[The association of adherence to a Mediterranean diet during early pregnancy and the risk of gastroschisis in the offspring]. / Asociación de la adherencia a la dieta mediterránea al inicio del embarazo y riesgo de gastrosquisis en la descendencia: un estudio de casos-controles.

OBJECTIVES: The aim of this study was to study the association of adherence to the Mediterranean diet in early pregnancy maternal and the offspring's risk of gastroschisis. METHODS: Case-control study. We describe 11 cases of gastroschisis in the region of Murcia from 2007 to 2012 and 34 concurrent controls. At the time of diagnosis each of the cases completed a validated Food Frequency Questionnaire (FFQ) consisting of 98 items on the periconceptional diet. Confounding factors: smoking, exposure to cannabis / marihuana, age of the parents, BMI, income and educational level. We conducted a descriptive and multivariate logistic regression statistical analysis. RESULTS: Mothers of children with gastroschisis were younger (20.8 years, 95% CI 17.3 to 24.2) and their diet consisted of less caloric intake, saturated fat and monounsaturated fats and proteins than controls. The Odds Ratio (OR) in the multivariate model controlling for confounding factors: maternal age (year) 0.70 (95% CI 0.51 to 0.96), monounsaturated fatty acids (oleic acid, g) 0.79 (95% CI 0.65 to 0, 97) and vegetable intake (rations/week) 0.70 (95% CI 0.48 to 1.00). CONCLUSION: A maternal diet rich in oleic acid and vegetable products may prevent vascular risk of onphalomesenteric arteries reducing the risk of gastroschisis.

Management of thyroid peroxidase antibody euthyroid women in pregnancy: comparison of the american thyroid association and the endocrine society guidelines.

The presence of thyroid autoantibodies is relatively high in women of childbearing age. There is evidence that positive thyroperoxidase antibody even in euthyroid women may increase the risk of spontaneous and recurrent pregnancy loss and preterm delivery. However, the evidence is not enough to justify recommendation on the screening of pregnant women for thyroid autoantibodies or LT4 supplementation for reducing maternal or fetal complications. In this paper we reviewed the related evidence and compared the new guidelines of the American Thyroid Association and Endocrine Society with respect to the screening and management of positive thyroperoxidase antibody in euthyroid pregnant women. As there was no major contradiction or disagreement between the two guidelines, either one of two guidelines may be used by clinicians for the appropriate management of thyroid autoimmunity during pregnancy.

[Integrating the environmental clinic history into prenatal counseling and health care in gastroschisis: 2 case reports]. / Integrando la historia clínica ambiental en el consejo prenatal y cuidado de 2 casos de gastrosquisis.

INTRODUCTION: Gastroschisis is a malformation with an unknown aetiology, likely involving genetic and environmental risk factors (RF). The aim of this paper is to develop the paediatric environmental clinical history (PECH) of two patients with gastroschisis. PATIENTS AND METHODS: Review of the medical literature using Pubmed and the Developmental and Reproductive Toxicology Database. Search teratogenic substances using the Hazardous Substances Data Bank. Keywords used were: "Gastroschisis" and "Gastroschisis and Risk Factor". RESULTS: Among the RFs known and present in both cases were: short cohabitation, unintended pregnancies of relatively young mothers, recent change of paternity, excessive alcohol intake, important nutritional deficiencies, and active and passive smoking. Additionally, one of the cases was exposed to cocaine, cannabis smoke and ionizing radiation from an orthopantography during pregnancy. CONCLUSIONS: 1. The PECH should be obtained in all patients with gastroschisis. 2. A thorough PECH requires a proper review of the related RFs and basic training to characterise and quantify environmental exposures. 3. Following these steps, useful recommendations to improve patient care and family advice in future pregnancies are provided.

[Neonatal tumours and congenital malformations]. / Tumores neonatales y malformaciones congénitas.

INTRODUCTION: The association between pediatric cancer and congenital abnormalities is well known but, there is no exclusive data on the neonatal period and the underlying etiopathogenic mechanisms are unknown. OBJECTIVES: First, to analyze the frequency of neonatal tumours associated with congenital abnormalities; and second, to comment on the likely etiopathogenic hypotheses of a relationship between neonatal tumours and congenital abnormalities. MATERIALS AND METHOD: Historical series of neonatal tumours from La Fe University Children's Hospital in Valencia (Spain), from January 1990 to December 1999. Histological varieties of neonatal tumours and associated congenital abnormalities were described. A systematic review of the last 25 years was carried out using Medline, Cancerlit, Index Citation Science and Embase. The search profile used was the combination of "neonatal/congenital-tumors/cancer/neoplasms" and "congenital malformations/birth defects". RESULTS: 72 neonatal tumours were identified (2.8% of all pediatric cancers diagnosed in our hospital) and in 15 cases (20.8%) there was some associated malformation, disease or syndrome. The association between congenital abnormalities and neonatal tumours were: a) angiomas in three patients: two patients with congenital heart disease with a choanal stenosis, laryngomalacia; b) neuroblastomas in two patients: horseshoe kidney with vertebral anomalies and other with congenital heart disease; c) teratomas in two patients: one with cleft palate with vertebral anomalies and other with metatarsal varus; d) one tumour of the central nervous system with Bochdaleck hernia; e) heart tumours in four patients with tuberous sclerosis; f) acute leukaemia in one patient with Down syndrome and congenital heart disease; g) kidney tumour in one case with triventricular hydrocephaly, and h) adrenocortical tumour: hemihypertrophy. The publications included the tumours diagnosed in different pediatric periods and without unified criteria to classify the congenital abnormalities. Little data exist on the neonatal period and the majority are from medical institutions registers. The prevalence varies from 15 to 31.6%. To explain this association, the hypotheses are based on prenatal exposures (preconceptional and transplacental exposure), to mutagenic and carcinogenic risk factors. CONCLUSIONS: Neonatal tumours are more often associated to congenital abnormalities than other pediatric cancers. The inclusion and classification criteria needs to be unified to better understand the association between the neonatal tumours and congenital abnormalities. The environmental history in all neonatal tumours associated to congenital abnormalities, including the constitutional and environmental risk factors, will help to improve our knowledge of the underlying prenatal mechanisms and to an advance in its prevention.

Effects of manganese on thyroid hormone homeostasis: potential links.

Manganese (Mn) is an essential trace nutrient that is potentially toxic at high levels of exposure. As a constituent of numerous enzymes and a cofactor, manganese plays an important role in a number of physiologic processes in mammals. The manganese-containing enzyme, manganese superoxide dismutase (Mn-SOD), is the principal antioxidant enzyme which neutralizes the toxic effects of reactive oxygen species. Other manganese-containing enzymes include oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases and glutamine synthetase. Environmental or occupational exposure to high levels of manganese can cause a neuropathy resembling idiopathic Parkinson's disease, commonly referred to as manganism. Manganism and Parkinson's disease are both characterized by motor deficits and damage to nuclei of the basal ganglia, particularly the substantia nigra, with altered dopamine (and its metabolites) contributing to these disorders. Dopamine, a major neurotransmitter plays a crucial role in the modulation of the cognitive function, working memory and/or attention of the prefrontal cortex and the hippocampus. Dopamine is also a known inhibitory modulator of thyroid stimulating hormone (TSH) secretion. The involvement of dopamine and dopaminergic receptors in neurodevelopment, as well as TSH modulation, led us to hypothesize that excessive manganese exposure may lead to adverse neurodevelopmental outcomes due to the disruption of thyroid homeostasis via the loss of dopaminergic control of TSH regulation of thyroid hormones. This disruption may alter thyroid hormone levels, resulting in some of the deficits associated with gestational exposure to manganese. While the effects of manganese in adult populations are relatively well documented, comprehensive data on its neurodevelopmental effects are sparse. Given the importance of this topic, we review the potential participation of thyroid hormone dyshomeostasis in the neurodevelopmental effects of manganese positing the hypotheses that manganese may directly or indirectly affect thyroid function by injuring the thyroid gland or dysregulating dopaminergic modulation of thyroid hormone synthesis.

Trimester-specific reference intervals for thyroxine and triiodothyronine in pregnancy in iodine-sufficient women using isotope dilution tandem mass spectrometry and immunoassays.

BACKGROUND: Accurate assessment of the pregnant woman's thyroid status is critical, for both the initiation of thyroid hormone therapy and for the adjustment of thyroid hormone dose in those already receiving thyroid hormone. Trimester-specific intervals are especially important during pregnancy when thyroid insufficiency may be associated with adverse obstetric outcome and fetal neurodevelopmental deficits. We defined pregnancy-specific reference intervals for thyroxine (T4) and 3,5,3'-triiodothyronine (T3). We used a novel isotope dilution tandem mass spectrometry (LC/MS/MS) method, and compare these to reference intervals obtained by immunoassays (IAs) performed on the same samples. METHODS: Concentrations of circulating T4 and T3 were measured simultaneously during first, second and third trimesters and postpartum in iodine-sufficient, healthy, singleton pregnancies using API-3000 LC/MS/MS with deuterium-labeled internal standard (L-thyroxine-d2). Immunoassays were conducted on the same samples (T4 Dade Behring RxL, T3 DPC-Immunolite). RESULTS: Linear regression is reported for method comparisons; for T4, the slope decreased from r=0.900 in nonpregnant women to 0.802-0.820 during pregnancy. For T3, correlations between LC/MS/MS and immunoassays were weaker in all cases (r=0.407-0.574). CONCLUSION: In this longitudinal study, we established trimester-specific reference intervals for T4 and T3 by LC/MS/MS and compare these to intervals obtained by immunoassays.

Trimester-specific changes in maternal thyroid hormone, thyrotropin, and thyroglobulin concentrations during gestation: trends and associations across trimesters in iodine sufficiency.

OBJECTIVES: To describe the interrelationships of thyroid functions based on trimester-specific concentrations in healthy, iodine-sufficient pregnant women across trimesters, and postpartum. METHODS: Circulating total 3,5,3'- triidothyronine (T(3)) and thyroxine (T(4)) concentrations were determined simultaneously using liquid chromatography tandem mass-spectrometry (LC/MS/MS). Free thyroxine (FT(4)), thyroid-stimulating hormone (TSH), and thyroglobulin (Tg) were measured using immunoassay techniques. Linear mixed effects models and correlations were calculated to determine trends and associations, respectively, in concentrations. RESULTS AND CONCLUSIONS: Trimester-specific T(3), FT(4), TSH, and Tg concentrations were significantly different between the first and third trimesters (all p < 0.05); second and third trimester values were not significantly different for FT(4), TSH, and Tg (all p > 0.25) although T3 was significantly higher in the third, relative to the second trimester. T(4) was not significantly different at any trimester (all p > 0.80). With two exceptions, analyte concentrations tended not to be correlated at each trimester and at 1-year postpartum. One exception was that T(3) and T(4) tended to be associated (all p < 0.05) at all time points except the third trimester (rho = 0.239, p > 0.05). T(4) and FT(4) concentrations tended to correlate positively during pregnancy (rho 0.361-0.382, all p < 0.05) but not postpartum (rho = 0.179, p > 0.05). Trends suggest that trimester-specific measurements of T(3), FT(4), Tg, and possibly TSH are warranted.

Perchlorate clinical pharmacology and human health: a review.

Potassium perchlorate has been used at various times during the last 50 years to treat hyperthyroidism. Since World War II ammonium perchlorate has been used as a propellant for rockets. In 1997, the assay sensitivity for perchlorate in water was improved from 0.4 mg/L (ppm) to 4 microg/L (ppb). As a result, public water supplies in Southern California were found to contain perchlorate ions in the range of 5 to 8 ppb, and those in Southern Nevada were found to contain 5 to 24 ppb. Research programs have been developed to assess the safety or risk from these exposures and to assist state and regulatory agencies in setting a reasonable safe level for perchlorate in drinking water. This report reviews the evidence on the human health effects of perchlorate exposure. Perchlorate is a competitive inhibitor of iodine uptake. All of its pharmacologic effects at current therapeutic levels or lower are associated with inhibition of the sodium-iodide symporter (NIS) on the thyroid follicular cell membrane. A review of the medical and occupational studies has been undertaken to identify perchlorate exposure levels at which thyroid hormone levels may be reduced or thyrotropin levels increased. This exposure level may begin in the 35 to 100 mg/d range. Volunteer studies have been designed to determine the exposure levels at which perchlorate begins to affect iodine uptake in humans. Such effects may begin at levels of approximately 1 mg/d. Environmental studies have assessed the thyroidal health of newborns and adults at current environmental exposures to perchlorate and have concluded that the present levels appear to be safe. Whereas additional studies are underway both in laboratory animals and in the field, it appears that a safe level can be established for perchlorate in water and that regulatory agencies and others are now trying to determine that level.