Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP-associated CpGs are enriched for environmental response genes, growth-factor signaling, and inflammation, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth

Climate change and environmental impacts on maternal and newborn health with focus on Arctic populations

In 2007, the Intergovernmental Panel on Climate Change (IPCC) presented a report on global warming and the impact of human activities on global warming. Later the Lancet commission identified six ways human health could be affected. Among these were not environmental factors which are also believed to be important for human health. In this paper we therefore focus on environmental factors, climate change and the predicted effects on maternal and newborn health. Arctic issues are discussed specifically considering their exposure and sensitivity to long range transported contaminants. Considering that the different parts of pregnancy are particularly sensitive time periods for the effects of environmental exposure, this review focuses on the impacts on maternal and newborn health. Environmental stressors known to affects human health and how these will change with the predicted climate change are addressed. Air pollution and food security are crucial issues for the pregnant population in a changing climate, especially indoor climate and food security in Arctic areas. The total number of environmental factors is today responsible for a large number of the global deaths, especially in young children. Climate change will most likely lead to an increase in this number. Exposure to the different environmental stressors especially air pollution will in most parts of the world increase with climate change, even though some areas might face lower exposure. Populations at risk today are believed to be most heavily affected. As for the persistent organic pollutants a warming climate leads to a remobilisation and a possible increase in food chain exposure in the Arctic and thus increased risk for Arctic populations. This is especially the case for mercury. The perspective for the next generations will be closely connected to the expected temperature changes; changes in housing conditions; changes in exposure patterns; predicted increased exposure to Mercury because of increased emissions and increased biological availability. A number of environmental stressors are predicted to increase with climate change and increasingly affecting human health. Efforts should be put on reducing risk for the next generation, thus global politics and research effort should focus on maternal and newborn health

A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health

Higher maternal pre-pregnancy body mass index (ppBMI) is associated with increased neonatal morbidity, as well as with pregnancy complications and metabolic outcomes in offspring later in life. The placenta is a key organ in fetal development and has been proposed to act as a mediator between the mother and different health outcomes in children. The overall aim of the present work is to investigate the association of ppBMI with epigenome-wide placental DNA methylation (DNAm) in 10 studies from the PACE consortium, amounting to 2631 mother-child pairs. We identify 27 CpG sites at which we observe placental DNAm variations of up to 2.0% per 10 ppBMI-unit. The CpGs that are differentially methylated in placenta do not overlap with CpGs identified in previous studies in cord blood DNAm related to ppBMI. Many of the identified CpGs are located in open sea regions, are often close to obesity-related genes such as GPX1 and LGR4 and altogether, are enriched in cancer and oxidative stress pathways. Our findings suggest that placental DNAm could be one of the mechanisms by which maternal obesity is associated with metabolic health outcomes in newborns and children, although further studies will be needed in order to corroborate these findings.We would like to thank the Pregnancy and Childhood Epigenetics (PACE) consortium, as well as all the families that participated in these studies for their generous contribution. This work was partially funded by GVSAN2018111086 from the Basque Department of Health and PI18/01142 from ISCIII - Spanish Ministry of Science and Innovation - cofounded by the ERDF “A way to make Europe” to JRB and LSM, respectively; and by the Joint Programming Initiative – A Healthy Diet for a Healthy Life (JPI HDHL) (NutriPROGRAM). ACP was supported by grant GVSAN2019111085 from the Basque Department of Health to NFJ. Detailed acknowledgements and funding for each participating cohort are described in Supplementary Note 1

A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: Blood samples and raw genetic data of neonatal subjects from each cohort are governed by their respective institutions and/or government agencies, and mostly could not be shared publicly without specific approvals. For example, for data from first author cohort, California Childhood Leukemia Study (CCLS), we respectfully are unable to share raw, individual genetic data freely with other investigators. Should we be contacted by other investigators who would like to use the data; we will direct them to the California Department of Public Health Institutional Review Board to establish their own approved protocol to utilize the data, which can then be shared peer-to-peer.Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P < 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends.National Institute of Environmental Health SciencesNational Cancer InstituteUS Environmental Protection Agenc

A systematic review of neurodevelopmental effects of prenatal and postnatal organophosphate pesticide exposure

Agricultural and residential use of organophosphate (OP) pesticides has increased in recent decades after banning some persistent pesticides. Although there is evidence of the effects of OPs on neurodevelopment and behaviour in adults, limited information is available about their effects in children, who might be more vulnerable to neurotoxic compounds. This paper was aimed at analysing the scientific evidence published to date on potential neurodevelopmental and behavioural effects of prenatal and postnatal exposure to OPs. A systematic review was undertaken to identify original articles published up to December 2012 evaluating prenatal or postnatal exposure to OPs in children and effects on neurodevelopment and/or behaviour. Articles were critically compared, focusing on the methodology used to assess exposure and adverse effects, as well as potential contributing factors that may modify both exposure and outcomes, such as genetic susceptibility to certain enzymes involved in OPs metabolisation (e.g. paraoxonase-1) and gender differences. Twenty articles met the inclusion criteria, 7 of which evaluated prenatal exposure to OPs, 8 postnatal exposure and 5 both pre- and postnatal exposure. Most of the studies evaluating prenatal exposure observed a negative effect on mental development and an increase in attention problems in preschool and school children. The evidence on postnatal exposure is less consistent, although 2 studies found an increase in reaction time in schoolchildren. Some paraoxonase-1 polymorphisms could enhance the association between OPs exposure and mental and psychomotor development. A large variability in epidemiological designs and methodologies used for assessing exposure and outcome was observed across the different studies, which made comparisons difficult. Prenatal and to a lesser extent postnatal exposure to OPs may contribute to neurodevelopmental and behavioural deficits in preschool and school children. Standardised methodologies are needed to allow results to be better compared and to perform a quantitative meta-analysis before drawing any final conclusions

Mortalidad por defectos del tubo neural en México, 1980-1997

Objetivo. Describir la mortalidad en México por defectos del tubo neural, durante el periodo 1980-1997. Material y métodos. Las tasas anuales de mortalidad estatales y nacionales, por defectos del tubo neural, se calcularon por 10 000 nacidos vivos. La tendencia temporal fue evaluada por el porcentaje de cambio anual obtenido mediante un modelo de regresión de Poisson. Se calculó la razón de mortalidad, tomando la media nacional como referencia. Las tasas y las razones se representaron gráficamente en mapas. Resultados. Durante el periodo la tasa bruta de mortalidad por defectos del tubo neural fue de 5.8 por 10 000 nacidos vivos. La anencefalia fue el tipo de defecto más frecuente (37.7%), seguida de la espina bífida sin hidrocefalia (31.6%). La tendencia nacional de la mortalidad por defectos del tubo neural fue ascendente entre 1980 y 1990 (porcentaje de cambio anual 7.5 IC 95% 6.5, 8.6) y descendente entre 1990-1997 (porcentaje de cambio anual -2.3 IC 95% -3.6, -0.9). Conclusiones. Las altas tasas de mortalidad por defectos del tubo neural fueron debidas principalmente a la elevada frecuencia de las anencefalias. El incremento observado parece no ser sólo atribuible a cuestiones puramente diagnósticas o de mejora en los registros. La influencia de factores asociados a estos defectos, como determinados polimorfismos genéticos, la deficiencia de ácido fólico, la obesidad materna, la exposición laboral a plaguicidas y la pobreza deberán evaluarse mediante estudios específicos. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.htm