Grandmothers’ smoking in pregnancy is associated with a reduced prevalence of early-onset myopia

Abstract Myopia (near sightedness) is the most common vision disorder resulting in visual impairment worldwide. We tested the hypothesis that intergenerational, non-genetic heritable effects influence refractive development, using grandparental prenatal smoking as a candidate exposure. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we found that the prevalence of myopia at age 7 was lower if the paternal grandmother had smoked in pregnancy, an association primarily found among grandsons compared to granddaughters. There was a weaker, non-sex-specific, reduction in the prevalence of myopia at age 7 if the maternal grandmother had smoked in pregnancy. For children who became myopic later (between 7 and 15 years of age) there were no associations with either grandmother smoking. Differences between early and late-onset myopia were confirmed with DNA methylation patterns: there were very distinct and strong associations with methylation for early-onset but not later-onset myopia.

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Ancestral smoking and developmental outcomes: A review of publications from a population birth cohort

Biology of Reproduction ◽

10.1093/biolre/ioab124 ◽

2021 ◽

Author(s):

Jean Golding ◽

Marcus Pembrey ◽

Yasmin Iles-Caven ◽

Sarah Watkins ◽

Matthew Suderman ◽

...

Keyword(s):

Adverse Effects ◽

Smoking During Pregnancy ◽

Beneficial Effects ◽

Smoking In Pregnancy ◽

Parents And Children ◽

Paternal Grandmother ◽

Sex Specificity ◽

Using Data ◽

Offspring Health ◽

In Pregnancy

Abstract The adverse effects on the child of maternal smoking in pregnancy is well-recognised, but little research has been carried out on the possible non-genetic effects of ancestral smoking prior to the pregnancy including parental initiation of cigarette smoking in their own childhoods or a grandmother smoking during pregnancy. Here we summarise the studies that have been published mainly using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). We demonstrate evidence that ancestral smoking prior to or during pregnancy can often be beneficial for offspring health and both ancestor- and sex-specific. More specifically, we report evidence of (i) adverse effects of the father starting to smoke pre-puberty on his son’s development; (ii) beneficial effects on the grandson if his maternal grandmother had smoked in pregnancy; and (iii) mainly adverse effects on the granddaughter when the paternal grandmother had smoked in pregnancy. The ancestor- and sex-specificity of these results is consistent with earlier studies reporting associations of health and mortality with ancestral food supply in their parents’ and grandparents’ pre-pubertal childhoods.

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Grandchild’s IQ is associated with grandparental environments prior to the birth of the parents

Wellcome Open Research ◽

10.12688/wellcomeopenres.16205.2 ◽

2021 ◽

Vol 5 ◽

pp. 198

Author(s):

Jean Golding ◽

Gerard van den Berg ◽

Kate Northstone ◽

Matthew Suderman ◽

Genette Ellis ◽

...

Keyword(s):

Animal Experiments ◽

Education Level ◽

Maternal Grandfather ◽

Developmental Variation ◽

Smoking In Pregnancy ◽

Parents And Children ◽

Paternal Grandfather ◽

Paternal Grandmother ◽

Avon Longitudinal Study ◽

In Pregnancy

Background. Despite convincing animal experiments demonstrating the potential for environmental exposures in one generation to have demonstrable effects generations later, there have been few relevant human studies. Those that have been undertaken have demonstrated associations, for example, between exposures such as nutrition and cigarette smoking in the grandparental generation and outcomes in grandchildren. We hypothesised that such transgenerational associations might be associated with the IQ of the grandchild, and that it would be likely that there would be differences in results between the sexes of the grandparents, parents, and children. Method. We used three-generational data from the Avon Longitudinal Study of Parents and Children (ALSPAC). We incorporated environmental factors concerning grandparents (F0) and focussed on three exposures that we hypothesised may have independent transgenerational associations with the IQ of the grandchildren (F2): (i) UK Gross Domestic Product (GDP) at grandparental birth year; (ii) whether grandfather smoked; and (iii) whether the grandmother smoked in the relevant pregnancy. Potential confounders were ages of grandparents when the relevant parent was born, ethnic background, education level and social class of each grandparent. Results. After adjustment, all three target exposures had specific associations with measures of IQ in the grandchild. Paternal grandfather smoking was associated with reduced total IQ at 15 years; maternal grandfather smoking with reduced performance IQ at 8 years and reduced total IQ at 15. Paternal grandmother smoking in pregnancy was associated with reduced performance IQ at 8, especially in grandsons. GDP at grandparents’ birth produced independent associations of reduced IQ with higher GDP; this was particularly true of paternal grandmothers. Conclusions. These results are complex and need to be tested in other datasets. They highlight the need to consider possible transgenerational associations in studying developmental variation in populations.

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Grandchild’s IQ is associated with grandparental environments prior to the birth of the parents

Wellcome Open Research ◽

10.12688/wellcomeopenres.16205.1 ◽

2020 ◽

Vol 5 ◽

pp. 198

Author(s):

Jean Golding ◽

Gerard van den Berg ◽

Kate Northstone ◽

Matthew Suderman ◽

Genette Ellis ◽

...

Keyword(s):

Animal Experiments ◽

Education Level ◽

Maternal Grandfather ◽

Developmental Variation ◽

Smoking In Pregnancy ◽

Parents And Children ◽

Paternal Grandfather ◽

Paternal Grandmother ◽

Avon Longitudinal Study ◽

In Pregnancy

Background: In spite of convincing animal experiments demonstrating the potential for environmental exposures in one generation to have demonstrable effects generations later, there have been few relevant human studies. Those that have been undertaken have demonstrated associations, for example, between exposures such as nutrition and cigarette smoking in the grandparental generation and outcomes in grandchildren. We hypothesised that such transgenerational associations might be associated with the IQ of the grandchild, and that it would be likely that there would be differences in results between the sexes of the grandparents, parents and children. Methods: We used three-generational data from the Avon Longitudinal Study of Parents and Children (ALSPAC). We incorporated environmental factors concerning grandparents (F0) and focussed on three exposures that we hypothesised may have independent transgenerational associations with the IQ of the grandchildren (F2): (i) UK Gross Domestic Product (GDP) at grandparental birth year; (ii) whether the grandfather smoked; and (iii) whether the grandmother smoked in the relevant pregnancy. Potential confounders were ages of grandparents when the relevant parent was born, ethnic background, education level and social class of each grandparent. Results: After adjustment, all three target exposures had specific associations with measures of IQ in the grandchild. Paternal grandfather smoking was associated with reduced total IQ at 15 years; maternal grandfather smoking with reduced performance IQ at 8 years and reduced total IQ at 15. Paternal grandmother smoking in pregnancy was associated with reduced performance IQ at 8, especially in grandsons. GDP at grandparents’ birth produced independent associations of reduced IQ with higher GDP; this was particularly true of paternal grandmothers. Conclusions: These results are complex and need to be tested in other datasets. They highlight the need to consider possible transgenerational associations in studying developmental variation in populations.

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Gestation at completion of prenatal questionnaires in ALSPAC

Wellcome Open Research ◽

10.12688/wellcomeopenres.15976.2 ◽

2020 ◽

Vol 5 ◽

pp. 100

Author(s):

Yasmin Iles-Caven ◽

Kate Northstone ◽

Jean Golding

Keyword(s):

Data Collection ◽

Pregnant Women ◽

First Trimester ◽

Environmental Data ◽

Parents And Children ◽

Using Data ◽

Time Critical ◽

Avon Longitudinal Study ◽

In Pregnancy ◽

Made In

Enrolling a cohort in pregnancy can be methodologically difficult in terms of structuring data collection. For example, some exposures of interest may be time-critical while other (often retrospective) data can be collected at any point during pregnancy. The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prime example of a cohort where certain data were collected at specific time points and others at variable times depending on the gestation at contact. ALSPAC aimed to enrol as many pregnant women as possible in a geographically defined area with an expected date of delivery between April 1991 and December 1992. The ideal was to enrol women as early in pregnancy as possible, and to collect information, when possible, at two fixed gestational periods (18 and 32 weeks). A variety of methods were used to enrol participants. Approximately 80% of eligible women resident in the study area were enrolled. Gestation at enrolment ranged from 4-41 (median = 14) weeks of pregnancy. Given this variation in gestation we describe the various decisions that were made in regard to the timing of questionnaires to ensure that appropriate data were obtained from the pregnant women. 45% of women provided data during the first trimester, this is less than ideal but reflects the fact that many women do not acknowledge their pregnancy until the first trimester is safely completed. Data collection from women at specific gestations (18 and 32 weeks) was much more successful (80-85%). Unfortunately, it was difficult to obtain environmental data during the first trimester. Given the time critical nature of exposures during this trimester, researchers must take the gestational age at which environmental data was collected into account. This is particularly important for data collected using the questionnaire named ‘Your Environment’ (using data known as the A files).

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Association of intrauterine alcohol exposure and offspring depression: A negative control analysis of maternal and partner consumption

10.1101/307462 ◽

2018 ◽

Author(s):

Kayleigh E Easey ◽

Nicholas J Timpson ◽

Marcus R Munafò

Keyword(s):

Alcohol Exposure ◽

Negative Control ◽

Adverse Outcomes ◽

Control Analysis ◽

Parents And Children ◽

Increased Risk ◽

Control Comparison ◽

Using Data ◽

Residual Confounding ◽

In Pregnancy

AbstractBackgroundPrevious research has suggested that intrauterine alcohol exposure is associated with a variety of adverse outcomes in offspring. However, few studies have investigated its association with offspring internalising disorders in late adolescence.MethodsUsing data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated the associations of maternal drinking in pregnancy with offspring depression at age 18. We also examined partner drinking as a negative control for intrauterine exposure for comparison.ResultsOffspring of mothers that consumed any alcohol at 18 weeks gestation were at increased risk of having a diagnosis of depression (OR 1.15, 95% CI 1.00 to 1.32), but there was no clear evidence of association between partners alcohol consumption during pregnancy and increased risk of offspring depression (OR 0.90, 95% CI 0.78 to 1.04).ConclusionsMaternal drinking in pregnancy was associated with increased risk of offspring depression at age 18. Residual confounding may explain this association, but the negative control comparison of paternal drinking provides some evidence that it may be causal, and this warrants further investigation.

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Patients with Alzheimer's disease have increased cellular amyloid uptake

10.1101/2022.01.12.22269196 ◽

2022 ◽

Author(s):

Dmitry V Zaretsky ◽

Maria V Zaretskaia ◽

Yaroslav I Molkov

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Onset ◽

Late Onset ◽

Strong Negative Correlation ◽

Cognitively Normal ◽

Intracellular Degradation ◽

Estimated Parameters ◽

Amyloid Aβ ◽

Using Data

Amyloid plaques are the main signature of Alzheimer's disease (AD). Beta-amyloid (Aβ) concentration in cerebrospinal fluid (CSF-Aβ) and the density of amyloid depositions have a strong negative correlation. However, AD patients have lower CSF-Aβ levels compared to cognitively normal people even after accounting for this correlation. The goal of this study was to infer variations of parameters in Aβ metabolism of AD patients that underlie this difference using data from the Alzheimer's Disease Neuroimaging Initiative cohort. We found that AD patients had dramatically increased rates of cellular amyloid uptake compared to individuals with normal cognition (NC). A group with late-onset mild cognitive impairment (LMCI) also exhibited stronger amyloid uptake, however this was less pronounced than in the AD group. Estimated parameters in the early-onset MCI group did not differ significantly from those in the NC group. Aβ cytotoxicity depends on both the amount of peptide internalized by cells and its intracellular degradation into toxic products. Based on our results, we speculate that AD and LMCI are associated with increased cellular amyloid uptake which leads to faster disease progression, whereas the early-onset MCI may be mediated by the increased production of toxic amyloid metabolites.

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The association of maternal-fetal attachment with smoking and smoking cessation during pregnancy in The FinnBrain Birth Cohort Study

BMC Pregnancy and Childbirth ◽

10.1186/s12884-020-03393-x ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Heidi Jussila ◽

Juho Pelto ◽

Riikka Korja ◽

Eeva Ekholm ◽

Marjukka Pajulo ◽

...

Keyword(s):

Smoking Cessation ◽

Cohort Study ◽

Early Pregnancy ◽

Smoking Behavior ◽

Birth Cohort Study ◽

Prenatal Smoking ◽

Smoking In Pregnancy ◽

Maternal Fetal Attachment ◽

Fetal Attachment ◽

In Pregnancy

Abstract Background Smoking in pregnancy constitutes a preventable risk factor for fetal/child development and maternal-fetal attachment (MFA) seems to contain a momentum that can break the chain of adverse outcomes by promoting maternal prenatal health practices. This study aimed to explore the association of MFA with smoking at any time during pregnancy and smoking cessation in early pregnancy, and the modifying role of MFA on the expected effects of education and prenatal psychological distress (PPD) on prenatal smoking behavior. Methods The pregnant women (n = 3766) participated in the The FinnBrain Birth Cohort Study in Finland between December 2011 and April 2015. The binary outcomes, smoking at any time during pregnancy and smoking cessation in early pregnancy, were obtained from self-reports at gestational weeks (gwks) 14 and 34 and The Finnish Medical Birth Register. MFA was assessed with the Maternal-Fetal Attachment Scale (MFAS) at gwks 24 and 34. Logistic regression analyses were used to determine the association between MFA and maternal prenatal smoking behavior. Findings The prevalence of smoking was 16.5%, and 58.1% of the smokers quit smoking during pregnancy. The independent associations of total MFA scores with prenatal smoking behavior were not established (aOR = 1.00-1.02, multiplicity adjusted p > 0.05). A higher score in the altruistic subscale of MFA, Giving of self, associated with a higher probability of smoking cessation (24 gwks: aOR = 1.13, 95% CI [1.04, 1.24], p = 0.007, multiplicity adjusted p = 0.062; 34 gwks: aOR = 1.17, 95% CI [1.07, 1.29], p < 0.001, multiplicity adjusted p = 0.008). The modifying effect of MFA on the observed associations between PPD and smoking in pregnancy and between maternal education and smoking in pregnancy / smoking cessation in early pregnancy was not demonstrated. Conclusions The altruistic dimension of maternal-fetal attachment associates with an increased probability of smoking cessation during pregnancy and therefore strengthening altruistic maternal-fetal attachment may constitute a promising novel approach for interventions aiming at promoting smoking cessation during pregnancy.

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Neonatal DNA methylation and early-onset conduct problems: A genome-wide, prospective study

Development and Psychopathology ◽

10.1017/s095457941700092x ◽

2017 ◽

Vol 30 (2) ◽

pp. 383-397 ◽

Cited By ~ 19

Author(s):

Charlotte A. M. Cecil ◽

Esther Walton ◽

Sara R. Jaffee ◽

Tom O'Connor ◽

Barbara Maughan ◽

...

Keyword(s):

Dna Methylation ◽

Conduct Problems ◽

Early Onset ◽

Pain Perception ◽

Poor Mental Health ◽

Monoamine Oxidase A ◽

Fk506 Binding Protein ◽

Parents And Children ◽

A Genome ◽

Using Data

AbstractEarly-onset conduct problems (CP) are a key predictor of adult criminality and poor mental health. While previous studies suggest that both genetic and environmental risks play an important role in the development of early-onset CP, little is known about potential biological processes underlying these associations. In this study, we examined prospective associations between DNA methylation (cord blood at birth) and trajectories of CP (4–13 years), using data drawn from the Avon Longitudinal Study of Parents and Children. Methylomic variation at seven loci across the genome (false discovery rate < 0.05) differentiated children who go on to develop early-onset (n= 174) versus low (n= 86) CP, including sites in the vicinity of the monoglyceride lipase (MGLL) gene (involved in endocannabinoid signaling and pain perception). Subthreshold associations in the vicinity of three candidate genes for CP (monoamine oxidase A [MAOA], brain-derived neurotrophic factor [BDNF], and FK506 binding protein 5 [FKBP5]) were also identified. Within the early-onset CP group, methylation levels of the identified sites did not distinguish children who will go on to persist versus desist in CP behavior over time. Overall, we found that several of the identified sites correlated with prenatal exposures, and none were linked to known genetic methylation quantitative trait loci. Findings contribute to a better understanding of epigenetic patterns associated with early-onset CP.

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Histological Features of Shallow Placental Implantation Unify Early-Onset and Late-Onset Preeclampsia

Pediatric and Developmental Pathology ◽

10.1177/1093526618803759 ◽

2018 ◽

Vol 22 (2) ◽

pp. 112-122 ◽

Cited By ~ 13

Author(s):

Jerzy Stanek

Keyword(s):

Early Onset ◽

Late Onset ◽

Unknown Etiology ◽

Hypertension In Pregnancy ◽

Pathological Mechanism ◽

Comparative Group ◽

Laminar Necrosis ◽

Chronic Villitis ◽

Early Onset Preeclampsia ◽

In Pregnancy

Preeclampsia is distinguishable from other hypertensive conditions of pregnancy by its high rates of decidual arteriopathy, the uterine type of chronic hypoxic placental injury, the occurrence of villous infarctions, and clusters of multinucleate trophoblasts in the maternal floor. To retrospectively study the clinical and placental phenotypes of 230 women with early-onset preeclampsia, 261 women with late-onset preeclampsia, and 5059 women without hypertension in pregnancy (comparative group), 24 clinical and 46 placental phenotypes were statistically compared (analysis of variance, χ2 with Bonferroni correction). The frequency of decidual arteriopathy (both hypertrophic and atherosis), patterns of chronic hypoxic placental injury, villous infarction, membrane laminar necrosis, membrane microscopic chorionic pseudocysts, clusters of maternal floor multinucleated trophoblasts, excessive number of extravillous trophoblasts, and intervillous thrombi was strikingly higher in both late-onset preeclampsia and early-onset preeclampsia than in the comparative group without hypertension in pregnancy. All 3 patterns of chronic hypoxic placental injury were 2- to 3-fold more common in preeclampsia. Although the preuterine pattern was as common in early-onset preeclampsia as it was in late-onset preeclampsia, the postuterine pattern was 2-fold more common in early-onset preeclampsia, and chronic villitis of unknown etiology was more common in late-onset preeclampsia than in the other 2 groups. Features of shallow placental implantation occurred at the same frequency in early-onset preeclampsia as in late-onset preeclampsia, which reflects an underlying common pathological mechanism in both subgroups of preeclampsia, while hypoxic lesions and patterns of placental injury were more common in early-onset preeclampsia than in late-onset preeclampsia, which correlates with more severe clinical outcomes of the former.

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