Sex-related differences in the development of fetal heart rate dynamics

Abstract

Background: Despite previous efforts to explain the general advantages of female fetuses over males regarding health, sex-related differences in the dynamics or complexity of fetal heart rate (FHR) variability and FHR maturation patterns have not yet been identified. Aim: To make linear and nonlinear comparisons of antepartum FHR indices, dynamics, complexity, and reactivity to the non-stress test (NST) and vibroacoustic-stimulation test (VAST) in male and female fetuses. Study design: A total of 3835 singleton term deliveries without maternal and fetal complications were divided into female (n = 1849) and male (n = 1986) groups, and subjected to comparison and analyses. Subjects: Linear FHR indices, approximate entropy (ApEn), sample entropy (SampEn), short-term/long-term exponents (alpha 1/alpha 2), correlation dimension (CD), NST and VAST criteria, and modified nonlinear reactive criteria (MNRC) were used to evaluate outcomes. Results: ApEn was consistently higher in female fetuses than in male ones. ApEn in female fetuses was maximal at 29-30 gestational weeks, while the increase in ApEn was delayed in male fetuses but more rapid, reaching its peak at 31-32 gestational weeks. In both sexes, CD increased up to term, and alpha 2 rapidly decreased up to 31-32 weeks in an analogous manner. The two sexes differed significantly in response to VAST at <31 gestational weeks and there was a structural difference in reactive patterns under MNRC. Conclusions: Female fetuses exhibit greater heart rate dynamics in early gestational periods, suggesting that their cardiovascular system matures earlier than that of males. Male fetuses undergo a compensatory period of rapid change to catch up with females at term.