Critical Moment of Fetal Heart Development Identified

Researchers and neonatologists studying fetal cardiac development have typically run into critical limitations, as many of the known structures of the human heart can only be identified in the latter stages of gestation. Now, a group of investigators at the University of Leeds has just published data, using cutting-edge imaging technology, that shows that major structures of a baby's heart form in just four days. Findings from the new study—published today in Scientific Reports in an article entitled “Ventricular Myocardium Development and the Role of Connexins in the Human Fetal Heart”—help identify the precise time when the four chambers of the heart develop, opening up the possibility that doctors could eventually be able to monitor babies during this critical phase of their development.

“We have identified a critical time of development of the human heart in pregnancy,” explained lead study investigator Eleftheria Pervolaraki, Ph.D., a visiting research fellow in the School of Biomedical Sciences at the University of Leeds. “We now have a map that we can use to interpret problems during development and look at ways of trying to resolve those problems.”

This image shows the fetal heart at the start of the four-day period when the major structures of a baby’s heart begin to form. [Eleftheria Pervolaraki/University of Leeds]

The current study involved the imaging of 23 fetal hearts with a gestational age range of 95 to 143 days in the womb. Moreover, the researchers looked at how the heart developed 13 to 20 weeks into pregnancy. The researchers used magnetic resonance imaging (MRI) technology, specifically written algorithms, and 3D computer software to visualize the growing heart.

“We employed diffusion tensor magnetic resonance imaging to explore the architecture and tissue organization of the developing heart aged 95–143 DGA [days gestational age],” the authors wrote. “We show that fractional anisotropy increases (from ~0.1 to ~0.5), diffusion coefficients decrease (from ~1 × 10−3mm²/sec to ~0.4 × 10−3mm²/sec), and fiber paths, extracted by tractography, increase linearly with gestation, indicative of the increasing organization of the ventricular myocytes.”

The authors continued, stating that “by 143 DGA, the developing heart has the classical helical organization observed in mature mammalian tissue. This was accompanied by an increase in connexin 43 and connexin 40 expression levels, suggesting their role in the development of the ventricular conduction system and that electrical propagation across the heart is facilitated in later gestation.”

Remarkably, the research team found that the most dramatic changes occurred over a four-day period 124 days into the pregnancy. Within this brief period, the muscle tissue of the heart rapidly organizes. Cardiac fibers were laid down to form the helix shape of the heart, within which the four chambers of the heart form. Without this essential architecture in place, the fetal heart cannot survive outside the womb.

The investigators noted that there was an incredible level of consistency around the fact that this phase of the heart's development started between the 16- and 17-week point, precisely at 124 days into pregnancy. Additionally, the team also identified a possible mechanism involved in heart development. During the critical four-day period, they found increased levels of two proteins: connexin 40 and connexin 43.

“The expression of connexin 40 and connexin 43 helps cells in the heart to communicate with each other,” remarked study co-author James Dachtler, Ph.D., a research fellow in the department of psychology at Durham University. “As the amount of these proteins increases, cells can 'speak' to each other more effectively, which is why we believe we observed this structural development of the heart.”

The scientists acknowledged that the development timeline of the human heart remains elusive because of the difficulties of measuring development in the womb. Currently, doctors can only effectively monitor a baby's heart after 20 weeks into a pregnancy, and by then developmental problems are difficult to resolve.

The research team believes the specialist imaging techniques that they used could be adapted for use in hospital clinics, allowing clinicians to spot whether a baby's heart is failing to form properly.

“Our findings highlight a key developmental window for the structural organization of the fetal heart,” the authors concluded.