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

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.

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

2019 ◽  
Vol 41 (16) ◽  
pp. 1542-1550 ◽  
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 (&lt;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.

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

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.

scholarly journals Maternal biological age assessed in early pregnancy is associated with gestational age at birth

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eva E. Lancaster ◽  
Dana M. Lapato ◽  
Colleen Jackson-Cook ◽  
Jerome F. Strauss ◽  
Roxann Roberson-Nay ◽  
...  
Keyword(s):  
Risk Factors ◽  
Preterm Birth ◽  
Early Pregnancy ◽  
Gestational Age ◽  
Cellular Aging ◽  
Biological Age ◽  
Potential Candidate ◽  
A Genome ◽  
Gestational Age At Birth ◽  
Age At Birth

AbstractMaternal age is an established predictor of preterm birth independent of other recognized risk factors. The use of chronological age makes the assumption that individuals age at a similar rate. Therefore, it does not capture interindividual differences that may exist due to genetic background and environmental exposures. As a result, there is a need to identify biomarkers that more closely index the rate of cellular aging. One potential candidate is biological age (BA) estimated by the DNA methylome. This study investigated whether maternal BA, estimated in either early and/or late pregnancy, predicts gestational age at birth. BA was estimated from a genome-wide DNA methylation platform using the Horvath algorithm. Linear regression methods assessed the relationship between BA and pregnancy outcomes, including gestational age at birth and prenatal perceived stress, in a primary and replication cohort. Prenatal BA estimates from early pregnancy explained variance in gestational age at birth above and beyond the influence of other recognized preterm birth risk factors. Sensitivity analyses indicated that this signal was driven primarily by self-identified African American participants. This predictive relationship was sensitive to small variations in the BA estimation algorithm. Benefits and limitations of using BA in translational research and clinical applications for preterm birth are considered.

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

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

scholarly journals Preterm birth and risk of chronic kidney disease from childhood into mid-adulthood: national cohort study

BMJ ◽  
2019 ◽  
pp. l1346 ◽  
Author(s):  
Casey Crump ◽  
Jan Sundquist ◽  
Marilyn A Winkleby ◽  
Kristina Sundquist
Keyword(s):  
Cohort Study ◽  
Preterm Birth ◽  
Environmental Factors ◽  
Gestational Age ◽  
Early Term ◽  
Extremely Preterm ◽  
National Cohort ◽  
Gestational Age At Birth ◽  
Age At Birth

Abstract Objective To investigate the relation between preterm birth (gestational age <37 weeks) and risk of CKD from childhood into mid-adulthood. Design National cohort study. Setting Sweden. Participants 4 186 615 singleton live births in Sweden during 1973-2014. Exposures Gestational age at birth, identified from nationwide birth records in the Swedish birth registry. Main outcome measures CKD, identified from nationwide inpatient and outpatient diagnoses through 2015 (maximum age 43 years). Cox regression was used to examine gestational age at birth and risk of CKD while adjusting for potential confounders, and co-sibling analyses assessed the influence of unmeasured shared familial (genetic or environmental) factors. Results 4305 (0.1%) participants had a diagnosis of CKD during 87.0 million person years of follow-up. Preterm birth and extremely preterm birth (<28 weeks) were associated with nearly twofold and threefold risks of CKD, respectively, from birth into mid-adulthood (adjusted hazard ratio 1.94, 95% confidence interval 1.74 to 2.16; P<0.001; 3.01, 1.67 to 5.45; P<0.001). An increased risk was observed even among those born at early term (37-38 weeks) (1.30, 1.20 to 1.40; P<0.001). The association between preterm birth and CKD was strongest at ages 0-9 years (5.09, 4.11 to 6.31; P<0.001), then weakened but remained increased at ages 10-19 years (1.97, 1.57 to 2.49; P<0.001) and 20-43 years (1.34, 1.15 to 1.57; P<0.001). These associations affected both males and females and did not seem to be related to shared genetic or environmental factors in families. Conclusions Preterm and early term birth are strong risk factors for the development of CKD from childhood into mid-adulthood. People born prematurely need long term follow-up for monitoring and preventive actions to preserve renal function across the life course.

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

Neonatology ◽  
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

<b><i>Introduction:</i></b> 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). <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.

Effects of Antenatal Depression and Antidepressant Treatment on Gestational Age at Birth and Risk of Preterm Birth

2007 ◽  
Vol 164 (8) ◽  
pp. 1206-1213 ◽  
Author(s):  
Rita Suri ◽  
Lori Altshuler ◽  
Gerhard Hellemann ◽  
Vivien K. Burt ◽  
Ana Aquino ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Gestational Age ◽  
Antidepressant Treatment ◽  
Antenatal Depression ◽  
Gestational Age At Birth ◽  
Age At Birth

scholarly journals Uterine distention as a factor in birth timing: retrospective nationwide cohort study in Sweden

BMJ Open ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. e022929 ◽  
Author(s):  
Jonas Bacelis ◽  
Julius Juodakis ◽  
Kristina M Adams Waldorf ◽  
Verena Sengpiel ◽  
Louis J Muglia ◽  
...  
Keyword(s):  
Cohort Study ◽  
Preterm Birth ◽  
Fetal Growth ◽  
Gestational Age ◽  
Large For Gestational Age ◽  
Maternal Height ◽  
Birth Timing ◽  
Gestational Age At Birth ◽  
Age At Birth ◽  
Singleton Pregnancies

ObjectivesTo determine whether uterine distention is associated with human pregnancy duration in a non-invasive observational setting.DesignRetrospective cohort study modelling uterine distention by interaction between maternal height and uterine load.SettingThe study is based on the 1990–2013 population data from all delivery units in Sweden.ParticipantsUncomplicated first pregnancies of healthy Nordic-born mothers with spontaneous onset of labour. Pregnancies were classified as twin (n=2846) or singleton (n=527 868). Singleton pregnancies were further classified as carrying a large for gestational age fetus (LGA, n=24 286) or small for gestational age fetus (SGA, n=33 780).Outcome measuresStatistical interaction between maternal height and uterine load categories (twin vs singleton pregnancies, and LGA vs SGA singleton pregnancies), where the outcome is pregnancy duration.ResultsIn all models, statistically significant interaction was found. Mothers carrying twins had 2.9 times larger positive linear effect of maternal height on gestational age than mothers carrying singletons (interaction p=5e−14). Similarly, the effect of maternal height was strongly modulated by the fetal growth rate in singleton pregnancies: the effect size of maternal height on gestational age in LGA pregnancies was 2.1 times larger than that in SGA pregnancies (interaction p<1e−11). Preterm birth OR was 1.4 when the mother was short, and 2.8 when the fetus was extremely large for its gestational age; however, when both risk factors were present together, the OR for preterm birth was larger than expected, 10.2 (interaction p<0.0005).ConclusionsAcross all classes, maternal height was significantly associated with child’s gestational age at birth. Interestingly, in short-statured women with large uterine load (twins, LGA), spontaneous delivery occurred much earlier than expected. The interaction between maternal height, uterine load size and gestational age at birth strongly suggests the effect of uterine distention imposed by fetal growth on birth timing.

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