Bhavesh Shah

Variations in Prevalence of Hypotension, Hypertension, and Vasopressor Use in NICUs

OBJECTIVE: Very low birth weight infants are vulnerable to hypotension and its associated complications. Vasopressors are used to raise blood pressure (BP), but indications for use are uncertain. Our objectives were (1) to study variations in BP stability among NICUs, (2) to investigate inter-NICU differences in vasopressor use, and (3) to address the association between intraventricular hemorrhage (IVH) and abnormal BPs.STUDY DESIGN: A total of 1288 infants with birth weight <1500 g were admitted to six NICUs in Massachusetts and Rhode Island over 21 months. The lowest and highest mean BPs were collected within the first 12 hours. Also recorded were the use of vasopressors within the first 24 hours and the occurrence of IVH. Logistic regressions were used to model outcomes, controlling for gestational age and illness severity using the Score for Neonatal Acute Physiology.RESULTS: Two of the six NICUs had significantly higher percentages of infants with at least one hypotensive BP, with prevalences of 24% to 45%. Percentages of infants treated with vasopressors ranged from 4% to 39%. This range of vasopressor use could not be explained by inter-NICU differences in birth weight, illness severity, or rates of hypotension. We found a borderline association between severe IVH and hypotension (odds ratio 1.6, p=0.055), but not between severe IVH and hypertension.CONCLUSION: Wide differences exist in the prevalence of hypotension, hypertension, and vasopressor use among NICUs. We also found an association between hypotension and IVH, but not between hypertension and IVH.

Variations in blood transfusions among newborn intensive care units

OBJECTIVES Very low birth weight (< 1500 g) infants frequently require packed red blood cell transfusions, and transfusion rates vary among neonatal intensive care units (NICUs). We analyzed transfusions and compared outcomes among NICUs. STUDY DESIGN In a 6-site prospective study, we abstracted all newborns weighing < 1500 g (total = 825) born between October 1994 and September 1995. Transfusion frequency and volume and phlebotomy number were analyzed by site and adjusted for birth weight and illness severity. We compared rates of intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, growth, and length of stay between the high and low transfuser NICUs. RESULTS Sites differed significantly in mean birth weight, illness severity, number of transfusions, pretransfusion hematocrit, blood draws, and donor number. Multivariate adjustment for these risks showed that the highest transfusing NICU transfused an additional 24 cc/kg per baby during the first 14 days and 47 cc/kg per baby after 15 days, relative to the lowest transfusing NICU. The presence of arterial catheters increased the frequency of blood transfusions. The rates of intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia were not higher in the 2 lowest transfusing NICUs, nor were there differences in 28-day weight gain or length of stay. CONCLUSIONS Major differences in transfusion practices for very low birth weight infants exist among NICUs. Because clinical outcomes were no different in lower transfuser NICUs, it is likely that transfusion and phlebotomy guidelines could result in fewer transfusions, fewer complications, and reduced cost.

Association of necrotizing enterocolitis with anemia and packed red blood cell transfusions in preterm infants

Objective:To determine association of anemia and red blood cell (RBC) transfusions with necrotizing enterocolitis (NEC) in preterm infants.Study Design:A total of 111 preterm infants with NEC ⩾stage 2a were compared with 222 matched controls. In all, 28 clinical variables, including hematocrit (Hct) and RBC transfusions were recorded. Propensity scores and multivariate logistic regression models were created to examine effects on the risk of NEC.Result:Controlling for other factors, lower Hct was associated with increased odds of NEC (odds ratio (OR)=1.10, P=0.01). RBC transfusion has a temporal relationship with NEC onset. Transfusion within 24 h (OR=7.60, P=0.001) and 48 h (OR=5.55, P=0.001) has a higher odds of developing NEC but this association is not significant by 96 h (OR=2.13, P=0.07), post-transfusion.Conclusion:Anemia may increase the risk of developing NEC in preterm infants. RBC transfusions are temporally related to NEC. Prospective studies are needed to better evaluate the potential influence of transfusions on the development of NEC.

Inflammation-initiating illnesses, inflammation-related proteins, and cognitive impairment in extremely preterm infants.

Neonatal inflammation is associated with perinatal brain damage. We evaluated to what extent elevated blood levels of inflammation-related proteins supplement information about the risk of impaired early cognitive function provided by inflammation-related illnesses. From 800 infants born before the 28th week of gestation, we collected blood spots on days 1, 7 and 14, for analysis of 25 inflammation-related proteins, and data about culture-positive bacteremia, necrotizing enterocolitis (Bell stage IIIb), and isolated perforation of the intestine, during the first two weeks, and whether they were ventilated on postnatal day 14. We considered a protein to be persistently or recurrently elevated if its concentration was in the top quartile (for gestational age and day blood was collected) on two separate days one week apart. We assessed the children at 2 years of age with the Bayley Mental Development Index (MDI). The combinations of NEC and ventilation on day 14, and of bacteremia and ventilation on day 14 consistently provided information about elevated risk of MDI <55, regardless of whether or not a variable for an elevated protein concentration was included in the model. A variable for a persistently or recurrently elevated concentration of each of the following proteins provided additional information about an increased risk of MDI <55: CRP, SAA, IL-6, TNF-alpha, IL-8, MIP-1beta, ICAM-1, E-SEL, and IGFBP-1. We conclude that elevated blood concentrations of inflammation-related proteins provide information about the risk of impaired cognitive function at age 2 years that supplements information provided by inflammation-associated illnesses.

Maternal Diabetic Control and Hypertrophic Cardiomyopathy in Infants of Diabetic Mothers

Hypertrophic cardiomyopathy has been well documented in infants of diabetic mothers (IDMs). If this asymmetric septal enlargement is an anabolic result of fetal hyperinsulinemia triggered by maternal hyperglycemia during the third trimester, maternal glycosylated hemoglobin (HbA1) levels, an indicator of glycemic control, should then correlate positively at delivery with newborn ventricular septal thickness. In this study of 20 infants of well-controlled diabetic mothers, no relationship was observed between echocardiographic evidence of hypertrophic cardiomyopathy and maternal HbA1 levels. Seven babies (35%) exhibited exaggerated septal thickening, but none had cardiac-specific symptoms. Although 60 percent of the IDMs were large for gestational age and 45 percent demonstrated neonatal hypoglycemia, neither of these complications correlated with maternal HbA 1. In this group of babies of well-controlled diabetic women, echocardiographic indicators of cardiomyopathy were common, but clinical evidence of cardiac embarrassment was not observed. Moreover, these data do not support third trimester maternal hyperglycemia as instrumental in the etiology of cardiomyopathy and other complications of IDMs.

Perinatal risk and severity of illness in newborns at 6 neonatal intensive care units.

OBJECTIVES This multisite study sought to identify (1) any differences in admission risk (defined by gestational age and illness severity) among neonatal intensive care units (NICUs) and (2) obstetric antecedents of newborn illness severity. METHODS Data on 1476 babies born at a gestational age of less than 32 weeks in 6 perinatal centers were abstracted prospectively. Newborn illness severity was measured with the Score for Neonatal Acute Physiology. Regression models were constructed to predict scores as a function of perinatal risk factors. RESULTS The sites differed by several obstetric case-mix characteristics. Of these, only gestational age, small for gestational age. White race, and severe congenital anomalies were associated with higher scores. Antenatal corticosteroids, low Apgar scores, and neonatal hypothermia also affected illness severity. At 2 sites, higher mean severity could not be explained by case mix. CONCLUSIONS Obstetric events and perinatal practices affect newborn illness severity. These risk factors differ among perinatal centers and are associated with elevated illness severity at some sites. Outcomes of NICU care may be affected by antecedent events and perinatal practices.

SNAP-II and SNAPPE-II and the Risk of Structural and Functional Brain Disorders in Extremely Low Gestational Age Newborns: The ELGAN Study

Background: Illness severity measures predict death and illnesses in the newborn. It is unknown how well they predict brain lesions evident on ultrasound scans or neurodevelopmental dysfunctions in preterm infants. Methods: A total of 1,399 inborn infants born before the 28th week of gestation were given Scores for Neonatal Acute Physiology (SNAP-II and SNAPPE-II) based on data collected within the first 12 h of admission to the intensive care unit and had a protocol brain ultrasound scan read independently by 2 sonologists. Of the surviving 1,149 infants, 1,014 (88%) had a neurologic examination at approximately 24 months post-term equivalent, and 975 (85%) had a Bayley Scales of Infant Development assessment. SNAP-II and SNAPPE-II were dichotomized at arbitrary cut-offs (30 for SNAP-II and 45 for SNAPPE-II), using the highest quartile and decile of the week of gestation as a cut-off, and at a Z score of >1 standard deviation from an external mean. Results: After adjustment for gestational age, high SNAP-II and SNAPPE-II scores predicted intraventricular hemorrhage, moderate/severe ventriculomegaly and echodense lesions in cerebral white matter. Only 2 SNAP-II extremes, the highest decile for gestational age and a Z score >1, also predicted echolucent lesions in the white matter. Neither SNAP-II nor SNAPPE-II predicted any statistically significant diagnosis of cerebral palsy. MDI and PDI scores <55 were consistently predicted by both high SNAP-II and SNAPPE-II, whereas scores in the 55–69 range were inconsistently predicted. High SNAP-II and SNAPPE-II inconsistently predicted a positive screen for autism spectrum disorder and small head circumference at 24 months. Conclusion: The physiologic instability in the first 12 post-natal hours identified by illness severity scores conveys information about the risks of brain damage and neurodevelopmental dysfunctions. This risk information might reflect postnatal characteristics in the causal chain. On the other hand, high SNAP scores might be indicators of immaturity and vulnerability.

Systemic Inflammation, Intraventricular Hemorrhage, and White Matter Injury

To see if the systemic inflammation profile of 123 infants born before the 28th week of gestation who had intraventricular hemorrhage without white matter injury differed from that of 68 peers who had both lesions, we compared both groups to 677 peers who had neither. Cranial ultrasound scans were read independently by multiple readers until concordance. The concentrations of 25 proteins were measured with multiplex arrays using an electrochemiluminescence system. Infants who had both hemorrhage and white matter injury were more likely than others to have elevated concentrations of C-reactive protein and interleukin 8 on days 1, 7, and 14, and elevated concentrations of serum amyloid A and tumor necrosis factor–α on 2 of these days. Intraventricular hemorrhage should probably be viewed as 2 entities: hemorrhage alone and hemorrhage with white matter injury. Each entity is associated with inflammation, but the combination has a stronger inflammatory signal than hemorrhage alone.

Efficacy of clonidine versus phenobarbital in reducing neonatal morphine sulfate therapy days for neonatal abstinence syndrome. A prospective randomized clinical trial

Objective:To compare the efficacy of clonidine versus phenobarbital in reducing morphine sulfate treatment days for neonatal abstinence syndrome (NAS).Study Design:Prospective, non-blinded, block randomized trial at a single level III NICU (Neonatal Intensive Care Unit). Eligible infants were treated with a combination of medications as per protocol. Primary outcome was treatment days with morphine sulfate. Secondary outcomes were the mean total morphine sulfate dose, outpatient phenobarbital days, adverse events and treatment failures.Results:A total of 82 infants were eligible, of which 68 were randomized with 34 infants in each study group. Adjusting for covariates phenobarbital as compared with clonidine had shorter morphine sulfate treatment days (−4.6, 95% confidence interval (CI): −0.3, −8.9; P=0.037) with no difference in average morphine sulfate total dose (1.1 mg kg−1, 95% CI: −0.1, 2.4; P=0.069). Post-discharge phenobarbital was continued for an average of 3.8 months (range 1 to 8 months). No other significant differences were noted.Conclusion:Phenobarbital as adjunct had clinically nonsignificant shorter inpatient but significant overall longer therapy time as compared with clonidine.

Neurobehavioral assessment of infants born at term and in utero exposure to serotonin reuptake inhibitors

BACKGROUND Some studies report neurobehavioral symptoms in neonates exposed to serotonin reuptake inhibitors (SRIs) in utero. However, maternal psychiatric illness during the last trimester of pregnancy, as a confounding factor, has not always been assessed. AIMS In this prospective study we compared neurobehavioral complications among neonates who were born to euthymic women who either took or did not take an SRI during the last trimester of pregnancy. STUDY DESIGN Exposed and unexposed infants were assessed for: 1) temperament as measured by the Neonatal Behavioral Assessment Scale (NBAS); 2) activity via Actiwatch electronic monitoring; 3) sleep state using trained observer ratings; and 4) perinatal complications through medical record review. T-tests, Fishers exact tests, and analyses of covariance were used to assess the relationship between clinical and neurobehavioral factors and exposure status. SUBJECTS 67 infants (61 controls and 6 exposed to SRIs). OUTCOME MEASURES Neonatal Assessment Behavioral Scale, APGAR scores, infant sleep state (% sleep, % wakeful), startles and tremulousness, gestational age, birth weight, and head circumference. RESULTS Infants exposed to SRIs in the third trimester had poorer motor development, lower 5-minute APGAR scores, and shorter mean gestational age as compared to unexposed infants. CONCLUSION Results of this study show differences in autonomic and gross motor activity between neonates who were or were not exposed to SRIs in utero after controlling for active maternal psychiatric illness. Future longitudinal work should compare longer term outcomes of exposed and unexposed infants of depressed mothers.