The Impact of Time to Initiate Therapeutic Hypothermia on Short-Term Neurological Outcomes in Neonates with Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Therapeutic hypothermia is the standard treatment for neonates with hypoxic-ischemic encephalopathy. Preclinical evidence indicates that the time to initiate therapeutic hypothermia correlates with its therapeutic success. This study aims to explore whether there is a correlation between the early initiation of therapeutic hypothermia and improved short-term neurological outcomes in cooled asphyxiated newborns. METHODS: A retrospective analysis was conducted, involving 68 neonates from two different neonatal intensive care units. The impact of time to initiate treatment, time to reach the target temperature, and time between initiation and target temperature was correlated with short-term outcomes on MRI. RESULTS: We did not find a significant difference between outcomes regarding the time to start treatment and the time to achieve the target temperature. Interestingly, neonates with a poor outcome were treated on average earlier than neonates with a favorable outcome but required more time to reach the target temperature. Additionally, the study results did not support the hypothesis that a shorter time to initiate treatment would lead to shorter times to achieve the target temperature. CONCLUSION: Based on our findings, it is recommended to prioritize a thorough evaluation of neonatal encephalopathy before initiating therapeutic hypothermia. Early initiation of treatment should be balanced with the time required for precise assessment to ensure better outcomes.

Achieving sufficient milk supply supports mothers to cope with premature birth.

AIM: To explore whether and how expressing breast milk is perceived as helpful in coping with negative emotions due to premature birth by mothers of very low birth weight (VLBW) infants. METHODS: Qualitative interviews and a retrospective cross-sectional questionnaire with mothers of VLBW infants were conducted and analysed using an exploratory sequential mixed-method design. Hypotheses were built using qualitative content analysis and quantitatively tested using multivariate regression analysis. RESULTS: Interviews with 12 mothers and questionnaires of 518 mothers were analysed. Coping with prematurity by expressing milk was seen as a way to maintain the caregiving role for the mothers, where three relevant factors arouse: making up for what happened, providing the best for their infant and fear of low milk supply. Quantitative analysis showed that mothers with a high milk supply (Coef. = 1.1, p < 0.000) and more feelings of guilt due to premature birth (Coef. = -0.1; p = 0.015) perceived expressing breast milk significantly more as a resource for coping. CONCLUSION: This study adds knowledge on how expressing breast milk for their VLBW infant may support mothers in coping with premature birth, by revealing the association with milk supply and feelings of guilt due to premature birth.

Lactation support in neonatal intensive care units in Germany from the mothers' perspective - a mixed-method study of the current status and needs.

BACKGROUND: Establishing successful lactation in mothers of very low birth weight (VLBW, <1500g) infants requires structured lactation support. Little is known about mothers' perspectives on lactation support in German neonatal intensive care units (NICUs). METHODS: This paper features a convergent mixed-method approach that includes a retrospective, cross-sectional questionnaire and interview data to showcase mothers' perceptions of lactation support in NICUs. Content analysis of the interviews (n = 12) and a descriptive analysis of quantitative data (n = 533) were performed to illustrate the current status and need for lactation support in German NICUs. RESULTS: The results show that lactation support in German NICUs is often inadequate and does not comply with recommendations based on the existing literature to encourage pumping and breastfeeding in mothers. The data imply that even if lactation is successfully initiated in most cases, it is often not maintained over time, which may be due to a lack of personal support and consistent information. CONCLUSION: The overall structures and institutional guidelines for lactation support should be encouraged to promote nutrition with mother´s own milk in German NICUs.

Pressure to provide milk among mothers of very low birth weight infants: an explorative study.

BACKGROUND: Pump-dependent mothers of very low birth weight (VLBW, < 1500g) infants experience specific challenges achieving sufficient milk supply in the neonatal intensive care unit (NICU) and are therefore less frequently able to achieve (exclusive) breast milk feeding. Stress due to the limitations on participating in the infant's care may contribute to this problem. Some explorative studies suggest that pressure to provide milk may be an additional stressor in mothers. However, the type of pressure to provide milk perceived by mothers of VLBW infants has rarely been examined. METHODS: A retrospective and anonymous questionnaire was conducted with mothers of VLBW infants aged 6 to 24 months at the time of data collection. Quantitative data and written comments were used to examine the mothers' perceptions. Descriptive and bivariate tests (Spearman´s rho, Pearson's chi2) were performed to show correlations between pressure to provide breast milk, parental stress (PSS:NICU: role alteration subscale), milk volume, and maternal factors. Pressure to provide milk was measured through two self-developed single items to differentiate between internal and external pressures. RESULTS: Data of n = 533 mothers of VLBW infants was analysed. More than 70% of the mothers agreed that they pressured themselves to provide milk for their infant. In contrast, 34% of the mothers agreed that they felt pressure from outside to provide milk. Higher milk volume 14 days post-partum was significantly correlated with higher internal (Spearman´s rho = 0.2017, p = 0.000) and higher external pressure to provide milk (Spearman´s rho = 0.2991; p = 0.000). Higher PSS:NICU parental role alteration scores were significantly correlated with more internal (Spearman´s rho = -0.2865, p = 0.000) and more external pressure to provide milk (Spearman´s rho = -0.1478; p = 0.002). Milk volume 14 days post-partum and the PSS:NICU were not significantly correlated (Spearman´s rho = -0.0190; p = 0.701). Qualitative analyses highlighted these results and enhanced the bidirectional relationships between maternal pressure to provide milk and milk volume. CONCLUSIONS: Especially internal pressure to provide milk is perceived by many mothers, being mutually dependent on milk supply and parental stress. Pressure to provide milk may be an important factor to decrease maternal stress in the NICU and, therefore, lead to more positive pumping and breastfeeding experiences. More research and validated instruments are needed to adequately measure pressure to provide milk with its different psychological, social, and environmental dimensions.

Microbiological Screening of Donor Human Milk.

Mother's own milk is recognized as the optimal feeding not only for term but also for preterm infants. In addition to risk reduction for sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity in the early infancy, feeding preterm infants with mother's own milk is also associated with a better neurodevelopmental outcome; lower rates of otitis media, gastroenteritis, and respiratory infections; and a reduced risk of cardiovascular disease, obesity, and diabetes later in life. Donor human milk is the best alternative if mother's own milk is not available or with short supply. There is growing evidence that the benefits of human milk are mediated by the human milk microbiota and by human milk oligosaccharides through their influence on the infant's gut microbiota. Unfortunately, although human milk contains beneficial bacteria, it may also contain pathogenic bacteria. The antimicrobial properties of human milk protect those infants fed with their own mother's raw milk. In donor human milk, however, the antimicrobial activity is diminished due to storage and in particular by pasteurization, hereby lowering the resistance against bacterial infections. Subsequently, microbiological screening of donor human milk might enhance its safety for preterm infants. Up to date, a consensus on recommendations for the microbiological testing of donor human milk is lacking. Existing local and national guidelines for the microbiological screening vary significantly in terms of timing and frequency of testing as well as their specific acceptance and discard criteria. We reviewed the literature about microbiological testing of donor human milk to provide evidence-based recommendations for donor human milk.

Correlation of Different MRI Scoring Systems with Long-Term Cognitive Outcome in Cooled Asphyxiated Newborns.

(1) Background: Cerebral MRI plays a significant role in assessing the extent of brain injury in neonates with neonatal encephalopathy after perinatal asphyxia. Over the last decades, several MRI scoring systems were developed to enhance the predictive accuracy of MRI. The aim of this study was to validate the correlation of four established MRI scoring systems with cognitive long-term outcomes in cooled asphyxiated newborns. (2) Methods: Forty neonates with neonatal encephalopathy treated with therapeutic hypothermia were included in this retrospective study. The MRI scans from the second week of life were scored using four existing MRI scoring systems (Barkovich, NICHD, Rutherford, and Weeke). The patients' outcome was assessed with the Bayley Scales of Infant Development (BSID-III) at the age of 2 years. To evaluate the correlation between the MRI scoring system with the cognitive scores of BSID-III, the correlation coefficient was calculated for each scoring system. (3) Results: All four MRI scoring systems showed a significant correlation with the cognitive scores of BSID-III. The strongest correlation was found between the Weeke Score (r2 = 0.43), followed by the Rutherford score (r2 = 0.39), the NICHD score (r2 = 0.22), and the Barkovich score (r2 = 0.17). (4) Conclusion: Our study confirms previously published results in an independent cohort and indicates that the Weeke and Rutherford scores have the strongest correlation with the cognitive score of BSID-III in cooled asphyxiated newborns.

Percutaneous, ultrasound-guided single- and multisite cannulation for veno-venous extracorporeal membrane oxygenation in neonates.

AIMS: Extracorporeal membrane oxygenation (ECMO) is a widely used technique to support neonates with severe respiratory failure. Data on percutaneous, ultrasound-guided veno-venous (VV) ECMO cannulation in neonates is still scarce. Aim of this study was to describe our institutional experience with ultrasound-guided percutaneous, VV ECMO cannulation in neonates with severe respiratory failure. METHODS: Neonates receiving ECMO support at our department between January 2017 and January 2021 were retrospectively identified. Patients receiving VV ECMO cannulation performed by the percutaneous Seldinger technique by single- or multisite cannulation were analyzed. RESULTS: A total of 54 neonates received ECMO cannulation performed by the percutaneous Seldinger technique. In 39 patients (72%) a 13 French bicaval dual-lumen cannula was inserted and in 15 patients (28%) two single-lumen cannulae were used. Cannulae positioning using the multisite approach was in all cases as desired. The tip of the 13 French cannula was located in the IVC in 35/39 patients, in four patients position was too proximal but did not dislocate during the ECMO run. One (2%) preterm neonate (weight 1.75 kg) developed a cardiac tamponade which was successfully managed with drainage. Median duration of ECMO was 7 days (interquartile range: 5-16 days). Forty-four patients (82%) were successfully weaned from ECMO and in 31/44 (71%) the ECMO cannulae were removed with a delay of 0.9-7.2 days (median 2.8 days) after weaning without noticing complications. CONCLUSIONS: A correct cannula placement using the ultrasound-guided percutaneous Seldinger technique, for both single- and multisite cannulation, seems feasible in most neonatal patients receiving VV ECMO.

Intravenous sildenafil for treatment of early pulmonary hypertension in preterm infants.

Data is lacking on the effect of continuous intravenous sildenafil treatment in preterm infants with early pulmonary hypertension (PH), especially in very low birth weight (VLBW) infants. Preterm infants (< 37 weeks of gestational age) with intravenous sildenafil treatment and diagnosis of PH between 01/12 and 12/21 were retrospectively screened for analysis. The primary clinical endpoint was defined as response to sildenafil according to the improvement of the oxygenation index (OI), the saturation oxygenation pressure index (SOPI) and PaO2/FiO2-ratio. Early-PH was defined as diagnosis < 28 day of life (DOL). 58 infants were finally included, with 47% classified as very low birth weight (VLBW) infants. The primary endpoint was reached in 57%. The likelihood to die during in-hospital treatment was more than three times higher (72 vs 21%, p < 0.001) in infants without response to sildenafil. The echocardiographic severity of PH and right-ventricular dysfunction (RVD) decreased significantly from baseline to 24 h (p = 0.045, and p = 0.008, respectively). Sildenafil treatment leads to significant improvement of the oxygenation impairment in 57% of the preterm infants, with similar response rates in VLBW infants. Intravenous sildenafil treatment is associated with a significant decrease of the PH-severity and RVD.

Structured lactation support and human donor milk for German NICUs-Protocol on an intervention design based on a multidimensional status quo and needs assessment (Neo-MILK).

INTRODUCTION: Mother's own milk is the best nutrition for every newborn and especially for vulnerable infants such as preterm infants with a very low birth weight below 1,500 grams (VLBW). If no MOM is available, human donor milk is the alternative of choice. Mothers of preterm born infants face challenging conditions that impair sufficient milk production. For this reason, it is particularly important to provide structural lactation support and, at the same time, to promote the establishment of human donor milk banks. METHODS AND ANALYSIS: Via a multidisciplinary approach the Neo-MILK study will develop an intervention for structured breastfeeding and lactation support. This will be based on a comprehensive status quo and needs assessment. In addition, the implementation of human donor milk banks (HDMB) will be supported by the development of standards. ETHICS AND DISSEMINATION: Intervention development is participatory, involving different disciplines and stakeholders. All surveys are subject to approval by the ethics committee. During the course of the project, the results will be communicated to the scientific community and the general public via publications, the project homepage and social media. TRIAL REGISTRATION NUMBER: DRKS00024799 (German Clinical Trials Register).

Evaluation of levosimendan as treatment option in a large case-series of preterm infants with cardiac dysfunction and pulmonary hypertension.

Levosimendan as a calcium-sensitizer is a promising innovative therapeutical option for the treatment of severe cardiac dysfunction (CD) and pulmonary hypertension (PH) in preterm infants, but no data are available analyzing levosimendan in cohorts of preterm infants. The design/setting of the evaluation is in a large case-series of preterm infants with CD and PH. Data of all preterm infants (gestational age (GA) < 37 weeks) with levosimendan treatment and CD and/or PH in the echocardiographic assessment between 01/2018 and 06/2021 were screened for analysis. The primary clinical endpoint was defined as echocardiographic response to levosimendan. Preterm infants (105) were finally enrolled for further analysis. The preterm infants (48%) were classified as extremely low GA newborns (ELGANs, < 28 weeks of GA) and 73% as very low birth weight infants (< 1500 g, VLBW). The primary endpoint was reached in 71%, without difference regarding GA or BW. The incidence of moderate or severe PH decreased from baseline to follow-up (24 h) in about 30%, with a significant decrease in the responder group (p < 0.001). The incidence of left ventricular dysfunction and bi-ventricular dysfunction decreased significantly from baseline to follow-up (24 h) in the responder-group (p = 0.007, and p < 0.001, respectively). The arterial lactate level decreased significantly from baseline (4.7 mmol/l) to 12 h (3.6 mmol/l, p < 0.05), and 24 h (3.1 mmol/l, p < 0.01).  Conclusion: Levosimendan treatment is associated with an improvement of both CD and PH in preterm infants, with a stabilization of the mean arterial pressure during the treatment and a significant decrease of arterial lactate levels. Future prospective trials are highly warranted. What is Known: • Levosimendan as a calcium-sensitizer and inodilator is known to improve the low cardiac output syndrome (LCOS), and improves ventricular dysfunction, and PH, both in pediatric as well as in adult populations. Data related to critically ill neonates without major cardiac surgery and preterm infants are not available. What is New: • This study evaluated the effect of levosimendan on hemodynamics, clinical scores, echocardiographic severity parameters, and arterial lactate levels in a case-series of 105 preterm infants for the first time. Levosimendan treatment in preterm infants is associated with a rapid improvement of CD and PH, an increase of the mean arterial pressure, and a significant decrease in arterial lactate levels, as surrogate marker for a LCOS. • How this study might affect research, practice, or policy. As no data are available regarding the use of levosimendan in this population, our results hopefully animate the research community to conduct future prospective trails analyzing levosimendan in randomized controlled trials (RCT) and observational control studies. Additionally, our results potentially motivate clinicians to introduce levosimendan as second second-line therapy in cases of severe CD and PH in preterm infants without improvement using standard treatment strategies.

Factors associated with the closure of obstetric units in German hospitals and its effects on accessibility.

BACKGROUND: An increase in regionalization of obstetric services is being observed worldwide. This study investigated factors associated with the closure of obstetric units in hospitals in Germany and aimed to examine the effect of obstetric unit closure on accessibility of obstetric care. METHODS: Secondary data of all German hospital sites with an obstetrics department were analyzed for 2014 and 2019. Backward stepwise regression was performed to identify factors associated with obstetrics department closure. Subsequently, the driving times to a hospital site with an obstetrics department were mapped, and different scenarios resulting from further regionalization were modelled. RESULTS: Of 747 hospital sites with an obstetrics department in 2014, 85 obstetrics departments closed down by 2019. The annual number of live births in a hospital site (OR = 0.995; 95% CI = 0.993-0.996), the minimal travel time between two hospital sites with an obstetrics department (OR = 0.95; 95% CI = 0.915-0.985), the availability of a pediatrics department (OR = 0.357; 95% CI = 0.126-0.863), and population density (low vs. medium OR = 0.24; 95% CI = 0.09-0.648, low vs. high OR = 0.251; 95% CI = 0.077-0.822) were observed to be factors significantly associated with the closure of obstetrics departments. Areas in which driving times to the next hospital site with an obstetrics department exceeded the 30 and 40 min threshold slightly increased from 2014 to 2019. Scenarios in which only hospital sites with a pediatrics department or hospital sites with an annual birth volume of ≥ 600 were considered resulted in large areas in which the driving times would exceed the 30 and 40 min threshold. CONCLUSION: Close distances between hospital sites and the absence of a pediatrics department at the hospital site associate with the closure of obstetrics departments. Despite the closures, good accessibility is maintained for most areas in Germany. Although regionalization may ensure high-quality care and efficiency, further regionalization in obstetrics will have an impact on accessibility.

Feasibility of bedside portable MRI in neonates and children during ECLS.

Magnetic resonance imaging (MRI) is the preferred neuroimaging technique in pediatric patients. However, in neonates and instable pediatric patients accessibility to MRI is often not feasible due to instability of patients and equipment not being feasible for MRI. Low-field MRI has been shown to be a feasible neuroimaging tool in pediatric patients. We present the first four patients receiving bedside high-quality MRI during ECLS treatment. We show that it is safe and feasible to perform bedside MRI in this patient population. This opens the route to additional treatment decisions and may guide optimized treatment in these patients.

How does stress affect maternal and paternal perceptions of relationship strain after a preterm birth? Results of a retrospective survey study.

AIM: Strain on couple relationships is associated with a lower well-being. As premature birth is known to pose stress to parents, this study explores whether interparental relationship strain comes to pass within mothers and fathers during their infant's stay in a neonatal intensive care unit. METHODS: A retrospective cross-sectional survey was conducted with parents who experienced a preterm birth (September to December 2020). Linear regression was used to analyse associations between stress and relationship strain. RESULTS: The study included 437 mothers and 301 fathers. Fathers experienced lower relationship strain (M = 2.49, SD = 1.00) than mothers (M = 3.37, SD = 1.04). Overall, a significant association between relationship strain and stress due to the infant's behaviour and appearance was found for mothers (ß = 0.16, p = 0.02) and fathers, with a significantly higher association for fathers (ß = 0.27, p ≤ 0.002). With regard to parental role alterations, only mothers showed a significant association (ß = 0.21, p ≤ 0.001). CONCLUSION: Although mothers showed higher levels of stress and relationship strain, stress may also have an impact on fathers. Therefore, research should focus on stress prevention measures to meet both maternal and paternal needs.

Heart rate control with landiolol hydrochloride in infants with ventricular dysfunction and pulmonary hypertension.

AIMS: Sinus tachycardia potentially leads to a deterioration of cardiac function in critically ill infants. The ultrashort-acting beta-blocker landiolol hydrochloride is a new pharmacological option for a selective heart rate (HR) control in patients with sinus tachycardia and heart failure. METHODS AND RESULTS: This study was a monocentric retrospective medical chart review study at the University Children's Hospital Bonn (Germany) from 01 January 2018 until 30 June 2020. This study included a cohort of 62 term and preterm infants with a diagnosis of ventricular dysfunction and/or pulmonary hypertension (PH), in combination with preexisting tachycardia and treatment with landiolol hydrochloride. Infants were allocated to subgroups according to weeks of gestational age (GA): born at <35 weeks of GA (Group A) and born at >35 weeks of GA (Group B). Tachycardia was defined depending on GA (<35 weeks of GA: >170 b.p.m.; ≥ 35 weeks of GA: >150 b.p.m.). The primary endpoint was defined as percentage of patients achieving HR normalization during the first 24 h of landiolol treatment. Twenty-nine infants were allocated to Group A and 33 infants to Group B. The overall median GA of the infants was 35.3 (23.3/41.3), with 53% female infants. The primary endpoint was achieved in 57 patients (91.9%). The median time to reach target HR was 1.8 (0.3-24) h. The median starting dose of landiolol was 8.8 (3.9-25.3) µk/kg/min, with a median dosing during the first 24 h of landiolol treatment of 9.9 (2.8-35.4) µk/kg/min. The median landiolol dose while achieving the target HR was 10 (2.4-44.4) µk/kg/min. The right ventricular dysfunction improved significantly in both groups 24 h after onset of landiolol infusion (P = 0.001 in Group A and P = 0.045 in Group B). The left ventricular and biventricular dysfunction improved significantly 24 h after onset of landiolol infusion in infants of Group B (P = 0.004 and P = 0.006, respectively). The severity of PH improved significantly after 24 h in infants of Group A (P < 0.001). During landiolol treatment, no severe drug-related adverse event was noted. CONCLUSIONS: The use of landiolol hydrochloride for HR control of non-arrhythmic tachycardia in critically ill infants is well tolerated. Reduction of HR can be guided quickly and landiolol treatment is associated with an improvement of ventricular dysfunction and PH.

Parental preference for webcams in neonatal intensive care units: an indicator of lacking trust?

BACKGROUND: Some neonatal intensive care units offer parents webcam systems for times when they cannot be in the ward. Leaving an infant in the ward can be challenging for parents, and trust in the neonatal healthcare professionals mitigates parents' worries of not knowing how their infant is doing while they are away. If parents lack trust in the neonatal healthcare professionals, they may attempt to compensate by using webcams. In this work, we examine whether an association exists between the parental preference to use a webcam and low trust in physicians and nursing staff. METHODS: In a nationwide, retrospective cross-sectional study, parents of infants with a birth weight below 1500 g were surveyed six to 18 months after their infant's birth. Parents who were not offered a webcam system in the ward were asked whether they would have opted for it. Trust was measured by the Trust in Physician and Trust in Nursing Staff scales. RESULTS: Of the parents who were not offered a webcam, 69% would have chosen to use a webcam if they had been granted the opportunity. The decision for or against a webcam was not significantly associated with either trust in physicians (OR = 0.654, 95% CI = 0.456, 0.937, p = .124) or trust in nursing staff (OR = 1.064, 95% CI = 0.783, 1.446, p = .932). CONCLUSIONS: While the majority of parents surveyed would opt for webcam usage, this preference should not be interpreted as an indicator of lacking trust in neonatal healthcare professionals.

Driving new technologies in hospitals: association of organizational and personal factors with the readiness of neonatal intensive care unit staff toward webcam implementation.

BACKGROUND: The use of webcam technology in neonatal intensive care units (NICUs) enables parents to see their child when the parents cannot be present at the NICU. The webcam's use has been gaining increasing attention. Lead physicians and lead nursing staff play a key role in the decision of whether to implement webcams. This study investigates factors that are associated with the readiness for the implementation of a webcam system among lead NICU staff. METHODS: A postal survey was conducted among all lead physicians and lead nursing staff in all German NICUs between December 2020 and April 2021 (total N = 416, one lead physician and one lead nursing staff per NICU, N = 208). On the basis of normalization process theory, personal (technology acceptance) and organizational (innovation climate) attributes were chosen to determine their association with the readiness for the implementation of a webcam system. The association of these factors was determined using multiple linear regression models for both lead physicians and lead nurses. RESULTS: Overall, a response rate of 66.59% (n = 277) was achieved. Technology acceptance proved to be a significant factor associated with the readiness for the implementation of a webcam system among lead physicians. Furthermore, staff already working with webcams in their NICUs indicated a significantly higher level of technology acceptance than staff without webcam experience and without any desire to use a webcam in the future. No significant association was found between innovation climate and the readiness for the implementation of a webcam system. CONCLUSIONS: Technology acceptance was identified as a factor associated with the readiness for the implementation of a webcam system. The insights from this study can be used to manage potential barriers regarding the readiness for implementation of webcams in NICUs. TRIAL REGISTRATION: The Neo-CamCare study is registered at the German Clinical Trials Register. DRKS-ID: DRKS00017755 . Date of Registration in DRKS: 25-09-2019.