EXPERT REACTION: Blood pressure risks for IVF kids

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Children born via IVF may be at greater risk of developing high blood pressure in their teens, according to international researchers. The small study monitored the blood pressure 54 children born by IVF who were in their teens and compared it to non-IVF children of similar age. Kids conceived through IVF had higher blood pressures than the non-IVF group and eight of the IVF kids also had hypertension (high blood pressure) compared to only one in the other group. The authors say that children conceived by IVF have a six times higher rate of hypertension and there is growing evidence that IVF alters the blood vessels in children, but the long-term consequences are not known.

Journal/conference: JACC

Link to research (DOI): 10.1016/j.jacc.2018.06.060

Organisation/s: University of Bern, Switzerland

Funder: This work was supported by the Swiss National Science Foundation, the Placide Nicod Foundation, the Swiss Society of Hypertension, the Swiss Society of Cardiology, and the Mach-Gaensslen Stiftung Schweiz

Media Release

From: American College of Cardiology

Children Born Through IVF May Have Higher Risk of Hypertension
By age sixteen, premature vascular aging persists in apparently healthy adolescents

WASHINGTON (Sept. 3, 2018) — Children conceived through assisted reproductive technologies may be at an increased risk of developing arterial hypertension early in life, among other cardiovascular complications, according to a Swiss study published today in the Journal of the American College of Cardiology.

Developed in 1978, assisted reproductive technologies (ART) has helped millions of individuals and families who cannot conceive naturally. The most common ART methods are in vitro fertilization and intracytoplasmic sperm injection, which can expose the gamete and embryo to a variety of environmental factors before implantation. Children conceived using ART make up 1.7 percent of all infants born in the United States every year and currently over six million persons worldwide.

The study authors assessed the circulatory system of 54 young, healthy ART adolescents (mean age 16) by measuring ambulatory blood pressure, as well as plaque build-up, blood vessel function and artery stiffness. Body mass index, birth weight, gestational age, and maternal BMI, smoking status and cardiovascular risk profile were similar between the ART adolescents and 43 age- and sex-matched control participants.

Through 24-hour ambulatory blood pressure monitoring, researchers discovered that ART adolescents had both a higher systolic and diastolic blood pressure than the control participants of natural conception at 119/71 mmHg versus 115/69, respectively. Most importantly, eight of the ART adolescents reached the criteria for the diagnosis of arterial hypertension (over 130/80 mmHg) whereas only one of the control participants met the criteria.

“The increased prevalence of arterial hypertension in ART participants is what is most concerning,” said Emrush Rexhaj, MD, director of Arterial Hypertension and Altitude Medicine at Inselspital, University Hospital in Bern, Switzerland and the lead author of the study. “There is growing evidence that ART alters the blood vessels in children, but the long-term consequences were not known. We now know that this places ART children at a six times higher rate of hypertension than children conceived naturally.”

The authors also studied these participants five years before this study and found that the arterial blood pressure between ART and control children was not different.

“It only took five years for differences in arterial blood pressure to show,” Rexhaj said. “This is a rapidly growing population and apparently healthy children are showing serious signs of concern for early cardiovascular risk, especially when it comes to arterial hypertension.”

In an accompanying editorial, Larry A. Weinrauch, MD, cardiologist at Mount Auburn Hospital said that the study’s small cohort may understate the importance of this problem for ART adolescents, especially since multiple birth pregnancies and maternal risk factors (such as eclampsia, chronic hypertension and diabetes) were excluded from the study.

“Early study, detection and treatment of ART conceived individuals may be the appropriate course of preventative action,” Weinrauch said. “We need to be vigilant in the development of elevated blood pressure among children conceived through ART to implement early lifestyle-based modifications and, if necessary, pharmacotherapy.”

Limitations of this study include that only single-birth children were studied, as well as that participants were recruited from one procreation center. Prematurity, low birth weight and preeclampsia (all known cardiovascular risk factors) were excluded from the study. These limitations may have resulted in a lower cardiovascular risk among the participants compared to the overall ART population.

The American College of Cardiology is the professional home for the entire cardiovascular care team. The mission of the College and its more than 52,000 members is to transform cardiovascular care and to improve heart health. The ACC leads in the formation of health policy, standards and guidelines. The College operates national registries to measure and improve care, offers cardiovascular accreditation to hospitals and institutions, provides professional medical education, disseminates cardiovascular research and bestows credentials upon cardiovascular specialists who meet stringent qualifications. For more, visit acc.org.

The Journal of the American College of Cardiology ranks among the top cardiovascular journals in the world for its scientific impact. JACC is the flagship for a family of journals—JACC: Cardiovascular Interventions, JACC: Cardiovascular Imaging, JACC: Heart Failure, JACC: Clinical Electrophysiology and JACC: Basic to Translational Science—that prides themselves in publishing the top peer-reviewed research on all aspects of cardiovascular disease. Learn more at JACC.org.

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Expert Reaction

These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.

Dr Yutang Wang is a Senior Lecturer in the School of Applied and Biomedical Sciences, Faculty of Science and Technology, Federation University Australia

One in 25 children were born through assisted reproductive technologies (ARTs) in Australia in 2014. However, the long-term cardiovascular consequences of ARTs are unknown. This paper, published in the Journal of the American College of Cardiology, showed that ART procedures could increase the risk of developing hypertension in apparently healthy adolescents and young adults.

This paper studied 54 ART-conceived participants (mean age 16) and 43 sex- and age-matched control participants. In this study, ART-conceived participants showed blood vessel dysfunction, vascular stiffness and atherosclerosis, all of which are cardiovascular risk factors. Blood pressure (BP) was recorded through 24-hour ambulatory BP monitoring, the most reliable method to measure BP.

ART-conceived subjects had significantly higher BP of 120/71 mm Hg compared to 116/69 mm Hg in the control. A 2‐mm Hg reduction in diastolic BP has been reported to be associated with a 6 per cent reduction in the risk of coronary heart disease and a 15 per cent reduction in the risk of stroke.

In addition, eight of the 52 ART participants, but only one of the 43 control participants, were classified with hypertension according to the ambulatory BP criteria of hypertension. Hypertension is a significant risk factor for many diseases, such as heart attack, kidney failure and stroke.

ARTs involve the manipulation of early embryos at a time when they may be particularly vulnerable to external disturbances. Therefore, it is not surprising that ARTs could increase individual’s susceptibility to some diseases.

Mice generated by IVF have a shortened lifespan compared with control mice. Whether this is the case in humans remains unknown.

Future research will tell us whether ARTs increase long-term cardiovascular diseases such as stroke and heart attack in humans, and research into methods to minimise such risks are urgently needed.

Last updated: 04 Sep 2018 1:17pm
Declared conflicts of interest:
None declared.
Robert Norman is Director of the Robinson institute and Professor of Reproductive and Periconceptual Medicine at the University of Adelaide

Several animal studies have reported that embryos created by IVF may lead to offspring with cardiovascular and metabolic problems.

This study claims similar problems in teenagers conceived by IVF and it may be that the first few days of exposure of an embryo to artificial culture media may affect a number of developing organs, including the heart and blood vessels.

The report is limited by relatively few subjects, relatively mild differences and children conceived at a time when more primitive culture conditions were in use.

It warrants a much larger study of the hundreds of thousands of IVF-conceived children in Australia who up until now have shown few medical consequences as a result of their conception.

Last updated: 04 Sep 2018 1:17pm
Declared conflicts of interest:
None declared.
Professor Michael Davies is a Professor of Reproductive Epidemiology in the Lifecourse and Intergenerational Health Research Group, Robinson Institute, at the University of Adelaide

It has been observed previously, both in our work and that of colleagues internationally, that children born from assisted reproductive technologies can have altered cardiovascular development, including congenital heart and vascular anomalies (1,2).

The present study extends this work to suggest that adverse alterations in vascular development and function after assisted conception may extend to those children who are apparently well at birth. 

The emergence of risk factors for cardiovascular disease in childhood is a significant concern as we understand that risk factors reliably track and amplify with age, and may result in serious clinical disease. 

The study included only apparently well children from uncomplicated pregnancies to identify treatment specific effects on cardiac function. As noted by the authors, the selection of apparently well children for the study may suggest that the total number of affected children due to all causes related to infertility treatment may be substantially greater. 

Subject to further confirmatory studies, the observed differences in the study are of public health significance.

Long-term follow-up studies of children born from assisted conception are often small and poorly designed, with a bias to showing no difference.

In this study showing a substantial difference, the modest sample size, pooling of treatment type, and use of a single study site limits our ability to generalise from the study sample to the broader population of ART births. Additionally, we cannot exclude the possible role of undiagnosed maternal factors that contribute to both the need for infertility treatment and familial vascular disorders.

However, the coherent set of adverse findings creates an imperative for replication in further studies.


Last updated: 04 Sep 2018 1:16pm
Declared conflicts of interest:
None declared.

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