Publications by authors named "Lawlor D"

Background: Observational studies suggested chronotype was associated with pregnancy and perinatal outcomes. Whether these associations are causal is unclear. Our aims are to use Mendelian randomization (MR) to explore (1) associations of evening preference with stillbirth, miscarriage, gestational diabetes, hypertensive disorders of pregnancy, perinatal depression, preterm birth and offspring birthweight; and (2) differences in associations of insomnia and sleep duration with those outcomes between chronotype preferences.

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Study Question: To what extent can hypertensive disorders in pregnancy (HDP) explain the higher risk of preterm birth following frozen embryo transfer (frozen-ET) and fresh embryo transfer (fresh-ET) in ART compared with naturally conceived pregnancies?

Summary Answer: HDP did not contribute to the higher risk of preterm birth in pregnancies after fresh-ET but mediated 20.7% of the association between frozen-ET and preterm birth.

What Is Known Already: Risk of preterm birth is higher after ART compared to natural conception.

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  • This study examines the effectiveness of third-trimester ultrasound in detecting small-for-gestational age (SGA) babies, highlighting concerns about low detection rates and risks associated with false results.
  • Researchers analyzed data from the DESiGN trial, focusing on stillbirth and neonatal morbidity outcomes among pregnancies classified as either false-negative, true-positive, false-positive, or true-negative for SGA.
  • Findings revealed that false-negative SGA results significantly increased the risk of stillbirth compared to true-positive diagnoses, while the implications of false-positive results were also evaluated, indicating potential risks in misclassification during antenatal screening.
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Genetic effects on changes in human traits over time are understudied and may have important pathophysiological impact. We propose a framework that enables data quality control, implements mixed models to evaluate trajectories of change in traits, and estimates phenotypes to identify age-varying genetic effects in GWAS. Using childhood BMI as an example trait, we included 71,336 participants from six cohorts and estimated the slope and area under the BMI curve within four time periods (infancy, early childhood, late childhood and adolescence) for each participant, in addition to the age and BMI at the adiposity peak and the adiposity rebound.

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Background: Bias from data missing not at random (MNAR) is a persistent concern in health-related research. A bias analysis quantitatively assesses how conclusions change under different assumptions about missingness using bias parameters that govern the magnitude and direction of the bias. Probabilistic bias analysis specifies a prior distribution for these parameters, explicitly incorporating available information and uncertainty about their true values.

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  • The study aimed to evaluate the hospitalization risks for perinatal conditions in children conceived through assisted reproductive technology (ART) versus naturally conceived children, with breakdowns by treatment type.
  • Conducted in the UK from 2002 to 2009, the research involved over 44,000 children born via ART and compared their hospital admissions to nearly 90,000 naturally conceived controls and their siblings.
  • Results showed that ART children had a higher risk of hospitalization for severe perinatal events compared to naturally conceived children, but no significant difference was found when comparing ART children to their naturally conceived siblings.
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  • The study investigates the relationship between aortic intima-media thickness (IMT) at 6 weeks of age and various vascular measures at 4 years, analyzing data from 518 participants.
  • It finds that while 6-week aortic IMT is slightly linked to carotid IMT at 4 years, there are no strong associations with other vascular measures like pulse wave velocity or blood pressure.
  • The results suggest limited tracking of vascular health from infancy to early childhood, highlighting the need for further longitudinal research to better understand early prevention strategies.
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Paternal exposures (and other non-maternal factors) around pregnancy could have important effects on offspring health. One challenge is that data on partners are usually from a subgroup of mothers with data, potentially introducing selection bias, limiting generalisability of findings. We aimed to investigate the potential for selection bias in studies using partner data.

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Background: In utero exposure to infections might set the stage for a chain of events leading to a wide spectrum of long-term health outcomes observed in children and adolescents. This proposal aims to investigate whether syphilis, zika, dengue and chikungunya during pregnancy can increase the risk of the offspring developing a non-infectious chronic condition during childhood and adolescence.

Objectives: 1) Estimate the risk of non-infectious chronic conditions associated to syphilis, zika, dengue and chikungunya during pregnancy and when appropriate, explore if the risk varies by timing during pregnancy when the infection is acquired (first, second or third trimester) and severity (such as severe or mild dengue); 2) Investigate whether in uterus exposure to maternal infection affects the growth pattern of children and adolescents; 3) Examine the extent to which the relationship between maternal infection and non-infectious chronic outcomes are mediated by intrauterine growth restriction and preterm birth.

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Objective: As endovascular interventions become safer and their use more prevalent for treating extracranial pseudoaneurysms, fewer pseudoaneurysms are treated with medical therapy alone. This study aimed to assess the indications for intervention and the safety of medical management.

Methods: A dual-center retrospective analysis was conducted on patients diagnosed with extracranial carotid and vertebral pseudoaneurysms between December 2006 and June 2023.

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  • Pregnancy causes significant changes in glucose metabolism, leading to increased insulin resistance and higher insulin secretion to regulate blood sugar levels.
  • Gestational diabetes mellitus (GDM) affects about 14% of pregnancies worldwide and can result in serious health issues for both mothers and their babies.
  • The review emphasizes the importance of studying genetic factors influencing GDM and calls for more collaborative research with diverse pregnancy cohorts to enhance prevention and treatment approaches.
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Objective: To identify whether maternal and pregnancy characteristics associated with stillbirth differ between preterm and term stillbirth.

Design: Secondary cohort analysis of the DESiGN RCT.

Setting: Thirteen UK maternity units.

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  • * We found 17 genetic loci associated with sleep duration impacting lipid levels, with 10 of them being newly identified and linked to sleep-related disturbances in lipid metabolism.
  • * The research points to potential drug targets that could lead to new treatments for lipid-related issues in individuals with sleep problems, highlighting the connection between sleep patterns and cardiovascular health.
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Background: The extent to which COVID-19 diagnosis and vaccination during pregnancy are associated with risks of common and rare adverse pregnancy outcomes remains uncertain. We compared the incidence of adverse pregnancy outcomes in women with and without COVID-19 diagnosis and vaccination during pregnancy.

Methods: We studied population-scale linked electronic health records for women with singleton pregnancies in England and Wales from 1 August 2019 to 31 December 2021.

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Background: Globally, caesarean births (CB), including emergency caesareans births (EmCB), are rising. It is estimated that nearly a third of all births will be CB by 2030.

Objectives: Identify and summarise the results from studies developing and validating prognostic multivariable models predicting the risk of EmCBs.

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Distribution of environmental hazards and vulnerability to their effects vary across socioeconomic groups. Our objective was to analyse the relationship between child socioeconomic position (SEP) at birth and the external exposome at pre-school age (0-4 years). This study included more than 60,000 children from eight cohorts in eleven European cities (Oslo, Copenhagen, Bristol, Bradford, Rotterdam, Nancy, Poitiers, Gipuzkoa, Sabadell, Valencia and Turin).

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Purpose: We aimed to investigate the associations between parental BMI and offspring BMI trajectories and to explore whether the parent-offspring BMI growth trajectory association differed according to family SEP or social mobility.

Methods: We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Children's weight and height were collected from 1 to 18 years.

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Background: Pubertal timing is heritable, varies between individuals, and has implications for life-course health. There are many different indicators of pubertal timing, and how they relate to each other is unclear. Our aim was to quantitatively compare nine indicators of pubertal timing.

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Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes.

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Hypotheses about what phenotypes to include in causal analyses, that in turn can have clinical and policy implications, can be guided by hypothesis-free approaches leveraging the epigenome, for example. Minimally adjusted epigenome-wide association studies (EWAS) using ALSPAC data were performed for example conditions, dysmenorrhea and heavy menstrual bleeding (HMB). Differentially methylated CpGs were searched in the EWAS Catalog and associated traits identified.

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Article Synopsis
  • Scientists looked at the timing of when girls start their periods (called menarche) and how it can affect their health later in life.
  • They studied about 800,000 women and found over a thousand genetic signals that influence when menstruation starts.
  • Some women have a much higher chance of starting their periods too early or too late based on their genetic makeup, suggesting that genes play a big role in this process!
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Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar observations in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not others, on glycated haemoglobin (HbA1c). To explore potential effects, we used MR methods to assess effects of accelerometer-derived sleep traits (duration, mid-point least active 5-h, mid-point most active 10-h, sleep fragmentation, and efficiency) on HbA1c/glucose in European adults from the UK Biobank (UKB) (n = 73,797) and the MAGIC consortium (n = 146,806).

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Background: Prenatal urban environmental exposures have been associated with blood pressure in children. The dynamic of these associations across childhood and later ages is unknown.

Objectives: The purpose of this study was to assess associations of prenatal urban environmental exposures with blood pressure trajectories from childhood to early adulthood.

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  • The Avon Longitudinal Study of Parents and Children (ALSPAC) initially aimed to gather clinical obstetric data through the National Health Service's STORK system but found it lacking in comprehensive antenatal and postnatal information.
  • To address this, a team was trained to extract detailed data from clinical records, which proved to be a time-intensive and costly process, funded through various grants.
  • As a result, detailed medical records for 8,369 pregnancies were compiled, providing important insights into maternal and neonatal health and its implications for long-term outcomes for both mothers and children.
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