Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease.

Although a rare disease, bilateral congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage kidney disease in children. Ultrasound-based prenatal prediction of postnatal kidney survival in CAKUT pregnancies is far from accurate. To improve prediction, we conducted a prospective multicenter peptidome analysis of amniotic fluid spanning 140 evaluable fetuses with CAKUT. We identified a signature of 98 endogenous amniotic fluid peptides, mainly composed of fragments from extracellular matrix proteins and from the actin binding protein thymosin-ß4. The peptide signature predicted postnatal kidney outcome with an area under the curve of 0.96 in the holdout validation set of patients with CAKUT with definite endpoint data. Additionally, this peptide signature was validated in a geographically independent sub-cohort of 12 patients (area under the curve 1.00) and displayed high specificity in non-CAKUT pregnancies (82 and 94% in 22 healthy fetuses and in 47 fetuses with congenital cytomegalovirus infection respectively). Change in amniotic fluid thymosin-ß4 abundance was confirmed with ELISA. Knockout of thymosin-ß4 in zebrafish altered proximal and distal tubule pronephros growth suggesting a possible role of thymosin ß4 in fetal kidney development. Thus, recognition of the 98-peptide signature in amniotic fluid during diagnostic workup of prenatally detected fetuses with CAKUT can provide a long-sought evidence base for accurate management of the CAKUT disorder that is currently unavailable.

Isolated hypospadias: The impact of prenatal exposure to pesticides, as determined by meconium analysis.

Although endocrine-disrupting chemicals (EDCs, including pesticides) are thought to increase the risk of hypospadias, no compounds have been formally identified in this context. Human studies may now be possible via the assessment of meconium as a marker of chronic prenatal exposure. The objective of the present study was to determine whether or not prenatal exposure to pesticides (as detected in meconium) constitutes a risk factor for isolated hypospadias. In a case-control study performed between 2011 and 2014 in northern France, male newborns with isolated hypospadias (n = 25) were matched at birth with controls (n = 58). Newborns with obvious genetic or hormonal anomalies, undescended testis, micropenis, a congenital syndrome or a family history of hypospadias were not included. Neonatal and parental data were collected. Foetal exposure was assessed by determining the meconium concentrations of the pesticides or metabolites (organophosphates, carbamates, phenylurea, and phenoxyherbicides) most commonly used in the region. Risk factors were assessed in a multivariate analysis. The pesticides most commonly detected in meconium were organophosphates (in up to 98.6% of samples, depending on the substance) and phenylurea (>85.5%). A multivariate analysis revealed an association between isolated hypospadias and the presence in meconium of the phenylurea herbicide isoproturon and of the phenoxyherbicide 2-methyl-4-chlorophenoxyacetic acid (odds ratio [95% confidence interval]: 5.94 [1.03-34.11] and 4.75 [1.20-18.76]) respectively). We conclude that prenatal exposure to these two herbicides (as assessed by meconium analysis) was correlated with the occurrence of isolated hypospadias. The results of our case-control study (i) suggest that prenatal exposure to pesticides interferes with the development of the male genitalia, and (ii) emphasize the importance of preventing pregnant women from being exposed to EDCs in general and pesticides in particular.

Response to Elwood, M. et al., Comment on: Maternal Exposure to Domestic Hair Cosmetics and Occupational Endocrine Disruptors Is Associated with a Higher Risk of Hypospadias in the Offspring. Int. J. Environ. Res. Public Health 2017, 14, 27.

Dear Editor, Thank you for inviting us to reply to a "Comment" paper to our published paper "Maternal Exposure to Domestic Hair Cosmetics and Occupational Endocrine Disruptors Is Associated with a Higher Risk of Hypospadias in the Offspring" (Authors: Elodie Haraux, Karine Braun, Philippe Buisson, Erwan Stéphan-Blanchard, Jannick Ricard, Camille Devauchelle, Bernard Boudailliez, Pierre Tourneux, Richard Gouron, Karen Chardon).[...].

Erratum: Haraux, E., et al. Maternal Exposure to Domestic Hair Cosmetics and Occupational Endocrine Disruptors Is Associated with a Higher Risk of Hypospadias in the Offspring. Int. J. Environ. Res. Public Health 2016, 14, 27.

Due to an error during production, some data presented in Table 1 in the Experimental section of the published paper [1] were incorrect.[...].

Maternal Exposure to Domestic Hair Cosmetics and Occupational Endocrine Disruptors Is Associated with a Higher Risk of Hypospadias in the Offspring.

Pregnant women are exposed to various chemical products at home and at work. Some of these products contain endocrine-disrupting chemicals (EDCs) such as cosmetics, pesticides, industrial chemicals, heavy metals, plastics or medications that could alter sexual differentiation and increase the risk of hypospadias. We evaluated maternal occupational and household exposures that could constitute risk factors for hypospadias. From 2011 to 2014, we enrolled 57 full-term newborns with hypospadias and three randomly selected controls per case (162 control newborns), matched for gestational age, from 11 maternity units in Picardy, France. Neonatal and parental data were collected at birth (personal characteristics, maternal lifestyle, and medical history). Maternal occupational exposure was assessed by a job-exposure matrix for EDCs from a job history questionnaire completed by mothers. Odds ratios (OR) and 95% confidence intervals (CI) were calculated with univariate and multivariable logistic regression, and adjusted for relevant covariates. Multivariate analysis showed a strong association between hypospadias and potential maternal occupational exposure to EDCs and maternal household use of hair cosmetics (OR 6.1, 95% CI: 1.1-34.9; OR: 9.6, 95% CI: 1.4-66.1, respectively). Our results suggest that maternal occupational exposure to EDCs is a risk factor for hypospadias and suggests a possible influence of household use of hair cosmetics during early pregnancy on the incidence of hypospadias in the offspring. A larger study with more accurate exposure assessment should evaluate the impact of EDCs in hair cosmetics on the incidence of hypospadias.

[Renal late effects in patients treated for cancer in childhood]. / Complications rénales à long terme chez les patients traités pour un cancer dans l'enfance.

Impaired renal function may occur following multimodal treatment of cancer in childhood. Renal late effects caused by chemotherapy, renal surgery and/or radiotherapy are now well described; but little is known about their prevalence and time of development. Herein, we provide a synthesis of the different renal complications that may occur with their physiopathology in relation with specific treatment exposures. This review summarized the literature that supported the recommendations issued by the long-term follow-up group of the "Société française des cancers de l'enfant (SFCE)" for childhood cancer survivors at risk for nephrotoxicity (www.sfce.org ; www.soc-nephrologie.org/SNP/index.htm). We developed these monitoring elements and the lifestyle recommendations for all asymptomatic survivors.

Darbepoetin, effective treatment of anaemia in paediatric patients with chronic renal failure.

Darbepoetin alpha (DA) is a unique long-acting treatment for anaemia in patients with chronic renal failure (CRF). This study assessed the mean dose of DA to achieve and maintain haemoglobin (Hb) levels between 11 g/dl and 13 g/dl in CRF children aged 11 years to 18 years. This observational, prospective study was conducted in 39 patients treated with DA. Twenty-nine patients were switched from recombinant human erythropoietin (r-HuEPO), and ten patients were naive to r-HuEPO. Naive patients received initial doses of 0.45 microg/kg of DA. Switched patients received a dose adjusted to the prior dose of r-HuEPO (200 IU r-HuEPO:1 microg DA). Among the switched patients, 79.3% received dialysis. No naive patients underwent dialysis. Overall, 74% of patients showed increased Hb level, with a mean value of 11.6 +/- 1.6 g/dl, using a mean DA dose of 0.63 +/- 0.48 microg/kg per week, and 66.7% patients reached the target Hb level. Hb increased in naive patients from 9.5 (95% CI: 7.7, 11.4) to 11.7 (95% CI: 10.9, 12.6) g/dl and in switched patients from 11.1 (95% CI: 10.6, 11.5) to 11.5 (95% CI: 10.8, 12.2) g/dl). Higher doses of DA were needed in the "switched" than in the "naive" patients to maintain Hb levels over 11 g/dl, respectively 0.73 (95% CI: 0.54, 0.92) and 0.34 (95% CI: 0.16, 0.52) microg/kg per week. Our results indicate the doses of DA necessary to treat CRF patients aged 11 years to 18 years. DA was an effective treatment to stabilise CRF patients at extended dosing intervals.