Cerebral Oxygenation and Autoregulation in Preterm Infants (Early NIRS Study).

OBJECTIVE: To determine if decreased cerebral oxygenation or altered cerebral autoregulation as measured by near-infrared spectroscopy (NIRS) in the first 96 postnatal hours is associated with an increased risk of death or severe neuroradiographic abnormalities in very preterm infants. STUDY DESIGN: The Early NIRS prospective, multicenter study enrolled very preterm infants with a birth weight of <1250 g from 6 tertiary neonatal intensive care units. Mean arterial blood pressure and cerebral oxygen saturation (Csat) were continuously monitored using a neonatal sensor until 96 hours of age. Moving window correlations between Csat and mean arterial blood pressure determined time periods with altered cerebral autoregulation, and percentiles of correlation were compared between infants with and without the adverse outcome of mortality or severe neuroradiographic abnormalities by early cranial ultrasound. RESULTS: Of 103 subjects with mean gestational age of 26 weeks, 21 (20%) died or had severe neuroradiographic abnormalities. Infants with adverse outcomes had a lower mean Csat (67 ± 9%) compared with those without adverse outcomes (72 ± 7%; P = .02). A Csat of <50% was identified as a cut-point for identifying infants with adverse outcome (area under the curve, 0.76). Infants with adverse outcomes were more likely to have significant positive or negative correlations between Csat and mean arterial blood pressure, indicating impaired cerebral autoregulation (P = .006). CONCLUSIONS: Early NIRS monitoring may detect periods of lower cerebral oxygenation and altered cerebral autoregulation, identifying preterm infants at risk for mortality or neuroradiographic injury. An improved understanding of the relationship between altered hemodynamics and cerebral oxygenation may inform future strategies to prevent brain injury.

Method of Blood Pressure Measurement in Neonates and Infants: A Systematic Review and Analysis.

OBJECTIVES: To determine the recommended blood pressure (BP) measurement methods in neonates after systematically analyzing the literature regarding proper BP cuff size and measurement location and method. STUDY DESIGN: A literature search was conducted in MEDLINE, PubMed, Embase, Cochrane Library, and CINAHL from 1946 to 2017 on BP in neonates <3 months of age (PROSPERO ID CRD42018092886). Study data were extracted and analyzed with separate analysis of Bland-Altman studies comparing measurement methods. RESULTS: Of 3587 nonduplicate publications identified, 34 were appropriate for inclusion in the analysis. Four studies evaluating BP cuff size support a recommendation for a cuff width to arm circumference ratio of approximately 0.5. Studies investigating measurement location identified the upper arm as the most accurate and least variable location for oscillometric BP measurement. Analysis of studies using Bland-Altman methods for comparison of intra-arterial to oscillometric BP measurement show that the 2 methods correlate best for mean arterial pressure, whereas systolic BP by the oscillometric method tends to overestimate intra-arterial systolic BP. Compared with intra-arterial methods, systolic BP, diastolic BP, and mean arterial pressure by oscillometric methods are less accurate and precise, especially in neonates with a mean arterial pressure <30 mm Hg. CONCLUSIONS: Proper BP measurement is critical in neonates with naturally lower BP and attention to BP cuff size, location, and method of measurement are essential. With decreasing use of intra-arterial catheters for long-term BP monitoring in neonates, further studies are urgently needed to validate and develop oscillometric methodology with enhanced accuracy.

Neuropsychological Functioning in Preterm-Born Twins and Singletons at Preschool Age.

OBJECTIVES: A limited body of research is available on the relationships between multiplicity of birth and neuropsychological functioning in preterm children who were conceived in the age of assisted reproductive technology and served by the modern neonatal intensive care unit. Our chief objective was to evaluate whether, after adjustment for sociodemographic factors and perinatal complications, twin birth accounted for a unique portion of developmental outcome variance in children born at-risk in the surfactant era. METHODS: We compared the neuropsychological functioning of 77 twins and 144 singletons born preterm (<34 gestational weeks) and served by William Beaumont Hospital, Royal Oak, MI. Children were evaluated at preschool age, using standardized tests of memory, language, perceptual, and motor abilities. RESULTS: Multiple regression analyses, adjusting for sociodemographic and perinatal variables, revealed no differences on memory or motor indices between preterm twins and their singleton counterparts. In contrast, performance of language and visual processing tasks was significantly lower in twins despite reduced perinatal risk in comparison to singletons. Effect sizes ranged from .33 to .38 standard deviations for global language and visual processing ability indices, respectively. No significant group by sex interactions were observed, and comparison of first-, or second-born twins with singletons yielded medium effect sizes (Cohen's d=.56 and .40, respectively). CONCLUSIONS: The modest twin disadvantage on language and visual processing tasks at preschool-age could not be readily attributable to socioeconomic or perinatal variables. The possibility of biological or social twinning-related phenomena as mechanisms underlying the observed performance gaps are discussed. (JINS, 2016, 22, 865-877).

Impact of Physician Characteristics on Late-Onset Sepsis (LOS) Evaluation in the NICU.

The threshold for a late-onset sepsis (LOS) evaluation varies considerably across NICUs. This unexplained variability is probably related in part to physician bias regarding when sepsis should be "ruled out". The aim of this study is to determine if physician characteristics (race, gender, immigration status, years of experience and academic rank) effect LOS evaluation in the NICU. This study includes a retrospective chart review of all Level III NICU infants who had a LOS evaluation over 54 months. Physician characteristics were compared between positive and negative blood culture groups and whether CBC and CRP were obtained at LOS evaluations. There were 341 LOS evaluations performed during the study period. Two patients were excluded due to a contaminant. Patients in this study had a birth weight of [median (Q1, Q3)]+ 992 (720, 1820) grams and birth gestation of [median (Q1, Q3)] 276/7 (252/7, 330/7) weeks. There are 10 neonatologists in the group, 5/10 being female and 6/10 being immigrant physicians. Experienced physicians were more likely to obtain a CBC at the time of LOS evaluation. Physician characteristics of race, gender and immigration status impacted whether to include a CRP as part of a LOS evaluation but otherwise did not influence LOS evaluation, including the likelihood of bacteremia.

Neonatal blood pressure by birth weight, gestational age, and postnatal age: a systematic review.

BACKGROUND: Blood pressure is a vital hemodynamic marker during the neonatal period. However, normative values are often derived from small observational studies. Understanding the normative range would help to identify ideal thresholds for intervention to treat hypotension or hypertension. Therefore, the aim of this study was to assess observed blood pressure values in neonates who have not received any blood-pressure modifying treatments from birth to three months postnatal age and whether these vary according to birth weight, gestational age and postnatal age. METHODS: This was a systematic review. A literature search was conducted in MEDLINE, PubMed, Embase, Cochrane Library, and CINAHL from 1946 to 2017 on blood pressure in neonates from birth to 3 months of age (PROSPERO ID CRD42018092886). Unpublished data were included where appropriate. RESULTS: Of 3,587 non-duplicate publications identified, 30 were included (one unpublished study). Twelve studies contained data grouped by birth weight, while 23 contained data grouped by gestational age. Study and clinical heterogeneity precluded meta-analyses thus results are presented by subgroup. A consistent blood pressure rise was associated with increasing birth weight, gestational age, and postnatal age. In addition, blood pressure seemed to rise more rapidly in the most preterm and low birth weight neonates. CONCLUSION: Despite blood pressure increasing with birth weight, gestational age, and postnatal age, there was marked blood pressure variability observed throughout. To better define hypotension and hypertension, future studies should develop consistent approaches for factors related to blood pressure variability, including the method and timing of measurement as well as statistical control of relevant patient characteristics.

In utero antidepressant exposure and neurodevelopment in preterm infants.

OBJECTIVE: To investigate the impact of in utero selective serotonin reuptake inhibitor (SSRI) exposure on neurodevelopment in a cohort of preterm infants. STUDY DESIGN: Retrospective case control study of preterm infants ≤36(6/7) weeks gestation with in utero SSRI exposure. Subjects were matched to controls by gestational age, year of birth, birth weight, gender, and age at neurodevelopmental assessment. Neurodevelopment was assessed with the Bayley Infant Neurodevelopmental Screener and the Bayley Scales of Infant Development. RESULTS: The 19 infants with in utero SSRI exposure were similar to controls in demographic data, birth weight, and in-hospital morbidity. The mean ± standard deviation (SD) Mental Developmental Index score for study infants at 36 months was 94 ± 15 versus 91 ± 10 for controls (p = 0.46). The mean ± SD Psychomotor Developmental Index score was also similar between groups: 79 ± 21 for study infants versus 75 ± 20 for control infants (p = 0.72). Other neurodevelopmental outcomes were comparable. CONCLUSION: In this cohort of preterm infants, in utero SSRI exposure was not associated with adverse neurodevelopment above the baseline risk for this degree of prematurity. Larger studies are needed to obviate the risk of a type II error.

Feasibility study of early blood pressure management in extremely preterm infants.

OBJECTIVE: To assess the feasibility of a randomized placebo controlled trial (RCT) of blood pressure (BP) management for extremely preterm infants. STUDY DESIGN: This was a prospective pilot RCT of infants 23-0/7 to 26-6/7 weeks gestation who had protocol-defined low BP in the first 24 postnatal hours. Enrolled infants were administered a study infusion (dopamine or placebo) and a study syringe medication (hydrocortisone or placebo). RESULTS: Of the 366 infants screened, 119 (33%) had low BP, 58 (16%) met all entry criteria, and 10 (3%) were enrolled. A total of 161 infants (44%) were ineligible because they received early indomethacin. Only 17% of eligible infants were enrolled. Problems with consent included insufficient time, parent unavailability, and physician unwillingness to enroll critically ill infants. Two infants were withdrawn from the study because of the potential risk of intestinal perforation with simultaneous administration of hydrocortisone and indomethacin. CONCLUSIONS: This pilot RCT was not feasible because of low eligibility and consent rates. An RCT of BP management for extremely preterm infants may require a waiver of consent for research in emergency care. The frequent use of early indomethacin and the associated risk of intestinal perforation when used with hydrocortisone may limit future investigations to only inotropic medications.

Antenatal and perinatal factors influencing neonatal blood pressure: a systematic review.

OBJECTIVE: A comprehensive understanding of the factors contributing to perinatal blood pressure is vital to ensure optimal postnatal hemodynamic support. The objective of this study was to review existing literature on maternal and perinatal factors influencing blood pressure in neonates up to 3 months corrected age. METHODS: A systematic search of published literature in OVID Medline, OVID Embase and the COCHRANE library identified publications relating to maternal factors affecting blood pressure of neonates up to corrected age of 3 months. Summary data were extracted and compared (PROSPERO CRD42018092886). RESULTS: Of the 3683 non-duplicate publications identified, 44 were eligible for inclusion in this review. Topics elicited were sociodemographic factors, maternal health status, medications, smoking during pregnancy, and cord management at birth. Limited data were available for each factor. Results regarding the impact of these factors on neonatal blood pressure were inconsistent across studies. CONCLUSIONS: There is insufficient evidence to draw definitive conclusions regarding the impact of various maternal and perinatal factors on neonatal blood pressure. Future investigations of neonatal cardiovascular therapies should account for these factors in their study design. Similarly, studies on maternal diseases and perinatal interventions should include neonatal blood pressure as part of their primary or secondary analyses.

Neonatal Blood Pressure Standards: What Is "Normal"?

Blood pressure (BP) is routinely measured in newborn infants. Published BP nomograms demonstrate a rise in BP following delivery in healthy infants at all gestational ages (GA) and evidence that BP values are higher with increasing birth weight and GA. However, the complex physiology that occurs in newborn infants and range of BP values observed at all GA make it difficult to identify "normal" BP for a specific infant at a specific time under specific conditions. As such, complete hemodynamic assessment should include the physical examination, perinatal history, other vital signs, and laboratory values in addition to BP values.

Cumulative Antenatal Risk and Kindergarten Readiness in Preterm-Born Preschoolers.

A suboptimal intrauterine environment is thought to increase the probability of deviation from the typical neurodevelopmental trajectory, potentially contributing to the etiology of learning disorders. Yet the cumulative influence of individual antenatal risk factors on emergent learning skills has not been sufficiently examined. We sought to determine whether antenatal complications, in aggregate, are a source of variability in preschoolers' kindergarten readiness, and whether specific classes of antenatal risk play a prominent role. We recruited 160 preschoolers (85 girls; ages 3-4 years), born ≤336/7 weeks' gestation, and reviewed their hospitalization records. Kindergarten readiness skills were assessed with standardized intellectual, oral-language, prewriting, and prenumeracy tasks. Cumulative antenatal risk was operationalized as the sum of complications identified out of nine common risks. These were also grouped into four classes in follow-up analyses: complications associated with intra-amniotic infection, placental insufficiency, endocrine dysfunction, and uteroplacental bleeding. Linear mixed model analyses, adjusting for sociodemographic and medical background characteristics (socioeconomic status, sex, gestational age, and sum of perinatal complications) revealed an inverse relationship between the sum of antenatal complications and performance in three domains: intelligence, language, and prenumeracy (p = 0.003, 0.002, 0.005, respectively). Each of the four classes of antenatal risk accounted for little variance, yet together they explained 10.5%, 9.8%, and 8.4% of the variance in the cognitive, literacy, and numeracy readiness domains, respectively. We conclude that an increase in the co-occurrence of antenatal complications is moderately linked to poorer kindergarten readiness skills even after statistical adjustment for perinatal risk.

Blood pressure, anti-hypotensive therapy, and neurodevelopment in extremely preterm infants.

OBJECTIVE: To compare neurodevelopment (ND) in 3 cohorts of extremely preterm infants: untreated with normal blood pressure (BP), untreated with low BP, and treated with low BP. STUDY DESIGN: We conducted a retrospective study of infants 23 to 25 weeks gestation. Low BP was defined as >or=3 mean arterial pressures

Ruptured retroperitoneal lymphatic malformation.

Retroperitoneal lymphatic malformations can cause significant displacement, pressure, or entrapment of adjacent organs raising suspicion of a malignant retroperitoneal tumor. They often mimic ascites but may rarely be a cause of ascites. Computed tomography (CT) imaging findings in an infant with a cystic retroperitoneal lymphatic malformation and massive chylous ascites are reported.

Early blood pressure, antihypotensive therapy and outcomes at 18-22†months' corrected age in extremely preterm infants.

OBJECTIVE: To investigate the relationships between early blood pressure (BP) changes, receipt of antihypotensive therapy and 18-22 months' corrected age (CA) outcomes for extremely preterm infants. DESIGN: Prospective observational study of infants 23(0/7)-26(6/7) weeks' gestational age (GA). Hourly BP values and antihypotensive therapy exposure in the first 24 h were recorded. Four groups were defined: infants who did or did not receive antihypotensive therapy in whom BP did or did not rise at the expected rate (defined as an increase in the mean arterial BP of ≥5 mm Hg/day). Random-intercept logistic modelling controlling for centre clustering, GA and illness severity was used to investigate the relationship between BP, antihypotensive therapies and infant outcomes. SETTING: Sixteen academic centres of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. MAIN OUTCOME MEASURES: Death or neurodevelopmental impairment/developmental delay (NIDD) at 18-22 months' CA. RESULTS: Of 367 infants, 203 (55%) received an antihypotensive therapy, 272 (74%) survived to discharge and 331 (90%) had a known outcome at 18-22 months' CA. With logistic regression, there was an increased risk of death/NIDD with antihypotensive therapy versus no treatment (OR 1.836, 95% CI 1.092 to 3.086), but not NIDD alone (OR 1.53, 95% CI 0.708 to 3.307). CONCLUSIONS: Independent of early BP changes, antihypotensive therapy exposure was associated with an increased risk of death/NIDD at 18-22 months' CA when controlling for risk factors known to affect survival and neurodevelopment. CLINICAL TRIAL REGISTRATION NUMBER: clinicaltrials.gov #NCT00874393.

Stronger and More Vulnerable: A Balanced View of the Impacts of the NICU Experience on Parents.

For parents, the experience of having an infant in the NICU is often psychologically traumatic. No parent can be fully prepared for the extreme stress and range of emotions of caring for a critically ill newborn. As health care providers familiar with the NICU, we thought that we understood the impact of the NICU on parents. But we were not prepared to see the children in our own families as NICU patients. Here are some of the lessons our NICU experience has taught us. We offer these lessons in the hope of helping health professionals consider a balanced view of the NICU's impact on families.

Feeding Intolerance and Poor Growth in Infants with Gastroschisis: Longitudinal Experience with Consecutive Patients over Thirteen Years.

OBJECTIVES: 1) To investigate in-hospital factors associated with delayed tolerance of full volume enteral nutrition and 2) To assess longitudinal growth in a contemporary population of infants with gastroschisis. DESIGN: Retrospective single-center study of all infants with gastroschisis Setting: Level III neonatal intensive care unit in a free-standing Children's Hospital Duration: 13.5 years MATERIALS & METHODS: Detailed data regarding demographics, nutritional support, growth, and infant outcomes was collected for all infants with gastroschisis. Linear regression was used to investigate in-hospital factors associated with feeding intolerance and poor growth. RESULTS: For 52 infants, the median gestational age at birth was 36 weeks, the median postnatal age to achieve full feeds was 22 days, and median in-hospital weight gain was 18 gm/day. With linear regression, there was a positive association between time to full feeds and both hospital length of stay (adjusted R2=0.503, p < 0.0001) and (unexpectedly) in-hospital weight gain (adjusted R2=0.125, p=0.0248). There was a negative association between in-hospital weight gain and preterm birth (adjusted R2=0.125, p=0.0356). For infants with longitudinal growth data, 35% had a weight < 5th percentile (of whom 67% were preterm). CONCLUSIONS: Many infants with gastroschisis have poor growth before and after hospital discharge. Aggressive feeding advancement may be a contributing factor to this finding and preterm infants may be at greater risk for poor growth than term infants.

A newborn with massive intra-abdominal haemorrhage.

We describe an unusual case of an intra-abdominal teratoma with massive bleeding presenting as sudden cardiovascular collapse immediately after birth. The infant required massive volume and blood product transfusion, alongside emergent tumour resection, in order to obtain haemostasis and haemodynamic stabilisation. Haemorrhage of a sacrococcygeal teratoma is a known entity, but we are not aware of a previous report of massive intra-abdominal haemorrhage due to a teratoma, immediately after birth. This case emphasises the need to consider intra-abdominal pathology, including a teratoma, in the differential diagnosis of any newborn with early hypovolaemic shock and abdominal distention.

Use of antihypotensive therapies in extremely preterm infants.

OBJECTIVE: To investigate the relationships among blood pressure (BP) values, antihypotensive therapies, and in-hospital outcomes to identify a BP threshold below which antihypotensive therapies may be beneficial. METHODS: Prospective observational study of infants 23(0/7) to 26(6/7) weeks' gestational age. Hourly BP values and antihypotensive therapy use in the first 24 hours were recorded. Low BP was investigated by using 15 definitions. Outcomes were examined by using regression analysis controlling for gestational age, the number of low BP values, and illness severity. RESULTS: Of 367 infants enrolled, 203 (55%) received at least 1 antihypotensive therapy. Treated infants were more likely to have low BP by any definition (P < .001), but for the 15 definitions of low BP investigated, therapy was not prescribed to 3% to 49% of infants with low BP and, paradoxically, was administered to 28% to 41% of infants without low BP. Treated infants were more likely than untreated infants to develop severe retinopathy of prematurity (15% vs 8%, P = .03) or severe intraventricular hemorrhage (22% vs 11%, P < .01) and less likely to survive (67% vs 78%, P = .02). However, with regression analysis, there were no significant differences between groups in survival or in-hospital morbidity rates. CONCLUSIONS: Factors other than BP contributed to the decision to use antihypotensive therapies. Infant outcomes were not improved with antihypotensive therapy for any of the 15 definitions of low BP investigated.