Conclusion: Real-time and non-invasive effect monitoring of drug therapy combined with model-based exposure provides relevant information to clinicians and can importantly improve therapy. The variability between and within patients emphasizes the importance of individual, objective evaluation of pharmacotherapy. These measurements, together with data on ADRs, allow for precision medicine in neonatology that should be brought to the bedside.

<b><i>Introduction:</i></b> Evaluation of pharmacotherapy during intensive care treatment is commonly based on subjective, intermittent interpretations of physiological parameters. Real-time visualization and analysis may improve drug effect evaluation. We aimed to evaluate the effects of the respiratory stimulant doxapram objectively in preterm infants using continuous physiological parameters. <b><i>Methods:</i></b> In this longitudinal observational study, preterm infants who received doxapram therapy were eligible for inclusion. Physiological data (1 Hz) were used to assess respiration and to evaluate therapy effects. The oxygen saturation (SpO₂)/fraction of inspired oxygen (FiO₂) ratio and the area under the 89% SpO₂ curve (duration × saturation depth below target) were calculated as measures of hypoxemia. Regression analyses were performed in 1-h timeframes to discriminate therapy failure (intubation or death) from success (no intubation). <b><i>Results:</i></b> Monitor data of 61 patients with a median postmenstrual age (PMA) at doxapram initiation of 28.7 (IQR 27.6–30.0) weeks were available. The success rate of doxapram therapy was 56%. Doxapram pharmacodynamics were reflected in an increased SpO₂ and SpO₂/FiO₂ ratio as well as a decrease in episodes with saturations below target (SpO₂ &#x3c;89%). The SpO₂/FiO₂ ratio, corrected for PMA and mechanical ventilation before therapy start, discriminated best between therapy failure and success (highest AUC ROC of 0.83). <b><i>Conclusion:</i></b> The use of continuous physiological monitor data enables objective and detailed interpretation of doxapram in preterm infants. The SpO₂/FiO₂ ratio is the best predictive parameter for therapy failure or success. Further implementation of real-time data analysis and treatment algorithms would provide new opportunities to treat newborns.

Using high-frequency monitoring data, we showed the detailed effects over time of pharmacotherapy. We could objectively determine the respiratory condition and the effects of doxapram treatment in preterm infants. This type of analysis might help to develop individualized drug treatments with tailored dose adjustments based on a closed-loop algorithm.

Clinical improvement after red blood cell (RBC) transfusions in preterm infants remains debated. This study aims to investigate the effect of RBC transfusion on the occurrence of desaturations and hypoxia, and other cardiorespiratory outcomes in preterm infants. In this longitudinal observational study, prospectively stored cardiorespiratory parameters of preterm infants who received at least one RBC transfusion between July 2016 and June 2017 were retrospectively analyzed. Sixty infants with 112 RBC transfusions, median GA of 26.7 weeks, were included. The number of desaturations and area < 80% SpO2 limit, as a measure of the hypoxic burden, were calculated in 24 h before and after RBC transfusion. A mixed effects model was used to account for repeated measurements. Overall, the mean (SE) number of desaturations per hour decreased from 3.28 (0.55) to 2.25 (0.38; p < 0.001), and area < 80% SpO2 limit decreased from 0.14 (0.04) to 0.08 (0.02) %/s (p = 0.02). These outcomes were stratified for the number of desaturations in 24 h prior to RBC transfusion. The largest effect was observed in the group with the highest mean number of desaturations (≥ 6) prior to RBC transfusion, with a decrease from 7.50 (0.66) to 4.26 (0.38) (p < 0.001) in the number of desaturations and 0.46 (0.13) to 0.20 (0.06) in the area < 80% SpO2. Perfusion index increased significantly after RBC transfusion (p < 0.001). No other significant effects of RBC transfusion on cardiorespiratory data were observed.Conclusions: RBC transfusions in preterm newborns could help decrease the incidence of desaturations and the area < 80% SpO2 as a measure of the hypoxic burden. The higher the number of desaturations prior to the RBC transfusion, the larger the effect observed. What is Known:•Red blood cell transfusions potentially prevent hypoxia in anemic preterm infants by increasing the circulatory hemoglobin concentration and improving tissue oxygenation.•There is not a predefined hemoglobin concentration cut-off for the occurrence of symptomatic anemia in preterm infants. What is New:•Oxygen desaturations and hypoxia in anemic preterm infants can be improved by RBC transfusions, especially if more desaturations have occurred before transfusion.•Cardiorespiratory monitor data may help identify infants who will benefit most from red blood cell transfusions.

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Background Early risk stratification for developing retinopathy of prematurity (ROP) is essential for tailoring screening strategies and preventing abnormal retinal development. This study aims to examine the ability of physiological data during the first postnatal month to distinguish preterm infants with and without ROP requiring laser treatment. Methods In this cohort study, preterm infants with a gestational age <32 weeks and/or birth weight <1500 g, who were screened for ROP were included. Differences in the physiological data between the laser and non-laser group were identified, and tree-based classification models were trained and independently tested to predict ROP requiring laser treatment. Results In total, 208 preterm infants were included in the analysis of whom 30 infants (14%) required laser treatment. Significant differences were identified in the level of hypoxia and hyperoxia, oxygen requirement, and skewness of heart rate. The best model had a balanced accuracy of 0.81 (0.72–0.87), a sensitivity of 0.73 (0.64–0.81), and a specificity of 0.88 (0.80–0.93) and included the SpO2/FiO2 ratio and baseline demographics (including gestational age and birth weight). Conclusions Routinely monitored physiological data from preterm infants in the first postnatal month are already predictive of later development of ROP requiring laser treatment, although validation is required in larger cohorts. Impact Routinely monitored physiological data from the first postnatal month are predictive of later development of ROP requiring laser treatment, although model performance was not significantly better than baseline characteristics (gestational age, birth weight, sex, multiple birth, prenatal glucocorticosteroids, route of delivery, and Apgar scores) alone. A balanced accuracy of 0.81 (0.72–0.87), a sensitivity of 0.73 (0.64–0.81), and a specificity of 0.88 (0.80–0.93) was achieved with a model including the SpO2/FiO2 ratio and baseline characteristics. Physiological data have potential to play a significant role for future ROP prediction and provide opportunities for early interventions to protect infants from abnormal retinal development.

Clinical improvement after red blood cell (RBC) transfusions in preterm infants remains debated. This study aims to investigate the effect of RBC transfusion on the occurrence of desaturations and hypoxia and other cardiorespiratory outcomes in preterm infants. In this longitudinal observational study, prospectively stored cardiorespiratory parameters of preterm infants who received at least one RBC transfusion between July 2016 and June 2017 were analyzed. Sixty infants with 112 RBC transfusions, median GA of 26.7 weeks, were included. The number of desaturations and area <80% SpO2 limit, as a measure of the hypoxic burden, were calculated in 24h before and after RBC transfusion. A mixed effects model was used to account for repeated measurements. Overall, mean (SE) number of desaturations per hour decreased from 3.28(0.55) to 2.25(0.38; p<0.001) and area <80% SpO2 limit decreased from 0.14(0.04) to 0.08(0.02) %/sec (p=0.02). These outcomes were stratified for number of desaturations in 24h prior to RBC transfusion. The largest effect was observed in the group with the highest mean number of desaturations (≥6) prior to RBC transfusion, with a decrease from 7.50(0.66) to 4.26(0.38) (p<0.001) in number of desaturations and 0.46(0.13) to 0.20(0.06) in area <80% SpO2. Perfusion index increased significantly after RBC transfusion (p<0.001). No other significant effects of RBC transfusion on cardiorespiratory data were observed.Conclusions: RBC transfusions in preterm newborns decrease the incidence of desaturations and the hypoxic burden. The higher the number of desaturations prior to the RBC transfusion, the larger the effect observed.

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