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C. Eenkhoorn

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Journal article (2026) - Chantal Eenkhoorn, Tom G. Goos, Arie Franx, Jenny Dankelman, H. Rob Taal, Sten P. Willemsen, Alex J. Eggink
This study aimed to establish reference values for heart rate frequency and variability indices in preterm neonates admitted to a neonatal intensive care unit of a tertiary care hospital during their first week of life. In this retrospective cohort study, the Generalized Additive Models for Location Scale and Shape framework was employed to establish reference values for heart rate indices across time-domain, frequency-domain and nonlinear-domain in neonates considering gestational age, postnatal age, sex and birth weight. Heart rate tracings of 594 neonates (45% female; median gestational age at birth 290 (IQR 266-305); 38% birth weight <p10, 6% birth weight >p90) were analyzed. Reference values were established for 25 heart rate indices. Nearly all heart rate indices were significantly influenced by gestational age, postnatal age and sex. Baseline heart rate decreased with gestational age, increased with postnatal age and was higher in females. Heart rate standard deviation increased with gestational age and postnatal age and was lower in female. Inclusion of birth weight significantly improved model fit for all HRV indices. This study highlights the importance of considering gestational and postnatal age, sex and birth weight when interpreting neonatal heart rate frequency and variability in preterm neonates. These findings support the need for personalized approaches for neonatal monitoring and interpretation. Future research should validate these values in larger, more diverse populations, including additional clinical factors such as neonatal complications and medication administration, to determine their clinical relevance. ...
Journal article (2026) - Chantal Eenkhoorn, Tom G. Goos, Arie Franx, Jenny Dankelman, Sten P. Willemsen, Alex J. Eggink
Objective: To establish reference values for fetal heart rate (FHR) indices across time, frequency and nonlinear domains throughout pregnancy in a tertiary hospital population, considering sex. The influence of the number of fetuses, birth weight,and time to delivery on FHR was evaluated. Methods: This retrospective cohort study analyzed the initial FHR tracing upon hospital admission between 24° and 41° weeks of gestation, excluding cases in labor, with medication use, or a confirmed medical indication. Reference values were established using the Generalized Additive Models for Location Scale and Shape framework. Likelihood ratio test assessed whether including clinical variables significantly improved model fit. Results: The cohort included 3219 fetuses, of which 48% were female and 91% singleton pregnancies. Median gestational age was 32+6. Birth weight was below p10 in 22% and above p90 in 9%. Median tracing duration was 42.5 min and median signal loss was 1.95%. Most indices were significantly associated with gestational age and several showed significant sex differences. Model fit significantly improved for multiple indices when including number of fetuses, birth weight, or time to delivery. Conclusions: This article presents gestational age- and sex-specific reference values for FHR in a large tertiary hospital population. The influence of gestational age was reaffirmed and significant differences related to sex, number of fetuses, birth weight, and time to delivery were identified. This enhances understanding of fetal autonomic regulation and supports a more individualized approach to predictive fetal monitoring. Further research is needed to determine the clinical utility of these reference values in practical monitoring and risk assessment. ...

A Clinical Study from the Week before to the Week after Birth

Journal article (2026) - Chantal Eenkhoorn, Tom G. Goos, Arie Franx, Jenny Dankelman, Rob R. Taal, Sten P. Willemsen, Alex J. Eggink
Objective This study aimed to explore the fetal heart rate trend in the week before birth, the transition from fetal to neonatal heart rate, and the neonatal heart rate trend in the week after birth in preterm neonates admitted to a tertiary care hospital, considering maternal and neonatal factors. Study Design A retrospective cohort study was conducted, including neonates born between 24 and 34 weeks of gestation. Baseline heart rate, average deceleration capacity, standard deviation, skewness, and sample entropy were assessed using interrupted time series and difference-in-differences analyses. Subgroup analyses were performed according to gestational age at birth, sex, birth weight, mode of delivery, Apgar score at 5minutes, umbilical cord pH, and neonatal medication. Results The fetal and neonatal heart rate of 123 patients was analyzed. After birth, step change of baseline (2.23bpm,p<0.05), average deceleration capacity (0.43bpm,p<0.001), and skewness (0.47 nu,p<0.001) increased, while sample entropy (−0.68 bits,p<0.001) and standard deviation (−1.15bpm,p<0.001) decreased. Postnatally, baseline increased in linear slope and decreased in quadratic slope (bothp<0.001). Average deceleration capacity decreased in linear slope (p<0.001). Sample entropy and standard deviation increased in linear slopes (bothp<0.001). Skewness increased in quadratic slope (p<0.05). Subgroup analyses revealed that delivery mode, medication, and birth weight modulated these trends. Conclusion This study provides unique insights into heart rate frequency and variability trends during the period around preterm birth. It highlights the dynamic physiological adaptation that occurs during the transition from intrauterine to extrauterine life in preterm infants and may help inform future research on fetal and neonatal monitoring and clinical management. Key Points Heart rate frequency and variability dynamics were assessed around preterm birth in a NICU cohort. After birth, heart rate frequency increased while variability measures decreased. Heart rate frequency and variability differed by gestational age, birth weight, medication, and delivery mode. ...
Journal article (2024) - Chantal Eenkhoorn, Tom G. Goos, Jenny Dankelman, Arie Franx, Alex J. Eggink
Introduction: In clinical practice, fetal heart rate monitoring is performed intermittently using Doppler ultrasound, typically for 30 minutes. In case of a non-reassuring heart rate pattern, monitoring is usually prolonged. Noninvasive fetal electrocardiography may be more suitable for prolonged monitoring due to improved patient comfort and signal quality. This study evaluates the performance and patient experience of four noninvasive electrocardiography devices to assess candidate devices for prolonged noninvasive fetal heart rate monitoring. Material and methods: Non-critically sick women with a singleton pregnancy from 24 weeks of gestation were eligible for inclusion. Fetal heart rate monitoring was performed during standard care with a Doppler ultrasound device (Philips Avalon-FM30) alone or with this Doppler ultrasound device simultaneously with one of four noninvasive electrocardiography devices (Nemo Fetal Monitoring System, Philips Avalon-Beltless, Demcon Dipha-16 and Dräger Infinity-M300). Performance was evaluated by: success rate, positive percent agreement, bias, 95% limits of agreement, regression line, root mean square error and visual agreement using FIGO guidelines. Patient experience was captured using a self-made questionnaire. Results: A total of 10 women were included per device. For fetal heart rate, Nemo performed best (success rate: 99.4%, positive percent agreement: 94.2%, root mean square error 5.1 BPM, bias: 0.5 BPM, 95% limits of agreement: −9.7 – 10.7 BPM, regression line: y = −0.1x + 11.1) and the cardiotocography tracings obtained simultaneously by Nemo and Avalon-FM30 received the same FIGO classification. Comparable results were found with the Avalon-Beltless from 36 weeks of gestation, whereas the Dipha-16 and Infinity-M300 performed significantly worse. The Avalon-Beltless, Nemo and Infinity-M300 closely matched the performance of the Avalon-FM30 for maternal heart rate, whereas the performance of the Dipha-16 deviated more. Patient experience scores were higher for the noninvasive electrocardiography devices. Conclusions: Both Nemo and Avalon-Beltless are suitable devices for (prolonged) noninvasive fetal heart rate monitoring, taking their intended use into account. But outside its intended use limit of 36 weeks’ gestation, the Avalon-Beltless performs less well, comparable to the Dipha-16 and Infinity-M300, making them currently unsuitable for (prolonged) noninvasive fetal heart rate monitoring. Noninvasive electrocardiography devices appear to be preferred due to greater comfort and mobility. ...
Journal article (2024) - C. Eenkhoorn, Sarah van den Wildenberg, T.G. Goos, J. Dankelman, Arie Franx, Alex J. Eggink
Objectives
To study the methodology and results of studies assessing the relationship between fetal heart rate and specified neonatal outcomes including, heart rate, infection, necrotizing enterocolitis, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, and seizure.

Methods
Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and CINAHL were searched from inception to October 5, 2023.

Results
Forty-two studies were included, encompassing 57,232 cases that underwent fetal monitoring and were evaluated for neonatal outcome. Heterogeneity was observed in the timing and duration of fetal heart rate assessment, classification guidelines used, number of assessors, and definition and timing of neonatal outcome assessment. Nonreassuring fetal heart rate was linked to lower neonatal heart rate variability. A significant increase in abnormal fetal heart rate patterns were reported in neonates with hypoxic-ischemic encephalopathy, but the predictive ability was found to be limited. Conflicting results were reported regarding sepsis, seizure and intraventricular hemorrhage. No association was found between necrotizing enterocolitis rate and fetal heart rate.

Conclusions
There is great heterogeneity in the methodology used in studies evaluating the association between fetal heart rate and aforementioned neonatal outcomes. Hypoxic-ischemic encephalopathy was associated with increased abnormal fetal heart rate patterns, although the predictive ability was low. Further research on developing and evaluating an automated early warning system that integrates computerized cardiotocography with a perinatal health parameter database to provide objective alerts for patients at-risk is recommended.
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