An important area concerning morbidity among infants with congenital heart defects (CHD) is related to feeding problems. Our objectives were to characterize the evolution of feeding milestones related to transition to per oral feeding among infants with CHD, and to identify associated variables impacting the feeding abilities. Specifically, we differentiated the feeding characteristics in neonates with acyanotic vs cyanotic CHD.
Feeding progress was tracked during the first hospitalization in a retrospective chart review study involving 76 infants (29 acyanotic, 47 cyanotic CHD). The ages at which the following milestones attained were recorded: first feeds, maximum gavage feeds, first nipple feeds and maximum nipple feeds, in addition to the length of hospital stay. Effects of perinatal factors, duration of respiratory support, vasopressor and narcotic use and use of cardiopulmonary bypass on the feeding milestones were also evaluated. ANOVA, t-test, and stepwise linear regression analysis were applied as appropriate. Data stated as mean±s.e.m., or %; P<0.05 was considered significant.
Prenatal and birth characteristics were similar (P = NS) between the neonates with acyanotic and cyanotic CHD. Cyanotic CHD required three times prolonged use of ventilation, narcotics and vasopressor use (all P<0.05, compared to the acyanotic group). In the acyanotic group, prolonged respiratory support correlated linearly with time to attain maximal gavage feeds and nippling (both, R2 = 0.8). In the cyanotic group, delayed initiation of gavage feeds and prolonged respiratory support both correlated linearly with time to attain maximal gavage feeds and nippling (both, R2 = 0.8). Age at first gavage feed correlated with maximum gavage feeds among neonates with cyanotic CHD, and first nipple feed correlated with maximum nipple feeds among all groups (P<0.01). Use of cardiopulmonary bypass in cyanotic CHD delayed the feeding milestones and prolonged the length of stay (both, P<0.05 vs non-bypass group); similar findings were not seen in the acyanotic group.
In contrast to neonates with acyanotic CHD, cyanotic CHD group had significant delays with (a) feeding readiness, (b) successful gastric feeding, (c) oromotor readiness and (d) successful oromotor skills. Co-morbid factors that may directly influence the delay in feeding milestones include the (a) duration of respiratory support and (b) use of cardiopulmonary bypass. Delays in achieving maximum gavage and maximum nippling may suggest foregut dysmotility and oropharyngeal dysphagia.
feeding problems; congenital heart defects; infant
To explore differences in maternal factors, including visitation and holding, among premature infants cared for in single patient rooms (SPR) compared to open-bay in the neonatal intensive care unit (NICU).
Eighty-one premature infants were assigned to a bed space in either the open-bay area or in a SPR upon NICU admission, based on bed space and staffing availability in each area. Parent visitation and holding were tracked through term equivalent, and parents completed a comprehensive questionnaire at discharge to describe maternal health. Additional maternal and medical factors were collected from the medical record. Differences in outcome variables were investigated using linear regression.
No significant differences in gestational age at birth, initial medical severity, hours of intubation, or other factors that could affect the outcome were observed across room type. Significantly more hours of visitation were observed in the first two weeks of life (p=.02) and in weeks three and four (p=.02) among infants in the SPR. More NICU stress was reported by mothers in the single patient room after controlling for social support (p=.04).
Increased parent visitation is an important benefit of the SPR, however, mothers with infants in the SPR reported more stress.
To determine (a) the proportion of asymptomatic infants born at ≥ 35 weeks gestation evaluated for early-onset sepsis (EOS) and exposed to postnatal antibiotics; (b) reasons for and outcomes of the evaluations, and (c) anticipated changes when applying the CDC 2010 guidelines to this study population.
Retrospective cohort study of infants born at ≥ 35 weeks gestation in 2008–2009 in a large maternity center.
7226 infants met study criteria: 1062 (14.7%) were evaluated for EOS and half of those evaluated received empiric antibiotics. 70.4% of evaluations were performed due to maternal intrapartum fever, but 23% were prompted by inadequate GBS prophylaxis alone. Three cases of blood culture-proven infection were identified.
Improved approaches are needed to identify asymptomatic infants at risk for EOS to decrease unnecessary evaluations and antibiotic exposure. Transition to the 2010 CDC GBS guidelines may eliminate a quarter of EOS evaluations among these infants.
group B Streptococcus; intrapartum antibiotic prophylaxis; neonatal screening; neonatal infection; asymptomatic infection; early-onset sepsis
To determine whether death and/or neurodevelopmental impairment (NDI) after severe intracranial hemorrhage (ICH; grade 3 or 4) differs by gestational age (GA) at birth in extremely low birth weight (ELBW) infants.
Demographic, perinatal and neonatal factors potentially contributing to NDI for ELBW infants (23 to 28 weeks gestation) were obtained retrospectively; outcome data came from the ELBW Follow-up Study. NDI was defined at 18 to 22 months corrected age as moderate/severe cerebral palsy, Bayley Scales of Infant Development II cognitive or motor score <70, and/or blindness or deafness. Characteristics of younger versus older infants with no versus severe ICH associated with death or NDI were compared. Generalized linear mixed models predicted death or NDI in each GA cohort.
Of the 6638 infants, 61.8% had no ICH and 13.6% had severe ICH; 39% of survivors had NDI. Risk-adjusted odds of death or NDI and death were higher in the lower GA group. Lower GA increased the odds of death before 30 days for infants with severe ICH. Necrotizing enterocolitis (particularly surgical NEC), late onset infection, cystic periventricular leukomalacia and post-natal steroids contributed to mortality risk. NDI differed by GA in infants without ICH and grade 3, but not grade 4 ICH. Contributors to NDI in infants with severe ICH included male gender, surgical NEC and post-hemorrhagic hydrocephalus requiring a shunt.
GA contributes to the risk of death in ELBW infants, but not NDI among survivors with severe ICH. Male gender, surgical NEC and need for a shunt add additional risk for NDI.
infant; premature; extremely low birth weight; death; neurodevelopmental impairment
We investigated whether particular demographic, maternal psychosocial, and infant factors identified mothers of very preterm infants at risk for postpartum depression or anxiety at the time of discharge from a level III urban Neonatal Intensive Care Unit (NICU).
A racially diverse cohort of mothers (N=73) of preterm infants (gestational age <30 weeks) completed a comprehensive questionnaire at discharge from the NICU assessing postpartum depression, anxiety, and psychosocial and demographic factors. Additionally, infants underwent brain magnetic resonance imaging prior to discharge.
Twenty percent of mothers had clinically significant levels of depression while 43% had moderate-severe anxiety. Being married (p<.01), parental role alteration (p<.01) and prolonged ventilation (p<.05) were associated with increased depressive symptoms. No psychosocial, demographic, or infant factors, including severity of brain injury, were associated with state anxiety levels.
Maternal factors, such as marital status, stress from parental role alteration, and infant factors, such as prolonged ventilation, are associated with increased depression. However, clinically significant levels of anxiety are common in mothers of very preterm infants with few identifiable risk factors. These findings support the need for universal screening within the NICU.
Risk Factors; Racial Differences; NICU
To ascertain the effect of obesity-related inflammation on maternal and fetal iron status. We hypothesized that obese pregnant women would have increased inflammation, hepcidin levels, and that their infants would have impaired iron status compared to lean controls.
Fifteen obese (Ob) and fifteen lean (Lc) women were recruited in their second trimester of pregnancy. Markers of iron status, inflammation and hepcidin were measured in maternal and cord blood. Student’s t test was used to compare obese and lean groups, and Pearson correlation coefficients were determined between maternal and cord blood values.
Maternal C-reactive protein (CRP) (p<0.01) and hepcidin (p<0.01) were higher, and cord blood iron (p<0.01) was lower in the obese group. Maternal BMI (p<0.01) and hepcidin (p<0.05) were negatively correlated with cord blood iron status.
Maternal obesity is associated with impaired maternal-fetal iron transfer, potentially through hepcidin upregulation.
Maternal obesity; iron deficiency; inflammation
To determine if children born prematurely exhibit atypical responses to normally occurring sensory stimuli, as measured by the Sensory Profile.
This is a cross-sectional study of children born at ≤32 weeks gestation, followed at 1 to 8 years of age. The Sensory Profile questionnaire was completed by each child’s primary caregiver. The overall Sensory Profile was considered atypical if any quadrant or section score was >2 s.d. from the mean of the Sensory Profile validation group. Bivariate analyses were performed to determine associations between risk factors for adverse neurodevelopment and overall atypical Sensory Profiles. A section or quadrant was considered atypical if its score was >2 s.d. from the mean. A test of proportions was used to compute observed versus expected scores for each section and quadrant (Sensory Profile scores were based on a normal distribution so one would expect approximately 95% of participants to score within 2 s.d. of the mean).
Of our 107 participants, 39% had an atypical score in at least one section or quadrant. No specific perinatal or neonatal risk factors were associated with atypical overall Sensory Profiles (P≥0.05 for all). Children born prematurely were at risk of having atypical scores in the auditory, tactile and vestibular processing sections, and in the four Sensory Profile quadrants (P<0.05).
Children born prematurely exhibit atypical sensory behaviors on the Sensory Profile. Further investigation to understand the underlying neural mechanisms and to develop effective interventions are critical to support neurodevelopment for these children.
Sensory Profile; prematurity; sensory behavior; follow-up
To 1) determine the proportion of mothers and infants who had levels of IgG antibody to pertussis antigens predicted to be potentially protective at delivery; 2) evaluate the efficiency of maternal-infant antibody transport; 3) extrapolate infant antibody titers at six weeks; and 4) identify maternal factors associated with potentially protective infant antibodies.
Sera from mother-infant pairs from February 2006 through April 2007 were tested for antibody to pertussis antigens by standardized ELISA (enzyme-linked immunosorbent assay). Potentially protective antibody levels were defined as >5 ELISA units (EU) for pertussis toxin (PT) and >10 EU for fimbriae (FIM) and pertactin (PRN). Serologic evidence of previous maternal infection was defined from antibody to four antigens by k-means cluster analysis.
In total, 21% (17/81) of mothers and 26% (21/81) of infants had potentially protective antibody levels at delivery. Mean infant-maternal antibody ratios for PT, FIM and PRN were 1.26, 1.36 and 1.31 respectively. At 6 weeks, 11% (9/81) of infants were predicted to have potentially protective antibody levels. Using cluster analysis, 9% (7/81) of mothers had evidence of previous pertussis infection. Infants born to these mothers were predicted to be more likely to have potentially protective antibodies at 6 weeks (43%) than those born to mothers without (8%) (p = 0.03).
Approximately 75% of infants were born with pertussis antibody levels lower than the modest levels associated with potential protection. Despite effective antibody transfer, nearly 90% of infants were predicted to have little antibody by 6 weeks. Maternal immunization before or during pregnancy might simulate previous pertussis infection and help protect infants through the first months of life.
Prematurity can disrupt the development of a specialized neural circuit known as suck central pattern generator (sCPG), which often leads to poor feeding skills. The extent to which suck can be entrained using a synthetically patterned orocutaneous input to promote its development in preterm infants who lack a functional suck is unknown.
To evaluate the effects of a new motorized ‘pulsating’ pacifier capable of entraining the sCPG in tube-fed premature infants who lack a functional suck and exhibit feeding disorders.
Prospective cohort study of 31 preterm infants assigned to either the oral patterned entrainment intervention (study) or non-treated (controls) group, matched by gestational age, birth weight, oxygen supplementation history, and oral feed status. Study infants received a daily regimen of orocutaneous pulse trains through a pneumatically-controlled silicone pacifier concurrent with gavage feeds.
The patterned orocutaneous stimulus was highly effective in accelerating the development of NNS in preterm infants. A repeated-measure multivariate analysis of covariance revealed significant increases in minute-rates for total oral compressions, NNS bursts, and NNS cycles, suck cycles per burst, and the ratiometric measure of NNS cycles as a percentage of total ororhythmic output. Moreover, study infants also manifest significantly greater success at achieving oral feeds, surpassing their control counterparts by a factor of 3.1× (72.8% daily oral feed versus 23.3% daily oral feed, respectively).
Functional expression of the sCPG among preterm infants who lack an organized suck can be induced through the delivery of synthetically patterned orocutaneous pulse trains. The rapid emergence of NNS in treated infants is accompanied by a significant increase in the proportion of nutrient taken orally.
suck central pattern generator; sensory experience; orofacial; non-nutritive suck; oral feed
To examine the role of vestibular inputs on respiratory and oromotor systems in healthy preterm infants.
27 preterm infants were quasi-randomly assigned to either the VestibuGlide treatment or control groups. VestibuGlide infants were held in a developmentally supportive position, given a pacifier and received a series of vestibular stimuli, counterbalanced across rate and acceleration conditions, 15 minutes 3x/day for 10 days. The control infants were also held in a developmentally supportive position, given a pacifier for 15 minutes 3x/day for 10 days but did not receive the VestibuGlide stimulation.
A multi-level regression model revealed that treatment infants increased their respiratory rate in response to vestibular stimulus and that the highest level of vestibular acceleration delivered to the infants (0.51 m/s2) resulted in a significant increase in breaths per minute.
Vestibular stimulation delivered to preterm infants prior to scheduled feeds effectively modulates respiratory rate and resets the respiratory central pattern generator.
respiration; non-nutritive suck
The objective of this study was to assess the predictive value of body mass index (BMI) at earlier ages on risk of overweight/obesity at age of 11 years.
This is a longitudinal study of 907 children from birth to age of 11 years. Predictors include BMI at earlier ages and outcome is overweight/obesity status at age of 11 years. Analyses were adjusted for covariates known to affect BMI.
At 11 years, 17% were overweight and 25% were obese. Children whose BMI was measured as ≥85th percentile once at preschool age had a twofold risk for overweight/obesity at 11 years of age. Risk increased by 11-fold if a child's BMI measured was noted more than once during this age. During early elementary years, if a child's BMI was>85th percentile once, risk for overweight/obesity at 11 years was fivefold and increased by 72-fold if noted more than two times. During late elementary years, if a child's BMI was>85th percentile once, risk for overweight/obesity was 26-fold and increased by 351-fold if noted more than two times. Risk of overweight/obesity at 11 years was noted with higher maternal prepregnancy weight, higher birth weight, female gender and increased television viewing.
Children in higher BMI categories at young ages have a higher risk of overweight/obesity at 11 years of age. Effect size was greater for measurements taken closer to 11 years of age. Pediatricians need to identify children at-risk for adolescent obesity and initiate counseling and intervention at earlier ages.
overweight; obesity; preschool; early elementary; late elementary
To determine the effects of fetal sex on aromatase and androgen receptor (AR) expression in the placenta of normal and preeclamptic pregnancies.
Placenta from preeclamptic (5-female and 6-male fetus) and healthy pregnancies (7-female and 7-male fetus) were examined by immunofluorescence, Western blotting and quantitative-RT-PCR.
Placental AR levels were significantly higher (P<0.05) in placentae of both male and female fetus compared to their respective sexes in normal pregnancies. The placental aromatase levels varied depending on fetal sex. If the fetus was female, aromatase levels were substantially higher (P<0.05) in preeclamptic than normal placentae. If the fetus was male, the aromatase levels were significantly lower (P<0.05) in preeclamptic than normal placentae. Placental aromatase levels were significantly higher (P<0.05) in male-than in female-bearing normal placentae.
Dysregulation in androgen production and signaling in preeclamptic placentae may contribute to placental abnormalities increasing the frequency of maternal-fetal complications associated with preeclampsia.
Preeclampsia; Placenta; Androgen receptor; Aromatase; Fetal sex
This study, conducted as a randomized clinical trial, focuses on acute care visits and rehospitalizations of mothers whose infants were delivered by cesarean section (n = 122) and infants (n = 123) for 8 weeks after hospital discharge. There were three maternal rehospitalizations. Maternal acute care visits were for wound infections or complications (27 of 34); 21 occurred in the first 4 weeks. Seventy-five percent of infant rehospitalizations were for infection or possible infection; 22 of 31 infant acute care visits occurred in first 4 weeks for bilirubin checks and infant care problems, and 21 of 25 visits in weeks 5 to 8 were for infections. Discharge teaching and home care in first 4 weeks after discharge and issues related to infant infections in the second 4-week period may reduce the need for rehospitalizations and acute care visits in both mothers who had cesarean section and their infants.
To examine the frequency, time of gestation, and reasons for antenatal hospitalizations in women with medically high-risk pregnancies.
This secondary analysis reports all antenatal hospitalizations from a clinical trial testing transitional care to women with high-risk pregnancies. Data were collected from 1992 to 1996. Pregnant women with pregestational (n = 16) or gestational diabetes (n = 21), hypertension (n = 29), and diagnosed (n = 47) or at high risk for preterm labor (n = 37) were included. Diagnoses for each hospitalization and lengths of stay were collected from chart review and validated by attending physicians. Gestation was determined via ultrasonography. The sample (N = 150) consisted of predominately African-American women, never married, between the ages of 15 and 40 with Medicaid insurance.
Eighty-three percent (n = 125) of the women had one or more antenatal hospitalization with a mean length of stay of 123 hours. All women with diabetes were hospitalized at least once. Women with pregestational diabetes had the greatest number of hospitalizations whereas those with gestational diabetes had the least. Major reasons for hospitalizations were preterm labor, glucose control, premature cervical dilation, and preeclampsia.
Some hospitalizations could potentially be avoided or reduced through expanded patient education, improved screening, and more aggressive monitoring for early signs and symptoms of impending complications.
Each year in the US approximately 50,000 neonates receive inpatient pharmacotherapy for the treatment of neonatal abstinence syndrome (NAS).
To compare the safety and efficacy of a traditional inpatient only approach with a combined inpatient and outpatient methadone treatment program.
Retrospective review (2007-9). Infants were born to mothers maintained on methadone or buprenorphine in an antenatal substance abuse program. All infants received methadone for NAS treatment as inpatient. Methadone weaning for the traditional group (75 pts) was inpatient while the combined group (46 pts) was outpatient.
Infants in the traditional and combined groups were similar in demographics, obstetrical risk factors, birth weight, GA and the incidence of prematurity (34 & 31%). Hospital stay was shorter in the combined than in the traditional group (13 vs 25d; p < 0.01). Although the duration of treatment was longer for infants in the combined group (37 vs 21d, p<0.01), the cumulative methadone dose was similar (3.6 vs 3.1mg/kg, p 0.42). Follow-up: Information was available for 80% of infants in the traditional and 100% of infants in the combined group. All infants in the combined group were seen ≤ 72 hours from hospital discharge. Breast feeding was more common among infants in the combined group (24 vs. 8% p<0.05). Following discharge there were no differences between the two groups in hospital readmissions for NAS. Prematurity (<37w GA) was the only predictor for hospital readmission for NAS in both groups (p 0.02, OR 5). Average hospital cost for each infant in the combined group was $13,817 less than in the traditional group.
A combined inpatient and outpatient methadone treatment in the management of NAS decreases hospital stay and substantially reduces cost. Additional studies are needed to evaluate the potential long term benefits of the combined approach on infants and their families.
To replicate genetic associations with respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in genes related to surfactant deficiency, inflammation and infection and the renin-angiotensin system.
We examined eight candidate genes for associations with RDS and BPD in 433 preterm (PTB - <37 weeks) infants (251 with RDS and 134 with BPD). Both case-control and family-based analyses were performed in preterm (<37 weeks) and very preterm (VPTB - <32 weeks) infants.
We replicated a previous finding that rs1923537, a marker downstream of surfactant protein D (SFTPD) is associated with RDS in VPTB infants in that the T allele was over-transmitted from parents to offspring with RDS (p=8.4×10−3). We also observed the A allele of rs4351 in the angiotensin-converting enzyme (ACE) gene was over-transmitted from parents to VPTB offspring with BPD (p=9.8×10−3).
These results give further insight into the genetic risk factors for complex neonatal respiratory diseases and provide more evidence of the importance of SFTPD and ACE in the etiology of RDS and BPD, respectively.
bronchopulmonary dysplasia; respiratory distress syndrome; single nucleotide polymorphism
To examine the risk and etiology of preterm delivery in women with polycystic ovary syndrome (PCOS).
Retrospective cohort study comparing preterm delivery rate among non-diabetic PCOS and non-PCOS women with singleton pregnancy. Multivariable logistic regression was used to identify predictors of preterm delivery among PCOS women.
Among 908 PCOS women with singleton pregnancy, 12.9% delivered preterm compared to 7.4% among non-PCOS women (p<0.01). Causes of preterm delivery among PCOS women included preterm labor (41%), cervical insufficiency (11%), hypertensive complications (20%), preterm premature rupture of membranes (15%), fetal-placental concerns (9%) and intrauterine fetal demise (5%). Maternal age, race/ethnicity and nulliparity were significant predictors of preterm delivery in PCOS, while body mass index and fertility medications were not.
A higher proportion of PCOS women delivered preterm (12.9%) compared to non-PCOS women, with the majority of cases due to spontaneous preterm birth. Future studies should explore etiologies and strategies to improve pregnancy outcomes in PCOS.
Polycystic ovary syndrome; pregnancy; preterm delivery
To explore nurses’ and physicians’ end-of-life (EOL) experiences in the newborn intensive care unit.
A hermeneutic phenomenology of health-care providers’ lived experiences with infant deaths in the newborn intensive care unit between January and August 2006 was conducted. Semistructured interviews were completed with individual providers. Demographic data were also collected. Analysis of themes and descriptive statistics were performed.
Twenty-one nurses and 11 physicians were interviewed. Providers described their experiences largely through an overall theme of ‘creating the best possible experience’ for parents. To support this theme, three subthemes (building relationships, preparing for the EOL and creating memories) were common between physicians and nurses. However, nurses and physicians articulated their roles and obligations differently within these subthemes. Additionally, three subthemes through which the providers described their personal experiences were found and these included moral distress, parental readiness and consent for autopsy.
A primary finding of this study was that a common overall obligation among nurses and physicians was to create the best possible experience for parents. Despite this commonality, the two disciplines approached the EOL and accomplished their common obligation from different vantage points.
health-care provider obligations; relationships; hermeneutic phenomenology; moral distress
To determine the contribution of infants born at the threshold of viability (defined as <750 g birth weight) and the role of regionalization of perinatal care on the neonatal mortality rate (NMR) in Colorado.
We performed a retrospective cohort study, evaluating all live births in Colorado from 1991 to 2003, and comparing the periods 1991 to 1996 versus 1997 to 2003.
The overall unadjusted NMR of the two time periods was 4.3 and 4.4 per 1000 live births, respectively (P=0.42). The contribution of infants with birth weights <750 g to the overall NMR increased from 45.0 to 54.5% (P<0.01). The odds of death for infants <750 g increased between time periods (Odd ratio 1.3, 95% Confidence interval 1.11, 1.61). However, NMR decreased between time periods for all birth weight categories, until infants <600 g. With respect to regionalization, the number of infants <750 g born in a level III care center increased slightly between the two time periods (69.6 versus 73.3%; P=0.04); however, adjusted analysis showed no difference in the practice of regionalization between time periods. Regardless of time period, infants who weighed <750 g born in a level III center had 60% lower mortality risk when compared to <750 g infants born in a non-level III center (P<0.01; 95% CI 0.30, 0.52).
Despite advances in neonatal medicine, the overall NMR in the state of Colorado remained unchanged between the time periods of 1991 to 1996 and 1997 to 2003. Infants at the threshold of viability continue to have a large impact on the Colorado NMR, making up a larger proportion of overall neonatal deaths. While the results demonstrate that the risk of mortality is significantly reduced for <750 g infants born in a level III center, the practice of regionalization has not changed between the two time periods. Improved efforts to standardize the referral practices to ensure delivery of <750 g infants in level III centers could potentially reduce the impact of these infants on the NMR. While the overall NMR in Colorado has not changed between the two time periods, the NMR for infants >600 g has significantly decreased, suggesting that the boundary delineating the threshold of viability needs reevaluation, as it may have been pushed lower than previously defined.
neonatal mortality rate; threshold of viability; regionalization; ELBW infants; prematurity
Both excess and insufficient levels of glucocorticoid in extremely low birth weight (ELBW) infants have been associated with adverse hospital outcomes, whereas excess glucocorticoid exposure has been associated with long-term adverse neurodevelopment. Our objective was to evaluate the relationship between neonatal cortisol concentrations and long-term outcomes of growth and neurodevelopment.
As part of a multicenter randomized trial of hydrocortisone treatment for prophylaxis of relative adrenal insufficiency, cortisol concentrations were obtained at 12 to 48 h of postnatal age and at days 5 to 7 on 350 intubated ELBW infants, of whom 252 survived and returned for neurodevelopmental follow-up at 18 to 22 months corrected age. Cortisol values from each time point were divided into quartiles. Growth and neurodevelopmental outcome were compared for each quartile.
Median cortisol value was 16.0 μg per 100 ml at baseline for all infants, and 13.1 μg per 100 ml on days 5 to 7 in the placebo group. Outcomes did not differ in each quartile between treatment and placebo groups. Low cortisol values at baseline or at days 5 to 7 were not associated with impaired growth or neurodevelopment at 18 to 22 months corrected age. High cortisol values were associated with an increase in cerebral palsy, related to the increased incidence of severe intraventricular hemorrhage (IVH) and periventricular leukomalacia.
Low cortisol concentrations were not predictive of adverse long-term outcomes. High cortisol concentrations, although predictive of short-term adverse outcomes such as IVH and periventricular leukomalacia, did not additionally predict adverse outcome. Further analysis into identifying factors that modulate cortisol concentrations shortly after birth could improve our ability to identify those infants who are most likely to benefit from treatment with hydrocortisone.
bronchopulmonary dysplasia; extremely preterm infants; hydrocortisone; outcomes of high-risk infants
Aggressive phototherapy (AgPT) is widely used and assumed to be safe and effective for even the most immature infants. We assessed whether the benefits and hazards for the smallest and sickest infants differed from those for other extremely low birth weight (ELBW; (≤1000 g) infants in our Neonatal Research Network trial, the only large trial of AgPT.
ELBW infants (n=1974) were randomized to AgPT or conservative phototherapy at age 12–36 hours. The effect of AgPT on outcomes (death; impairment; profound impairment; death or impairment [primary outcome], and death or profound impairment) at 18–22 months corrected age was related to BW stratum (501–750 g; 751–1000 g) and baseline severity of illness using multilevel regression equations. The probability of benefit and of harm was directly assessed with Bayesian analyses.
Baseline illness severity was well characterized using mechanical ventilation and FiO2 at 24 hours age. Among mechanically ventilated infants ≤750 g BW (n =684), a reduction in impairment and in profound impairment was offset by higher mortality (p for interaction <0.05) with no significant effect on composite outcomes. Conservative Bayesian analyses of this subgroup identified a 99% (posterior) probability that AgPT increased mortality, a 97% probability that AgPT reduced impairment, and a 99% probability that AgPT reduced profound impairment.
Findings from the only large trial of AgPT suggest that AgPT may increase mortality while reducing impairment and profound impairment among the smallest and sickest infants. New approaches to reduce their serum bilirubin need development and rigorous testing.
Phototherapy; bilirubin; severity of illness; ELBW infant; impairment; randomized clinical trial; statistical interaction; Bayesian analysis
Moderately premature infants, defined here as those born between 30 0/7 and 34 6/7 weeks gestation, comprise 3.9% of all births in the United States and 32% of all preterm births. While long-term outcomes for these infants are better than for less mature infants, morbidity and mortality are still substantially increased in comparison to infants born at term. There is an added survival benefit resulting from birth at a tertiary neonatal care center, and although many of these infants require tertiary level care, delivery at lower level hospitals and subsequent neonatal transfer are still common.
Our primary aim was to determine the impact of maternal characteristics and antenatal medical management on the early neonatal course of the moderately premature infant. The secondary aim was to create a clinical prediction rule to determine which infants require intubation and mechanical ventilation in the first 24 hours of life. Such a prediction rule could inform the decision to transfer maternal-fetal patients prior to delivery to a facility with a Level III Neonatal Intensive Care Unit (NICU), where optimal care could be provided without the requirement for a neonatal transfer.
Data for this analysis came from the cohort of infants in the Moderately Premature Infant Project (MPIP) database, a multi-center cohort study of 850 infants born at gestational age 30 0/7 to 34 6/7 weeks, who were discharged home alive. We built a logistic regression model to identify maternal characteristics associated with need for tertiary care, as measured by administration of surfactant. Using statistically significant covariates from this model, we then created a numerical decision rule to predict need for tertiary care.
In multivariate modeling, 4 factors were associated with reduction in the need for tertiary care, including, surfactant administration, including non-White race (OR=0.5, [0.3, 0.7], older gestational age, female gender (OR=0.6 [0.4, 0.8]) and use of antenatal corticosteroids (OR=0.5, [0.3, 0.8]). The clinical prediction rule to discriminate between infants who received surfactant, versus those who did not, had an area under the curve of 0.77 [0.73, 0.8].
Four antenatal risk factors are associated with a requirement for Level III NICU care as defined by the need for surfactant administration. Future analyses will examine a broader spectrum of antenatal characteristics and revalidate the prediction rule in an independent cohort.
infant; newborn; transport; clinical prediction rule; ROC Curve
Evaluate the efficacy of phototherapy (PT) devices and the outcomes of extremely premature infants treated with those devices.
This substudy of the National Institute of Child Health and Human Development Neonatal Research Network PT trial included 1404 infants treated with a single type of PT device during the first 24±12 h of treatment. The absolute (primary outcome) and relative decrease in total serum bilirubin (TSB) and other measures were evaluated. For infants treated with one PT type during the 2-week intervention period (n =1223), adjusted outcomes at discharge and 18 to 22 months corrected age were determined.
In the first 24 h, the adjusted absolute (mean (±s.d.)) and relative (%) decrease in TSB (mg dl−1) were: light-emitting diodes (LEDs) −2.2 (±3), −22%; Spotlights −1.7 (±2), −19%; Banks −1.3 (±3), −8%; Blankets −0.8 (±3), −1%; (P<0.0002). Some findings at 18 to 22 months differed between groups.
LEDs achieved the greatest initial absolute reduction in TSB but were similar to Spots in the other performance measures. Long-term effects of PT devices in extremely premature infants deserve rigorous evaluation.
extremely low birth weight; neonatal jaundice; neurodevelopmental outcome; phototherapy
To determine fatty acid levels in the US donor milk supply.
Donor human milk samples from Iowa (n=62), Texas (n=5), North Carolina (n=5), and California (n=5) were analyzed by gas chromatography. Levels in Iowa donor milk were compared before and after pasteurization using Student’s t-test. Docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels were compared among all milk banks using ANOVA.
ARA (0.4 pre, 0.4 post, p=0.18) and DHA (0.073 pre, 0.073 post, p=0.84) were not affected by pasteurization. DHA varied between banks (p <0.0001), whereas ARA did not (p = 0.3). DHA levels from all banks were lower than published values for maternal milk and infant formula (p<0.0001).
Pasteurization of breastmilk does not affect DHA or ARA levels. However, DHA content in US donor milk varies with bank location and may not meet the recommended provision for preterm infants.
Long chain polyunsaturated fatty acids (LCPUFA); docosahexaenoic acid (DHA); arachidonic acid (ARA); donor human milk; neonatal nutrition