Assisted reproductive technology (ART), widely used in the treatment of infertility, may result in adverse cardiovascular health outcomes in offspring, new data suggest.
In an observational cohort study done in China, children conceived by ART had increased blood pressure and unfavorable changes in left ventricular structure and function compared with children who were naturally conceived, investigators report.
The findings, published online today in JAMA Network Open, suggest the need for more research to investigate the potential mechanisms and long-term outcomes associated with these differences, Linlin Cui, MD, PhD, from the Center for Reproductive Medicine, Shandong University, Jinan, China, and colleagues, write.
It is estimated that more than 8 million infants have been born using ART since the first "test tube baby," Louise Brown, was born in the UK in 1978. They account for 2% to 6% of births in high-income countries, the authors note.
"ART requires the in vitro manipulation of gametes and embryos in a synthetic culture environment, and these nonphysiological exposures may be associated with adverse outcomes in embryonic development and offspring health," they write.
Unfavorable obstetric outcomes, including preterm birth, low birth weight, and small-for-gestational-age infants, have been linked to ART, as have risk factors for cardiovascular disease.
"Evidence from the developmental origins of health and disease theory also suggests that adverse events (eg, restricted fetal growth and preterm birth) in early life are associated with increased risk of cardiovascular disease later in life. Therefore, the cardiovascular health of offspring conceived by ART has gained much attention," the authors say.
In the current study, the researchers compared the cardiovascular health of 382 children conceived by ART with that of 382 children who were naturally conceived. Subjects were recruited from November 2017 to February 2019, and were matched by sex, age, and maternal age at the child's birth.
Blood pressure was measured, and echocardiography was performed to determine left ventricular structural and functional parameters.
Children conceived by ART had statistically significantly increased height (mean 130 cm [4 ft, 3 in] vs 128 cm [4 ft, 2 in]; P = .007) and body mass index (mean 17.6 vs 17.1; P = .03), compared with naturally conceived children.
They also had statistically significantly increased mean systolic blood pressure (105.5 mm Hg vs 103.5 mm Hg; adjusted P < .001), diastolic blood pressure (67.2 mm Hg vs 62.2 mm Hg, adjusted P < .001).
The prevalence of elevated blood pressure was also higher in the ART group (80 children, 21%) compared with the naturally conceived group (50 children, 13%), and the prevalence of high blood pressure was also higher in the ART group (69 children, 18.1%) compared with the naturally conceived group (54 children, 14.1%; adjusted P = .002).
ART children also had more left ventricular systolic dysfunction. In the ART group, the mean left ventricular ejection fraction was 64.6% compared with 66.7% for the naturally conceived children (P < .001). ART children also had more diastolic dysfunction early/late mitral/tricuspid diastolic velocities ratio, 1.66 vs 2.21; (adjusted P < .001).
In addition, ART children were found to have statistically significantly increased parameters of left ventricular structure, including mean left ventricular mass index (31.97 g/m2.7 vs 28.28 g/m2.7; adjusted P < .001), and right wall thickness (RWT 3.30 mm vs 2.98 mm; adjusted P < .001).
There was also a statistically significantly increased prevalence of left ventricular hypertrophy among ART children compared with naturally conceived children (9 children vs 2; P = .03), high right wall thickness (61 children vs 0; P < .001), and left ventricular remodeling patterns, including concentric remodeling (60 children vs 0), eccentric hypertrophy (8 children vs 2) and concentric hypertrophy (1 child vs 0).
The authors note their study limitations. For one, they write that they cannot make conclusions about whether the adverse cardiovascular profile associated with ART is due to the procedure itself or other unknown confounders not measured in the study.
They also point out that because there are no unified criteria to define LVH, high RWT, or LV geometric remodelling patterns, they used sex-specific and age-specific 95th percentile cutoffs based on definitions established among Western children, and the cutoffs may be too high to be used among Chinese children. Another potential limitation is that all children conceived by ART in this study were from a single medical center in China and therefore the findings "should be generalized with caution."
The investigators conclude that their findings may have significance for clinical and public health, and they furthermore suggest increased surveillance in the ART population.
"Because childhood is a critical window for early detection, potential intervention, and improvement of cardiac health among children conceived by ART, it may be possible to reverse the unfavorable alterations in their cardiac structure and function. Further studies are necessary to confirm the association."
The study was funded by the National Key Research and Development Program of China, the Shandong Provincial Key Research and Development Program, the National Natural Science Foundation of China, and the Shandong Province Medical and Health Technology Development Project. The authors of the study have disclosed no relevant financial relationships.
JAMA Network Open. Published online November 4, 2021. Abstract
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