased erythrocyte parameters, increased leukocyte counts, and decreased total protein, albumin, and/or calcium were noted in some dogs in the 300 mg/kg/day group following 6 months of dosing. Small pyloric ulcerations were seen at 100 and 300 mg/kg/day dosages for up to 6 months. In both rats and dogs, no accumulation of tepoxalin or its carboxylic acid metabolite was detected in plasma following multiple dosing over a range of 5 to 50 mg/kg/day for rats and 20 to 300 mg/kg/day for dogs. Plasma concentrations of the carboxylic acid metabolite were severalfold higher than those of the parent compound. The no-effect dosages in rats (5 mg/kg/day) and dogs (20 mg/kg/day) were approximately one and six times the ED50 (3.5 mg/kg), respectively, for inhibition of inflammatory effects in the adjuvant arthritic rat without gastric mucosal damage. In terms of severity, the relative lack of gastrointestinal side effects, within the estimated therapeutic dose range, distinguishes tepoxalin from most marketed anti-inflammatory drugs.

Multiple factors as mediators of the reduced incidence of low birth weight in an urban clinic population.

A five year prospective observational study was initiated in 1985 at Howard University to describe the nutritional, clinical, dietary, lifestyle, environmental, and socioeconomic characteristics of women who enrolled in the hospital prenatal clinic. The participants were nulliparous, between the ages of 18 and 35 years, free of diabetes and abnormal hemoglobins (sickle cell disease, thalassemia, and hemoglobin C), and had been admitted prior to the 29th week of gestation. During the three year period from 1985-1988, the incidence of low birth weight (LBW) in 239 deliveries to project participants was 8.3%, whereas that of women simultaneously enrolled in the prenatal clinic with the same eligibility requirements, but not recruited for the research project, was 21.9% (P = 0.001). The incidence of LBW in infants of African American women with these eligibility requirements who were delivered by private physicians but were not enrolled in the project, was 6.3%. The reduction in LBW of infants delivered to participants in this study is attributed to the enhanced social and psychological support by project staff during their pregnancies. The caring, sensitive demeanor of the research project staff may have empowered the participants to (a) give greater compliance (91 vs. 70%) in the ingestion of the routine physician-prescribed vitamin/mineral supplement, which provided nutrients low (less than 70% of the 1989 RDAs) in their customary diets, such as folate, pyridoxine, iron, zinc, and magnesium and (b) show greater accountability in keeping prenatal clinic appointments.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemical profile of African American women during three trimesters of pregnancy and at delivery.

The data presented are the results from a prospective observational study which was conducted to investigate the effects of nutrition and other related factors on the outcome of pregnancy in nulliparous African American women 16-35 years old. Fasting blood samples were collected from the women during the first, second and third trimesters of pregnancy. At delivery, both maternal and cord samples were collected. Biochemical variables such as, serum folate, vitamin B12, ascorbic acid, vitamin E, ferritin, selected minerals as well as complete blood count (CBC) and red cell folate were analyzed in the blood samples. The concentrations of hematocrit, hemoglobin, white blood cells, red blood cells and vitamin B12 were below the reference non-pregnant ranges throughout gestation. Maternal concentrations of folate and vitamin E increased sequentially with increased gestational age. Serum ferritin, during the third trimester, declined to 58% of the first trimester concentration. Maternal levels of ferritin at delivery were one third of the values found in the infant (cord) sample. Cord levels of folate, ascorbic acid and vitamin B12 were higher than the concentrations in the maternal delivery samples. The data suggest that among this group of pregnant women, major physiological changes, such as plasma volume expansion which alters blood chemistry and maternal to fetal transfer of nutrients, were similar to the findings of other investigators. In this population however, the findings for serum and whole blood folate are contrary to those reported by other researchers, and the sequential increase in the maternal concentration of the vitamin during pregnancy could be attributed to the use of vitamin supplements.

Maternal low level lead and pregnancy outcomes.

We examined the relationship between the concentrations of blood lead and pregnancy outcomes in a subset of 349 African American women who enrolled in the program project, "Nutrition, Other Factors, and the Outcome of Pregnancy." Vitamin-mineral supplement users had significantly higher serum levels of ascorbic acid and vitamin E. Also, in supplement users, there were significantly lower mean concentrations of maternal blood lead. Inverse correlations were found between maternal levels of lead and the antioxidant vitamins, vitamin E and ascorbic acid. In addition, significant Pearson's correlations were observed between maternal blood lead levels and the following variables: positive correlations with calcium, phosphorus, mean corpuscular volume; inverse correlations with gestational age, Ponderal Index, infant orientation, and hematologic values. In the total subset, the three trimester sample means for maternal blood lead concentrations were not significantly different for mothers of infants who weighed less than 2500 g (low birth weight) and those who were delivered infants who weighed 2500 g or more. Clinically, nutrition may play a role in the reduction of potentially adverse effects from lead during pregnancy, i.e. protection of the fetus against lead toxicity and/or free radical damage through the antioxidant actions of vitamin E and ascorbic acid. Even when maternal blood lead levels are within the so-called "safe" range, maternal/use of a vitamin supplement supplying vitamin E and ascorbic acid during pregnancy may offer protection.

Effects of beta-carotene and retinyl palmitate on corn oil-induced superoxide dismutase and catalase in rats.

The present study was undertaken to determine the effects of beta-carotene on corn oil-induced superoxide dismutase and catalase. Six groups of male Buffalo rats were fed the following diets for 6 wk: a control diet containing recommended levels of beta-carotene and retinyl palmitate, a retinol diet containing 10 times the recommended level of retinyl palmitate, and a beta-carotene diet containing 10 times the recommended levels of beta-carotene and adequate levels of retinyl palmitate. Each vitamin combination was fed with either 5% (wt/wt) corn oil (low fat) or 20% corn oil (high fat). Plasma total beta-carotene levels were highest in the beta-carotene groups. Levels varied inversely with the level of fat in the control group and directly with fat in the beta-carotene group. Transport of beta-carotene appeared to parallel that of cholesterol in that 36 and 35%, respectively, were associated with the low density lipoprotein fraction. Accumulation of beta-carotene in the liver was apparent from the observation that levels in liver were much higher than those in plasma. Superoxide dismutase activity was much lower in the beta-carotene groups than in the retinol groups, irrespective of level of fat, and catalase activity was also lower in the beta-carotene group, but it was in proportion to the level of fat. These findings suggest that beta-carotene functions as an antioxidant in vivo.

Effect of salicylamide on the growth of a Morris hepatoma in rats fed 8% and 25% casein diets.

To investigate the effect of 2% salicylamide and protein feeding levels on animal and tumor growth, male ACI rats were injected with Morris hepatoma #3924A (1 X 10(6) cells) 1 week following the conversion to diets containing 8% or 25% casein (+/- 2% salicylamide). The animals were sacrificed on day 19 after tumor transplantation. Tumor area and tumor weight were significantly higher in animals on the 25% versus the 8% casein diets. Reduction in body weight gain and protein efficiency ratio (PER) were observed in drug-treated and tumor-bearing animals. Total serum protein and liver protein were significantly reduced in all tumor-bearing animals when compared to non-tumor-bearing rats. Liver protein from animals with tumors was significantly higher among those fed salicylamide, in comparison with the tumor bearing non-drug-treated animals. Overall, these results show that the growth of Morris hepatoma #3924A in ACI rats is enhanced by increased dietary protein and is significantly reduced by a low-protein diet and/or a salicylamide dietary supplement.