Does Accidental Hypothermia Increase Morbidity and Mortality in Mature Neonates?

Accidental hypothermia in mature neonates requiring hospitalization is a clinical complication that has not been studied in detail. In the present study, the effect of accidental hypothermia on common morbidity in neonates in the postnatal period was investigated. We did temperature measurements in 616 mature neonates after birth, after transfer to the maternity ward and at check-up at age of 48-72 hours of life. Additionally, nurses checked temperature until discharge at every diaper change in 302 of all included neonates who were small for gestational age (SGA) or whose mothers had green fluid or premature rupture of membranes (PROM). We investigated if there was a correlation between infection, hyperbilirubinemia, hypoglycemia, SGA, gestational diabetes, PROM, green amniotic fluid, positive GBS status of the mother, and accidental hypothermia in the first 48-72 hours of life. Mature neonates showed transient accidental hypothermia in the first 24 hours of life. No significant correlation between infection (p=0.571), hyperbilirubinemia (p=0.837), hypoglycemia (p=0.072), and accidental hypothermia could be seen. There was a significant correlation between SGA (p=0.020), PROM (p=0.008), and accidental hypothermia, while hyperthermia was associated with infection (p=0.009) and green amniotic fluid (p=0.004). SGA and PROM represent perinatal risk factors for postnatal transient accidental hypothermia in mature neonates. Increased morbidity or mortality associated with postnatal accidental hypothermia has not been demonstrated.Akzidentelle Hypothermie bei Reifgeborenen, die einer Hospitalisierung bedürfen, ist eine bisher nicht näher analysierte klinische Komplikation. In der vorliegenden Arbeit wurde die Abhängigkeit einer akzidentellen Hypothermie von typischen Erkrankungen der Postnatalperiode untersucht. Wir führten bei 616 Reifgeborenen Temperaturmessungen nach Geburt, nach Verlegung auf die Wochenstation und bei der Vorsorgeuntersuchung U2 durch. Zusätzlich kontrollierten wir bei 302 der 616 Neugeborenen mit Small for gestational age (SGA), grünem Fruchtwasser oder vorzeitigem Blasensprung (PROM) die Temperatur bei jedem Windelwechsel bis zur Entlassung. Wir untersuchten, ob es einen Zusammenhang zwischen Infektion, Hyperbilirubinämie, Hypoglykämie, SGA, Gestationsdiabetes, PROM, grünem Fruchtwasser, positivem GBS-Status der Mutter und akzidenteller Auskühlung innerhalb der ersten 48-72 Lebensstunden gab. Reifgeborene zeigten in den ersten 24 Lebensstunden transiente akzidentelle Hypothermien. Es konnte kein signifikanter Zusammenhang zwischen Infektion (P=0.571), Hyperbilirubinämie (p=0.837), Hypoglykämie (p=0.072) und akzidenteller Hypothermie festgestellt werden. Es bestand ein signifikanter Zusammenhang zwischen SGA (p=0.020), PROM (p=0.008) und akzidenteller Hypothermie, während Hyperthermie war mit Infektion (p=0.009) und grünem Fruchtwasser (p=0.004) assoziiert war. SGA und PROM stellen perinatale Risikofaktoren für postnatale transiente, akzidentelle Hypothermien bei Reifgeborenen dar. Eine erhöhte Morbidiät bzw. Mortalität im Zusammenhang mit postnataler akzidenteller Hypothermie konnte nicht nachgewiesen werden.

Complex Compound Inheritance of Lethal Lung Developmental Disorders Due to Disruption of the TBX-FGF Pathway.

Primary defects in lung branching morphogenesis, resulting in neonatal lethal pulmonary hypoplasias, are incompletely understood. To elucidate the pathogenetics of human lung development, we studied a unique collection of samples obtained from deceased individuals with clinically and histopathologically diagnosed interstitial neonatal lung disorders: acinar dysplasia (n = 14), congenital alveolar dysplasia (n = 2), and other lethal lung hypoplasias (n = 10). We identified rare heterozygous copy-number variant deletions or single-nucleotide variants (SNVs) involving TBX4 (n = 8 and n = 2, respectively) or FGF10 (n = 2 and n = 2, respectively) in 16/26 (61%) individuals. In addition to TBX4, the overlapping ∼2 Mb recurrent and nonrecurrent deletions at 17q23.1q23.2 identified in seven individuals with lung hypoplasia also remove a lung-specific enhancer region. Individuals with coding variants involving either TBX4 or FGF10 also harbored at least one non-coding SNV in the predicted lung-specific enhancer region, which was absent in 13 control individuals with the overlapping deletions but without any structural lung anomalies. The occurrence of rare coding variants involving TBX4 or FGF10 with the putative hypomorphic non-coding SNVs implies a complex compound inheritance of these pulmonary hypoplasias. Moreover, they support the importance of TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling in human lung organogenesis and help to explain the histopathological continuum observed in these rare lethal developmental disorders of the lung.

Comparison of different neonatal illness severity scores in predicting mortality risk of extremely low birth weight infants.

To compare different illness severity scores in predicting mortality risk of extremely low birth weight infants (ELBWI). From January 1st, 2019 to January 1st, 2020, all ELBWI admitted in the Children's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital and the First Affiliated Hospital of Nanjing Medical University were included in the study. ELBWI with admission age ≥1 h, gestational age ≥37 weeks and incomplete data required for scoring were excluded. The clinical data were collected, neonatal critical illness score (NCIS), score for neonatal acute physiology version Ⅱ (SNAP-Ⅱ), simplified version of the score for neonatal acute physiology perinatal extension (SNAPPE-Ⅱ), clinical risk index for babies (CRIB) and CRIB-Ⅱ were calculated. The scores of the fatal group and the survival group were compared, and the receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the above illness severity scores for the mortality risk of ELBWI. Pearson correlation analysis was used to analyze the correlation between illness scores and birth weight, illness scores and gestational age. A total of 192 ELBWI were finally included, of whom 114 cases survived (survival group) and 78 cases died (fatal group). There were significant differences in birth weight, gestational age and Apgar scores between fatal group and survival group (all <0.01). There were significant differences in NCIS, SNAP-Ⅱ, SNAPPE-Ⅱ, CRIB and CRIB-Ⅱ between fatal group and survival group (all <0.01). The CRIB had a relatively higher predictive value for the mortality risk. Its area under the ROC curve (AUC) was 0.787, the sensitivity was 0.678, the specificity was 0.804, and the Youden index was 0.482. The scores of NCIS, SNAP-Ⅱ, SNAPPE-Ⅱ, CRIB and CRIB-Ⅱ were significantly correlated with birth weight and gestational age (all <0.05). The correlation coefficients of CRIB-Ⅱ and CRIB with birth weight and gestational age were relatively large, and the correlations coefficients of NCIS with birth weight and gestational age were the smallest (0.191 and 0.244, respectively). Among these five illness severity scores, CRIB has better predictive value for the mortality risk in ELBWI. NCIS, which is widely used in China, has relatively lower sensitivity and specificity, and needs to be further revised.

Moderating Effects of Race and Preoperative Comorbidity on Surgical Mortality in Infants.

BACKGROUND: We sought to investigate the risk of pediatric surgical mortality associated with the combined effects of key preoperative comorbidities and race. METHODS: We performed a retrospective study that included infants who underwent inpatient surgical procedures between 2012 and 2017 and were entered into the NSQIP-P registry. We assessed additive moderation by estimating the proportion of mortality risk attributable to the combined effects of race and the presence of a preoperative comorbidity (attributable proportion [AP]). RESULTS: The study group was comprised of 58466 surgical cases, of whom 15711(26.9%) were neonates and 42755(73.1%) older infants. Among neonates, a history of prematurity carried a poorer prognosis in black babies than their white peers (OR:1.53, 95%CI:1.20,1.95). Additionally, there was evidence of additive moderation by race on the association between prematurity and postoperative mortality (AP: 23.9%; 95%CI: 3.8,43.9, P value = 0.020). In older infants, presence of preoperative sepsis carried almost two times higher risk of mortality for black patients than their white counterparts (OR:1.81; 95%CI:1.21,2.73). This explained 38.4% of mortality cases in black patients with preoperative sepsis (95%CI:14.0,62.7; P = 0.002). A history of prematurity also carried a greater risk of mortality in older infants of black race (OR:1.69; 95%CI: 1.27, 2.24), accounting for 24.2% of mortality cases (AP:24.2%; 95%CI:0.90, 47.5, P = 0.041). CONCLUSIONS: We quantified the surgical burden of mortality resulting from the differential impact of key comorbidities on black neonates and infants. Our data suggest that race-specific interventions to mitigate the incidence of the identified comorbidities could narrow the racial disparities in post surgical mortality.

Risk Factors for Mortality among Newborns with Neonatal Seizures.

OBJECTIVE: The aim of the study is to examine the incidence and risk factors for death among neonates who developed neonatal seizures (NS) in an ethnically distinctive community with high consanguinity rate in Israel. METHODS: Retrospective study was conducted at a single institution on data between January 2001 and January 2016. All neonates diagnosed with NS developed up to age 28 days were included. Mortality was defined as death within the first year of life. RESULTS: Of all 69,460 neonates born during the study period, 118 (1.7 per 1,000 live births) developed NS; 35 (29.7%) died within the first year while 83 (70.3%) survived. The leading causes of death were developmental brain malformation (31.4%), genetic/metabolic (20%), hypoxic ischemic encephalopathy (20%), intracranial hemorrhage (11.4%) and infections (11.4%). Any consanguinity between the parents was found in 18 and 14.6% among the survivors and deceased groups, respectively (p = 0.24). Developmental brain malformations that lead to death were present in 3.6 and 31.4% in the survivors and deceased groups, respectively (p = 0.001; relative risk 8.70; 95% confidence interval 2.58-29.27). Stepwise backward logistic regression analysis revealed that developmental brain malformations (p < 0.0001), use of more than one antiepileptic medication (p = 0.006), and multiorgan failure (p = 0.004) were significant risk factors that predicted death. CONCLUSION: The results of the current study show that developmental brain malformations that cause NS were the leading risk factor for death.

Neonatal Outcomes of Triplet Pregnancies Conceived via In Vitro Fertilization versus Other Methods of Conception.

OBJECTIVE: This study aims to investigate neonatal outcomes of triplet gestations conceived via in vitro fertilization (IVF) compared with those not conceived by IVF. STUDY DESIGN: This is a retrospective cohort study of women who delivered a triplet gestation ≥24 weeks at a large academic center (2005-2016). Women with unknown mode of conception were excluded. Women who conceived via IVF were compared with those conceiving spontaneously or through non-IVF fertility treatments. The primary outcome was a composite severe neonatal morbidity (respiratory distress syndrome, necrotizing enterocolitis, severe intraventricular hemorrhage, retinopathy of prematurity, neonatal sepsis, or death). Bivariate comparisons were made by mode of conception and unadjusted generalized estimating equations were used to estimate odds ratios (OR) after accounting for the clustering of neonate by mother. RESULTS: Among 82 women included in this analysis, 51 (62%) conceived via IVF. Women who conceived via IVF were older (35.2 vs. 30.7, p < 0.001) and more likely to be of non-Hispanic white race/ethnicity (91.8 vs. 70.0%, p < 0.01) and married (100 vs. 90.0%, p = 0.02) when compared with women who did not conceive via IVF. Although women who conceived via IVF delivered at an earlier gestational age than those who did not (32.9 ± 3.0 vs. 33.7 ± 2.6 weeks, p = 0.02), there was no significant difference in composite neonatal morbidity (34.0 vs. 28.0%, p = 0.32; OR: 1.33, 95% CI: 0.60-2.91). Additionally, there were no significant differences between the groups with regard to other neonatal outcomes examined, including fetal growth restriction, birthweight, umbilical artery pH <7, neonatal intensive care unit admissions, duration in the NICU, need for mechanical ventilation, or duration of mechanical ventilation. CONCLUSION: Neonatal outcomes among triplet gestations did not differ by IVF in this well-characterized, single-center cohort.

Effect of Vasopressin on Systemic and Pulmonary Hemodynamics in Neonates.

OBJECTIVE: Despite its increasing use in neonates, the literature on the use of vasopressin (VP) in neonates is limited. The aim of this study is to evaluate the systemic and pulmonary effects of VP in neonates and to assess its safety among them. STUDY DESIGN: This retrospective study enrolled all neonates in two level III neonatal intensive care units in Winnipeg, Manitoba, who had received VP therapy between 2011 and 2016. Infants with congenital malformations/chromosomal disorders were excluded. The changes in cardiovascular and pulmonary parameters were collected from patient charts. The primary outcome was the mean blood pressure (MBP) post-VP initiation. Secondary outcomes included systolic blood pressure (SBP) and diastolic blood pressure (DBP), vasoactive inotropic score (VIS), pH, urine output, lactate, base deficit (BD), mean airway pressure (MAP), and oxygen requirement. RESULTS: A total of 33 episodes from 26 neonates were analyzed. The postnatal age at VP initiation was 14 days (interquartile range [IQR]: 4-25), and the median starting dose was 0.3 mU/kg/min (IQR: 0.2-0.5). MBP improved significantly after VP initiation from 28 to 39 mm Hg 24 hours after VP initiation (p < 0.001). Similar changes are observed with SBP and DBP. VIS declined from 15 to 6 at 24 hours, while pH, lactate, BD, and oxygen requirement improved significantly. While urine output marginally improved, there were no changes to MAP 24 hours post-VP initiation. Hyponatremia was observed in 21 episodes (64%) and severe hyponatremia in 7 episodes (33%). CONCLUSION: VP appears to be a promising rescue therapy in catecholamine resistant shock or refractory pulmonary hypertension in neonates.

C-reactive protein/albumin ratio is a prognostic indicator for predicting surgical intervention and mortality in neonates with necrotizing enterocolitis.

PURPOSE: The role of hypoalbuminemia and raised C-reactive protein (CRP) levels in predicting critical prognosis has been described extensively in adult literature. However, there are limited studies in pediatrics, particularly neonates. The CRP/albumin (CRP/ALB) ratio is often associated with higher mortality, organ failure and prolonged hospital stay. We hypothesized that the serum CRP/ALB ratio has a prognostic value in predicting surgery and mortality in neonates with necrotizing enterocolitis (NEC). METHODS: Retrospective review of all neonates with clinical and radiological evidence of non-perforated NEC that were treated in a tertiary-level referral hospital between 2009 and 2018. General patient demographics, laboratory parameters and outcomes were recorded. Receiver operating characteristics analysis was performed to evaluated optimal cut-offs and area under the curve (AUC) with 95% confidence intervals (CI). RESULTS: A total of 191 neonates were identified. Of these, 103 (53.9%) were born at ≤ 28 weeks of gestation and 101 (52.9%) had a birth weight of ≤ 1000 g. Eighty-four (44.0%) patients underwent surgical intervention for NEC. The overall survival rate was 161/191 (84.3%). A CRP/ALB ratio of ≥ 3 on day 2 of NEC diagnosis was associated with a statistically significant higher likelihood for surgery [AUC 0.71 (95% CI 0.63-0.79); p < 0.0001] and mortality [AUC 0.66 (95% CI 0.54-0.77); p = 0.0150], respectively. CONCLUSIONS: A CRP/ALB ratio of ≥ 3 on day 2 is indicative of a critical pathway in neonates with radiologically confirmed, non-perforated NEC. This could be used as an additional criterion to guide parental counselling in NEC for surgical intervention and mortality.

Association of Maternal SARS-CoV-2 Infection in Pregnancy With Neonatal Outcomes.

Importance: The outcomes of newborn infants of women testing positive for SARS-CoV-2 in pregnancy is unclear. Objective: To evaluate neonatal outcomes in relation to maternal SARS-CoV-2 test positivity in pregnancy. Design, Setting, and Participants: Nationwide, prospective cohort study based on linkage of the Swedish Pregnancy Register, the Neonatal Quality Register, and the Register for Communicable Diseases. Ninety-two percent of all live births in Sweden between March 11, 2020, and January 31, 2021, were investigated for neonatal outcomes by March 8, 2021. Infants with malformations were excluded. Infants of women who tested positive for SARS-CoV-2 were matched, directly and using propensity scores, on maternal characteristics with up to 4 comparator infants. Exposures: Maternal test positivity for SARS-CoV-2 in pregnancy. Main Outcomes and Measures: In-hospital mortality; neonatal resuscitation; admission for neonatal care; respiratory, circulatory, neurologic, infectious, gastrointestinal, metabolic, and hematologic disorders and their treatments; length of hospital stay; breastfeeding; and infant test positivity for SARS-CoV-2. Results: Of 88 159 infants (49.0% girls), 2323 (1.6%) were delivered by mothers who tested positive for SARS-CoV-2. The mean gestational age of infants of SARS-CoV-2-positive mothers was 39.2 (SD, 2.2) weeks vs 39.6 (SD, 1.8) weeks for comparator infants, and the proportions of preterm infants (gestational age <37 weeks) were 205/2323 (8.8%) among infants of SARS-CoV-2-positive mothers and 4719/85 836 (5.5%) among comparator infants. After matching on maternal characteristics, maternal SARS-CoV-2 test positivity was significantly associated with admission for neonatal care (11.7% vs 8.4%; odds ratio [OR], 1.47; 95% CI, 1.26-1.70) and with neonatal morbidities such as respiratory distress syndrome (1.2% vs 0.5%; OR, 2.40; 95% CI, 1.50-3.84), any neonatal respiratory disorder (2.8% vs 2.0%; OR, 1.42; 95% CI, 1.07-1.90), and hyperbilirubinemia (3.6% vs 2.5%; OR, 1.47; 95% CI, 1.13-1.90). Mortality (0.30% vs 0.12%; OR, 2.55; 95% CI, 0.99-6.57), breastfeeding rates at discharge (94.4% vs 95.1%; OR, 0.84; 95% CI, 0.67-1.05), and length of stay in neonatal care (median, 6 days in both groups; difference, 0 days; 95% CI, -2 to 7 days) did not differ significantly between the groups. Twenty-one infants (0.90%) of SARS-CoV-2-positive mothers tested positive for SARS-CoV-2 in the neonatal period; 12 did not have neonatal morbidity, 9 had diagnoses with unclear relation to SARS-CoV-2, and none had congenital pneumonia. Conclusions and Relevance: In a nationwide cohort of infants in Sweden, maternal SARS-CoV-2 infection in pregnancy was significantly associated with small increases in some neonatal morbidities. Given the small numbers of events for many of the outcomes and the large number of statistical comparisons, the findings should be interpreted as exploratory.

Gestational Age and Risk of Mortality in Term-Born Critically Ill Neonates Admitted to PICUs in Australia and New Zealand.

OBJECTIVES: Gestational age at birth is declining, probably because more deliveries are being induced. Gestational age is an important modifiable risk factor for neonatal mortality and morbidity. We aimed to investigate the association between gestational age and mortality in hospital for term-born neonates (≥ 37 wk') admitted to PICUs in Australia and New Zealand. DESIGN: Observational multicenter cohort study. SETTING: PICUs in Australia and New Zealand. PATIENTS: Term-born neonates (≥ 37 wk) admitted to PICUs. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS:: We studied 5,073 infants born with a gestational age greater than or equal to 37 weeks and were less than 28 days old when admitted to a PICU in Australia or New Zealand between 2007 and 2016. The association between gestational age and mortality was estimated using a multivariable logistic regression model, adjusting for age, sex, indigenous status, Pediatric Index of Mortality version 2, and site. The median gestational age was 39.1 weeks (interquartile range, 38.2-40 wk) and mortality in hospital was 6.6%. Risk of mortality declined log-linearly with gestational age. The adjusted analysis showed a 20% (95% CI, 11-28%) relative reduction in mortality for each extra week of gestation beyond 37 weeks. The effect of gestation was stronger among those who received extracorporeal life support: each extra week of gestation was associated with a 44% (95% CI, 25-57%) relative reduction in mortality. Longer gestation was also associated with reduced length of stay in hospital: each week increase in gestation, the average length of stay decreased by 4% (95% CI, 2-6%). CONCLUSIONS: Among neonates born at "term" who are admitted to a PICU, increasing gestational age at birth is associated with a substantial reduction in the risk of dying in hospital. The maturational influence on outcome was more strongly noted in the sickest neonates, such as those requiring extracorporeal life support. This information is important in view of the increasing proportion of planned births in both high- and low-/middle-income countries.

Mortality and Neurodevelopmental Outcomes in the Heart Rate Characteristics Monitoring Randomized Controlled Trial.

OBJECTIVE: To test whether the composite outcome of death or neurodevelopmental impairment (NDI) at 18-22 months corrected age for infants ≤1000 g at birth is decreased by continuous monitoring of heart rate characteristics during neonatal intensive care. STUDY DESIGN: We studied a subset of participants enrolled in a multicenter randomized trial of heart rate characteristics monitoring. Survivors were evaluated at 18-22 months corrected age with a standardized neurologic examination and the Bayley Scales of Infant Development-III (BSID-III). NDI was defined as Gross Motor Function Classification System of >2 (moderate or severe cerebral palsy), BSID-III language or cognitive scores of <70, severe bilateral hearing impairment, and/or bilateral blindness. RESULTS: The composite outcome, death or NDI, was obtained for 628 of 884 study infants (72%). The prevalence of this outcome was 44.4% (136/306) among controls (infants randomized to heart rate characteristics monitored but not displayed) and 38.9% (125/322) among infants randomized to heart rate characteristics monitoring displayed (relative risk, 0.87; 95% CI, 0.73-1.05; P = .17). Mortality was reduced from 32.0% (99/307) among controls to 24.8% (81/326) among monitoring displayed infants (relative risk, 0.75; 95% CI, 0.59 to 0.97; P = .028). The composite outcomes of death or severe CP and death or mildly low Bayley cognitive score occurred less frequently in the displayed group (P < .05). CONCLUSIONS: We found no difference in the composite outcome of death or NDI for extremely preterm infants whose heart rate characteristics were and were not displayed during neonatal intensive care. Two outcomes that included mortality or a specific NDI were less frequent in the displayed group.

Center, Gestational Age, and Race Impact End-of-Life Care Practices at Regional Neonatal Intensive Care Units.

OBJECTIVE: To assess the impact of intercenter variation and patient factors on end-of-life care practices for infants who die in regional neonatal intensive care units (NICUs). STUDY DESIGN: We conducted a retrospective cohort analysis using the Children's Hospital Neonatal Database during 2010-2016. A total of 6299 nonsurviving infants cared for in 32 participating regional NICUs were included to examine intercenter variation and the effects of gestational age, race, and cause of death on 3 end-of-life care practices: do not attempt resuscitation orders (DNR), cardiopulmonary resuscitation within 6 hours of death (CPR), and withdrawal of life-sustaining therapies (WLST). Factors associated with these practices were used to develop a multivariable equation. RESULTS: Dying infants in the cohort underwent DNR (55%), CPR (21%), and WLST (73%). Gestational age, cause of death, and race were significantly and differently associated with each practice: younger gestational age (<28 weeks) was associated with CPR (OR 1.7, 95% CI 1.5-2.1) but not with DNR or WLST, and central nervous system injury was associated with DNR (1.6, 1.3-1.9) and WLST (4.8, 3.7-6.2). Black race was associated with decreased odds of WLST (0.7, 0.6-0.8). Between centers, practices varied widely at different gestational ages, race, and causes of death. CONCLUSIONS: From the available data on end-of-life care practices for regional NICU patients, variability appears to be either individualized or without consistency.

Stem cell therapy for preventing neonatal diseases in the 21st century: Current understanding and challenges.

Diseases of the preterm newborn such as bronchopulmonary dysplasia, necrotizing enterocolitis, cerebral palsy, and hypoxic-ischemic encephalopathy continue to be major causes of infant mortality and long-term morbidity. Effective therapies for the prevention or treatment for these conditions are still lacking as recent clinical trials have shown modest or no benefit. Stem cell therapy is rapidly emerging as a novel therapeutic tool for several neonatal diseases with encouraging pre-clinical results that hold promise for clinical translation. However, there are a number of unanswered questions and facets to the development of stem cell therapy as a clinical intervention. There is much work to be done to fully elucidate the mechanisms by which stem cell therapy is effective (e.g., anti-inflammatory versus pro-angiogenic), identifying important paracrine mediators, and determining the timing and type of therapy (e.g., cellular versus secretomes), as well as patient characteristics that are ideal. Importantly, the interaction between stem cell therapy and current, standard-of-care interventions is nearly completely unknown. In this review, we will focus predominantly on the use of mesenchymal stromal cells for neonatal diseases, highlighting the promises and challenges in clinical translation towards preventing neonatal diseases in the 21st century.

Incidence, risk factors, and outcomes of acute kidney injury in neonates after surgical procedures.

BACKGROUND: Acute kidney injury (AKI) is common and associated with poor outcomes in critically ill neonates. The objective of this study was to study the incidence, risk factors, and clinical outcomes of AKI in neonates receiving non-cardiac surgery. METHODS: We performed a single-center retrospective study between January 2017 and December 2018 of neonates who had received abdominal and thoracic surgical procedures. AKI was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patient information, clinical data, and outcomes were collected and analyzed. Logistic regression was used to analyze risk factors of AKI and association between AKI and mortality. RESULTS: Fifty-four (33.8%) of 160 patients developed AKI after surgical procedures. Compared with neonates without AKI, neonates with AKI had higher mortality rate (18.5% VS 5.7%, p = 0.022), lower gestational age (30.5 weeks, interquartile range [IQR] 28-33.5, VS 34.5 weeks, IQR 33-37.5, p = 0.035), higher rates of very low birth weight (33.3% VS 17.0%, p = 0.019), longer duration of mechanical ventilation (0.5 days, IQR 0-1.5, VS 0 days, IQR 0-1, p = 0.043) and higher rates of sepsis (35.2% VS 19.8%, p = 0.034). Risk factors of AKI included gestational age under 32 weeks (OR 4.8, 95% CI 1.8-12.6; p = 0.001), sepsis (OR 4.3, 95% CI 1.7-11.3; p = 0.003), operation time longer than 120 min (OR 2.7, 95% CI 1.1-6.6; p = 0.024), and diagnosis of necrotizing enterocolitis (OR 3.5, 95% CI 1.3-9.1; p = 0.011). AKI after surgery was significantly associated with mortality (OR 4.3, 95% CI 1.1-16.9; p = 0.036). CONCLUSIONS: AKI is common and associated with poor outcomes in surgical neonates. Early recognition and intervention of AKI in these patients are important.

Early-onset fetal growth restriction: A systematic review on mortality and morbidity.

INTRODUCTION: Severe early-onset fetal growth restriction is an obstetric condition with significant risks of perinatal mortality, major and minor neonatal morbidity, and long-term health sequelae. The prognosis of a fetus is influenced by the extent of prematurity and fetal weight. Clinical care is individually adjusted. In literature, survival rates vary and studies often only include live-born neonates with missing rates of antenatal death. This systematic review aims to summarize the literature on mortality and morbidity. MATERIAL AND METHODS: A broad literature search was conducted in OVID MEDLINE from 2000 to 26 April 2019 to identify studies on fetal growth restriction and perinatal death. Studies were excluded when all included children were born before 2000 because (neonatal) health care has considerably improved since this period. Studies were included that described fetal growth restriction diagnosed before 32 weeks of gestation and antenatal mortality and neonatal mortality and/or morbidity as outcome. Quality of evidence was rated with the GRADE instrument. RESULTS: Of the 2604 publications identified, 25 studies, reporting 2895 pregnancies, were included in the systematic review. Overall risk of bias in most studies was judged as low. The quality of evidence was generally rated as very low to moderate, except for 3 large well-designed randomized controlled trials. When combining all data on mortality, in 355 of 2895 pregnancies (12%) the fetus died antenatally, 192 died in the neonatal period (8% of live-born neonates) and 2347 (81% of all pregnancies) children survived. Of the neonatal morbidities recorded, respiratory distress syndrome (34% of the live-born neonates), retinopathy of prematurity (13%) and sepsis (30%) were most common. Of 476 children that underwent neurodevelopmental assessment, 58 (12% of surviving children, 9% of all pregnancies) suffered from cognitive impairment and/or cerebral palsy. CONCLUSIONS: When combining the data of 25 included studies, survival in fetal growth restriction pregnancies, diagnosed before 32 weeks of gestation, was 81%. Neurodevelopmental impairment was assessed in a minority of surviving children. Individual prognostic counseling on the basis of these results is hampered by differences in patient and pregnancy characteristics within the included patient groups.

Using propensity scores to estimate the effectiveness of maternal and newborn interventions to reduce neonatal mortality in Nigeria.

BACKGROUND: Nigeria is the largest country in sub-Saharan Africa, with one of the highest neonatal mortality rates and the second highest number of neonatal deaths in the world. There is broad international consensus on which interventions can most effectively reduce neonatal mortality, however, there is little direct evidence on what interventions are effective in the Nigerian setting. METHODS: We used the 2013 Nigeria Demographic and Health Survey (NDHS) and the follow-up 2014 Verbal and Social Autopsy study of neonatal deaths to estimate the association between neonatal survival and mothers' and neonates' receipt of 18 resources and interventions along the continuum of care with information available in the NDHS. We formed propensity scores to predict the probability of receiving the intervention or resource and then weighted the observations by the inverse of the propensity score to estimate the association with mortality. We examined all-cause mortality as well as mortality due to infectious causes and intrapartum related events. RESULTS: Among 19,685 livebirths and 538 neonatal deaths, we achieved adequate balance for population characteristics and maternal and neonatal health care received for 10 of 18 resources and interventions, although inference for most antenatal interventions was not possible. Of ten resources and interventions that met our criteria for balance of potential confounders, only early breastfeeding was related to decreased all-cause neonatal mortality (relative risk 0.42, 95% CI 0.32-0.52, p <  0.001). Maternal decision making and postnatal health care reduced mortality due to infectious causes, with relative risks of 0.29 (95% CI 0.09-0.88; 0.030) and 0.46 (0.22-0.95; 0.037), respectively. Early breastfeeding and delayed bathing were related to decreased mortality due to intrapartum events, although these are not likely to be causal associations. CONCLUSION: Access to immediate postnatal care and women's autonomous decision-making have been among the most effective interventions for reducing neonatal mortality in Nigeria. As neonatal mortality increases relative to overall child mortality, accessible interventions are necessary to make further progress for neonatal survival in Nigeria and other low resource settings.

Necrotizing Enterocolitis and Associated Mortality in Neonates With Congenital Heart Disease: A Multi-Institutional Study.

OBJECTIVE: There are scarce data about the prevalence and mortality of necrotizing enterocolitis in neonates with congenital heart disease. The purpose of this study is to provide a multi-institutional description and comparison of the overall prevalence and mortality of necrotizing enterocolitis in neonates with congenital heart disease. DESIGN: Retrospective multi-institutional study. SETTING: The Pediatric Health Information System database. PATIENTS: Neonates with congenital heart disease between 2004 and 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary study measure is the prevalence of necrotizing enterocolitis. Secondary measures include in-hospital mortality, hospital charges, ICU length of stay, hospital length of stay, and 30-day readmission. The prevalence of necrotizing enterocolitis was 3.7% (1,448/38,770) and varied significantly among different congenital heart disease diagnoses. The lowest prevalence of necrotizing enterocolitis was in transposition of the great arteries (n = 104, 2.1%). Compared with transposition of the great arteries, necrotizing enterocolitis occurred more frequently in neonates with hypoplastic left heart syndrome (odds ratio, 2.7; 95% CI, 2.1-3.3), truncus arteriosus (odds ratio, 2.6; 95% CI, 1.9-3.5), common ventricle (odds ratio, 2.1; 95% CI, 1.5-2.8), and aortic arch obstruction (odds ratio, 1.4; 95% CI, 1.1-1.7). Prematurity is a significant risk factor for necrotizing enterocolitis and for mortality in neonates with necrotizing enterocolitis, conferring varying risk by cardiac diagnosis. Unadjusted mortality associated with necrotizing enterocolitis was 24.4% (vs 11.8% in neonates without necrotizing enterocolitis; p < 0.001), and necrotizing enterocolitis increased the adjusted mortality in neonates with transposition of the great arteries (odds ratio, 2.5; 95% CI, 1.5-4.4), aortic arch obstruction (odds ratio, 1.8; 95% CI, 1.3-2.6), and tetralogy of Fallot (odds ratio, 1.6; 95% CI, 1.1-2.4). Necrotizing enterocolitis was associated with increased hospital charges (p < 0.0001), ICU length of stay (p = 0.001), and length of stay (p = 0.001). CONCLUSIONS: The prevalence of necrotizing enterocolitis among neonates with congenital heart disease is 3.7% and is associated with increased in-hospital mortality, length of stay, and hospital charges. The prevalence and associated mortality of necrotizing enterocolitis in congenital heart disease vary among different heart defects.

Length of Resuscitation for Severely Depressed Newborns.

OBJECTIVE: Current guidelines for neonatal resuscitation suggest it may be reasonable to stop resuscitation after 10 minutes in infants born with no detectable heartbeat. This study describes the length of resuscitation provided in a cohort of profoundly compromised newborn infants. STUDY DESIGN: Chart review of a regional hospital system database of newborn infants from 2010 to 2017 with a documented 10-minute Apgar score of 0 or 1. RESULTS: From a total birth population of 49,876 infants, 172 newborns were identified. Of these, 133 infants did not receive resuscitation and died while receiving comfort care. In the 39 resuscitated infants, 15 (38%) achieved return of spontaneous circulation (ROSC) at an average of 20 minutes; 32 of these 39 newborns (82%) died within 24 hours. Average time to ROSC for survivors was 17.8 minutes. Death or severe neurologic disability at 15 to 24 months of age was present in 92% (36/39) of resuscitated infants. CONCLUSION: Prolonged resuscitation of newborns is rare. In this cohort, 92% died or had severe neurodevelopmental disability. Infants with ROSC received 20 minutes of resuscitation. Infants with ROSC typically did not survive beyond 24 hours unless they survived to discharge. To increase the number of infants with ROSC, continuing resuscitation beyond 10 minutes may be reasonable.

'This sickness is not hospital sickness': a qualitative study of the evil eye as a source of neonatal illness in Ghana.

Previous research has described the evil eye as a source of illness for pregnant women and their newborns. This study sought to explore the perceptions of the evil eye among mothers whose newborns had experienced a life-threatening complication across three regions of Ghana. As part of a larger, quantitative study, trained research assistants identified pregnant and newly delivered women (and their newborns) who had survived a life-threatening complication at three tertiary care hospitals in southern Ghana to participate in open-ended, qualitative interviews about their experiences in March-August 2015. All interviews were audio-recorded and transcribed verbatim into English and analysis using the constant comparative method of theme generation. A total of 37 mothers were interviewed, 20 about neonatal illnesses and 17 about maternal illnesses. Six of the 20 mothers interviewed about their newborn's illnesses spoke at length about the evil eye being a potential cause of newborn illness. The evil eye was described in a variety of terms, but commonalities included a person looking at a pregnant woman, her newborn baby, the baby's clothes and even the mother's food, causing harm, even unintentionally. Prevention required mothers covering themselves while pregnant and keeping the baby away from others until it was old enough to ward off the evil eye. Treatment required traditional medicine, yet some indicated that allopathic medicine could help. The evil eye appears to serve a social control mechanism, encouraging pregnant women to dress modestly, stay indoors as much as possible and behave appropriately. The evil eye is a pervasive, universally understood phenomenon across three regions of Ghana, even amongst a hospitalized population receiving allopathic health care for life-threatening complications of childbirth. Understanding the role of the evil eye in newborn illness attribution is important for clinicians, researchers and programmatic staff to effectively address barriers to care seeking.

Predicting Outcome in Neonates with Possible Clinical Sepsis by Estimating an Early Score for Neonatal Acute Physiology-II (SNAP-II).

OBJECTIVES: To determine role of Score for Neonatal Acute Physiology-II (SNAP-II) and its individual parameters assessed within 12 h of suspicion of neonatal sepsis in predicting outcomes; study its distribution across gestational ages and determine its relation with survival duration among expired neonates. METHODS: This prospective observational study conducted in a newborn unit of a tertiary care teaching hospital over 1 year included intramural neonates with birth weight ≥1000 g and gestation ≥28 weeks suspected with sepsis and assigned SNAP-II score within 12 h of suspicion. On day 14 of enrollment, they were categorized into three outcome groups: death (D), survival with organ dysfunction (SOD) and survival without organ dysfunction (SWOD). RESULTS: One hundred and ten neonates were enrolled and 100 analyzed. Mean SNAP-II score was 22 ± 22 (median: 13; interquartile range: 5-32.5). Seventy-six percent, 16% and 8% neonates belonged to SWOD, D and SOD groups, respectively. SNAP-II score and its individual parameters varied significantly among all outcome groups (p < 0.001). SNAP-II cutoffs of 44/115, 44/115, 38/115 and 33/115 were found to be highly predictive of D, D vs. SOD, D/SOD vs. SWOD and SWOD vs. SOD, respectively (sensitivity: 87.5-99%; specificity: 75-99%). The score was unaffected by gestational age (p = 0.80). Neonates with culture positive sepsis/meningitis had higher SNAP-II scores (p = 0.001). CONCLUSIONS: SNAP-II and its individual parameters found to have high sensitivity and specificity in predicting outcomes in possible neonatal sepsis and may have a role in predicting severity of disease progression and rapidity of deterioration among non-survivors, pending validation in larger studies.