The main findings of this study are that, of the time intervals that compose fetal cardiac electrophysiological activity, atrial and ventricular depolarization times clearly increase in the second and third trimester of pregnancy and that these changes are in part dependent on gender. Furthermore, ventricular repolarization duration and intervals not involving depolarization do not demonstrate these dependencies.
Our results are in general agreement with those in Stinstra et al  which included a large amount of data contributed by a number of laboratories. However that study had the difficulty that the data showed systematic differences between the data of the contributing centers. There may be various reasons for this bias resulting from different recording and evaluation techniques . The work presented here largely avoids these technical difficulties and we may thus expect the observed trends and variance to reflect more closely the physiological factors involved.
A further difficulty in comparing the published results of different groups is that the documentation of the changes during pregnancy takes on various forms. The reports may include mean and extreme values averaged over ≥ 4 week periods [1, 3, 5–7] or regression-based estimated values [8, 17, 20]. The data may be plotted with or without confidence intervals [4–8, 17, 20]. In some of the work, estimations of age dependency are given, based on correlation and/or regression analysis [1, 4–8, 17, 20]. In this report we have given most of this information on all CTI we examined and we have included a week by week descriptive analysis for those CTI displaying a distinct dependency on age, namely the P wave, PR and PQ interval as well as the QRS complex. Considering the size of the study population and the relatively consistent recording and evaluation procedures applied in accordance with accepted standards , these values may serve as reference values.
We did not consider it appropriate to take the effect of gestational age into account for the QT and QTc intervals although they showed a statistically significant slope in the regression analysis. These intervals, as well as the ST segment and T wave, were characterized by low coefficients of determination (< 0.08), indicating that the effect of age was minimal with a wide spread of data at any specific gestational age and a large data overlap over extended gestational periods. Thus a realistic estimation of their duration can be made independently of age.
The distinct relationship between depolarization times and age has often been posited to reflect changes in heart size over gestation [e.g. ]: the larger the cardiac chambers, the more time needed for the depolarization wave to travel over the myocardium. Indeed, mammalian hearts display a dependency on body mass with respect to organ size and conduction time . The weight of the fetal heart has been shown increase over time both with respect to body weight and gestational age  and estimations of fetal cardiac dimensions and mass based on ultrasound recording show a steady increase over time [23–25]. The estimation of these dependencies are, more often than not, described more adequately using quadratic polynomials than a linear model. This reflects the slowing of the increase in size with a concomitant higher variance towards the end of pregnancy. With respect to the change of QRS duration over time, we found a similar trend in the data and, consequently, that nonlinear models fitted more appropriately. This has also been noted by others on the basis of fetal ECG data [9, 26] and further supports the notion of the link between fetal cardiac dimension and interval duration.
We compared representative CTI values in the terminal period of pregnancy, based on our data, to neonatal and infant PR, QRS and QT times found in the literature [27, 28]. These showed a high degree of agreement for the duration of AV conduction and ventricular depolarization. With respect to the T wave, the FMCG measures of location were lower than those reported for the newborns. This may be attributed to the rate dependency of the QT times, as the prepartal heart rate is higher than postpartal. Another reason for the difference may be the difficulty in the determination of the FMCG T wave, its low amplitude waveform shape leading to underestimation of its length.
On the basis of our findings, one further factor leading to the greater variance of QRS duration towards the end of pregnancy can be presumed to be fetal gender: a trend to lower values for females was distinguishable after the 30th week. Gender based differences in QRS duration have also been noted by Brambati and Pardi , albeit not statistically significant. Furthermore, in pediatric populations, QRS duration has been shown to be shorter in girls than in boys [28, 29]. Females are characterized by a lower birth weight than males, in particularly at later gestational ages . This trend was also present in our subjects (males 3716 ± 555 g, females 3438 ± 497 g, p = 0.088). In the light of the above, the trend to shorter female QRS duration may correspond at least in part to their lower body weight. This fact will be of importance, for example, when investigating the possible association between growth retardation and CTI [17, 20] in order to avoid masking reduced QRS duration in male subjects.
The results with respect to biometric data were inconclusive: only head circumference displayed a weak relationship to QRS duration. This was surprising, in particular for birth weight, as such a dependency has been reported in a larger collective . One of the reasons for the lack of correlation in our data may have been due to the fact that only 15 FMCG recordings performed within one week of birth were available for analysis. Furthermore, the relationships between fetal depolarization times, heart size and body weight discussed above are largely based on longitudinal studies. Examining the relationship on a cross section of subjects within a narrow range of time at the end of pregnancy when most biometric values are stabilizing will make the identification of a trend difficult and will likely require a substantial number of cases. It is however interesting to note that head circumference, which showed a weak correlation to QRS, has been identified as being more reliable than other biometric parameters in the estimation of fetal age [31, 32].
The overall high number of FMCG recordings permitted a reliable statistical description of the data with respect to the gestational period observed. However, the results are limited by the moderate number per week of gestation (ca. ). We did not deem this enough to give a stable description per week and we preferred instead to extrapolate weekly values on the basis of regression analysis parameters. A higher number of subjects and recordings would alleviate this limitation. Another aspect which must be kept in mind is that the precise determination of gestational age is a prerequisite for the correct estimation of dependency. We established gestational age as the computed interval between the date of last normal menses and the date of recording. Although other measures exist , we chose this procedure as it is commonly used and we did not always have access to ultrasound biometrics or other documentation.