Vivien Phillips

Both Extremes of Arterial Carbon Dioxide Pressure and the Magnitude of Fluctuations in Arterial Carbon Dioxide Pressure Are Associated With Severe Intraventricular Hemorrhage in Preterm Infants

OBJECTIVE. The goal was to test the hypothesis that extremes of Paco2 during the first 4 days after birth are associated with severe intraventricular hemorrhage (grades 3 and 4). METHODS. A single-center retrospective review of clinical and blood gas data in the first 4 postnatal days for 849 infants with birth weights of 401 to 1250 g was performed. The univariate and multivariate relationships of severe intraventricular hemorrhage with maximal and minimal Paco2, Paco2 averaged over time (time-weighted Paco2), and measures of Paco2 fluctuation (SD of Paco2 and difference in Paco2 [maximum minus minimum]) were assessed. RESULTS. Birth weight (mean ± SD) was 848 ± 212 g, and the median gestational age was 26 weeks. Infants with severe intraventricular hemorrhage had higher maximal Paco2 (median: 72 vs 59 mm Hg) and time-weighted Paco2 (mean: 49 vs 47 mm Hg) values but lower minimal Paco2 values (32 vs 37 mm Hg). High Paco2, low Paco2, SD of Paco2, and difference in Paco2 predicted severe intraventricular hemorrhage, but time-weighted average Paco2 was not as predictive. CONCLUSIONS. Both extremes and fluctuations of Paco2 are associated with severe intraventricular hemorrhage. It may be prudent to avoid extreme hypocapnia and hypercapnia during the period of risk for intraventricular hemorrhage.

Estimating blood needs for very-low-birth-weight infants

BACKGROUND: Red blood cell (RBC) transfusions are crucial for the care of very‐low‐birth‐weight (VLBW) infants. These infants frequently require multiple, small‐volume RBC transfusions, with potential exposure to multiple donors. Optimal protocols provide dedicated RBC units to reduce exposures and avoid RBC wastage.

Behavioral problems and socioemotional competence at 18 to 22 months of extremely premature children

Using a large sample of EP toddlers, this study reports increased rates of behavioral and socioemotional problems and associated risk factors. BACKGROUND: Behavior and socioemotional development are crucial aspects of child development . METHODS: A total of 2505 children born at <27 weeks’ gestation was evaluated at 18 to 22 months’ corrected age between January 1, 2008 and December 12, 2012 (86% follow-up). The Brief Infant and Toddler Social and Emotional Assessment was used to evaluate behavioral and socioemotional problems. Cognition and language were evaluated by using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Logistic regression analysis was used to evaluate for perinatal and demographic factors associated with behavioral problems (≥75th percentile) and delayed socioemotional competence (≤15th percentile). Structural equation modeling with bootstrapping was used to identify possible associated risk factors and Bayley-III scores as mediators. RESULTS: Thirty-five percent (873) of children had behavioral problems, and 26% (637) displayed deficits in socioemotional competence. Male sex, public insurance, mothers with less than a high school education, and lower maternal age were associated with behavioral problems. Deficits in competence were associated with lower birth weight, public insurance, mothers with less than a high school education, and abnormal neuromotor exam. Bayley-III language and cognitive scores were significant mediators of the relationships between risk factors and both behavioral and competence scores (P < .05). CONCLUSIONS: Extremely premature children are at risk for behavioral problems and deficits in socioemotional competence. Sociodemographic factors were associated with both socioemotional competence and behavioral problems. Deficits in socioemotional competence were also associated with neuromotor abnormalities and cognitive and language function

Associations of Maternal and Infant Testosterone and Cortisol Levels With Maternal Depressive Symptoms and Infant Socioemotional Problems.

This study examined the associations of testosterone and cortisol levels with maternal depressive symptoms and infant socioemotional (SE) problems that are influenced by infant gender. A total of 62 mothers and their very-low-birth weight (VLBW) infants were recruited from a neonatal intensive care unit at a tertiary medical center in the southeast United States. Data were collected at three time points (before 40 weeks’ postmenstrual age [PMA] and at 3 months and 6 months of age corrected for prematurity). Measures included infant medical record review, maternal interview, biochemical assays of salivary hormone levels in mother-VLBWinfant pairs, and standard questionnaires. Generalized estimating equations with separate analyses for boys and girls showed that maternal testosterone level was negatively associated with depressive symptoms in mothers of boys, whereas infant testosterone level was negatively associated with maternal report of infant SE problems in girls after controlling for characteristics of mothers and infants and number of days post birth of saliva collection. Not surprisingly, the SE problems were positively associated with a number of medical complications. Mothers with more depressive symptoms reported that their infants had more SE problems. Mothers with higher testosterone levels reported that girls, but not boys, had fewer SE problems. In summary, high levels of testosterone could have a protective role for maternal depressive symptoms and infant SE problems. Future research need to be directed toward clinical application of these preliminary results.

Seasonal Variation in Solar Ultra Violet Radiation and Early Mortality in Extremely Preterm Infants.

BACKGROUND Vitamin D production during pregnancy promotes fetal lung development, a major determinant of infant survival after preterm birth. Because vitamin D synthesis in humans is regulated by solar ultraviolet B (UVB) radiation, we hypothesized that seasonal variation in solar UVB doses during fetal development would be associated with variation in neonatal mortality rates. METHODS This cohort study included infants born alive with gestational age (GA) between 23 and 28 weeks gestation admitted to a neonatal unit between 1996 and 2010. Three infant cohort groups were defined according to increasing intensities of solar UVB doses at 17 and 22 weeks gestation. The primary outcome was death during the first 28 days after birth. RESULTS Outcome data of 2,319 infants were analyzed. Mean birth weight was 830 ± 230 g and median gestational age was 26 weeks. Mortality rates were significantly different across groups (p = 0.04). High-intensity solar UVB doses were associated with lower mortality when compared with normal intensity solar UVB doses (hazard ratio: 0.70; 95% confidence interval: 0.54-0.91; p = 0.01). CONCLUSION High-intensity solar UVB doses during fetal development seem to be associated with risk reduction of early mortality in preterm infants. Prospective studies are needed to validate these preliminary findings.

Dose-Response Effects of Early Vitamin D Supplementation on Neurodevelopmental and Respiratory Outcomes of Extremely Preterm Infants at 2 Years of Age: A Randomized Trial

Background: Many extremely preterm infants have low vitamin D concentrations at birth, but early childhood outcomes after vitamin D supplementation have not been reported. Objective: To determine a dose-response relationship between increasing doses of enteral vitamin D in the first 28 days after birth and cognitive scores at 2 years of age. Methods: In this phase II double-blind dose-response randomized trial, infants with gestational ages between 23 and 27 weeks were randomly assigned to receive placebo or a vitamin D dose of 200 or 800 IU/day from day 1 of enteral feeding to postnatal day 28. The primary outcome of this follow-up study was Bayley III cognitive score at 22-26 months of age. Results: Seventy of 80 survivors had a follow-up evaluation at 2 years of age (88%). There were no significant differences in cognitive scores between supplementation groups (p = 0.47). Cognitive scores did not differ between the higher vitamin D dose group and the placebo group (median difference favoring the 800 IU group: +5 points; 95% CI: −5 to 15; p = 0.23). The linear trend between increasing doses of vitamin D and reduction of neurodevelopmental impairment (placebo group: 54%; 200 IU group: 43%; 800 IU group: 30%; p = 0.08) or language impairment (placebo group: 64%; 200 IU group: 57%; 800 IU group: 45%; p = 0.15) was not statistically significant. Respiratory outcomes at 2 years of age (need for supplemental oxygen or asthma medications) did not differ between groups. Conclusion: In extremely preterm infants, early vitamin D supplementation did not significantly improve cognitive scores. Though underpowered for clinically meaningful differences in early childhood outcomes, this trial may help determine dosing for further investigation of vitamin D supplementation.

Associations Between Hormonal Biomarkers and Cognitive, Motor, and Language Developmental Status in Very Low Birth Weight Infants

Background Male infants are more prone to health problems and developmental delays than female infants. Objectives On the basis of theories of gender differences in brain development and social relationships, we explored associations between testosterone and cortisol levels with infant cognitive, motor, and language development (“infant development”) in very low birth weight (VLBW) infants, controlling for mother–infant interactions, characteristics of mothers and infants, and days of saliva collection after birth. Methods A total of 62 mother–VLBW infant pairs were recruited from the newborn intensive care unit of a tertiary medical center in the Southeast United States. Data were collected through infant medical record review, biochemical measurement, observation of mother–infant interactions, and standard questionnaires. Infant development was assessed at 6 months corrected age (CA), and mother–infant interactions were observed at 3 and 6 months CA. Results General linear regression with separate analyses for each infant gender showed that high testosterone levels were positively associated with language development of male infants after controlling for mother–infant interactions and other covariates, whereas high cortisol levels were negatively associated with motor development of female infants after controlling for mother–infant interactions. Conclusions Steroid hormonal levels may well be more fundamental factors for assessing infant development than infant gender or mother–infant interactions at 6 months CA.

290 BREAST MILK FEEDING IN LOW BIRTH WEIGHT INFANTS: INFLUENCES AND BARRIERS.

Background Clinical studies have demonstrated that feeding human breast milk to premature infants can prevent several of the associated comorbid conditions. Often, the initial high rate of pumping breast milk at birth can wane by 1 month postpartum. Additionally, there appear to be socioeconomic and racial disparities in initiating and continuing to pump breast milk. The goal of this study was to determine these barriers in order to develop specific interventions to increase the rate of prolonged breast milk feeding. Methods An extensive survey instrument was designed to ask questions about breastfeeding. Mothers of UAB inborn infants with a birth weight less than 1,500 g and alive at 30 days were interviewed with the survey. The questions included maternal and infant demographic information. In addition, specific questions were designed to determine the prenatal influences regarding feeding, including breastfeeding. There were also questions pertaining to the immediate postpartum period as well as the first month about breast milk pumping. Three distinct populations were defined: never pumped, pumped but discontinued by 30 days, and those still providing breast milk at 30 days. The demographic information and the answers to the survey were used as variables and analyzed using logistic regression with a 95% confidence interval. Results From July 1, 2003 to June 30, 2004, 102 mothers were surveyed. The median maternal age was 24 years. The racial composition was 54% white, 43% black, and 3% other. Almost 60% of the mothers had Medicaid. There was no difference in breast pumping rates based on race or socioeconomic status. Regarding initiation, 15% never attempted pumping while 58% were still pumping at 30 days. There was a strong association with not pumping in the mothers who had never considered breastfeeding in the prenatal period (OR 4.4, 95% CI 1.9, 19.1). The strongest prenatal influence regarding breastfeeding was the obstetrician (OB). The strongest factor associated with pumping breast milk at 30 days was husband/father of child involvement (OR 14.1, 95% CI 1.1, 174 and OR 9.3, 95% CI 2.2, 36, respectively). Conclusions Prenatal OB and paternal influences were the strongest determinants in successful prolonged breast milk pumping. Implications While important to provide postnatal lactation support, it appears that prenatal counseling is an major potential area for interventions designed to increase breastfeeding in general and possibly providing breast milk to premature infants.

184 HIGH LEVELS OF PaCO2 AND INTRAVENTRICULAR HEMORRHAGE IN VERY LOW BIRTH WEIGHT INFANTS

Background Increases in PaCO2 lead to increases in cerebral blood flow (CBF) and may therefore predispose to intraventricular hemorrhage (IVH). Periventricular leukomalacia (PVL) correlates with hypocarbia in ventilated very low birth weight (VLBW) infants possibly due to decreases in CBF. The safe upper and lower limits of PaCO2 in VLBW infants need to be determined. Hypothesis Higher levels of PaCO2 are associated with an increased risk of IVH. Design/Methods Medical records review of 561 VLBW infants 401 to 1250 g at birth admitted to a Level III neonatal intensive care unit between 1/1/ 2000 and 12/31/ 2002. Data collected included main prenatal and neonatal variables, including severe IVH (grades III and IV) and blood gases in the first 4 days after birth. The highest, lowest, and time-weighted average PaCO2 were collected and included in uni- and multivariable analyses with severe IVH as the dependent variable. Results Mean birth weight (± SD) was 840 g (± 209) and median gestational age was 26 weeks. The maximum PaCO2 (median [25th-75th centiles]) 72 [62-88] vs. 59 [50-70] mm Hg, p < .001) and the time-weighted average CO2 (mean 49 vs. 47 mm Hg, p = .003) were significantly higher, and the minimum PaCO2 was lower (32 [28-37] vs. 36 [30-42], p < .001) in patients with severe IVH. Both extremes of PaCO2 predicted severe IVH but the time-weighted average PaCO2 had lower accuracy (AUC of the ROC curve for maximum PaCO2 = 0.71; minimum PaCO2 = 0.66; time-weighted average PaCO2 = 0.58 [p < .05 vs. max and min PaCO2]). A maximum PaCO2 > 60 mm Hg had 79% sensitivity and 53% specificity, and a minimum PaCO2 < 38 mm Hg had 78% sensitivity and 45% specificity for severe IVH. Multiple logistic regression analyses identified maximum PaCO2, minimum PaCO2, time-weighted average PaCO2, gestational age, 5 minute Apgar score, and use of prenatal steroids as the major variables independently associated with severe IVH. Conclusions Extreme levels of PaCO2 are associated with severe IVH in VLBW infants, but bias cannot be excluded. Although causality cannot be inferred from this analysis, a careful evaluation of the data from randomized trials on minimal ventilation on the relationship between PaCO2 and IVH is required to determine if a “threshold effect” does exist.