Sustained bloodstream release of persistent organic pollutants induced by extensive weight loss after bariatric surgery: Implications for women of childbearing age.

BACKGROUND: Lipophilic persistent organic pollutants (POPs) are stored in adipose tissues and released in case of weight loss. OBJECTIVES: To analyze the kinetics and characteristics of this release during drastic weight loss after bariatric surgery and compare the results in case of women of childbearing age (WCBA) with critical blood concentration thresholds. METHODS: 100 morbidly obese patients (73 women including 53 of childbearing age and 27 men) were screened before and 3, 6 and 12 months after bariatric surgery for serum concentrations of 67 congeners or metabolites of banned or not yet banned organohalogenated persistent pollutants, including highly lipophilic polychlorobiphenyls (PCBs), organochlorine pesticides (OCPs), brominated flame retardants (BFRs), and less lipophilic perfluorinated alkylated substances (PFASs). RESULTS: Circulating levels of all chemicals, except PFASs, increased progressively after surgery, reaching after one year an increase between 30 and 139% compared to initial pre-surgical levels; median levels increased for PCB153 from 36.8 to 86.4 ng/g lw (+130%), for dichlorodiphenyldichloroethylene (p,p'-DDE) from 59.8 to 136.1 ng/g lw (+120%), and for hexachlorobenzene (HCB) from 9.8 to 20.3 ng/g lw (+110%). Weight loss averaging 30% of initial body weight at 12 months in both sexes (mean: 40.0 kg for men, 36.1 kg for women), was the main parameter related to the concentration increases (3.1 to 3.6% per kilogram weight loss). They were not dependent on initial BMI, presence of metabolic syndrome or type of surgical procedure but influenced by gender and biochemical properties such as degree of chlorination for PCBs and/or lipophilicity since PFASs did not increase at all. ∑PCB6 in blood after one year exceeded the critical concentration threshold for 24.5% women of childbearing age (13/53) versus 3.6% (2/53) before surgery. DISCUSSION: Massive weight loss within the first year following bariatric surgery is associated with a sustained increase of circulating lipophilic POPs. Short- and long-term consequences should be considered, mostly for childbearing age obese women, because of potential health risks for the future fetus and breastfeeding infant.

Human Health and Ocean Pollution.

Background: Pollution - unwanted waste released to air, water, and land by human activity - is the largest environmental cause of disease in the world today. It is responsible for an estimated nine million premature deaths per year, enormous economic losses, erosion of human capital, and degradation of ecosystems. Ocean pollution is an important, but insufficiently recognized and inadequately controlled component of global pollution. It poses serious threats to human health and well-being. The nature and magnitude of these impacts are only beginning to be understood. Goals: (1) Broadly examine the known and potential impacts of ocean pollution on human health. (2) Inform policy makers, government leaders, international organizations, civil society, and the global public of these threats. (3) Propose priorities for interventions to control and prevent pollution of the seas and safeguard human health. Methods: Topic-focused reviews that examine the effects of ocean pollution on human health, identify gaps in knowledge, project future trends, and offer evidence-based guidance for effective intervention. Environmental Findings: Pollution of the oceans is widespread, worsening, and in most countries poorly controlled. It is a complex mixture of toxic metals, plastics, manufactured chemicals, petroleum, urban and industrial wastes, pesticides, fertilizers, pharmaceutical chemicals, agricultural runoff, and sewage. More than 80% arises from land-based sources. It reaches the oceans through rivers, runoff, atmospheric deposition and direct discharges. It is often heaviest near the coasts and most highly concentrated along the coasts of low- and middle-income countries. Plastic is a rapidly increasing and highly visible component of ocean pollution, and an estimated 10 million metric tons of plastic waste enter the seas each year. Mercury is the metal pollutant of greatest concern in the oceans; it is released from two main sources - coal combustion and small-scale gold mining. Global spread of industrialized agriculture with increasing use of chemical fertilizer leads to extension of Harmful Algal Blooms (HABs) to previously unaffected regions. Chemical pollutants are ubiquitous and contaminate seas and marine organisms from the high Arctic to the abyssal depths. Ecosystem Findings: Ocean pollution has multiple negative impacts on marine ecosystems, and these impacts are exacerbated by global climate change. Petroleum-based pollutants reduce photosynthesis in marine microorganisms that generate oxygen. Increasing absorption of carbon dioxide into the seas causes ocean acidification, which destroys coral reefs, impairs shellfish development, dissolves calcium-containing microorganisms at the base of the marine food web, and increases the toxicity of some pollutants. Plastic pollution threatens marine mammals, fish, and seabirds and accumulates in large mid-ocean gyres. It breaks down into microplastic and nanoplastic particles containing multiple manufactured chemicals that can enter the tissues of marine organisms, including species consumed by humans. Industrial releases, runoff, and sewage increase frequency and severity of HABs, bacterial pollution, and anti-microbial resistance. Pollution and sea surface warming are triggering poleward migration of dangerous pathogens such as the Vibrio species. Industrial discharges, pharmaceutical wastes, pesticides, and sewage contribute to global declines in fish stocks. Human Health Findings: Methylmercury and PCBs are the ocean pollutants whose human health effects are best understood. Exposures of infants in utero to these pollutants through maternal consumption of contaminated seafood can damage developing brains, reduce IQ and increase children's risks for autism, ADHD and learning disorders. Adult exposures to methylmercury increase risks for cardiovascular disease and dementia. Manufactured chemicals - phthalates, bisphenol A, flame retardants, and perfluorinated chemicals, many of them released into the seas from plastic waste - can disrupt endocrine signaling, reduce male fertility, damage the nervous system, and increase risk of cancer. HABs produce potent toxins that accumulate in fish and shellfish. When ingested, these toxins can cause severe neurological impairment and rapid death. HAB toxins can also become airborne and cause respiratory disease. Pathogenic marine bacteria cause gastrointestinal diseases and deep wound infections. With climate change and increasing pollution, risk is high that Vibrio infections, including cholera, will increase in frequency and extend to new areas. All of the health impacts of ocean pollution fall disproportionately on vulnerable populations in the Global South - environmental injustice on a planetary scale. Conclusions: Ocean pollution is a global problem. It arises from multiple sources and crosses national boundaries. It is the consequence of reckless, shortsighted, and unsustainable exploitation of the earth's resources. It endangers marine ecosystems. It impedes the production of atmospheric oxygen. Its threats to human health are great and growing, but still incompletely understood. Its economic costs are only beginning to be counted.Ocean pollution can be prevented. Like all forms of pollution, ocean pollution can be controlled by deploying data-driven strategies based on law, policy, technology, and enforcement that target priority pollution sources. Many countries have used these tools to control air and water pollution and are now applying them to ocean pollution. Successes achieved to date demonstrate that broader control is feasible. Heavily polluted harbors have been cleaned, estuaries rejuvenated, and coral reefs restored.Prevention of ocean pollution creates many benefits. It boosts economies, increases tourism, helps restore fisheries, and improves human health and well-being. It advances the Sustainable Development Goals (SDG). These benefits will last for centuries. Recommendations: World leaders who recognize the gravity of ocean pollution, acknowledge its growing dangers, engage civil society and the global public, and take bold, evidence-based action to stop pollution at source will be critical to preventing ocean pollution and safeguarding human health.Prevention of pollution from land-based sources is key. Eliminating coal combustion and banning all uses of mercury will reduce mercury pollution. Bans on single-use plastic and better management of plastic waste reduce plastic pollution. Bans on persistent organic pollutants (POPs) have reduced pollution by PCBs and DDT. Control of industrial discharges, treatment of sewage, and reduced applications of fertilizers have mitigated coastal pollution and are reducing frequency of HABs. National, regional and international marine pollution control programs that are adequately funded and backed by strong enforcement have been shown to be effective. Robust monitoring is essential to track progress.Further interventions that hold great promise include wide-scale transition to renewable fuels; transition to a circular economy that creates little waste and focuses on equity rather than on endless growth; embracing the principles of green chemistry; and building scientific capacity in all countries.Designation of Marine Protected Areas (MPAs) will safeguard critical ecosystems, protect vulnerable fish stocks, and enhance human health and well-being. Creation of MPAs is an important manifestation of national and international commitment to protecting the health of the seas.

Frequency and Incidence of Carney Complex Manifestations: A Prospective Multicenter Study With a Three-Year Follow-Up.

INTRODUCTION: Carney Complex (CNC) is a rare multiple endocrine and nonendocrine neoplasia syndrome. Manifestations and genotype-phenotype correlations have been described by retrospective studies, but no prospective study evaluating the occurrence of the different manifestations has been available so far. METHODS: This multicenter national prospective study included patients with CNC, primary pigmented nodular adrenal disease (PPNAD), or a pathogenic PRKAR1A mutation; after a full initial workup, participants were followed for 3 years with annual standardized evaluation. RESULTS: The cohort included 70 patients (50 female/20 male, mean age 35.4 ± 16.7 years, 81% carrying PRKAR1A mutation). The initial investigations allowed identification of several manifestations. At the end of the 3-year follow-up, the newly diagnosed manifestations of the disease were subclinical acromegaly in 6 patients, bilateral testicular calcifications in 1 patient, and cardiac myxomas in 2 patients. Recurrences of cardiac myxomas were diagnosed in 4 patients during the 3-year follow-up study period. Asymptomatic abnormalities of the corticotroph and somatotroph axis that did not meet criteria of PPNAD and acromegaly were observed in 11.4% and 30% of the patients, respectively. Patients carrying the PRKAR1A c.709-7del6 mutation had a mild phenotype. CONCLUSION: This study underlines the importance of a systematic follow-up of the CNC manifestations, especially a biannual screening for cardiac myxoma. By contrast, regular screening for the other manifestations after a first extensive workup could be spread out, leading to a lighter and more acceptable follow-up schedule for patients. These are important results for recommendations for long-term management of CNC patients.

Endocrine Disrupting Chemicals Interfere With Leydig Cell Hormone Pathways During Testicular Descent in Idiopathic Cryptorchidism.

Cryptorchidism, a frequent genital malformation in male newborn, remains in most cases idiopathic. On the basis of experimental, epidemiological, and clinical data, it has been included in the testicular dysgenesis syndrome and believed to be influenced, together with genetic and anatomic factors, by maternal exposure to endocrine disrupting chemicals (EDCs). Here, we analyze how EDCs may interfere with the control of testicular descent, which is regulated by two Leydig cell hormones, testosterone, and insulin like peptide 3 (INSL3).

[Thyroid and the environment]. / Thyroïde et environnement.

It has long been known that the thyroid depends upon the environment for regular iodine supply, avoiding iodine deficiency or excess. Thyroid function may be altered by natural compounds present in water or foodstuff (such as iodine or phyto-goitrogens), or by synthetic compounds, either administered knowingly (in case of medicine), or as an untoward event in case of exposure to industrial products and pesticides, massively produced and polluting the environment. Compounds with an impact on thyroid homeostasis are called thyroid disruptors (TD). TD may disrupt the thyroid economy at any level of regulation: thyroid hormone synthesis, metabolism, or transport; cellular level including thyroid hormone signaling; tumorigenesis or more indirectly via the triggering of an autoimmune process. Compounds such as polychlorinated biphenyls (PCBs) may act at multiple levels. PT effects on human health depend on parameters linked to the individual person (age at exposure, iodine status, diet, professional exposure, place of living, family history of thyroid disease, detoxification enzyme genetic variants) and on parameters linked to the compounds themselves (chemical structure, lipo- or hydro-solubility, modes of exposure, metabolites activity, "cocktail effect"). The toxic effects of TD do not necessarily follow the rules of classical toxicology (low-dose effects, non-monotonic curves). The main clinical risks are the deleterious impact on neurocognition and behavior for the fetus and the young child, and possibly the elderly, while in adults the main concerns are tumori/goitrogenesis and autoimmune thyroid disease. The potential socioeconomic impact for society warrants an active and major involvement in research to find solutions in a multidisciplinary approach.

[Endocrine disruptors, reproduction and hormone-dependent cancers]. / Perturbateurs endocriniens - Reproduction et cancers hormono-dépendants.

Endocrine disruptors are natural or synthetic chemical compounds which are present in the environment and which are able to interfere with hormonal regulation pathways and to induce human health deleterious effects. While their precise implication in human health and diseases is still matter of debates, it becomes likely that they have to be considered as risk factors in numerous chronic diseases: developmental and reproductive defects and hormone dependent cancers (present review), metabolic diseases (obesity and type 2 diabetes), neurodevelopmental or neurodegenerative diseases. Low doses exposure during critical windows of exposure such as foetal, perinatal and peri-pubertal periods, or chronic exposure with bioaccumulation in the adipose tissue, and possible synergic effects of several compounds ("cocktail effect") may participate to the genetic/environment interface suspected to participate to the pathophysiology of many diseases.

Neurotoxicant exposure during pregnancy is a confounder for assessment of iodine supplementation on neurodevelopment outcome.

CONTEXT: The developing brain is vulnerable to iodine deficiency (ID) and environmental neuro-toxicants. OBJECTIVES: To assess neurocognitive development of children whose mothers have received (or not) iodine supplementation during pregnancy, in an area of borderline ID, while assessing in utero exposure to environmental neuro-toxicants. DESIGN/PATIENTS: Among 86 children born from normal euthyroid women who participated in our prospective interventional study on iodine supplementation (150 µg/day) started early in pregnancy, 44 (19 with iodine supplementation, 25 controls) were assessed at two years using the Bayley test. Information on parents' education and habits (smoking), and on child development was recorded. Thyroid tests at each trimester of pregnancy and on cord blood (CB) were available, as well as milk concentrations of selected environmental compounds known for their neurotoxicity, including heavy metals and PCBs. RESULTS: There was no difference in Bayley tests for children born to mothers with and without iodine supplementation, but sample size was small. Language and Social-Emotional Scales were negatively correlated with TBG at all times tested, while PCB 118 correlated negatively with all Language scales. Among maternal and CB thyroid tests, only CB thyroglobulin, the best marker of iodine status, correlated (negatively) with neurodevelopment scales (Motor and Expressive Language). CONCLUSIONS: This pilot study suggests that PCB118 has a negative impact on neurocognitive development, possibly mitigating the benefit of iodine supplementation in an area of borderline ID. We propose that exposure to environmental neurotoxicants should be taken into account when designing studies on the benefit of iodine supplementation in pregnancy. The potential interactions between TBG, environmental neurotoxicants and brain development warrant further studies.

The history of Distilbène® (Diethylstilbestrol) told to grandchildren--the transgenerational effect.

The Distilbène® story is a dramatic episode which belongs to the history of medicine. It provided several useful lessons such as the importance of evidence-based medicine and the hazard to develop treatments during pregnancy without careful animal verifications. However, this experience has also provided unexpected progress by suggesting new pathophysiological concepts: fetal programming of adult diseases and/or transgenerational transmission of environmental effects through epigenetic modifications.

ARMC5 Mutations in a Large Cohort of Primary Macronodular Adrenal Hyperplasia: Clinical and Functional Consequences.

CONTEXT: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of primary adrenal Cushing's syndrome (CS). ARMC5 germline mutations have been identified recently in PBMAH. OBJECTIVE: To determine the prevalence of ARMC5 mutations and analyze genotype-phenotype correlation in a large cohort of unrelated PBMAH patients with subclinical or clinical CS. PATIENTS AND METHODS: ARMC5 was sequenced in 98 unrelated PBMAH index cases. PBMAH was identified by bilateral adrenal nodular enlargement on computed tomography scan. The effect on apoptosis of ARMC5 missense mutants was tested in H295R and HeLa cells. Clinical and hormonal data were collected including midnight and urinary free cortisol levels, ACTH, androgens, renin/aldosterone ratio, cortisol after overnight dexamethasone suppression test, cortisol and 17-hydroxyprogesterone after ACTH 1-24 stimulation and illegitimate receptor responses. Computed tomography and histological reports were analyzed. RESULTS: ARMC5-damaging mutations were identified in 24 patients (26%). The missense mutants and the p.F700del deletion were unable to induce apoptosis in both H295R and HeLa cell lines, unlike the wild-type gene. ARMC5-mutated patients showed an overt CS more frequently, compared to wild-type patients: lower ACTH, higher midnight plasma cortisol, urinary free cortisol, and cortisol after dexamethasone suppression test (P = .003, .019, .006, and <.001, respectively). Adrenals of patients with mutations were bigger and had a higher number of nodules (P = .001 and <.001, respectively). CONCLUSIONS: ARMC5 germline mutations are common in PBMAH. Index cases of mutation carriers show a more severe hypercortisolism and larger adrenals. ARMC5 genotyping may help to identify clinical forms of PBMAH better and may also allow earlier diagnosis of this disease.

A negative correlation between insulin-like peptide 3 and bisphenol A in human cord blood suggests an effect of endocrine disruptors on testicular descent during fetal development.

STUDY QUESTION: Does a relationship exist between insulin-like peptide 3 (INSL3) and selected environmental endocrine disruptors (EEDs) in human cord blood (cb)? SUMMARY ANSWER: In the whole population (cryptorchid and control boys) cbINSL3 correlated negatively with cb free bisphenol A (BPA) providing indirect evidence for an impact of EEDs on fetal Leydig cell INSL3 production. WHAT IS KNOWN ALREADY: INSL3 is a major regulator of testicular descent. This hormone has been shown to be decreased in cord blood from boys with idiopathic cryptorchidism, the most frequent male malformation. Fetal exposure to several EEDs has been suspected to be involved in the occurrence of idiopathic cryptorchidism. STUDY DESIGN, SIZE, DURATION: Correlations between cb INSL3 or testosterone and cb free bioactive BPA and maternal milk polychlorinated biphenyls (PCB153), dichlorodiphenyldichloroethylene (DDE), and monobutyl phthalate (mBP) were assessed in newborn boys in a prospective case-control study. All boys (n = 6246) born after 34 weeks of gestation were systematically screened at birth for cryptorchidism over a 3-year period (2002-2005), and a diagnosis of cryptorchidism confirmed by a senior paediatrician. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 52 cryptorchid (26 transient, 26 persistent) and 128 control boys born at two hospitals in southern France. INSL3 was assayed in CB by a modified validated enzyme-linked immunosorbent assay. Testosterone was measured in CB after diethyl-ether extraction by means of ultra-pressure liquid chromatography-tandem mass spectrometry. Free cbBPA was measured after an extraction step with a radioimmunoassay validated after comparison of values obtained by high-pressure liquid chromatography-mass spectrometry. The xenobiotic analysis in mothers' milk was performed after fat extraction by gas chromatography-mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE: EED concentrations were not increased in the cryptorchid versus control group although a trend for increased mBP (P = 0.09) was observed. In the whole study population, cb levels of BPA correlated negatively with INSL3 (P = 0.01; R² = 0.05) but not with testosterone. No other EED correlated with INSL3 or with testosterone. LIMITATIONS, REASONS FOR CAUTION: The levels of BPA and INSL3 in cb may not reflect chronic fetal exposure to EEDs. The deleterious impact of EEDs on fetal testicular descent during specific windows of development has yet to be demonstrated. WIDER IMPLICATIONS OF THE FINDINGS: The negative correlation between cb free BPA and INSL3 provides indirect evidence for an impact of EEDs on human fetal Leydig cell INSL3 production and points to cbINSL3 as a possible target of EED action during fetal testis development.

Cord blood insulin-like peptide 3 (INSL3) but not testosterone is reduced in idiopathic cryptorchidism.

BACKGROUND: Cryptorchidism, the most frequent congenital malformation in full-term male newborns, increases the risk of hypofertility and testicular cancer. Most cases remain idiopathic but epidemiological and experimental studies have suggested a role of both genetic and environmental factors. Physiological testicular descent is regulated by two major Leydig hormones: insulin-like peptide 3 (INSL3) and testosterone. OBJECTIVES: To study the endocrine context at birth as a reflection of late pregnancy in isolated idiopathic cryptorchidism and to analyse the possible disruptions of INSL3 and/or testosterone. METHODS: From a prospective case-control study at Nice University Hospital, we assessed 180 boys born after 34 weeks gestation: 52 cryptorchid (48 unilateral, 4 bilateral; 26 transient, 26 persistent), and 128 controls matched for term, weight and time of birth. INSL3 and testosterone were measured in cord blood and compared in both groups as were other components of the pituitary-gonadic axis: LH, HCG, FSH, AMH and SHBG. RESULTS: INSL3 was decreased in cryptorchid boys (P = 0·031), especially transient cryptorchid (P = 0·029), while testosterone was unchanged as were the other hormones measured. INSL3 was significantly decreased (P = 0·018) in the group of 20 with nonpalpable testes compared with the group of 21 with palpable testes (15 suprascrotal, five inguinal, one high scrotal) according to Scorer classification. In the whole population, INSL3 correlated positively with LH and negatively with AMH, but with no other measured hormones. CONCLUSIONS: INSL3 but not testosterone is decreased at birth in idiopathic cryptorchidism, especially in transient forms. This hormonal decrease may contribute to the impaired testicular descent along with genetic and anatomical factors. Whether foetal environment (nutritional and/or toxicological) interferes with INSL3 secretion in humans remains to be confirmed.

Bisphenol A: an endocrine and metabolic disruptor.

Bisphenol A (BPA), initially designed, like diethylstilbestrol, as a synthetic estrogen, has been rapidly and widely used for its cross-linking properties in the manufacture of polycarbonate plastics and epoxy resins. Because of incomplete polymerization and degradation of the polymers by exposure to higher than usual temperatures, BPA leaches out from food and beverage containers, as well as from dental sealants. In humans, free active unconjugated BPA is metabolized by rapid glucurono- or sulfo-conjugation and eliminated via renal clearance. However, exposure to environmental nanomolar concentrations of BPA is ubiquitous and continuous via different routes: oral, air, skin. In rodents, fetal and perinatal exposure to such environmentally relevant doses of BPA has been shown to affect the brain, liver, gut, adipose tissue, endocrine pancreas, mammary gland and reproductive tract and function. Similar concentrations are also able in vitro to impact human malignant breast, prostate, male germ or adipocyte cell lines (with a promoting effect and by interfering with chemotherapy drugs), or to stimulate pancreatic ß cell insulin secretion. High levels of BPA have recently been correlated with obesity, diabetes, cardiovascular diseases, polycystic ovarian disease or low sperm count. However, before the real impact of BPA on human health can be clearly assessed, prospective longitudinal epidemiological studies are needed as well as characterization of selective biomarkers to verify long-term exposure and selective imprinting.

Iodine Supplementation throughout Pregnancy Does Not Prevent the Drop in FT4 in the Second and Third Trimesters in Women with Normal Initial Thyroid Function.

OBJECTIVES: The aim of the study was to determine the evolution of thyroid tests throughout pregnancy and postpartum in healthy women with and without iodine supplementation. METHODS: This was a prospective, randomized, interventional study of iodine supplementation (150 µg/day) from the first trimester until 3 months postpartum versus controls. 111 pregnant women with normal initial thyroid tests were enrolled, undergoing comprehensive thyroid assessment at each trimester. We present results of longitudinal and cross-sectional analyses. RESULTS: Initial ioduria suggested mild iodine deficiency in both groups, while third-trimester ioduria rose to levels of iodine sufficiency in the iodine-supplemented group. In the longitudinal study, free T4 (FT4) levels decreased in the second and third trimesters compared to the first trimester in both groups, with no change in TSH, and rose postpartum, though lower than the first trimester. FT3 levels and the total T4 (TT4)/thyroxine-binding globulin (TBG) ratio followed the same evolution as FT4. TT4 levels rose due to TBG increase. Thyroglobulin (Tg) of iodine group remained stable, contrasting with the rise in the control group. In the cross-sectional study, there was no difference between the two groups in thyroid tests at any time-point, except for lower Tg in the second trimester and postpartum visits in the iodine group. CONCLUSIONS: In healthy, mildly iodine-deficient pregnant women, a 'drop' of FT4 and TT4/TBG without TSH increase occurs between the first and second trimesters, and is not prevented by iodine supplementation, suggesting physiology. Therefore, FT4 is valuable to assess thyroid function in pregnancy in clinical practice with appropriate trimester-specific reference range. It brings up reflection on threshold for diagnosis and treatment of hypothyroxinemia.

Relative impact of iodine supplementation and maternal smoking on cord blood thyroglobulin in pregnant women with normal thyroid function.

OBJECTIVE: To assess the impact on cord blood (CB) thyroglobulin (Tg) of early iodine supplementation during pregnancy. METHODS: A total of 111 healthy pregnant women with normal thyroid function were included in a prospective randomized study and divided into two groups with (150 µg/day) or without iodine supplementation started during the first trimester. Maternal smoking was assessed qualitatively by self-reported statements and quantitatively by cotininuria. Exhaustive thyroid tests were performed at delivery in the mother and in CB. RESULTS: Third-trimester ioduria documented compliance with iodine supplementation (160 vs. 76 µg/l in controls). CB Tg was not different between the iodine and control groups (median 77 vs. 79.5 ng/ml, respectively) and did not correlate with maternal ioduria. CB Tg was higher in newborns from smoking mothers (114 vs. 64.7 ng/ml) and correlated with self-reported smoking status more than with maternal cotininuria. Nonsmokers had no difference in CB Tg whether they took iodine supplementation or not, as opposed to smokers, who tended to benefit from supplementation. CONCLUSIONS: Iodine supplementation does not significantly impact CB Tg in healthy nonsmoker pregnant women selected for normal thyroid function, as opposed to maternal smoking. CB Tg appears to be a marker of in utero tobacco exposure. In areas of mild iodine deficiency, iodine supplementation could especially benefit the fetuses of smokers.

Cord blood thyroid tests in boys born with and without cryptorchidism: correlations with birth parameters and in utero xenobiotics exposure.

BACKGROUND: In utero exposure to environmental chemicals can result in reproductive toxicity via endocrine disruption mechanisms. Whether some of those contaminants also have an impact on fetal thyroid function or pathways, and, thus, potentially on neuropsychological development, is still debated. METHODS: We used samples from a cord blood (CB) and milk bank, established for a research on cryptorchidism and xenobiotic exposure to compounds known for their anti-androgenic and/or estrogenic activity, to study CB thyroid tests and their correlation with CB and milk xenobiotics concentrations in boys born in Nice area. RESULTS: No difference was found in thyroid tests between 60 cryptorchid boys and 76 matched controls (median thyroid stimulating hormone 5.97 vs. 6.55 mUI/L, free thyroxine [fT4] 13.1 vs. 12.9 pmol/L, free triiodothyronine [fT3] 1.9 vs. 2.1 pmol/L), with no influence of season of birth, gestational age, maternal smoking, or mode of delivery (except for higher fT4 in control boys born vaginally). FT4 was correlated with fetal growth only in cryptorchid boys. Since we had previously shown differences between cryptorchid and controls exposure, we studied correlations of thyroid tests with xenobiotics in control boys only. All tested CB or maternal milk was contaminated by one or more selected xenobiotics, mainly polychlorinated biphenyls (PCBs), dichloro diphenyl dichloroethylène (DDE), dibutylphthalate, hexachlorobenzene, and bisphenol A. We found a significant negative correlation between fT4 and concentrations of PCB118, PC180, and DDE in milk (respectively r = -0.342, p < 0.03, r = -0.296, p = 0.031, r = -0.315, p = 0.016), persisting after adjustment for mode of delivery. There was a significant positive correlation of fT3 with milk concentrations of PCB138, PCB153, ΣPCB, and dibutylphthalate (respectively r = 0.31, p = 0.016, r = 0.28, p = 0.029; r = 0.34, p = 0.0079 and r = 0.272, p = 0.0295), with a trend for PCB180 (r = 0.259, p = 0.061). There was no correlation of thyroid stimulating hormone with any of the measured xenobiotics, except for a weak negative trend with CB bisphenol A (r = -0.25, p = 0.077). CONCLUSIONS: CB thyroid tests are within normal range in cryptorchid boys, similar to controls. Our data in controls suggest a possible weak correlation between in utero exposure to some xenobiotics (PCBs, DDE) and fT3 and fT4 CB concentrations, with usually negative correlations with fT4 and positive with fT3 concentrations, which we speculate could suggest an impact on deiodinases.

Exposure to selected endocrine disruptors and neonatal outcome of 86 healthy boys from Nice area (France).

In utero and lactational exposure to endocrine disruptors is thought to be potentially harmful on fetal and infant development. Data of exposure in France is scarce. This is a prospective study with (1) collection of 84 cord bloods (CB) and 69 milks from 86 mothers delivering healthy boys (gestational age >or= 34 weeks) at two maternity wards in Southern France, between 2002 and 2005 and (2) screening for 15 xenobiotics with anti-androgenic and/or estrogenic effects: DDE, 7 PCBs, dibutylphthalate and its metabolite mBP, HCB, lindane, linuron, procymidone and vinclozoline. Correlations were made with delivery and neonatal outcomes. All CB and milks were contaminated by one or more xenobiotics (mainly PCBs, DDE, HCB, and phthalates) with good correlation between CB and milk concentrations. Compared to other geographical areas, exposure was usually in the lower bracket. Milk [PCB180] was associated with lower birth weight. Infant head circumference correlated negatively with [HCB] and positively with [mBP] in CB. There was a similar but not significant trend for birth weight and length. [DDE] in milk was higher in older mothers and in women born in Africa. In utero and lactational exposure is ubiquitous in our area. Contamination of milk with HCB, mBP, and PCB 180 showed weak correlations with infant growth. This snapshot of exposure in an area with no major industry will serve for further monitoring.