We promote open science by publishing analysis plans/protocols prior to staring data collection and analyses and placing completed projects on pre-print servers once the project is completed, where all contributing partners support this. Our peer-reviewed publications, preprints, and analysis plans/protocols are listed below. All publications are open access.
Peer reviewed publications
2024
In a study of up to 83,969 women (and up to 55,568 of their male partners) from the Norwegian Mother, Father and Child Cohort Study and the Trøndelag Health Study, we found that higher levels of a genetic score for higher liability of coronary heart associated with higher risk of any hypertensive disorders of pregnancy , pre-eclampsia, small for gestational age and stillbirth, and lower risk of large for gestational age in women. Their partners genetic score showed a week association with preterm birth. These findings suggest that hypertensive disorders of pregnancy, small for gestational age, and stillbirth may unmask women with a genetically predicted liability for coronary heart disease. As coronary heart disease is associated with infertility, this liability might explain some of the effects of conception by ART on these outcomes. This needs further exploration.
This meta-analysis of four cohort studies from the Japan Birth Cohort Consortium found that infertility treatment was positively associated with hypertensive disorders of pregnancy in women regardless of age.
This cohort study included 14,609 singletons from three pregnancy cohorts and found that offspring of couples with infertility relative to those of fertile couples have increasingly higher BMI over the years, suggestively higher blood pressure levels, and tend to have greater values of LDL-C and lower values of HDL-C with age.
This cohort study used a UK birth cohort with replication in four independent European cohorts to assess associations of prenatal urban environmental exposures with blood pressure trajectories from childhood to early adulthood, replicated findings suggesting that higher prenatal humidity and temperature could modulate blood pressure changes across childhood. These findings have generated an interest in further exploration of climate measures and the potential effects of climate change on future reproduction and infertility.
2023
This study primarily used data from a pregnancy cohort, the Norwegian Mother, Father and Child Cohort Study to examine effects of health behaviours (alcohol and caffeine consumption, body-mass index (BMI), and smoking) on fertility outcomes and found that smoking behaviour and BMI showed the most consistent associations for increased time to conception and a younger age at first birth.
This study used data from national registries in Denmark (1994–2014), Finland (1990–2014) and Norway and Sweden (1988–2015) to study 5 722 826 singleton pregnancies, including 119 900 ART-conceived and 37 590 exposure-discordant sibships, and found that singletons conceived by ART had higher perinatal mortality than naturally conceived singletons at the population level. However, within sibships, perinatal mortality was much lower for ART-conceived compared with their naturally conceived siblings.
In this cohort study, among 2 496 441 parous individuals in Denmark, Finland, Norway, and Sweden, those who gave birth after ART were not at increased risk of later CVD compared with individuals who conceived without ART when adjusting for other CVD risk factors. No significant differences in the risk of ischemic heart disease, cerebrovascular disease, stroke, cardiomyopathy, heart failure, pulmonary embolism, or deep vein thrombosis were noted.
This cohort study of 35,000 European, Singaporean, and Australian offspring found that blood pressure, heart rate, and glucose levels were similar in children conceived using ART and their naturally conceived peers. The study also found that those who were conceived by ART had slightly higher cholesterol levels in childhood, which did not persist to adulthood, and some indication of slightly higher blood pressure in adulthood.
This cohort study of 24,000 people aged from newborns to older adults found broadly similar metabolic profiles across life in people born after exposure to common pregnancy and perinatal complications and those not exposed to common pregnancy and perinatal complications. Most associations were in newborns rather than older ages, and perinatal (preterm birth, small and large for gestational age) rather than pregnancy (pre-eclampsia, gestational hypertension, gestational diabetes) complications. This study provides methods that we will adapt to explore effects of conception by ART on multiple metabolites in order to address our aim of exploring molecular mediators of any effects of infertility or ART on later health.
2022
In this large electronic health record linkage study of 4,590,853 singleton births from Denmark, Norway and Sweden, including 78,642 conceived by fresh-embryo transfer and 18,084 by frozen-embryo transfer, we found risk of stillbirth was similar after fresh- and frozen-embryo transfer compared with singletons conceived without medical assistance, whereas neonatal mortality risk was higher, possibly mediated by the high risk of preterm birth, when compared with singletons conceived without medical assistance. Our results gave no clear support for choosing one treatment over the other to reduce neonatal mortality.
This study integrated Mendelian randomisation and metabolomics data to probe the effect of 46 maternal metabolic traits on offspring birthweight, and found that maternal gestational glucose and glutamine were causally related to offspring birthweight. This methodological paper provides us with methods that we will use to explore causal mediation between infertility and/or ART conception and perinatal and later health outcomes.
This population-based cohort study included 31,629 women and 17,630 men participating in the Trøndelag Health Study and observed modestly increased risks of CVD outcomes in women and some weak associations in men, although with no strong statistical evidence on sex differences.
In this UK record linkage study of 1.6 million person-years of follow-up), singletons born after ART had increased risk of any hospital admission compared with naturally conceived population controls (hazard ratio, 1.08; 95% confidence interval, 1.05-1.10) but not when compared with naturally conceived siblings (hazard ratio, 1.01; 95% confidence interval, 0.94-1.09). We observed increased risk of diagnoses related to neoplasms and diseases of the respiratory, musculoskeletal, digestive, and genitourinary systems, compared with population but not sibling controls. and lower risk of injury, poisoning, and consequences of external causes compared with naturally conceived population controls. The attenuation of associations in relation to their naturally conceived siblings suggests that main (population controls) associations may be attributed to the influence of parental factors, such as subfertility on child health and increased parental concerns, than ART.
Elhakeem A, Taylor AE, Inskip HM, et al. Association of assisted reproductive technology with offspring growth and adiposity from infancy to early adulthood. JAMA Network Open
In this cohort study of up to 158 066 infants, children, adolescents and young adults from Europe, Asia-Pacific, and Canada, those conceived using ART were shorter, lighter, and thinner by most estimates from infancy up to early adolescence compared with their naturally conceived peers. Differences were small across all ages and reduced with older age. An analysis plan and preprint publication for this paper are listed in the relevant sections.
Preprints
2023
Analysis plans / Protocols
2022