Background: Owing to the association between dysfunctional maternal autonomic regulation and pregnancy complications, assessing non-invasive features reflecting autonomic activity—e.g., heart rate variability (HRV) and the morphology of the photoplethysmography (PPG) pulse wave—may aid in tracking maternal health. However, women with early pregnancy complications typically receive medication, such as corticosteroids, and the effect of corticosteroids on maternal HRV and PPG pulse wave morphology is not well-researched. Methods: We performed a prospective, observational study assessing the effect of betamethasone (a commonly used corticosteroid) on non-invasively assessed features of autonomic regulation. Sixty-one women with an indication for betamethasone were enrolled and wore a wrist-worn PPG device for at least four days, from which five-minute measurements were selected for analysis. A baseline measurement was selected either before betamethasone administration or sufficiently thereafter (i.e., three days after the last injection). Furthermore, measurements were selected 24, 48, and 72 h after betamethasone administration. HRV features in the time domain and frequency domain and describing heart rate (HR) complexity were calculated, along with PPG morphology features. These features were compared between the different days. Results: Maternal HR was significantly higher and HRV features linked to parasympathetic activity were significantly lower 24 h after betamethasone administration. Features linked to sympathetic activity remained stable. Furthermore, based on the PPG morphology features, betamethasone appears to have a vasoconstrictive effect. Conclusions: Our results suggest that administering betamethasone affects maternal autonomic regulation and cardiovasculature. Researchers assessing maternal HRV in complicated pregnancies should schedule measurements before or sufficiently after corticosteroid administration.

Due to the association between dysfunctional maternal autonomic regulation and pregnancy complications, tracking non-invasive features of autonomic regulation derived from wrist-worn photoplethysmography (PPG) measurements may allow for the early detection of deteriorations in maternal health. However, even though a plethora of these features-specifically, features describing heart rate variability (HRV) and the morphology of the PPG waveform (morphological features)-exist in the literature, it is unclear which of these may be valuable for tracking maternal health. As an initial step towards clarity, we compute comprehensive sets of HRV and morphological features from nighttime PPG measurements. From these, using logistic regression and stepwise forward feature elimination, we identify the features that best differentiate healthy pregnant women from non-pregnant women, since these likely capture physiological adaptations necessary for sustaining healthy pregnancy. Overall, morphological features were more valuable for discriminating between pregnant and non-pregnant women than HRV features (area under the receiver operating characteristics curve of 0.825 and 0.74, respectively), with the systolic pulse wave deterioration being the most valuable single feature, followed by mean heart rate (HR). Additionally, we stratified the analysis by sleep stages and found that using features calculated only from periods of deep sleep enhanced the differences between the two groups. In conclusion, we postulate that in addition to HRV features, morphological features may also be useful in tracking maternal health and suggest specific features to be included in future research concerning maternal health.

We compare CRC, i.e., the reciprocal interaction between the cardiac and respiratory systems, between healthy pregnant and nonpregnant women for the first time. Although CRC is present in both groups, CRC is reduced during healthy pregnancy; there is less synchronization between maternal cardiac and respiratory activity and a smaller response in maternal heart rate to respiratory inhalations and exhalations. Stratifying this analysis by sleep stages reveals that differences are most prominent during deep sleep.

BackgroundResearchers have long suspected a mutual interaction between maternal and fetal heart rhythms, referred to as maternal-fetal cardiac coupling (MFCC). While several studies have been published on this phenomenon, they vary in terms of methodologies, populations assessed, and definitions of coupling. Moreover, a clear discussion of the potential clinical implications is often lacking. Subsequently, we perform a scoping review to map the current state of the research in this field and, by doing so, form a foundation for future clinically oriented research on this topic. MethodsA literature search was performed in PubMed, Embase, and Cochrane. Filters were only set for language (English, Dutch, and German literature were included) and not for year of publication. After screening for the title and the abstract, a full-text evaluation of eligibility followed. All studies on MFCC were included which described coupling between heart rate measurements in both the mother and fetus, regardless of the coupling method used, gestational age, or the maternal or fetal health condition. Results23 studies remained after a systematic evaluation of 6,672 studies. Of these, 21 studies found at least occasional instances of MFCC. Methods used to capture MFCC are synchrograms and corresponding phase coherence indices, cross-correlation, joint symbolic dynamics, transfer entropy, bivariate phase rectified signal averaging, and deep coherence. Physiological pathways regulating MFCC are suggested to exist either via the autonomic nervous system or due to the vibroacoustic effect, though neither of these suggested pathways has been verified. The strength and direction of MFCC are found to change with gestational age and with the rate of maternal breathing, while also being further altered in fetuses with cardiac abnormalities and during labor. ConclusionFrom the synthesis of the available literature on MFCC presented in this scoping review, it seems evident that MFCC does indeed exist and may have clinical relevance in tracking fetal well-being and development during pregnancy.

Objective. Appropriate adaptation of the maternal autonomic nervous system to progressing gestation is essential to a healthy pregnancy. This is partly evidenced by the association between pregnancy complications and autonomic dysfunction. Therefore, assessing maternal heart rate variability (HRV)-a proxy measure for autonomic activity-may offer insights into maternal health, potentially enabling the early detection of complications. However, identifying abnormal maternal HRV requires a thorough understanding of normal maternal HRV. While HRV in women of childbearing age has been extensively investigated, less is known concerning HRV during pregnancy. Subsequently, we investigate the differences in HRV between healthy pregnant women and their non-pregnant counterparts. Approach. We use a comprehensive suite of HRV features (assessing sympathetic and parasympathetic activity, heart rate (HR) complexity, HR fragmentation, and autonomic responsiveness) to quantify HRV in large groups of healthy pregnant (n = 258) and non-pregnant women (n = 252). We compare the statistical significance and effect size of the potential differences between the groups. Main results. We find significantly increased sympathetic and decreased parasympathetic activity during healthy pregnancy, along with significantly attenuated autonomic responsiveness, which we hypothesize serves as a protective mechanism against sympathetic overactivity. HRV differences between these groups typically had a large effect size (Cohen's d > 0.8), with the largest effect accompanying the significantly reduced HR complexity and altered sympathovagal balance observed in pregnancy (Cohen's d > 1.2). Significance. Healthy pregnant women are autonomically distinct from their non-pregnant counterparts. Subsequently, assumptions based on HRV research in non-pregnant women cannot be readily translated to pregnant women.

While the effect of antenatally administered corticosteroids on fetal heart rate (HR) and heart rate variability (HRV) is well established, little information is available on how these drugs affect maternal physiology. In this secondary analysis of a prospective, observational cohort study, we quantify how corticosteroids affect maternal HR and HRV, which serve as a proxy measure for autonomic regulation. Abdominal ECG measurements were recorded before and in the five days following the administration of betamethasone—a corticosteroid commonly used for fetal maturation—in 46 women with singleton pregnancies. Maternal HR and HRV were determined from these recordings and compared between these days. HRV was assessed with time- and frequency-domain features, as well as non-linear and complexity features. In the 24 h after betamethasone administration, maternal HR was significantly increased (p < 0.01) by approximately 10 beats per minute, while HRV features linked to parasympathetic activity and HR complexity were significantly decreased (p < 0.01 and p < 0.001, respectively). Within four days after the initial administration of betamethasone, HR decreases and HRV features increase again, indicating a diminishing effect of betamethasone a few days after administration. We conclude that betamethasone administration results in changes in maternal HR and HRV, despite the heterogeneity of the studied population. Therefore, its recent administration should be considered when evaluating these cardiovascular metrics.

Inadequate development of the fetal autonomic nervous system (ANS) during gestation can lead to health problems not only in the perinatal period but well into adulthood. Assessing fetal heart rate variability (fHRV) may allow for tracking fetal autonomic development and identification of abnormalities. A HRV methodology which is well-suited to this purpose is phase rectified signal averaging (PRSA). While PRSA has been used in assessing autonomic dysfunction related to complications such as fetal growth restriction, knowledge on how PRSA features change with gestational age is limited. In this paper, we use PRSA to analyze a dataset comprising of repeated abdominal ECG measurements acquired throughout healthy pregnancy (29 participants, 184 recordings) to capture how PRSA features evolve over the second half of gestation. Results show that all features change significantly $(p < 0.01)$, typically increasing from 22 to around 31 weeks (likely due to quicker signaling between nerve cells, corresponding to the rapidly maturing parasympathetic nervous system) and then stabilizing or slightly decreasing thereafter owing to better control of the heart rate by the mature fetal ANS. We conclude that PRSA features change with progressing gestation and may be a useful tool for tracking the maturation of the fetal ANS.

Pregnancy complications are associated with insufficient adaptation of the maternal autonomic nervous system to the physiological demands of pregnancy. Consequently, assessing maternal heart rate variability (mHRV)-which reflects autonomic regulation-is a promising tool for detecting early deterioration in maternal health. However, before mHRV can be used to screen for complications, an understanding of the factors influencing mHRV during healthy pregnancy is needed. In this retrospective observational study, we develop regression models to unravel the effects of maternal demographics (age, body mass index (BMI), gestational age (GA), and parity), cardiorespiratory factors (heart rate and breathing rate), and inter-subject variation on mHRV. We develop these models using two datasets which are comprised of, respectively, single measurements in 290 healthy pregnant women and repeated measurements (median = 8) in 29 women with healthy pregnancies. Our most consequential finding is that between one-third and two-thirds of the variation in mHRV can be attributed to inter-subject variability. Additionally, median heart rate dominantly affects mHRV (p < 0.001), while BMI and parity have no effect. Moreover, we found that median breathing rate, age, and GA all impact mHRV (p < 0.05). These results suggest that personalized, long-term monitoring would be necessary for using mHRV for obstetric screening.

Autonomic regulation is essential in enabling a healthy pregnancy. In fact, several pregnancy complications are associated with autonomic dysfunction. Better understanding of the maternal autonomic state during healthy pregnancy may aid in the early detection of such complications. One aspect of autonomic regulation is autonomic responsiveness, which can by assessed by phase rectified signal averaging (PRSA). While other areas of research have found blunted physiological responses in pregnancy, this paper presents the first investigation of maternal autonomic responsiveness as assessed by PRSA. We find significantly reduced rates of responses, as well as an attenuated capacity for heart rate acceleration when comparing pregnant women to non-pregnant controls. We hypothesize that this attenuated autonomic control may serve to protect the mother against her imbalanced autonomic state, as increased sympathetic and decreased parasympathetic modulation accompany healthy pregnancies. Clinical Relevance- Maternal autonomic responsiveness is attenuated in pregnancy in comparison to non-pregnant women. Understanding maternal autonomic state not only improves our knowledge of gestational physiology but also forms the basis for the early detection of pregnancy complications associated with maternal autonomic dysfunction.

Changes in the maternal autonomic nervous system are essential in facilitating the physiological changes that pregnancy necessitates. Insufficient autonomic adaptation is linked to complications such as hypertensive diseases of pregnancy. Consequently, tracking autonomic modulation during progressing pregnancy could allow for the early detection of emerging deteriorations in maternal health. Autonomic modulation can be longitudinally and unobtrusively monitored by assessing heart rate variability (HRV). Yet, changes in maternal HRV (mHRV) throughout pregnancy remain poorly understood. In previous studies, mHRV is typically assessed only once per trimester with standard HRV features. However, since gestational changes are complex and dynamic, assessing mHRV comprehensively and more frequently may better showcase the changing autonomic modulation over pregnancy. Subsequently, we longitudinally (median sessions = 8) assess mHRV in 29 healthy pregnancies with features that assess sympathetic and parasympathetic activity, as well as heart rate (HR) complexity, HR responsiveness and HR fragmentation. We find that vagal activity, HR complexity, HR responsiveness, and HR fragmentation significantly decrease. Their associated effect sizes are small, suggesting that the increasing demands of advancing gestation are well tolerated. Furthermore, we find a notable change in autonomic activity during the transition from the second to third trimester, highlighting the dynamic nature of changes in pregnancy. Lastly, while we saw the expected rise in mean HR with gestational age, we also observed increased autonomic deceleration activity, seemingly to counter this rising mean HR. These results are an important step towards gaining insights into gestational physiology as well as tracking maternal health via mHRV.

Pregnancy is a period of continuous change in the maternal cardiovascular system, partly mediated by the autonomic nervous system. Insufficient autonomic adaptation to increasing gestation is associated with pregnancy complications, such as hypertensive disorders of pregnancy and preterm birth (both major causes of perinatal morbidity and mortality). Consequently, maternal heart rate variability (mHRV), which is a proxy measure for autonomic activity, is increasingly assessed in these cohorts to investigate the pathophysiology of their complications. A better pathophysiological understanding could facilitate the early detection of these complications, which remains challenging. However, such studies (typically performed in pregnancies leading to hospitalization) have generated conflicting findings. A probable reason for these conflicting findings is that these study cohorts were likely administered routine obstetric medications during the study period of which the effects on mHRV are largely unknown. Subsequently, we design a longitudinal, observational study to quantifying the effect of these medications—particularly corticosteroids, which are known to affect fetal HRV—on mHRV to improve the interpretation of past and future studies. We will enroll 61 women admitted to a tertiary obstetric unit with an indication to receive corticosteroids antenatally. Participants’ mHRV will be continuously acquired throughout their hospitalization with wrist-worn photoplethysmography to facilitate a within-patient comparison of the effect of corticosteroids on mHRV.

Important changes occur in the maternal autonomic nervous system with advancing gestation. Tracking maternal autonomic modulation with heart rate variability (HRV) may hold opportunities for early detection of pregnancy complications such as hypertensive disorders of pregnancy (HPD) since these are associated with autonomic dysfunction. However, traditional HRV features often show conflicting trends over gestation. In this paper we implement phase rectified signal averaging (PRSA) to longitudinally track autonomic response throughout gestation. Since other fields of investigation have shown attenuated autonomic responsivity in healthy pregnancy, we hypothesized that assessing PRSA longitudinally over pregnancy would elicit a clearer trajectory of autonomic modulation. We found that autonomic responsiveness becomes significantly attenuated towards the end of pregnancy, although not to a degree that is comparable to diseased states. PRSA features show clear downward trends across pregnancy, with an uptick right before pregnancy ends, perhaps showing increased autonomic activity in preparation for delivery. We conclude that longitudinal analysis using PRSA holds promise as a potential screening tool for high-risk pregnancies.

The current clinical definition of Apnea of Prematurity (AOP) in infants is cessations of breathing exceeding 20 s, or at least 10 s accompanied by bradycardia under 100 beats per minute (bpm) or desaturation below 80%. AOP has a negative effect on infant health as it can increase the risk of hypoxemia, hypoglycaemia, neurological injury and sepsis. However, the detrimental effects of AOP are poorly understood, in large part because apneas are difficult to monitor owing to limitations in the current modalities for monitoring respiration. This study investigates the respiratory dynamics of preterm infants by implementing, with modifications, a pre-existing breathing cessation-detection algorithm. Unlike other studies, we also analyze short cessations in breathing (2-5 s), so as to better quantify respiratory dynamics, temporally track respiratory stability and to investigate whether short cessations in breathing are related to apnea. We found that isolated 2-5 s cessations have a significant impact on the total time of breathing cessation, increasing it from 3.0% to 4.3%. Furthermore, short cessations in breathing are positively correlated to apnea. Finally, there are multiple periodic increases in cessations of breathing within a day.