Heart rate variability and pregnancy

Currently, much attention is being paid to molecular biology in almost all fields of medicine. To most researchers, a normal pregnancy might evoke the right genetic mix in the control of fetal development, or the integrated performance of key placental molecular mechanisms, such as the delicate balance between clotting and haemorrhage [1], ensuring the right supply of nutrients to the conceptus. Concomitance analysis of the Medline database (1966 to date) indicated that of the 471 000 articles referring to pregnancy only approximately 2% simultaneously address hypertension. This suggests that relatively little research focuses on the possibility of an association with haemodynamic disturbances, such as a transient or permanent rise in arterial pressure. In keeping with this concept, the number of studies dealing with pre-eclampsia, or eclampsia, is only approximately 1% of the total number of articles generally addressing pregnancy, although these conditions might be important not only clinically, but also as models of reversible alteration of peripheral haemodynamic regulation, as a consequence of both an abnormal vasoconstriction and increased sympathetic drive [2]. To better understand the potential role of arterial pressure dysregulation, it should be appreciated that, in human pregnancy, normalcy of arterial pressure values may be much lower than the standard limit of 140/90 mmHg, considering the usual young age and the attending peripheral vasodilatation. Thus, alterations of arterial pressure values in human pregnancy would probably be better examined in the context of hypertension as a continuum of changes both in haemodynamics and in its underlying regulation [3], particularly if aiming at preventing complications. In this issue of the journal, Rang et al. [4] state ‘Early haemodynamic changes in pregnancy are … related to changes in autonomic cardiovascular control. Failure in early adaptation may result in pregnancy-related cardiovascular complications, such as pre-eclampsia'. As a corollary, the authors argue ‘Various non-invasive methods provide information on the autonomic nervous system and could be of interest as a screening method for pre-eclampsia'. The underlying tenet that information [5] derived from physiological measures could be of clinical value, given the right model and context, appears to supersede older fears that mathematical manipulations of data could only provide epiphenomena of little relevance [6]. In the field of hypertension, we believe that the review by Rang et al. [4], who take the innovative stand that assessment of autonomic performance could prove valuable as an early screening method, is worthy of attention for three reasons: (i) the surrogate model of autonomic dysregulation; (ii) the specific goal of preventing pregnancy-related complications and, thus, (iii) the importance of non-invasive methodologies. First, Rang et al. [4], argue that since ‘a higher sympathetic nervous activity has been observed in pre-eclampsia … changes in autonomic control preced[ing] the onset of pre-eclampsia could provide … early identification'. Taking this into consideration, these authors screened the literature for studies simultaneously considering ‘pregnancy, pre-eclampsia and the autonomic nervous system’ and, in the 36 relevant articles identified, looked for methods to evaluate the ‘sympathetic and parasympathetic neural activity'. It should be recalled that autonomic regulation of the SA node depends upon a complex interplay between the efferent nerve activity of the two autonomic arms, the humoral milieu, the receptor signalling chain and the spontaneous depolarization of pace-maker cells [7]. The efferent sympathetic and vagal activities contain both low and high frequency rhythms, which are highly coherent with similar rhythms that can be found in the beat-by-beat variability signals derived from the RR interval and the arterial pressure series [7,8]. Time and frequency domain measures derived from computer analysis of these variability signals [9] can provide markers of the changing balance between sympathetic and vagal modulation [7], particularly when using dynamic protocols [5]. Although discussion is still ongoing on specific aspects of the methodology, a consensus document [10] highlighted the major technical aspects of the techniques most frequently employed. Furthermore, Rang et al. [4] provide a valuable table of comparison between the various techniques so far employed in the field of pregnancy-related hypertension, focusing clearly on the importance of dynamic approaches, and permitting a (reasonable) comparison among different studies. However, these authors could have more fully updated some of the interpretations offered. The recent findings by Montano et al. [11] showing that, in autonomic neurons, respiratory rhythms are maintained after atropine administration do not support, for example, older models [12] implying an excessive role of vagus nerve on either the respiratory or low frequency components of RR variability. In this context, the importance of using absolute or normalized units to compute the power of individual spectral components, as well as the crucial role of recording respiration, to correctly define respiratory rate and thus avoid the bias of entrainment, should be appreciated. To most researchers, the summary description of cardiovascular reflexes will be helpful [4], although some experts might find it difficult to accept unqualified simplifications such as ‘analysis of … blood pressure responses can be used to evaluate sympathetic vasomotor function'. In conclusion, Rang et al. [4] should be thanked for having provided a short summary of the current literature on the possible usefulness of autonomic evaluation in the clinical management of human pregnancy: an emphasis on non-invasive methods, and the side-by-side presentation of older and newer techniques is a strength. However, space limitation prevented a fuller appreciation of more modern tools, such as the possibility of specifically addressing various aspects of baroreflex function [13]. As with all beginnings, together with some useful answers, the merit warranted for their review derives probably more from the questions remaining, such as whether autonomic evaluation could predict the occurrence of pre-eclampsia or, perhaps more generally, hypertension. Obviously more data and focused research are required to support updated new clinical standards.