Association Between Urinary Biomarkers and CKD in Extremely Low Gestational Age Neonates.

RATIONALE & OBJECTIVE: Children born before 28 weeks' gestation are at increased risk of chronic kidney disease (CKD). Urine biomarkers may shed light on mechanistic pathways and improve the ability to forecast CKD. We evaluated whether urinary biomarkers in neonates of low gestational age (GA) are associated with a reduced estimated glomerular filtration rate (eGFR) over time. STUDY DESIGN: A cohort study of neonates with an exploratory case-control study of a subset of the cohort. SETTING & PARTICIPANTS: 327 neonates born at 24-27 weeks' gestation with 2-year eGFR data from the PENUT (Preterm Erythropoietin Neuroprotection Trial) and the REPaIReD (Recombinant Erythropoietin for Prevention of Infant Renal Disease) study. EXPOSURES: 11 urinary biomarkers measured at 27, 30, and 34 weeks' postmenstrual age for the primary cohort study and 10 additional biomarkers for the exploratory case-control study. OUTCOMES: eGFR<90mL/min/1.73m2 at 2 years corrected for GA. ANALYTICAL APPROACH: Linear mixed models to assess differences in biomarker values between neonates in whom CKD did and did not develop, accounting for multiple comparisons using Bonferroni-Holm correction in the cohort study only. Cohort analyses were adjusted for sex, GA, and body mass index. Cases were matched to controls on these variables in the case-control study. RESULTS: After adjusting for weeks of GA, urinary levels of α-glutathione-S-transferase (log difference, 0.27; 95% CI, 0.12-0.43), albumin (log difference, 0.13; 95% CI, 0.02-0.25), and cystatin C (log difference, 0.19; 95% CI, 0.04-0.34) were higher in those in whom CKD developed than in those in whom it did not. Urinary albumin and cystatin C levels did not remain significantly different after Bonferroni-Holm correction. In the exploratory case-control analysis, there were no differences in any biomarkers between cases and controls. LIMITATIONS: Early deaths and a high number of subjects without eGFR at 2 years corrected for GA. CONCLUSIONS: Measurement of urinary biomarkers may assist in monitoring neonates who are at risk for CKD. Additional studies are needed to confirm these findings. FUNDING: Grants from government (National Institutes of Health). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01378273. PLAIN-LANGUAGE SUMMARY: Approximately 15 million neonates worldwide are born prematurely, and 2 million are born before 28 weeks' gestation. Many of these children go on to experience chronic kidney disease. Urine biomarkers may allow for early recognition of those at risk for the development of kidney disease. In this study of more than 300 children born before 28 weeks' gestational age, we found higher mean urinary levels of α-glutathione-S-transferase at 27, 30, and 34 weeks in children whose estimated glomerular filtration rate was<90mL/min/1.73m2 at 2 years compared with children whose estimated glomerular filtration rate was>90mL/min/1.73m2 at 2 years. Measurement of urinary biomarkers may assist in monitoring neonates who are at risk for chronic kidney disease. Additional studies are needed to confirm our findings.

Disrupted resting-sate brain network dynamics in children born extremely preterm.

The developing brain has to adapt to environmental and intrinsic insults after extremely preterm (EPT) birth. Ongoing maturational processes maximize their fit to the environment and this can provide a substrate for neurodevelopmental failures. Resting-state functional magnetic resonance imaging was used to scan 33 children born EPT, at < 27 weeks of gestational age, and 26 full-term controls at 10 years of age. We studied the capability of a brain area to propagate neural information (intrinsic ignition) and its variability across time (node-metastability). This framework was computed for the dorsal attention network (DAN), frontoparietal, default-mode network (DMN), and the salience, limbic, visual, and somatosensory networks. The EPT group showed reduced intrinsic ignition in the DMN and DAN, compared with the controls, and reduced node-metastability in the DMN, DAN, and salience networks. Intrinsic ignition and node-metastability values correlated with cognitive performance at 12 years of age in both groups, but only survived in the term group after adjustment. Preterm birth disturbed the signatures of functional brain organization at rest in 3 core high-order networks: DMN, salience, and DAN. Identifying vulnerable resting-state networks after EPT birth may lead to interventions that aim to rebalance brain function.

The relationship between inflammatory markers and retinopathy of prematurity in extremely premature infants.

PURPOSE: This study aimed to evaluate the relationships among blood parameters, clinical factors, and retinopathy of prematurity (ROP) in extremely premature (EP) infants. METHODS: This retrospective study included 153 EP infants who were categorized into two groups based on the presence of inflammatory diseases such as necrotizing enterocolitis, neonatal sepsis, bronchopulmonary dysplasia, severe intraventricular hemorrhage, preeclampsia, and premature rupture of membranes. Complete blood count parameters, neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio, platelet-lymphocyte ratio (PLR), systemic inflammatory index, and platelet mass index were recorded during the first week and first month after birth. The study analyzed the impact of parameters obtained through blood tests during the first week and first month on the development of ROP and the requirement for treatment. RESULTS: In this study, 96 infants were diagnosed with inflammatory diseases. After multivariate regression analyses, the duration of mechanical ventilation (p = 0.010) was found to be the only factor that led to ROP development. Moreover, lower gestational age (GA) (p = 0.006), higher NLR (p = 0.026), and lower PLR (p = 0.019) were observed in infants requiring treatment compared to infants with spontaneous resolution of ROP in this group. 57 infants did not have inflammatory diseases. Although the duration of mechanical ventilation (p = 0.041) and low levels of platelets (PLT) (p = 0.046) measured in the first month postnatally were significantly found to be associated with ROP developement, no parameter affecting the required treatment could be determined. CONCLUSION: EP infants with longer mechanical ventilation durations and lower PLT counts are vulnerable to ROP development. GA, PLR, and NLR are predictive factors for treatment.

Attitudes and values towards decisions at the margin of viability among expectant mothers at risk for preterm birth.

AIM: To explore how expectant mothers at risk for preterm birth would like to be involved in decision-making at the margin of viability and what they would base their decisions on. METHODS: This cross-sectional observational study included a mixed-methods post-hoc analysis alongside a previously reported randomised clinical trial. Expectant mothers between 280/7 and 366/7 weeks' gestation who were hospitalised for risk of preterm birth responded to written case vignettes of an impending preterm birth at the margin of viability. Participants responded to closed and open-ended questions that were theoretically coded for attitudes and values towards shared decision-making. RESULTS: Sixty-four expectant mothers were included in the analysis, 36 provided written perspectives. Decision-making was perceived as an enormous burden and a potential source of guilt and regret. Weighing personal values in terms of 'fighting for the baby' and 'quality of life' were used to inform the decision-making process. Explicitly stating that any decision is a good decision, empowerment through co-constructing shared decisions rather than simply presenting choices, sharing the clinicians' personal views, and honest, and empathetic counselling were perceived as supportive. CONCLUSION: Mothers at risk for preterm birth provided specific insights into their decision-making patterns that may be helpful to clinicians.

Predicting attachment in Portuguese infants born very or extremely preterm: Understanding the roles of infant regulatory behavior, maternal sensitivity, and risk factors.

A growing body of research shows that early attachment relationships are foundational for children's later developmental and psychosocial outcomes. However, findings are mixed regarding whether preterm birth predicts later attachment, but insecurity is generally more prevalent among infants at higher medical and/or social/familial risk. This longitudinal study aimed to identify specific relational, familial/demographic, and perinatal predictors of attachment in a sample of 63 Portuguese infants born very or extremely preterm (VEPT, <32 gestational weeks) and their mothers from diverse socioeconomic backgrounds. One-third of the mothers had social/family risk factors (e.g., single parent, immigrant, unemployed, low education, and/or low income). At 3 months (corrected age), dyads were observed during social interaction in the Face-to-Face Still-Face paradigm (FFSF) and during free play. At 12 months, mother-infant dyads were observed in Ainsworth's Strange Situation. Over half (58.7%) of the infants were classified as insecurely attached. Social-Positive Oriented regulatory behavior pattern, higher maternal sensitivity, higher infant cooperation during free play, number of siblings and an absence of social/family risk factors were associated with attachment security. Perinatal variables were unrelated to attachment. Findings indicate that both relational and social contextual factors contribute to attachment in this biologically vulnerable sample.

Un creciente cuerpo investigativo muestra que las relaciones afectivas tempranas son fundamentales para posteriores resultados de desarrollo y sicosociales de los niños. Sin embargo, los resultados son variados acerca de si el nacimiento prematuro predice la afectividad posterior, pero la inseguridad es generalmente más prevalente entre infantes bajo más alto riesgo médico y/o social/familiar. Este estudio longitudinal se propuso identificar factores específicos de predicción de la afectividad, relacionales, familiar/demográficos y perinatales en un grupo muestra de 63 infantes portugueses nacidos muy o extremadamente prematuros (VEPT, < 32 semanas gestacionales) y sus madres de diversos niveles socioeconómicos. Un tercio de las madres tenían factores de riesgo social/familiar (v.g. madre soltera, inmigrante, desempleada, de baja educación y/o de bajos recursos económicos). A los tres meses (edad corregida), se les observó a las díadas durante la interacción social en el paradigma de Cara a Cara y Rostro Inmutable (FFSF) y durante el juego libre. A los 12 meses, se les observó a las díadas madre-infante por medio de la Situación Extraña de Ainsworth. Se clasificó más de la mitad (58.7%) de los infantes como afectivamente inseguros. Entre los factores de predicción de la afectividad segura se incluyó un patrón de conducta regulatoria con orientación social positiva durante FFSF, una sensibilidad materna más alta y la cooperación del infante durante el juego libre, así como la ausencia de factores de riesgo sociales/familiares. Las variables perinatales no estuvieron relacionadas con la afectividad. Los resultados indican que los factores contextuales, tanto relacionales como sociales contribuyen a la afectividad en este grupo biológicamente vulnerable.

Antenatal Steroids, Prophylactic Indomethacin, and the Risk of Spontaneous Intestinal Perforation.

OBJECTIVE: To estimate if the odds of spontaneous intestinal perforation (SIP) are increased when antenatal steroids (ANS) given close to delivery are combined with indomethacin on day 1 after birth (Indo-D1). STUDY DESIGN: A retrospective cohort study using the Neonatal Research Network (NRN) database of inborn infants, gestational age 220-286 weeks or birth weight of 401-1000 g, born between January 1, 2016 and December 31, 2019, and surviving >12 hours. The primary outcome was SIP through 14 days. Time of last ANS dose prior to delivery was analyzed as a continuous variable (using 169 hours for durations >168 hours or no steroid exposure). Associations between ANS, Indo-D1, and SIP were obtained from a multilevel hierarchical generalized linear mixed model after covariate adjustment. This yielded aOR and 95% CI. RESULTS: Of 6851 infants, 243 had SIP (3.5%). ANS exposure occurred in 6393 infants (93.3%) and IndoD1 was given to 1863 infants (27.2%). The time (median, IQR) from last dose of ANS to delivery was 32.5 hours (6-81) vs 37.1 hours (7-110) for infants with or without SIP, respectively (P = .10). Indo-D1 was given to 51.9 vs 26.3% of infants with SIP vs no SIP, respectively (P < .0001). Adjusted analysis indicated no interaction between time of last ANS dose and Indo-D1 for SIP (P = .7). Indo-D1 but not ANS was associated with increased odds of SIP (aOR: 1.73, 1.21-2.48, P = .003). CONCLUSION: The odds of SIP were increased after receipt of Indo-D1. Exposure to ANS prior to Indo-D1 was not associated with an increase in SIP.

Thrombocytopenia and neonatal outcomes among extremely premature infants exposed to maternal hypertension.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with neonatal hematological disturbances, such as thrombocytopenia. The association of HDP to platelet counts in the context of extreme prematurity, to trends of platelet counts during neonatal hospitalization, and to frequency of platelet transfusions remain to be explored. PROCEDURE: Retrospective study of infants born at less than 29 weeks born between 2015 and 2019. Platelet counts were collected on initial complete blood count, at 2 weeks, 32 weeks post-menstrual age (PMA), 36 weeks PMA, and closest to discharge. We examined the association between HDP and platelet counts at each time point, frequency of platelet transfusions and intraventricular hemorrhage (IVH) grade 3 or more. RESULTS: Total 296 infants were included, 43 exposed to HDP. Infants exposed had lower platelet counts at each time point, as well as a higher prevalence of platelet less than 150 × 109 /L on one of the time points (32% vs. 65%, p < .001). Infants exposed to maternal hypertension were more frequently exposed to platelet transfusions (63% vs. 18%, p < .001). Mixed effect model demonstrated an association between HDP and a lower trend in platelet counts at each time point (ß = -94 × 103 /µl, p < .001). Although initial platelet count was associated with severe IVH, it was not associated to exposure to HDP. CONCLUSION: Premature infants exposed to HDP have a higher prevalence of thrombocytopenia, increased frequency of platelet transfusion, and an altered trend in platelet counts during neonatal hospitalization.

Pulmonary hypertension in preterm infants with moderate-to-severe bronchopulmonary dysplasia (BPD).

AIM: To describe clinical characteristics of pulmonary hypertension (PH) associated with moderate to severe BPD (MSBPD) in premature infants born ≤32 weeks gestation. METHODS: This was a single centre retrospective cohort study, with reanalysis of echocardiographic studies for PH of infants born ≤32 weeks gestation with MSBPD admitted to a tertiary surgical neonatal service. RESULTS: In total, 268 babies with MSBPD were included in the study. Incidence of BPD-associated PH (BPD-PH) was 12.6% (34), of which 41% infants were observed to have severe PH. On multivariate analysis, need for positive pressure respiratory support at 36 weeks post menstrual age (PMA) was independently associated with PH (p = 0.001; 95% CI 2-13.5) Presence of PH and severity of PH were associated with increased mortality. Of babies with MSBPD-PH, 32% died before discharge from the neonatal unit. CONCLUSION: Babies with MSBPD and PH are more likely to die before discharge from the neonatal unit. Need for positive pressure respiratory support at 36 weeks PMA is independently associated with PH. Babies with MSBPD with less than severe PH are also associated with increased mortality when compared to babies with MSBPD with no PH.

Adults born prematurely prefer a periviability guideline that considers multiple prognostic factors beyond gestational age.

AIM: The aim of the study was to explore the perspectives of adults born prematurely on guidelines for management at extreme premature birth and personalisation at the limit of viability. METHODS: We conducted four 2-h online focus group interviews in the Netherlands. RESULTS: Twenty-three participants born prematurely were included in this study, ranging in age from 19 to 56 years and representing a variety of health outcomes. Participants shared their perspectives on different types of guidelines for managing extremely premature birth. They agreed that a guideline was necessary to prevent arbitrary treatment decisions and to avoid physician bias. All participants favoured a guideline that is based upon multiple prognostic factors beyond gestational age. They emphasised the importance of discretion, regardless of the type of guideline used. Discussions centred mainly on the heterogeneity of value judgements about outcomes after extreme premature birth. Participants defined personalisation as 'not just looking at numbers and statistics'. They associated personalisation mainly with information provision and decision-making. Participants stressed the importance of involving families in decision-making and taking their care needs seriously. CONCLUSION: Adults born prematurely prefer a periviability guideline that considers multiple prognostic factors and allows for discretion.

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.

Group B Streptococcus Infection in Extremely Preterm Neonates and Neurodevelopmental Outcomes at 2 Years.

BACKGROUND: This study was performed to determine the incidence of group B Streptococcus (GBS) disease among extremely preterm infants and assess to risk of death or neurodevelopmental impairment (NDI) at a corrected age of 18-26 months. METHODS: In this observational cohort study of infants enrolled in a multicenter registry, the incidence of GBS disease was assessed in infants born in 1998-2016 at 22-28 weeks' gestation and surviving for >12 hours. The composite outcome, death or NDI, was assessed in infants born in 1998-2014 at 22-26 weeks' gestation. Infection was defined as GBS isolation in blood or cerebrospinal fluid culture at ≤72 hours (early-onset disease [EOD]) or >72 hours (late-onset disease [LOD]) after birth. Using Poisson regression models, the outcome was compared in infants with GBS disease, infants infected with other pathogens, and uninfected infants. RESULTS: The incidence of GBS EOD (2.70/1000 births [95% confidence interval (CI), 2.15-3.36]) and LOD (8.47/1000 infants [7.45-9.59]) did not change significantly over time. The adjusted relative risk of death/NDI was higher among infants with GBS EOD than in those with other infections (adjusted relative risk, 1.22 [95% CI, 1.02-1.45]) and uninfected infants (1.44 [1.23-1.69]). Risk of death/NDI did not differ between infants with GBS LOD and comparator groups. GBS LOD occurred at a significantly later age than non-GBS late-onset infection. Among infants surviving >30 days, the risk of death was higher with GBS LOD (adjusted relative risk, 1.90 [95% CI, 1.36-2.67]), compared with uninfected infants. CONCLUSIONS: In a cohort of extremely preterm infants, the incidence of GBS disease did not change during the study period. The increased risk of death or NDI with GBS EOD, and of death among some infants with GBS LOD, supports the need for novel preventive strategies for disease reduction. CLINICAL TRIALS REGISTRATION: NCT00063063.

Ventilation and respiratory outcome in extremely preterm infants: trends in the new millennium.

Ventilation and respiratory care have substantially changed over the last decades in extremely premature neonates but the impact on respiratory health remains largely unclear. To determine changes in respiratory care and disease frequency in extremely premature infants, a retrospective single-centre cohort study of extremely preterm infants was performed. All infants born alive between 24 + 0 and 27 + 6 weeks of gestation in 2000-2001 (Epoch 1), 2009-2010 (Epoch 2), and 2018-2019 (Epoch 3) were included. The primary outcome of this study was the incidence of bronchopulmonary dysplasia (BPD, diagnosed according to three different criteria) or death. Secondary outcomes included the usage of different ventilation modes, changes in pharmacotherapy, and the incidence of significant extra-pulmonary morbidities. A total of 184 neonates were included of whom 151 survived until 36 weeks of corrected GA (cGA). Oxygen or positive pressure dependence increased over time (26.1%, 41.7%, and 56.1% respectively), with higher adjusted odds in Epoch 3 for the composite outcome "BPD or death" (adjusted odds ratio: 2.55 [95%CI 1.19-5.61]). Severity-based definitions showed increasing trends in survivors only. Time spent on invasive mechanical ventilation was similar throughout the years, but the use of non-invasive ventilation significantly increased in Epoch 3 (32.0 [95%CI 25.0-37.0] vs 27.0 [95%CI 26.0-32.0] vs 53.0 [95%CI 46.0-58.0] days). Moreover, mortality-adjusted rates of severe IVH, NEC, or intestinal perforation and multiple sepsis tended to decrease.   Conclusion: In spite of significant clinical advancements and adherence to novel treatment guidelines in our neonatal intensive care unit, the incidence of BPD increased over time. What is Known: • Rates of BPD are stable or increase in population-based studies. • Extremely preterm infants are particularly susceptible to developing BPD. What is New: • Despite increased use of evidence-based corticosteroid administration and early initiation of caffeine, the incidence of BPD has not decreased over the past decade.  • Increased usage of non-invasive ventilation is associated with an increase of BPD incidence.

Extremely low gestational age neonates and resuscitation: survey on perspectives of Canadian neonatologists.

OBJECTIVES: Resuscitation care planning for extremely low gestational age neonates (ELGANs) is complex and ethically charged. Increasing survival at lower gestational ages has had a significant impact on this complexity. It also has an impact on healthcare resource utilization and policy development in Canada. This study sought to determine the current attitudes and practices of neonatologists in Canada, and to assess moral distress associated with resuscitation decisions in the ELGAN population. It also aimed to explore the perspectives of adopting a shared decision-making approach where further data with regard to best interests and prognosis are gathered in an individualized manner after birth. METHODS: Neonatologists in Canadian level III NICUs were surveyed in 2020. RESULTS: Amongst the 65 responses, 78% expressed moral distress when parents request non-resuscitation at 24 weeks. Uncertainty around long-term outcomes in an era with improved chances of morbidity-free survival was the most prominent factor contributing to moral distress. 70% felt less moral distress deciding goals of care after the baby's initial resuscitation and preferred an individualized approach to palliation decisions based on postnatal course and assessment. CONCLUSIONS: While most current guidelines still support the option of non-resuscitation for infants born at less than 25 weeks, we show evidence of moral distress among Canadian neonatologists that suggests the consideration of routine resuscitation from 24 weeks and above is a more ethical approach in the current era of improved outcomes. Canadian neonatologists identified less moral distress when goals of care are developed postnatally, with availability of more evidence for prognostication, instead of antenatally based primarily on gestational age.

Neonatal Cranial Ultrasound Findings among Infants Born Extremely Preterm: Associations with Neurodevelopmental Outcomes at 10 Years of Age.

OBJECTIVE: To examine the association between neonatal cranial ultrasound (CUS) abnormalities among infants born extremely preterm and neurodevelopmental outcomes at 10 years of age. STUDY DESIGN: In a multicenter birth cohort of infants born at <28 weeks of gestation, 889 of 1198 survivors were evaluated for neurologic, cognitive, and behavioral outcomes at 10 years of age. Sonographic markers of white matter damage (WMD) included echolucencies in the brain parenchyma and moderate to severe ventricular enlargement. Neonatal CUS findings were classified as intraventricular hemorrhage (IVH) without WMD, IVH with WMD, WMD without IVH, and neither IVH nor WMD. RESULTS: WMD without IVH was associated with an increased risk of cognitive impairment (OR 3.5, 95% CI 1.7, 7.4), cerebral palsy (OR 14.3, 95% CI 6.5, 31.5), and epilepsy (OR 6.9; 95% CI 2.9, 16.8). Similar associations were found for WMD accompanied by IVH. Isolated IVH was not significantly associated these outcomes. CONCLUSIONS: Among children born extremely preterm, CUS abnormalities, particularly those indicative of WMD, are predictive of neurodevelopmental impairments at 10 years of age. The strongest associations were found with cerebral palsy.

Association between extremely preterm caesarean delivery and maternal depressive and anxious symptoms: a national population-based cohort study.

OBJECTIVE: To evaluate whether caesarean delivery before 26 weeks of gestation was associated with symptoms of depression and anxiety in mothers in comparison with deliveries between 26 and 34 weeks. DESIGN: Prospective national population-based EPIPAGE-2 cohort study. SETTING: 268 neonatology departments in France, March to December 2011. POPULATION: Mothers who delivered between 22 and 34 weeks and whose self-reported symptoms of depression (Center for Epidemiologic Studies Depression Scale: CES-D) and anxiety (State-Trait Anxiety Inventory: STAI) were assessed at the moment of neonatal discharge. METHODS: The association of caesarean delivery before 26 weeks with severe symptoms of depression (CES-D ≥16) and anxiety (STAI ≥45) was assessed by weighted and design-based log-linear regression model. MAIN OUTCOME MEASURES: Severe symptoms of depression and anxiety in mothers of preterm infants. RESULTS: Among the 2270 women completing CES-D and STAI questionnaires at the time of neonatal discharge, severe symptoms of depression occurred in 25 (65.8%) women having a caesarean before 26 weeks versus in 748 (50.6%) women having a caesarean after 26 weeks. Caesarean delivery before 26 weeks was associated with severe symptoms of depression compared with caesarean delivery after 26 weeks (adjusted relative risk [aRR] 1.42, 95% CI 1.12-1.81) adjusted to neonatal birthweight and severe neonatal morbidity among other factors. There was no evidence of an association between mode of delivery and symptoms of anxiety. CONCLUSIONS: Mothers having a caesarean delivery before 26 weeks' gestation are at high risk of symptoms of depression and may benefit from specific preventive care. TWEETABLE ABSTRACT: Mothers having caesarean delivery before 26 weeks' gestation are at high risk of symptoms of depression.

Chronic Inflammatory Placental Lesions Correlate With Bronchopulmonary Dysplasia Severity in Extremely Preterm Infants.

OBJECTIVE: Correlation of BPD with placental pathology is important for clarification of the multifactorial pathogenesis of BPD; however, previous reports have yielded varying results. We report placental findings in no/mild BPD compared to moderate/severe BPD, and with and without pulmonary hypertension (PH). METHODS: Eligible infants were 230/7-276/7 weeks gestational age. BPD was defined by the need for oxygen at ≥28 days with severity based on need for respiratory support at ≥36 weeks. Acute and chronic inflammatory placental lesions and lesions of maternal and fetal vascular malperfusion were examined. RESULTS: Of 246 eligible infants, 146 (59%) developed moderate/severe BPD. Thirty-four (23%) infants developed PH, all but 1 being in the moderate/severe BPD group. Chronic deciduitis (32% vs 16%, P = .003), chronic chorioamnionitis (23% vs 12%, P = .014), and ≥ 2 chronic inflammatory lesions (13% vs 3%, P = .007) were more frequent in the moderate/severe BPD group. Development of PH was associated with placental villous lesions of maternal vascular malperfusion (30% vs 15%, P = .047). CONCLUSIONS: The association of chronic inflammatory placental lesions with BPD severity has not been previously reported. This supports the injury responsible for BPD as beginning before birth in some neonates, possibly related to cytokines associated with these chronic inflammatory lesions.

Exploring implicit bias in the perceived consequences of prematurity amongst health care providers in North Queensland - a constructivist grounded theory study.

BACKGROUND: A study was done to explore the attitudes of relevant health care professionals (HCP) towards the provision of intensive care for periviable and extremely premature babies. METHODS/DESIGN: Applying a constructivist grounded theory methodology, HCP were interviewed about their attitudes towards the provision of resuscitation and intensive care for extremely premature babies. These babies are at increased risk of death and neurodisability when compared to babies of older gestations. Participants included HCP of varying disciplines at a large tertiary centre, a regional centre and a remote centre. Staff with a wide range of experience were interviewed. RESULTS: Six categories of i) who decides, ii) culture and context of families, iii) the life ahead, iv) to treat a bit or not at all, v) following guidelines and vi) information sharing, emerged. Role specific implicit bias was found as a theoretical construct, which depended on the period for which care was provided relative to the delivery of the baby. This implicit bias is an underlying cause for the negativity seen towards extreme prematurity and is presented in this paper. HCP caring for women prior to delivery have a bias towards healthy term babies that involves overestimation of the risks of extreme prematurity, while neonatal staff were biased towards suffering in the neonatal period and paediatricians recognise positivity of outcomes regardless of neurological status of the child. The implicit bias found may explain negativity towards intensive care of periviable neonates. CONCLUSION: Understanding the presence and origins of role specific implicit bias may enable HCP to work together to improve care for parents preparing for the delivery of extremely premature babies.

Advances in extracorporeal membrane oxygenator design for artificial placenta technology.

Extreme prematurity, defined as a gestational age of fewer than 28 weeks, is a significant health problem worldwide. It carries a high burden of mortality and morbidity, in large part due to the immaturity of the lungs at this stage of development. The standard of care for these patients includes support with mechanical ventilation, which exacerbates lung pathology. Extracorporeal life support (ECLS), also called artificial placenta technology when applied to extremely preterm (EPT) infants, offers an intriguing solution. ECLS involves providing gas exchange via an extracorporeal device, thereby doing the work of the lungs and allowing them to develop without being subjected to injurious mechanical ventilation. While ECLS has been successfully used in respiratory failure in full-term neonates, children, and adults, it has not been applied effectively to the EPT patient population. In this review, we discuss the unique aspects of EPT infants and the challenges of applying ECLS to these patients. In addition, we review recent progress in artificial placenta technology development. We then offer analysis on design considerations for successful engineering of a membrane oxygenator for an artificial placenta circuit. Finally, we examine next-generation oxygenators that might advance the development of artificial placenta devices.

Respiratory and Cardiovascular Outcomes in Survivors of Extremely Preterm Birth at 19 Years.

Rationale: Growth and development during adolescence may modify the respiratory and vascular differences seen among extremely preterm (EP) individuals in childhood and early adolescence.Objectives: To assess the trajectory of respiratory and cardiovascular outcomes during transition to adulthood in a national longitudinal cohort study of births before 26 weeks of gestation in the United Kingdom and Ireland.Methods: A total of 129 EP participants and 65 control subjects attended for a center-based evaluation at 19 years of age. Standardized measures of spirometry, hemodynamics, functional capacity, and markers of inflammation were obtained from EP subjects with and without neonatal bronchopulmonary dysplasia and term-born control subjects at 19 years of age and compared with previous assessments.Measurements and Main Results: Compared with the control group, the EP group was significantly impaired on all spirometric parameters (mean FEV1z-score, -1.08 SD [95% confidence interval, -1.40 to -0.77]) and had lower fractional exhaled nitric oxide concentrations (13.9 vs. 24.4 ppb; P < 0.001) despite a higher proportion with bronchodilator reversibility (27% vs. 6%). The EP group had significantly impaired exercise capacity. All respiratory parameters were worse after neonatal bronchopulmonary dysplasia, and respiratory function differences were similar at 11 and 19 years. The augmentation index was 6% higher in the EP group and associated with increased total peripheral resistance (difference in means, 96.4 [95% confidence interval, 26.6-166.2] dyne/s/cm-5) and elevation in central, but not peripheral, blood pressure. Central systolic and diastolic blood pressures increased more quickly during adolescence in the EP group than in the control group.Conclusions: Clinicians should address both cardiovascular and respiratory risks in adult survivors of extremely preterm birth.

End-organ saturations correlate with aortic blood flow estimates by echocardiography in the extremely premature newborn - an observational cohort study.

BACKGROUND: Near-infrared spectroscopy (NIRS) measures of cerebral saturation (Csat) and renal saturation (Rsat) in extreme premature newborns may be affected by systemic blood flow fluctuations. Despite increasing clinical use of NIRS to monitor tissue saturation in the premature infant, validation of NIRS measures as a correlate of blood flow is still needed. We compared echocardiography (ECHO) derived markers of ascending aorta (AscAo) and descending aorta (DesAo) blood flow with NIRS measurements obtained during the ECHO. METHODS: Newborns < 29 weeks' gestation (2013-2017) underwent routine NIRS monitoring. Csat, Rsat and systemic saturation at the time of ECHO were retrospectively analyzed and compared with Doppler markers of aortic flow. Renal and cerebral fractional tissue oxygen extraction (rFTOE and cFTOE, respectively) were calculated. Mixed effects models evaluated the association between NIRS and Doppler markers. RESULTS: Forty-nine neonates with 75 Csat-ECHO and 62 Rsat-ECHO observations were studied. Mean post-menstrual age was 28.3 ± 3.8 weeks during the ECHO. Preductal measures including AscAo velocity time integral (VTI) and AscAo output were correlated with Csat or cFTOE, while postductal measures including DesAo VTI, DesAo peak systolic velocity, and estimated DesAo output were more closely correlated with Rsat or rFTOE. CONCLUSIONS: NIRS measures are associated with aortic blood flow measurements by ECHO in the extremely premature population. NIRS is a tool to consider when following end organ perfusion in the preterm infant.