Butterflies and Ribbons: Supporting Families Experiencing Perinatal Loss in Multiple Gestation.

Introduction: In neonatology, multiple pregnancies are common. Unfortunately, it is not rare for one baby to die. Communication with parents in these circumstances has been demonstrated to be sub-optimal. Methods: Two educational programs were evaluated with pre- and post-course surveys, questionnaires administered to participants, and audits. Results: In the online Butterfly project (UK; n = 734 participants), all participants reported that the training exceeded or met their expectations, 97% reported they learned new skills, and 48% had already applied them. Participants expressed gratitude in their open-ended answers: "I feel a lot more confident in supporting parents in this situation". In the Ribbon project (workshop for neonatal clinicians, Quebec; n = 242), 97% were satisfied with the training and reported feeling more comfortable caring for bereaved parents. Knowledge improved pre-post training. Audits revealed that 100% of cases were identified on the incubator and the baby's/babies' admission card, all changed rooms after the death of their co-twin/triplet, and all had the name of their co-twin/triplet on the discharge summary. All clinicians (55) knew what the ribbon symbol meant when asked during surprise audits at the bedside. Conclusion: Different educational strategies to optimize communication with families after the perinatal loss of a co-twin are appreciated and have a positive impact.

Survival and Long-Term Outcomes of Children Who Survived after End-of-Life Decisions in a Neonatal Intensive Care Unit.

OBJECTIVE: To investigate long-term outcomes of infants who survive despite life-and-death discussions with families and a decision to withdraw or withhold life-sustaining interventions (WWLST) in one neonatal intensive care unit. STUDY DESIGN: Medical records for neonatal intensive care unit admissions from 2012 to 2017 were reviewed for presence of WWLST discussions or decisions, as well as the 2-year outcome of all children who survived. WWLST discussions were prospectively recorded in a specific book; follow-up to age 2 years was determined by retrospective chart review. RESULTS: WWLST discussions occurred for 266 of 5251 infants (5%): 151 (57%) were born at term and 115 (43%) were born preterm. Among these discussions, 164 led to a WWLST decision (62%) and 130 were followed by the infant's death (79%). Of the 34 children (21%) surviving to discharge after WWLST decisions, 10 (29%) died before 2 years of age and 11 (32%) required frequent medical follow-up. Major functional limitations were common among survivors, but 8 were classified as functionally normal or with mild-to-moderate functional limitations. CONCLUSIONS: When a WWLST decision was made in our cohort, 21% of the infants survived to discharge. By 2 years of age, the majority of these infants had died or had major functional limitations. This highlights the uncertainty of WWLST decisions during neonatal intensive care and the importance of ensuring that parents are informed of all possibilities. Additional studies including longer-term follow-up and ascertaining the family's views will be important.

Gratitude, fragility and strength: Perspectives of adults born preterm about prematurity.

AIM: The aim of the study was to explore how young adults thought that being born preterm had affected their lives. METHODS: Adult participants of a research cohort were questioned about their perspectives. Answers were analysed using mixed methods. RESULTS: Forty-five participants evaluated their health at median score of 8/10. When asked about the meaning of being born preterm, 65% had positive self-centred answers, invoking two main themes: being stronger/'a fighter'/more resilient and being a survivor/chosen; 42% also reported negative themes, such as having health problems and a difficult start. All heard about their prematurity from their parents, 55% with positive child-centred or healthcare system-centred themes, 19% with neutral themes; 35% also heard negative parent-centred themes (tragic experience, guilt, mother's health). When asked which words were associated with prematurity, participants mainly chose positive words for themselves and their family, but more negative words for how the media and society depicted prematurity. Answers were not correlated with adverse objective health measures. CONCLUSION: Participants evaluated their health in a balanced fashion. Preterm-born adults often feel that they have experienced positive transformations as a result of their traumatic start. They often have feelings of gratitude and strength, independent of health problems.

Fragility and resilience: parental and family perspectives on the impacts of extreme prematurity.

OBJECTIVES: Extremely preterm babies have a significant risk of neurodevelopmental impairment (NDI). There has been little investigation regarding the impact of prematurity on families. The objective of this study was to explore parental perspectives regarding the impact of prematurity on themselves/their family. METHODS: Over 1 year, parents of children born <29 weeks' gestational age (GA) who were between 18 months old and 7 years old and came for their follow-up visit were invited to participate. They were asked to categorise the impacts of prematurity on their life and their family as positive, negative or both and to describe those impacts in their own words. Thematic analysis was performed by a multidisciplinary group, including parents. Logistic regression was performed to compare parental responses. RESULTS: Among parents (n=248, 98% participation rate), most (74%) reported that their child's prematurity had both positive and negative impacts on their life or their family's life, while 18% reported only positive impacts and 8% only negative impacts. These proportions were not correlated with GA, brain injury, nor level of NDI. The positive impacts reported included: an improved outlook on life, such as gratitude and perspective (48%), stronger family relationships (31%) and the gift of the child (28%). The negative themes were stress and fear (42%), loss of equilibrium due to medical fragility (35%) and concerns about developmental outcomes including the child's future (18%). CONCLUSION: Parents report both positive and negative impacts after an extremely preterm birth, independent of disability. These balanced perspectives should be included in neonatal research, clinical care and provider education.

Pulmonary important outcomes after extremely preterm birth: Parental perspectives.

AIM: To describe pulmonary important outcomes (PIO) reported by parents of children born extremely preterm. METHODS: Over 1-year, all parents of children aged 18 months-7-years born <29 weeks' GA were asked regarding their perspectives. The proportion of parents who described PIO and the themes they invoked were examined. Results were analysed using mixed methods. RESULTS: Among parental responses (n = 285, 98% participation rate), 44% spoke about PIO, invoking 24 themes pertaining to NICU hospitalisation and/or long-term respiratory health. Some themes had an impact primarily on the child (e.g. exercise limitation), while the majority had an impact on the whole family (e.g. hospital readmissions). None mentioned oxygen at 36 weeks nor bronchopulmonary dysplasia (BPD). The proportion of responses invoking PIO were statistically similar between parents of children with and without BPD, born before or after 25 weeks or with birthweight < or ≥750 g. PIO were more likely to be mentioned in males and among those readmitted for respiratory problems. CONCLUSION: Parents describe many PIO, most related to the functional impact of lung disease on their child (and family), rather than the diagnosis of BPD itself. Most of these PIO are not primary outcomes in large neonatal trials nor collected in neonatal databases.

Guilt and Regret Experienced by Parents of Children Born Extremely Preterm.

OBJECTIVES: To explore decisional regret of parents of babies born extremely preterm and analyze neonatal, pediatric, and parental factors associated with regret. STUDY DESIGN: Parents of infants born <29 weeks of gestational age, aged between 18 months and 7 years, attending neonatal follow-up were enrolled. Hospital records were reviewed to examine morbidities and conversations with parents about levels of care. Parents were asked the following question: "Knowing what you know now, is there anything you would have done differently?" Mixed methods were used to analyze responses. RESULTS: In total, 248 parents (98% participation) answered, and 54% reported they did not have regret. Of those who reported regret (n = 113), 3 themes were most frequently invoked: 35% experienced guilt, thinking they were responsible for the preterm birth; 28% experienced regret about self-care decisions; and 20% regretted decisions related to their parental role, generally wishing they knew sooner how to get involved. None reported regret about life-and-death decisions made at birth or in the neonatal intensive care unit. Impairment at follow-up, gestational age, and decisions about levels/reorientation of care were not associated with regret. More mothers reported feeling guilt about the preterm birth (compared with fathers); parents of children with severe lesions on ultrasonography of the head were less likely to report regret. CONCLUSIONS: Approximately one-half of the parents of infants born extremely preterm had regrets regarding their neonatal intensive care unit stay. Causes of regret and guilt should be addressed and minimized.

Epidemiology of post-hemorrhagic ventricular dilatation in very preterm infants.

OBJECTIVE: To describe the incidence, trends, management's variability and short-term outcomes of preterm infants with severe post-hemorrhagic ventricular dilatation (sPHVD). METHODS: We reviewed infants <33 weeks' gestation who had PHVD and were admitted to the Canadian Neonatal Network between 2010 and 2018. We compared perinatal characteristics and short-term outcomes between those with sPHVD and those with mild/moderate PHVD and those with and without ventriculo-peritoneal (VP) shunt. RESULTS: Of 29,417 infants, 2439 (8%) had PHVD; rate increased from 7.3% in 2010 to 9.6% in 2018 (P = 0.005). Among infants with PHVD, sPHVD (19%) and VP shunt (29%) rates varied significantly across Canadian centers and between geographic regions (P < 0.01 and P = 0.0002). On multivariable analysis, sPHVD was associated with greater mortality, seizures and meningitis compared to mild/moderate PHVD. CONCLUSIONS: Significant variability in sPHVD and VP shunt rates exists between centers and regions in Canada. sPHVD was associated with increased mortality and morbidities.

Avoidance of routine endotracheal intubation and general anesthesia for primary closure of gastroschisis: a systematic review and meta-analysis.

PURPOSE: Over the last few decades, several articles have examined the feasibility of attempting primary reduction and closure of gastroschisis without general anesthesia (GA). We aimed to systematically evaluate the impact of forgoing routine intubation and GA during primary bedside reduction and closure of gastroschisis. METHODS: The primary outcome was closure success. Secondary outcomes were mortality, time to enteral feeding, and length of hospital stay. RESULTS: 12 studies were included: 5 comparative studies totalling 192 patients and 7 descriptive case studies totalling 56 patients. Primary closure success was statistically equivalent between the two groups, but trended toward improved success with GA/intubation (RR = 0.86, CI 0.70-1.03, p = 0.08). Mortality was equivalent between groups (RR = 1.26, CI 0.26-6.08, p = 0.65). With respect to time to enteral feeds and length of hospital stay, outcomes were either equivalent between the two groups or favored the group that underwent primary closure without intubation and GA. CONCLUSION: There are few comparative studies examining the impact of performing primary bedside closure of gastroschisis without GA. A meta-analysis of the available data found no statistically significant difference when forgoing intubation and GA. Foregoing GA also did not negatively impact time to enteral feeds, length of hospital stay, or mortality.

Next generation sequencing in neonatology: what does it mean for the next generation?

Rapid whole genome sequencing (WGS) and whole exome sequencing (WES), sometimes referred to as "next generation sequencing" (NGS) are now recommended by some experts as a first-line diagnostic test to diagnose infants with suspected monogenic conditions. Estimates of how often NGS leads to diagnoses or changes in management vary widely depending on the population being studied and the indications for testing. Finding a genetic variant that is classified as pathogenic may not necessarily equate with being able to predict the resultant phenotype or to give a reliable prognosis. Molecular diagnoses do not usually lead to changes in clinical management but they often end a family's diagnostic Odyssey and allow informed decisions about future reproductive choices. The likelihood that NGS will be beneficial for patients and families in the NICU remains uncertain. The goal of this paper is to highlight the implications of these ambiguities in interpreting the results of NGS. To do that, we will first review the types of cases that are admitted to NICUs and show why, at least in theory, NGS is unlikely to be useful for most NICU patients and families and may even be harmful for some, although it can help families in some cases. We then present a number of real cases in which NGS results were obtained and show that they often lead to unforeseen and unpredictable consequences. Finally, we will suggest ways to communicate with families about NGS testing and results in order to help them understand the meaning of NGS results and the uncertainty that surrounds them.

The ethics of family integrated care in the NICU: Improving care for families without causing harm.

The philosophy of care in Neonatal Intensive care Units (NICU) has changed with increasing integration of families. We examined parents' and clinicians' perspective about Family Integrated Care (FiCare) in our quaternary NICU. We found that parents and clinicians reported many benefits for families. They were all enthusiastic about FiCare for non-medical items such as changing diapers and skin-to-skin care; for more medical items, such as presenting at rounds, being present during resuscitation or procedures, most physicians wished for more parental involvement, more than other professionals, even parents. All parents described how FiCare benefited them, had empowered them, helped them feel like parents and become a family; but several parents, who could not participate as much or did not want to assume clinical roles, reported feeling guilty. Having a flexible, yet transparent FiCare philosophy is key, as opposed to having homogeneous goals. For example, an aim to have all parents present at rounds in a quality improvement initiative can cause harm to some families. We suggest how to ethically improve FiCare in the best interest of families while minimizing harms. It is important for FiCare not to be "Family Imposed Care." Optimizing FiCare can only be done when parents' priorities guide our actions, while also keeping in mind clinicians' perspectives and respecting the reality of each NICU.

The most immature infants: Is evidence-based practice possible?

INTRODUCTION: At extremely low gestational ages, preterm infants are markedly physiologically immature, thus their responses to common clinical interventions may differ from more mature preterm babies. This study was performed to describe the evidence base which is available to make care decisions for such infants. METHODS: A literature search of recent large neonatal randomized controlled trials (RCTs) was performed to determine the representation of infants <25 weeks of gestation, and whether it is clear if the overall results applied to the most immature infants. RESULTS: Among 30 multi-centre RCTs in neonatology from the last 5 years, many excluded the most immature infants, and those that included them rarely presented the impacts of the intervention on the most at-risk group. Over 25,000 infants of under 32 weeks gestational age (GA) were included in these trials. Eight trials presented results of the primary outcome for infants of <26 weeks GA (n = 2,152) and a further four trials for infants <25 weeks, n = 711. CONCLUSION: The evidence base for treatment decisions for the highest risk infants in the NICU is severely limited. RCTs in extremely preterm infants should not exclude the highest risk group, and lower limits of gestational age (or body weight) should be avoided, any infant receiving intensive care should be eligible regardless of how immature. The results among the most immature infants should be presented separately, or be easily available, in order to build a database of effective treatments among infants of 22,23, and 24 weeks GA.

Impact of Deferred Cord Clamping on Mortality and Severe Neurologic Injury in Twins Born at <30 Weeks of Gestation.

OBJECTIVE: To determine whether deferred cord clamping (DCC) compared with early cord clamping (ECC) was associated with reduction in death and/or severe neurologic injury among twins born at <30 weeks of gestation. STUDY DESIGN: We performed a retrospective cohort study including all liveborn twins of <30 weeks admitted to a tertiary-level neonatal intensive care unit (NICU) in Canada between 2015 and 2018 using the Canadian Neonatal/Preterm Birth Network database. We compared DCC ≥30 seconds vs ECC <30 seconds. Our primary outcome was a composite of death and/or severe neurologic injury (severe intraventricular hemorrhage grade III/IV and/or periventricular leukomalacia). Secondary outcomes included neonatal morbidity and health care utilization outcomes. We calculated aORs and ß coefficients for categorical and continuous variables, along with 95% CI. Models were fitted with generalized estimated equations accounting for twin correlation. RESULTS: We included 1597 twins (DCC, 624 [39.1%]; ECC, 973 [60.9%]). Death/severe neurologic injury occurred in 17.8% (n = 111) of twins who received DCC and in 21.7% (n = 211) of those who received ECC. The rate of death/severe neurologic injury did not differ significantly between the DCC and ECC groups (aOR 1.07; 95% CI, 0.78-1.47). DCC was associated with reduced blood transfusions (adjusted ß coefficient, -0.49; 95% CI, -0.86 to -0.12) and NICU length of stay (adjusted ß coefficient, -4.17; 95% CI, -8.15 to -0.19). CONCLUSIONS: The primary composite outcome of death and/or severe neurologic injury did not differ between twins born at <30 weeks of gestation who received DCC and those who received ECC, but DCC was associated with some benefits.

Cerebral oxygen saturation and autoregulation during hypotension in extremely preterm infants.

BACKGROUND: The impact of the permissive hypotension approach in clinically well infants on regional cerebral oxygen saturation (rScO2) and autoregulatory capacity (CAR) remains unknown. METHODS: Prospective cohort study of blinded rScO2 measurements within a randomized controlled trial of management of hypotension (HIP trial) in extremely preterm infants. rScO2, mean arterial blood pressure, duration of cerebral hypoxia, and transfer function (TF) gain inversely proportional to CAR, were compared between hypotensive infants randomized to receive dopamine or placebo and between hypotensive and non-hypotensive infants, and related to early intraventricular hemorrhage or death. RESULTS: In 89 potentially eligible HIP trial patients with rScO2 measurements, the duration of cerebral hypoxia was significantly higher in 36 hypotensive compared to 53 non-hypotensive infants. In 29/36 hypotensive infants (mean GA 25 weeks, 69% males) receiving the study drug, no significant difference in rScO2 was observed after dopamine (n = 13) compared to placebo (n = 16). Duration of cerebral hypoxia was associated with early intraventricular hemorrhage or death.  Calculated TF gain (n = 49/89) was significantly higher reflecting decreased CAR in 16 hypotensive compared to 33 non-hypotensive infants. CONCLUSIONS: Dopamine had no effect on rScO2 compared to placebo in hypotensive infants. Hypotension and cerebral hypoxia are associated with early intraventricular hemorrhage or death. IMPACT: Treatment of hypotension with dopamine in extremely preterm infants increases mean arterial blood pressure, but does not improve cerebral oxygenation. Hypotensive extremely preterm infants have increased duration of cerebral hypoxia and reduced cerebral autoregulatory capacity compared to non-hypotensive infants. Duration of cerebral hypoxia and hypotension are associated with early intraventricular hemorrhage or death in extremely preterm infants. Since systematic treatment of hypotension may not be associated with better outcomes, the diagnosis of cerebral hypoxia in hypotensive extremely preterm infants might guide treatment.

Hypotension in Preterm Infants (HIP) randomised trial.

OBJECTIVE: To determine whether restricting the use of inotrope after diagnosis of low blood pressure (BP) in the first 72 hours of life affects survival without significant brain injury at 36 weeks of postmenstrual age (PMA) in infants born before 28 weeks of gestation. DESIGN: Double-blind, placebo-controlled randomised trial. Caregivers were masked to group assignment. SETTING: 10 sites across Europe and Canada. PARTICIPANTS: Infants born before 28 weeks of gestation were eligible if they had an invasive mean BP less than their gestational age that persisted for ≥15 min in the first 72 hours of life and a cerebral ultrasound free of significant (≥ grade 3) intraventricular haemorrhage. INTERVENTION: Participants were randomly assigned to saline bolus followed by either a dopamine infusion (standard management) or placebo (5% dextrose) infusion (restrictive management). PRIMARY OUTCOME: Survival to 36 weeks of PMA without severe brain injury. RESULTS: The trial terminated early due to significant enrolment issues (7.7% of planned recruitment). 58 infants were enrolled between February 2015 and September 2017. The two groups were well matched for baseline variables. In the standard group, 18/29 (62%) achieved the primary outcome compared with 20/29 (69%) in the restrictive group (p=0.58). Additional treatments for low BP were used less frequently in the standard arm (11/29 (38%) vs 19/29 (66%), p=0.038). CONCLUSION: Though this study lacked power, we did not detect major differences in clinical outcomes between standard or restrictive approach to treatment. These results will inform future studies in this area. TRIAL REGISTRATION NUMBER: NCT01482559, EudraCT 2010-023988-17.