Estimation of Saliva Cotinine Cut-Off Points for Active and Passive Smoking during Pregnancy-Polish Mother and Child Cohort (REPRO_PL)

A reliable assessment of smoking status has significant public health implications and is essential for research purposes. The aim of this study was to determine optimal saliva cotinine cut-off values for smoking during pregnancy. The analyses were based on data from 1771 women from the Polish Mother and Child Cohort. Saliva cotinine concentrations were assessed by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-ESI + MS/MS). The saliva cotinine cut-off value for active smoking was established at 10 ng/mL (sensitivity 96%, specificity 95%) and for passive smoking at 1.5 ng/mL (sensitivity 63%, specificity 71%). About 5% of the self-reported non-smoking women were classified as smokers based on the cotinine cut-off value. Significantly more younger, single, and less educated self-reported non-smokers had a cotinine concentration higher than 10 ng/mL compared to those who were older, married, and who had a university degree. Close to 30% of the non-smokers who indicated that smoking was not allowed in their home could be classified as exposed to passive smoking based on the cut-off value. The study suggests that self-reported smoking status is a valid measure of active smoking, whereas in the case of passive smoking, a combination of questionnaire data and biomarker verification may be required

Environmental Tobacco Smoke Exposure during Pregnancy and Child Neurodevelopment

The developing fetus is especially vulnerable to environmental toxicants, including tobacco constituents. The aim of this study was to assess the impact of environmental tobacco smoke (ETS) exposure during pregnancy on child neurodevelopment within the first two years of life. The study population consisted of 461 non-smoking pregnant women (saliva cotinine level <10 ng/mL). Maternal passive smoking was assessed based on the cotinine level in saliva analyzed by the use of high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-ESI + MS/MS) and by questionnaire data. The cotinine cut-off value for passive smoking was established at 1.5 ng/mL (sensitivity 63%, specificity 71%). Psychomotor development was assessed in children at the age of one- and two-years using the Bayley Scales of Infant and Toddler Development. Approximately 30% of the women were exposed to ETS during pregnancy. The multivariate linear regression model indicated that ETS exposure in the 1st and the 2nd trimesters of pregnancy were associated with decreasing child language functions at the age of one (β = -3.0, p = 0.03, and β = -4.1, p = 0.008, respectively), and two years (β = -3.8, p = 0.05, and β = -6.3, p = 0.005, respectively). A negative association was found for cotinine level ≥1.5 ng/mL in the 2nd trimester of pregnancy and child cognition at the age of 2 (β = -4.6, p = 0.05), as well as cotinine levels ≥1.5 ng/mL in all trimesters of pregnancy and child motor abilities at two years of age (β = -3.9, p = 0.06, β = -5.3, p = 0.02, and β = -4.2, p = 0.05, for the 1st, the 2nd, and the 3rd trimester of pregnancy, respectively; for the 1st trimester the effect was of borderline statistical significance). This study confirmed that ETS exposure during pregnancy can have a negative impact on child psychomotor development within the first two years of life and underscore the importance of public health interventions aiming at reducing this exposure

Maternal stress during pregnancy and neurodevelopmental outcomes of children during the first 2 years of life

AIM: A growing body of literature documents associations between maternal stress in pregnancy and child development, but findings across studies are often inconsistent. The aim of this study was to estimate the association between exposure to different kinds of prenatal stress and child psychomotor development. METHODS: The study population consisted of 372 mother-child pairs from Polish Mother and Child Cohort. The analysis was restricted to the women who worked at least 1 month during pregnancy period. Maternal psychological stress during pregnancy was assessed based on: the Subjective Work Characteristics Questionnaire, Perceived Stress Scale and Social Readjustment Rating Scale. The level of satisfaction with family functioning and support was evaluated by APGAR Family Scale. Child psychomotor development was assessed at the 12th and 24th months of age by Bayley Scales of Infant and Toddler Development. RESULTS: Negative impact on child cognitive development at the age of two was observed for the Perceived Stress Scale (β = -0.8; P = 0.01) and the Social Readjustment Rating Scale (β = -0.4; P = 0.03) after adjusting for the variety of confounders. Occupational stress, as well as satisfaction with family functioning, was not significantly associated with child psychomotor development (P > 0.05). CONCLUSIONS: The study supports the findings that prenatal exposure to maternal stress is significantly associated with decreased child cognitive functions. In order to further understand and quantify the effects of prenatal stress on child neurodevelopment further studies are needed. This will be important for developing interventions that provide more assistance to pregnant women, including emotional support or help to manage psychological stress

Micronutrients during pregnancy and child psychomotor development: Opposite effects of Zinc and Selenium

Studies on the impact of micronutrient levels during different pregnancy periods on child psychomotor functions are limited. The aim of this study was to evaluate the association between maternal plasma concentrations of selected micronutrients, such as: copper (Cu), zinc (Zn), selenium (Se), and child neuropsychological development. The study population consisted of 539 mother-child pairs from Polish Mother and Child Cohort (REPRO_PL). The micronutrient levels were measured in each trimester of pregnancy, at delivery and in the cord blood. Psychomotor development was assessed in children at the age of 1 and 2 years using the Bayley Scales of Infant and Toddler Development. The mean plasma Zn, Cu and Se concentrations in the 1st trimester of pregnancy were 0.91±0.27mg/l, 1.98±0.57mg/l and 48.35±10.54μg/l, respectively. There were no statistically significant associations between Cu levels and any of the analyzed domains of child development. A positive association was observed between Se level in the 1st trimester of pregnancy and child language and motor skills (β=0.18, p=0.03 and β=0.25, p=0.005, respectively) at one year of age. Motor score among one-year-old children decreased along with increasing Zn levels in the 1st trimester of pregnancy and in the cord blood (β=-12.07, p=0.003 and β=-6.51, p=0.03, respectively). A similar pattern was observed for the association between Zn level in the 1st trimester of pregnancy and language abilities at one year of age (β=-7.37, p=0.05). Prenatal Zn and Se status was associated with lower and higher child psychomotor abilities, respectively, within the first year of life. Further epidemiological and preclinical studies are necessary to confirm the associations between micronutrient levels and child development as well as to elucidate the underlying mechanisms of their effects

Identification and characterization of an inhibitory fibroblast growth factor receptor 2 (FGFR2) molecule, up-regulated in an Apert Syndrome mouse model

AS (Apert syndrome) is a congenital disease composed of skeletal, visceral and neural abnormalities, caused by dominant-acting mutations in FGFR2 [FGF (fibroblast growth factor) receptor 2]. Multiple FGFR2 splice variants are generated through alternative splicing, including PTC (premature termination codon)-containing transcripts that are normally eliminated via the NMD (nonsense-mediated decay) pathway. We have discovered that a soluble truncated FGFR2 molecule encoded by a PTC-containing transcript is up-regulated and persists in tissues of an AS mouse model. We have termed this IIIa–TM as it arises from aberrant splicing of FGFR2 exon 7 (IIIa) into exon 10 [TM (transmembrane domain)]. IIIa–TM is glycosylated and can modulate the binding of FGF1 to FGFR2 molecules in BIAcore-binding assays. We also show that IIIa–TM can negatively regulate FGF signalling in vitro and in vivo. AS phenotypes are thought to result from gain-of-FGFR2 signalling, but our findings suggest that IIIa–TM can contribute to these through a loss-of-FGFR2 function mechanism. Moreover, our findings raise the interesting possibility that FGFR2 signalling may be a regulator of the NMD pathway

Combinatorial Roles of Heparan Sulfate Proteoglycans and Heparan Sulfates in Caenorhabditis elegans Neural Development

Heparan sulfate proteoglycans (HSPGs) play critical roles in the development and adult physiology of all metazoan organisms. Most of the known molecular interactions of HSPGs are attributed to the structurally highly complex heparan sulfate (HS) glycans. However, whether a specific HSPG (such as syndecan) contains HS modifications that differ from another HSPG (such as glypican) has remained largely unresolved. Here, a neural model in C. elegans is used to demonstrate for the first time the relationship between specific HSPGs and HS modifications in a defined biological process in vivo. HSPGs are critical for the migration of hermaphrodite specific neurons (HSNs) as genetic elimination of multiple HSPGs leads to 80% defect of HSN migration. The effects of genetic elimination of HSPGs are additive, suggesting that multiple HSPGs, present in the migrating neuron and in the matrix, act in parallel to support neuron migration. Genetic analyses suggest that syndecan/sdn-1 and HS 6-O-sulfotransferase, hst-6, function in a linear signaling pathway and glypican/lon-2 and HS 2-O-sulfotransferase, hst-2, function together in a pathway that is parallel to sdn-1 and hst-6. These results suggest core protein specific HS modifications that are critical for HSN migration. In C. elegans, the core protein specificity of distinct HS modifications may be in part regulated at the level of tissue specific expression of genes encoding for HSPGs and HS modifying enzymes. Genetic analysis reveals that there is a delicate balance of HS modifications and eliminating one HS modifying enzyme in a compromised genetic background leads to significant changes in the overall phenotype. These findings are of importance with the view of HS as a critical regulator of cell signaling in normal development and disease