Accelerated epigenetic aging at birth interacts with parenting hostility to predict child temperament and subsequent psychological symptoms

Abstract In an effort to elucidate new factors that may contribute to developmental psychopathology, the current study examined whether accelerated epigenetic aging at birth related to children's differential susceptibility to the effects of aversive parenting on early emerging mental health risk. Using data from a multiethnic birth cohort, the interaction between Horvath's methylation age in umbilical cord blood and hostile parenting behaviors was examined in relation to perceptions of infant's temperament at 6 months and to children's psychological symptoms at 3 years in 154 families. Results broadly revealed that children with higher levels of accelerated methylation aging evinced more unpredictable temperaments and more psychological symptoms if their mothers reported more hostile parenting, but showed fewer difficulties if mothers engaged in less hostile parenting; children with lower levels of accelerated methylation age did not show associations between hostility and temperament or psychological symptoms. Effects were not accounted for by gestational age at birth, demographic factors, or the distribution of cell subtypes. These findings suggest that accelerated epigenetic age may function as a form of differential susceptibility, signaling increased risk for psychopathology in more aversive contexts but decreased risk in less aversive early environments. Taken together, they point to a novel biological process to consider within risk for psychopathology.

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512: Are appropriately sized fetuses who “fall off the curve” at increased risk for small-for-gestational age at birth?

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2017.11.038 ◽

2018 ◽

Vol 218 (1) ◽

pp. S306-S307

Author(s):

Nathan R. Blue ◽

Mariam Savabi ◽

Meghan E. Beddow ◽

Vivek R. Katukuri ◽

Cody M. Fritts ◽

...

Keyword(s):

Gestational Age ◽

Small For Gestational Age ◽

Increased Risk ◽

Gestational Age At Birth ◽

Age At Birth

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Risk of hypertension into adulthood in persons born prematurely: a national cohort study

European Heart Journal ◽

10.1093/eurheartj/ehz904 ◽

2019 ◽

Vol 41 (16) ◽

pp. 1542-1550 ◽

Cited By ~ 7

Author(s):

Casey Crump ◽

Jan Sundquist ◽

Kristina Sundquist

Keyword(s):

Cohort Study ◽

Preterm Birth ◽

Environmental Factors ◽

Gestational Age ◽

Large Population ◽

Increased Risk ◽

Extremely Preterm ◽

National Cohort ◽

Gestational Age At Birth ◽

Age At Birth

Abstract Aims Preterm birth has been associated with elevated blood pressure early in life; however, hypertension risks from childhood into adulthood remain unclear. We conducted a large population-based study to examine gestational age at birth in relation to hypertension risks from childhood into adulthood. Methods and results A national cohort study was conducted of all 4 193 069 singleton live births in Sweden during 1973–2014, who were followed up for hypertension identified from nationwide inpatient and outpatient (specialty and primary care) diagnoses from any health care encounters through 2015 (maximum age 43 years; median 22.5). Cox regression was used to examine gestational age at birth in relation to hypertension risk while adjusting for other perinatal and maternal factors, and co-sibling analyses assessed the potential influence of unmeasured shared familial (genetic and/or environmental) factors. In 86.8 million person-years of follow-up, 62 424 (1.5%) persons were identified with hypertension (median age 29.8 years at diagnosis). Adjusted hazard ratios for new-onset hypertension at ages 18–29 years associated with preterm (<37 weeks) and extremely preterm (22–27 weeks) birth were 1.28 [95% confidence interval (CI), 1.21–1.36] and 2.45 (1.82–3.31), respectively, and at ages 30–43 years were 1.25 (1.18–1.31) and 1.68 (1.12–2.53), respectively, compared with full-term birth (39–41 weeks). These associations affected males and females similarly and appeared substantially related to shared genetic or environmental factors in families. Conclusions In this large national cohort, preterm birth was associated with increased risk of hypertension into early adulthood. Persons born prematurely may need early preventive evaluation and long-term monitoring for the development of hypertension.

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High-Dose Erythropoietin in Extremely Low Gestational Age Neonates Does Not Alter Risk of Retinopathy of Prematurity

Neonatology ◽

10.1159/000511262 ◽

2020 ◽

pp. 1-8

Author(s):

Dennis E. Mayock ◽

Zimeng Xie ◽

Bryan A. Comstock ◽

Patrick J. Heagerty ◽

Sandra E. Juul ◽

...

Keyword(s):

Birth Weight ◽

Gestational Age ◽

Retinopathy Of Prematurity ◽

High Frequency ◽

High Dose ◽

Heart Murmur ◽

Treatment Groups ◽

Increased Risk ◽

Gestational Age At Birth ◽

Age At Birth

Introduction: The Preterm Erythropoietin (Epo) Neuroprotection (PENUT) Trial sought to determine the safety and efficacy of early high-dose Epo as a potential neuroprotective treatment. We hypothesized that Epo would not increase the incidence or severity of retinopathy of prematurity (ROP). Methods: A total of 941 infants born between 24–0/7 and 27–6/7 weeks’ gestation were randomized to 1,000 U/kg Epo or placebo intravenously for 6 doses, followed by subcutaneous or sham injections of 400 U/kg Epo 3 times a week through 32 weeks post-menstrual age. In this secondary analysis of PENUT trial data, survivors were evaluated for ROP. A modified intention-to-treat approach was used to compare treatment groups. In addition, risk factors for ROP were evaluated using regression methods that account for multiples and allow for adjustment for treatment and gestational age at birth. Results: Of 845 subjects who underwent ROP examination, 503 were diagnosed with ROP with similar incidence and severity between treatment groups. Gestational age at birth, birth weight, prenatal magnesium sulfate, maternal antibiotic exposure, and presence of heart murmur at 2 weeks predicted the development of any ROP, while being on high-frequency oscillator or high-frequency jet ventilation (HFOV/HFJV) at 2 weeks predicted severe ROP. Conclusion: Early high-dose Epo followed by maintenance dosing through 32 weeks does not increase the risk of any or severe ROP in extremely low gestational age neonates. Gestational age, birth weight, maternal treatment with magnesium sulfate, antibiotic use during pregnancy, and presence of a heart murmur at 2 weeks were associated with increased risk of any ROP. Treatment with HFOV/HFJV was associated with an increased risk of severe ROP.

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Gestational age at birth and child special educational needs: a UK representative birth cohort study

Archives of Disease in Childhood ◽

10.1136/archdischild-2020-320213 ◽

2021 ◽

pp. archdischild-2020-320213

Author(s):

Neora Alterman ◽

Samantha Johnson ◽

Claire Carson ◽

Stavros Petrou ◽

Oliver Rivero-Arias ◽

...

Keyword(s):

Cohort Study ◽

Gestational Age ◽

Sociodemographic Factors ◽

Educational Needs ◽

Birth Cohort Study ◽

Special Educational Needs ◽

Early Term ◽

Increased Risk ◽

Gestational Age At Birth ◽

Age At Birth

ObjectiveTo examine the association between gestational age at birth across the entire gestational age spectrum and special educational needs (SENs) in UK children at 11 years of age.MethodsThe Millennium Cohort Study is a nationally representative longitudinal sample of children born in the UK during 2000–2002. Information about the child’s birth, health and sociodemographic factors was collected when children were 9 months old. Information about presence and reasons for SEN was collected from parents at age 11. Adjusted relative risks (aRRs) were estimated using modified Poisson regression, accounting for confounders.ResultsThe sample included 12 081 children with data at both time points. The overall prevalence of SEN was 11.2%, and it was inversely associated with gestational age. Among children born <32 weeks of gestation, the prevalence of SEN was 27.4%, three times higher than among those born at 40 weeks (aRR=2.89; 95% CI 2.02 to 4.13). Children born early term (37–38 weeks) were also at increased risk for SEN (aRR=1.33; 95% CI 1.11 to 1.59); this was the same when the analysis was restricted to births after labour with spontaneous onset. Birth before full term was more strongly associated with having a formal statement of SEN or SEN for multiple reasons.ConclusionChildren born at earlier gestational ages are more likely to experience SEN, have more complex SEN and require support in multiple facets of learning. This association was observed even among children born early-term and when labour began spontaneously.

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Increased Risk Of Early-Onset Neonatal Sepsis After Laser Surgery For Twin-to-Twin Transfusion Syndrome

Twin Research and Human Genetics ◽

10.1017/thg.2016.21 ◽

2016 ◽

Vol 19 (3) ◽

pp. 234-240 ◽

Cited By ~ 3

Author(s):

Liselotte E. M. van Kempen ◽

Depeng Zhao ◽

Sylke J. Steggerda ◽

Vincent Bekker ◽

Johanna M. Middeldorp ◽

...

Keyword(s):

Blood Culture ◽

Positive Blood Culture ◽

Gestational Age ◽

Neonatal Sepsis ◽

Early Onset ◽

Laser Surgery ◽

Premature Delivery ◽

Increased Risk ◽

Gestational Age At Birth ◽

Age At Birth

Objective: To investigate the occurrence of early-onset neonatal sepsis (EOS) in twin–twin transfusion syndrome (TTTS) managed with laser surgery.Study design: We performed a prospective cohort study of all consecutive TTTS cases treated with laser surgery (TTTS group) delivered at the Leiden University Medical Center. We recorded the occurrence of EOS, defined as a positive blood culture ≤72 hours postpartum (proven sepsis) or administration of a full course of antibiotics due to risk factors or signs of sepsis, in the absence of a positive blood culture (suspected sepsis). Perinatal variables in the TTTS group were compared with uncomplicated monochorionic twins (no-TTTS group). A multivariate model was generated, examining the association between EOS and gestational age at birth, interval between laser surgery and birth, anterior placenta, laser period (first study period: 2002–2008; second study period: 2009–2015), and preterm premature rupture of membranes (PPROM).Results: The rates of combined suspected and proven EOS in the TTTS group and no-TTTS group were 16% (68/416) and 10% (55/542), respectively (relative ratio [RR] 1.74, 95% confidence interval [CI] 1.19–2.55). Multivariate analysis showed that EOS in the TTTS group was independently associated with lower gestational age at birth (odds ratio [OR] 0.75, 95% CI 0.63–0.88), first study period (OR 2.25, 95% CI 1.08–4.67) and PPROM (OR 2.47, 95% CI 1.28–4.75).Conclusion: The rate of EOS in the TTTS group is low, but increased compared to the no-TTTS group. EOS in TTTS is independently associated with premature delivery, earlier laser period, and PPROM.

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Preterm birth, low fetal growth and risk of suicide in adulthood: a national cohort and co-sibling study

International Journal of Epidemiology ◽

10.1093/ije/dyab038 ◽

2021 ◽

Author(s):

Casey Crump ◽

Jan Sundquist ◽

Kenneth S Kendler ◽

Alexis C Edwards ◽

Kristina Sundquist

Keyword(s):

Preterm Birth ◽

Environmental Factors ◽

Fetal Growth ◽

Gestational Age ◽

Cox Regression ◽

Suicide Death ◽

Increased Risk ◽

National Cohort ◽

Gestational Age At Birth ◽

Age At Birth

Abstract Background Adverse perinatal exposures have been associated with psychiatric disorders and suicidal behaviours later in life. However, the independent associations of gestational age at birth or fetal growth with suicide death, potential sex-specific differences, and causality of these associations are unclear. Methods A national cohort study was conducted of all 2 440 518 singletons born in Sweden during 1973–98 who survived to age 18 years, who were followed up through 2016. Cox regression was used to compute hazard ratios (HRs) for suicide death associated with gestational age at birth or fetal growth while mutually adjusting for these factors, sociodemographic characteristics and family history of suicide. Co-sibling analyses assessed the influence of unmeasured shared familial (genetic and/or environmental) factors. Results In 31.2 million person-years of follow-up, 4470 (0.2%) deaths by suicide were identified. Early preterm birth (22–33 weeks) was associated with an increased risk of suicide among females [adjusted hazard ratio (HR), 1.97; 95% confidence interval CI), 1.29, 3.01; P = 0.002) but not males (0.90; 0.64, 1.28; P = 0.56), compared with full-term birth (39–41 weeks). Small for gestational age was associated with a modestly increased risk of suicide among females (adjusted HR, 1.27; 95% CI, 1.08, 1.51; P = 0.005) and males (1.14; 1.03, 1.27; P = 0.02). However, these associations were attenuated and non-significant after controlling for shared familial factors. Conclusions In this large national cohort, preterm birth in females and low fetal growth in males and females were associated with increased risks of suicide death in adulthood. However, these associations appeared to be non-causal and related to shared genetic or prenatal environmental factors within families.

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Black American Maternal Prenatal Choline, Offspring Gestational Age at Birth, and Developmental Predisposition to Mental Illness

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa171 ◽

2020 ◽

Author(s):

Sharon K Hunter ◽

M Camille Hoffman ◽

Lizbeth McCarthy ◽

Angelo D’Alessandro ◽

Anna Wyrwa ◽

...

Keyword(s):

Pregnant Women ◽

Gestational Age ◽

Black Americans ◽

Mental Illnesses ◽

Black American ◽

American Women ◽

Black American Women ◽

Increased Risk ◽

Gestational Age At Birth ◽

Age At Birth

Abstract Black Americans have increased risk for schizophrenia and other mental illnesses with prenatal origins. Prenatal choline promotes infant brain development and behavioral outcomes, but choline has not been specifically assessed in Black Americans. Pregnant women (N = 183, N = 25 Black Americans) enrolled in a study of prenatal stressors and interactions with prenatal choline. Black American women had lower 16-week gestation plasma choline than Whites. Lower choline was not related to obesity, income, or metabolic genotypes. Pregnant women in rural Uganda have higher choline levels than Black American women. Black Americans’ lower choline was associated with higher hair cortisol, indicative of higher stress. Lower maternal choline was associated with offsprings’ lower gestational age at birth and with decreased auditory P50 inhibition, a marker of inhibitory neuron development. Behavioral development was assessed on the Infant Behavior Questionnaire-R-SF (IBQ-R) at 3 months. Lower Black American maternal gestational choline was associated with lower infant IBQ-R Orienting/Regulation, indicating decreased attention and relation to caregivers. Additional evidence for developmental effects of choline in Black Americans comes from a randomized clinical trial of gestational phosphatidylcholine supplementation versus placebo that included 15 Black Americans. Phosphatidylcholine increased gestational age at birth and newborn P50 inhibition and decreased Social Withdrawn and Attention problems at 40 months of age in Black Americans’ offspring compared to placebo. Inhibitory and behavioral deficits associated with lower prenatal choline in offspring of Black American women indicate potential developmental predispositions to later mental illnesses that might be ameliorated by prenatal choline or phosphatidylcholine supplementation.

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Greater genetic risk for adult psychiatric diseases increases vulnerability to adverse outcome after preterm birth

Scientific Reports ◽

10.1038/s41598-021-90045-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Harriet Cullen ◽

Saskia Selzam ◽

Konstantina Dimitrakopoulou ◽

Robert Plomin ◽

A. David Edwards

Keyword(s):

Bipolar Disorder ◽

Preterm Birth ◽

Gestational Age ◽

Interaction Effect ◽

Genetic Risk ◽

Autism Spectrum ◽

Cognitive Outcome ◽

Increased Risk ◽

Gestational Age At Birth ◽

Age At Birth

AbstractPreterm birth is an extreme environmental stress associated with an increased risk of later cognitive dysfunction and mental health problems. However, the extent to which preterm birth is modulated by genetic variation remains largely unclear. Here, we test for an interaction effect between psychiatric polygenic risk and gestational age at birth on cognition at age four. Our sample comprises 4934 unrelated individuals (2066 individuals born < 37 weeks, 918 born < = 34 weeks). Genome-wide polygenic scores (GPS’s) were calculated for each individual for five different psychiatric pathologies: Schizophrenia, Bipolar Disorder, Major Depressive Disorder, Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder. Linear regression modelling was used to estimate the interaction effect between psychiatric GPS and gestational age at birth (GA) on cognitive outcome for the five psychiatric disorders. We found a significant interaction effect between Schizophrenia GPS and GA (β = 0.038 ± 0.013, p = 6.85 × 10–3) and Bipolar Disorder GPS and GA (β = 0.038 ± 0.014, p = 6.61 × 10–3) on cognitive outcome. Individuals with greater genetic risk for Schizophrenia or Bipolar Disorder are more vulnerable to the adverse effects of birth at early gestational age on brain development, as assessed by cognition at age four. Better understanding of gene-environment interactions will inform more effective risk-reducing interventions for this vulnerable population.

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Gestational age at birth and wheezing trajectories at 3–11 years

Archives of Disease in Childhood ◽

10.1136/archdischild-2017-314541 ◽

2018 ◽

Vol 103 (12) ◽

pp. 1138-1144 ◽

Cited By ~ 4

Author(s):

Caroline Leps ◽

Claire Carson ◽

Maria A Quigley

Keyword(s):

Medication Use ◽

Asthma Medication ◽

The Other ◽

Millennium Cohort Study ◽

Increased Risk ◽

Uk Millennium Cohort Study ◽

The Uk ◽

Gestational Age At Birth ◽

Age At Birth

ObjectiveChildren born preterm have an increased risk of asthma in early childhood. We examined whether this persists at 7 and 11 years, and whether wheezing trajectories across childhood are associated with preterm birth.DesignData were from the UK Millennium Cohort Study, which recruited children at 9 months, with follow-up at 3, 5, 7 and 11 years.OutcomesAdjusted ORs (aOR) were estimated for recent wheeze and asthma medication use for children born <32, 32–33, 34–36 and 37–38 weeks’ gestation, compared with children born at full term (39–41 weeks) at 7 (n=12 198) and 11 years (n=11 690). aORs were also calculated for having ‘early-remittent’ (wheezing at ages 3 and/or 5 years but not after), ‘late’ (wheezing at ages 7 and/or 11 years but not before) or ‘persistent/relapsing’ (wheezing at ages 3 and/or 5 and 7 and/or 11 years) wheeze.ResultsBirth <32 weeks, and to a lesser extent at 32–33 weeks, were associated with an increased risk of wheeze and asthma medication use at ages 7 and 11, and all three wheezing trajectories. The aOR for ‘persistent/relapsing wheeze’ at <32 weeks was 4.30 (95% CI 2.33 to 7.91) and was 2.06 (95% CI 1.16 to 2.69) at 32–33 weeks. Birth at 34–36 weeks was not associated with asthma medication use at 7 or 11, nor late wheeze, but was associated with the other wheezing trajectories. Birth at 37–38 weeks was not associated with wheeze nor asthma medication use.ConclusionsBirth <37 weeks is a risk factor for wheezing characterised as ‘early-remittent’ or ‘persistent/relapsing’ wheeze.

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Accelerated Epigenetic Aging in Peripheral Blood Does not Predict Dementia Risk

Current Alzheimer Research ◽

10.2174/1567205018666210823100721 ◽

2021 ◽

Vol 18 ◽

Author(s):

P.D. Fransquet ◽

P. Lacaze ◽

R. Saffery ◽

R.C. Shah ◽

R. Vryer ◽

...

Keyword(s):

Dna Methylation ◽

Strong Evidence ◽

Peripheral Blood ◽

Later Life ◽

Epigenetic Biomarkers ◽

Dementia Risk ◽

Epigenetic Aging ◽

Epigenetic Age ◽

Increased Risk ◽

Epigenetic Age Acceleration

Background: There is strong evidence that epigenetic age acceleration is associated with increased risk of later-life diseases and all-cause mortality. However, there is currently limited evidence that suggests accelerated epigenetic age is associated with dementia risk. Objective: This study aims to clarify whether epigenetic biomarkers of accelerated aging can pre- dict dementia risk, which is an important consideration as aging is the greatest risk factor for the disease. Methods: DNA methylation was measured in peripheral blood samples provided by 160 partici- pants from the ASPirin in Reducing Events in the Elderly study, including 73 pre-symptomatic de- mentia cases and 87 controls matched for age, sex, and smoking and education status. Epigenetic age was calculated using Horvath, Hannum, GrimAge and PhenoAge DNA methylation clocks, and age acceleration (the disparity between chronological age and epigenetic age) was determined. Results: There was no difference in age acceleration between dementia cases and controls. In males, only Hannum’s intrinsic epigenetic age acceleration was increased in pre-symptomatic de- mentia cases compared to controls (Δ +1.8 years, p = 0.03). Conclusion: These findings provide no strong evidence that accelerated epigenetic aging measured in peripheral blood can predict dementia risk.

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