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European Heart Journal Feb 2024Low birth weight is a common pregnancy complication, which has been associated with higher risk of cardiometabolic disease in later life. Prior Mendelian randomization...
BACKGROUND AND AIMS
Low birth weight is a common pregnancy complication, which has been associated with higher risk of cardiometabolic disease in later life. Prior Mendelian randomization (MR) studies exploring this question do not distinguish the mechanistic contributions of variants that directly influence birth weight through the foetal genome (direct foetal effects), vs. variants influencing birth weight indirectly by causing an adverse intrauterine environment (indirect maternal effects). In this study, MR was used to assess whether birth weight, independent of intrauterine influences, is associated with cardiovascular disease risk and measures of adverse cardiac structure and function.
METHODS
Uncorrelated (r2 < .001), genome-wide significant (P < 5 × 10-8) single nucleotide polymorphisms were extracted from genome-wide association studies summary statistics for birth weight overall, and after isolating direct foetal effects only. Inverse-variance weighted MR was utilized for analyses on outcomes of atrial fibrillation, coronary artery disease, heart failure, ischaemic stroke, and 16 measures of cardiac structure and function. Multiple comparisons were accounted for by Benjamini-Hochberg correction.
RESULTS
Lower genetically-predicted birth weight, isolating direct foetal effects only, was associated with an increased risk of coronary artery disease (odds ratio 1.21, 95% confidence interval 1.06-1.37; P = .031), smaller chamber volumes, and lower stroke volume, but higher contractility.
CONCLUSIONS
The results of this study support a causal role of low birth weight in cardiovascular disease, even after accounting for the influence of the intrauterine environment. This suggests that individuals with a low birth weight may benefit from early targeted cardiovascular disease prevention strategies, independent of whether this was linked to an adverse intrauterine environment during gestation.
Topics: Pregnancy; Female; Humans; Birth Weight; Genome-Wide Association Study; Coronary Artery Disease; Brain Ischemia; Stroke; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide
PubMed: 37738114
DOI: 10.1093/eurheartj/ehad631 -
Nature Genetics Nov 2023A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report...
A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.
Topics: Female; Humans; Pregnancy; Birth Weight; Fetal Development; Genome-Wide Association Study; Insulin; Placenta; Male
PubMed: 37798380
DOI: 10.1038/s41588-023-01520-w -
JAMA Network Open Sep 2023Newborn screening via biochemical tests is in use worldwide. The availability of genetic sequencing has allowed rapid screening for a substantial number of monogenic...
IMPORTANCE
Newborn screening via biochemical tests is in use worldwide. The availability of genetic sequencing has allowed rapid screening for a substantial number of monogenic disorders. However, the outcomes of this strategy have not been evaluated in a general newborn population.
OBJECTIVE
To evaluate the outcomes of applying gene panel sequencing as a first-tier newborn screening test.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included newborns who were prospectively recruited from 8 screening centers in China between February 21 and December 31, 2021. Neonates with positive results were followed up before July 5, 2022.
EXPOSURES
All participants were concurrently screened using dried blood spots. The screen consisted of biochemical screening tests and a targeted gene panel sequencing test for 128 conditions. The biochemical and genomic tests could both detect 43 of the conditions, whereas the other 85 conditions were screened solely by the gene panel.
MAIN OUTCOMES AND MEASURES
The primary outcomes were the number of patients detected by gene panel sequencing but undetected by the biochemical test.
RESULTS
This study prospectively recruited 29 601 newborns (15 357 [51.2%] male). The mean (SD) gestational age was 39.0 (1.5) weeks, and the mean (SD) birth weight was 3273 (457) g. The gene panel sequencing screened 813 infants (2.7%; 95% CI, 2.6%-2.9%) as positive. By the date of follow-up, 402 infants (1.4%; 95% CI, 1.2%-1.5%) had been diagnosed, indicating the positive predictive value was 50.4% (95% CI, 50.0%-53.9%). The gene panel sequencing identified 59 patients undetected by biochemical tests, including 20 patients affected by biochemically and genetically screened disorders and 39 patients affected by solely genetically screened disorders, which translates into 1 out of every 500 newborns (95% CI, 1/385-1/625) benefiting from the implementation of gene panels as a first-tier screening test.
CONCLUSIONS AND RELEVANCE
In this cohort study, the use of gene panel sequencing in a general newborn population as a first-tier screening test improved the detection capability of traditional screening, providing an evidence-based suggestion that it could be considered as a crucial method for first-tier screening.
Topics: Infant, Newborn; Infant; Humans; Male; Female; Cohort Studies; Neonatal Screening; Birth Weight; China; Genomics
PubMed: 37656460
DOI: 10.1001/jamanetworkopen.2023.31162 -
Aging Dec 2023Obesity, birth weight and lifestyle factors have been found associated with the risk of frailty in observational studies, but whether these associations are causal is...
Obesity, birth weight and lifestyle factors have been found associated with the risk of frailty in observational studies, but whether these associations are causal is uncertain. We conducted a two-sample Mendelian randomization study to investigate the associations. Genetic instruments associated with the exposures at the genome-wide significance level ( < 5 × 10) were selected from corresponding genome-wide association studies ( = 143,677 to 703,901 individuals). Summary-level data for the frailty index were obtained from the UK Biobank ( = 164,610) and Swedish TwinGene ( = 10,616). The β of the frailty index was 0.15 ( = 3.88 × 10) for 1 standard deviation increase in the prevalence of smoking initiation, 0.19 ( = 3.54 × 10) for leisure screen time, 0.13 ( = 5.26 × 10) for body mass index and 0.13 ( = 1.80 × 10) for waist circumference. There was a suggestive association between genetically predicted higher birth weight and moderate-to-vigorous intensity physical activity with the decreased risk of the frailty index. We observed no causal association between genetically predicted age of smoking initiation and alcoholic drinks per week with the frailty index. This study supports the causal roles of smoking initiation, leisure screen time, overall obesity, and abdominal obesity in frailty. The possible association between higher birth weight, proper physical activity and a decreased risk of frailty needs further confirmation.
Topics: Humans; Birth Weight; Frailty; Mendelian Randomization Analysis; Genome-Wide Association Study; Obesity; Body Mass Index; Life Style; Polymorphism, Single Nucleotide
PubMed: 38095641
DOI: 10.18632/aging.205290 -
Public Health Jul 2023Lockdown was implemented in many countries during the pandemic, which led to myriad changes in pregnant women's lives. However, the potential impacts of the COVID-19... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Lockdown was implemented in many countries during the pandemic, which led to myriad changes in pregnant women's lives. However, the potential impacts of the COVID-19 pandemic on neonatal outcomes remain unclear. We aimed to evaluate the association between the pandemic and neonatal birth weight.
STUDY DESIGN
This was a systematic review and meta-analysis of the previous literature.
METHODS
We searched the MEDLINE and Embase databases up to May 2022 and extracted 36 eligible studies that compared neonatal birth weight between the pandemic and the prepandemic period. The following outcomes were included: mean birth weight, low birth weight (LBW), very low birth weight (VLBW), macrosomia, small for gestational age (SGA), very small for gestational age (VSGA), and large for gestational age (LGA). Statistical heterogeneity among studies was assessed to determine whether a random effects model or fixed effects model was conducted.
RESULTS
Of the 4514 studies identified, 36 articles were eligible for inclusion. A total of 1,883,936 neonates during the pandemic and 4,667,133 neonates during the prepandemic were reported. We identified a significant increase in mean birth weight (pooled mean difference [95% confidence interval (CI)] = 15.06 [10.36, 19.76], I = 0.0%, 12 studies) and a reduction in VLBW (pooled OR [95% CI] = 0.86 [0.77, 0.97], I = 55.4%, 12 studies). No overall effect was identified for other outcomes: LBW, macrosomia, SGA, VSGA, and LGA. There was publication bias for mean birth weight with a borderline significance (Egger's P = 0.050).
CONCLUSION
Pooled results showed the pandemic was significantly associated with an increase in mean birth weight and a reduction in VLBW, but not for other outcomes. This review provided clues about the indirect effects of the pandemic on neonatal birth weight and more healthcare measures needed to improve neonatal long-term health.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Birth Weight; Pregnancy Outcome; Pandemics; Fetal Macrosomia; COVID-19; Communicable Disease Control
PubMed: 37201437
DOI: 10.1016/j.puhe.2023.04.009 -
Journal of Hypertension Jun 2023Although preterm-born and low-birth-weight individuals have an increased risk of cardiovascular diseases in adulthood, little is known regarding early cardiovascular and...
OBJECTIVE
Although preterm-born and low-birth-weight individuals have an increased risk of cardiovascular diseases in adulthood, little is known regarding early cardiovascular and renal damage (CVRD) or hypertension in adulthood. Our study investigated the association of birth weight with early CVRD markers as well as the heritability of birth weight in an initially healthy family-based cohort.
METHODS
This study was based on 1028 individuals from the familial longitudinal STANISLAS cohort (399 parents/629 children) initiated in 1993-1995, with a fourth examination conducted in 2011-2016. Analyses performed at the fourth visit included pulse-wave velocity, central pressure, ambulatory blood pressure, hypertension status, diastolic dysfunction/distensibility, left ventricular mass indexed (LVMI), carotid intima-media thickness and kidney damage. The family structure of the cohort allowed birth weight heritability estimation.
RESULTS
Mean (±SD) birth weight was 3.3 ± 0.6 kg. Heritability was moderate (42-44%). At the fourth visit, individuals were 37 years old (32.0-57.0), 56% were women and 13% had antihypertensive treatment. Birth weight was strongly and negatively associated with hypertension [odds ratio (OR) 95% confidence interval (CI) 0.61 (0.45-0.84)]. A nonlinear association was found with LVMI, participants with a birth weight greater than 3 kg having a higher LVMI. A positive association ( β 95% CI 5.09 (1.8-8.38)] was also observed between birth weight and distensibility for adults with normal BMI. No associations were found with other CVRD.
CONCLUSION
In this middle-aged population, birth weight was strongly and negatively associated with hypertension, and positively associated with distensibility in adults with normal BMI and with LVMI for higher birth weights. No associations were found with other CVRD markers.
Topics: Adult; Middle Aged; Child; Infant, Newborn; Humans; Female; Male; Cohort Studies; Blood Pressure; Birth Weight; Carotid Intima-Media Thickness; Blood Pressure Monitoring, Ambulatory; Risk Factors; Hypertension; Kidney
PubMed: 37071444
DOI: 10.1097/HJH.0000000000003438 -
Journal of the American Heart... Jul 2023Background High and low birth weight are independently associated with increased cardiovascular disease risk in adulthood. Clonal hematopoiesis of indeterminate...
Background High and low birth weight are independently associated with increased cardiovascular disease risk in adulthood. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related clonal expansion of hematopoietic cells with preleukemic somatic mutations, predicts incident cardiovascular disease independent of traditional cardiovascular risk factors. Whether birth weight predicts development of CHIP later in life is unknown. Methods and Results A total of 221 047 adults enrolled in the UK Biobank with whole exome sequences and self-reported birth weight were analyzed. Of those, 22 030 (11.5%) had low (<2.5 kg) and 29 292 (14.7%) high birth weight (>4.0 kg). CHIP prevalence was higher among participants with low (6.0%, =0.049) and high (6.3%, <0.001) versus normal birth weight (5.7%, ref.). Multivariable-adjusted logistic regression analyses demonstrated that each 1-kg increase in birth weight was associated with a 3% increased risk of CHIP (odds ratio, 1.03 [95% CI, 1.00-1.06]; =0.04), driven by a stronger association observed between birth weight and CHIP (odds ratio, 1.04 per 1-kg increase [95% CI, 1.01-1.08]; =0.02). Mendelian randomization analyses supported a causal relationship of longer gestational age at delivery with CHIP. Multivariable Cox regression demonstrated that CHIP was independently and additively associated with incident cardiovascular disease or death across birth weight groups, with highest absolute risks in those with CHIP plus high or low birth weight. Conclusions Higher birth weight is associated with increased risk of developing CHIP in midlife, especially CHIP. These findings identify a novel risk factor for CHIP and provide insights into the relationships among early-life environment, CHIP, cancer, and cardiovascular disease.
Topics: Adult; Humans; Cardiovascular Diseases; Clonal Hematopoiesis; Birth Weight; Hematopoiesis; Risk Factors; Mutation
PubMed: 37345823
DOI: 10.1161/JAHA.123.030220 -
Frontiers in Endocrinology 2023Associations between lower birth weight and higher polycystic ovary syndrome (PCOS) risk have been reported in previous observational studies, however, the causal...
Associations between lower birth weight and higher polycystic ovary syndrome (PCOS) risk have been reported in previous observational studies, however, the causal relationship is still unknown. Based on decomposed fetal and maternal genetic effects on birth weight (n = 406,063), we conducted a two-sample Mendelian randomization (MR) analysis to assess potential causal relationships between fetal genome predicted birth weight and PCOS risk using a large-scale genome-wide association study (GWAS) including 4,138 PCOS cases and 20,129 controls. To further eliminate the maternally transmitted or non-transmitted effects on fetal growth, we performed a secondary MR analysis by utilizing genetic instruments after excluding maternally transmitted or non-transmitted variants, which were identified in another birth weight GWAS (n = 63,365 parent-offspring trios from Icelandic birth register). Linkage disequilibrium score regression (LDSR) analysis was conducted to estimate the genetic correlation. We found little evidence to support a causal effect of fetal genome determined birth weight on the risk of developing PCOS (primary MR analysis, OR: 0.86, 95% CI: 0.52 to 1.43; secondary MR analysis, OR: 0.86, 95% CI: 0.54 to 1.39). In addition, a marginally significant genetic correlation (r = -0.14, se = 0.07) between birth weight and PCOS was revealed LDSR analysis. Our findings indicated that observed associations between birth weight and future PCOS risk are more likely to be attributable to genetic pleiotropy driven by the fetal genome rather than a causal mechanism.
Topics: Female; Pregnancy; Humans; Birth Weight; Polycystic Ovary Syndrome; Genome-Wide Association Study; Mendelian Randomization Analysis; Prenatal Care
PubMed: 37351103
DOI: 10.3389/fendo.2023.1140499 -
Annals of Epidemiology Jun 2023The strength of the association between obesity and mortality rate (MR) varies by body mass index (BMI) and sociodemographic groups. We test the hypothesis that the...
PURPOSE
The strength of the association between obesity and mortality rate (MR) varies by body mass index (BMI) and sociodemographic groups. We test the hypothesis that the association between obesity and MR varies, in part, due to the moderating effect of parental BMI and birth weight.
METHODS
Data come from the 1958 National Child Development Study, an ongoing longitudinal dataset initiated in 1958 with baseline measures of birth weight from 18,059 infants born in Great Britain over 1 week. We tested whether the association between BMI and MR was moderated by parental BMI and birth weight using generalized additive proportional hazards models.
RESULTS
The association between adult BMI and MR was moderated by birth weight and maternal BMI, such that the association between BMI and MR was weaker among individuals with a higher birth weight (P = .0148) and stronger among individuals born to mothers with a higher BMI (P = .032). At any given level of BMI approximately greater than 25, individuals with low birth weight or born to mothers with a higher BMI, had a higher MR. Paternal BMI did not significantly modify the relationship between BMI and MR (P = .5168).
CONCLUSIONS
Results suggest that the relationship between obesity and MR is modified by birth weight and maternal BMI.
Topics: Infant; Male; Female; Child; Adult; Humans; Birth Weight; Obesity; Mothers; Body Mass Index; Longitudinal Studies
PubMed: 37015307
DOI: 10.1016/j.annepidem.2023.03.010 -
Acta Obstetricia Et Gynecologica... Dec 2023The association between extreme birth spacing and adverse outcomes is controversial, and available evidence is fragmented into different classifications of birth spacing. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The association between extreme birth spacing and adverse outcomes is controversial, and available evidence is fragmented into different classifications of birth spacing.
MATERIAL AND METHODS
We conducted a systematic review of observational studies to evaluate the association between birth spacing (i.e., interpregnancy interval and interoutcome interval) and adverse outcomes (i.e., pregnancy complications, adverse birth outcomes). Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated using a random-effects model, and the dose-response relationships were evaluated using generalized least squares trend estimation.
RESULTS
A total of 129 studies involving 46 874 843 pregnancies were included. In the general population, compared with an interpregnancy interval of 18-23 months, extreme intervals (<6 months and ≥ 60 months) were associated with an increased risk of adverse outcomes, including preterm birth, small for gestational age, low birthweight, fetal death, birth defects, early neonatal death, and premature rupture of fetal membranes (pooled OR range: 1.08-1.56; p < 0.05). The dose-response analyses further confirmed these J-shaped relationships (p < 0.001-0.009). Long interpregnancy interval was only associated with an increased risk of preeclampsia and gestational diabetes (p < 0.005 and p < 0.001, respectively). Similar associations were observed between interoutcome interval and risk of low birthweight and preterm birth (p < 0.001). Moreover, interoutcome interval of ≥60 months was associated with an increased risk of cesarean delivery (pooled OR 1.72, 95% CI 1.04-2.83). For pregnancies following preterm births, an interpregnancy interval of 9 months was not associated with an increased risk of preterm birth, according to dose-response analyses (p = 0.008). Based on limited evidence, we did not observe significant associations between interpregnancy interval or interoutcome interval after pregnancy losses and risk of small for gestational age, fetal death, miscarriage, or preeclampsia (pooled OR range: 0.76-1.21; p > 0.05).
CONCLUSIONS
Extreme birth spacing has extensive adverse effects on maternal and infant health. In the general population, interpregnancy interval of 18-23 months may be associated with potential benefits for both mothers and infants. For women with previous preterm birth, the optimal birth spacing may be 9 months.
Topics: Pregnancy; Infant; Infant, Newborn; Humans; Female; Pregnancy Outcome; Premature Birth; Birth Intervals; Pre-Eclampsia; Birth Weight; Abortion, Spontaneous; Pregnancy Complications; Fetal Growth Retardation; Mothers; Fetal Death
PubMed: 37675816
DOI: 10.1111/aogs.14648