Meconium "aspiration" (or respiratory distress associated with meconium-stained amniotic fluid?).

The designation meconium aspiration syndrome (MAS) reflects a spectrum of disorders in infants born with meconium-stained amniotic fluid, ranging from mild tachypnea to severe respiratory distress and significant mortality. The frequency of MAS is highest among infants with post-term gestation, thick meconium, and birth asphyxia. Pulmonary hypertension is an important component in severe cases. Prenatal hypopharyngeal suctioning and postnatal endotracheal intubation and suctioning of vigorous infants are not effective. Intubation and suctioning of non-breathing infants is controversial and needs more investigation. Oxygen, mechanical ventilation, and inhaled nitric oxide are the mainstays of treatment. Surfactant is often used in infants with severe parenchymal involvement. High-frequency ventilation and extracorporeal membrane oxygenation are usually considered rescue therapies.

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).

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.

Physical growth in the neonatal intensive-care unit and neuropsychological performance at preschool age in very preterm-born singletons.

We studied the associations between early postnatal growth gains and neuropsychological outcome in very preterm-born children. Specifically, we wished to establish whether relationships exist between gains in head circumference (relative to gains in body-weight or length), from birth to hospital discharge, and intellectual, language, or motor, performance at preschool age. We used data from 127 preschoolers, born <33 weeks, all graduates of the William Beaumont Hospital Neonatal Intensive-Care Unit (NICU) in Royal Oak, MI. Cognitive, motor, and language outcomes were evaluated using the Wechsler Preschool and Primary Scales of Intelligence-Revised, Peabody Developmental Scales - 2(nd) Edition, and the Preschool Language Scale - 3(rd) Edition, respectively. Differences between Z-scores at birth and hospital discharge, calculated for three anthropometric measures (head circumference, weight, length), were variables of interest in separate simultaneous multiple regression procedures. We statistically adjusted for sex, socioeconomic status, birth weight, length of hospitalization, perinatal complications, and intrauterine growth. Examination of the relationships between anthropometric indices and outcome measures revealed a significant association between NICU head growth and global intelligence, with the Z-difference score for head circumference accounting for a unique portion of the variance in global intelligence (ηp(2) =.04). Early postnatal head growth is significantly associated with neuropsychological outcome in very preterm-born preschoolers. To conclude, despite its relative brevity, NICU stay, often overlapping with the end of 2(nd) and with the 3(rd) trimester of pregnancy, appears to be a sensitive developmental period for brain substrates underlying neuropsychological functions.

Early blood gas predictors of bronchopulmonary dysplasia in extremely low gestational age newborns.

Aim. To determine among infants born before the 28th week of gestation to what extent blood gas abnormalities during the first three postnatal days provide information about the risk of bronchopulmonary dysplasia (BPD). Methods. We studied the association of extreme quartiles of blood gas measurements (hypoxemia, hyperoxemia, hypocapnea, and hypercapnea) in the first three postnatal days, with bronchopulmonary dysplasia, among 906 newborns, using multivariable models adjusting for potential confounders. We approximated NIH criteria by classifying severity of BPD on the basis of the receipt of any O2 on postnatal day 28 and at 36 weeks PMA and assisted ventilation. Results. In models that did not adjust for ventilation, hypoxemia was associated with increased risk of severe BPD and very severe BPD, while infants who had hypercapnea were at increased risk of very severe BPD only. In contrast, infants who had hypocapnea were at reduced risk of severe BPD. Including ventilation for 14 or more days eliminated the associations with hypoxemia and with hypercapnea and made the decreased risk of very severe BPD statistically significant. Conclusions. Among ELGANs, recurrent/persistent blood gas abnormalities in the first three postnatal days convey information about the risk of severe and very severe BPD.

Postnatal growth and neuropsychological performance in preterm-birth preschoolers.

OBJECTIVE: Compromised postnatal growth is an important risk factor accounting for poorer neuropsychological performance of preterm children during the preschool years, yet its unique contribution to explaining outcome variance within this high risk group has yet to be determined. Therefore, we examined within a large preterm sample (1) the relationships between head growth, measured either at birth or preschool age, and outcome; (2) the relationships of binary versus dimensional head growth measures and performance; and (3) the unique contribution of preschool-age head growth, after adjustment for general physical development (indexed by stature), to variance in neuropsychological functioning. METHOD: We evaluated 264 preterm (<36 weeks) preschoolers, without severe handicaps, using cognitive, language, and motor skill measures. Multiple regression analyses, adjusting for sociodemographic factors and pre-, peri-, and postnatal confounds, were used to study associations between growth indices and performance. RESULTS: While suboptimal head growth classification at birth was significantly associated only with motor performance, suboptimal head growth at preschool age explained a significant portion of variance in intellectual and language measures (g = .46 to .60). Treating preschool head size as a continuous dimension yielded null results, however, with body-height explaining a significant portion of the variance across several domains. CONCLUSION: Among postnatal anthropometric indices, preschool stature, rather than head circumference, remains a consistent correlate of preschool outcome in preterm children, highlighting the contribution of general physical development to neuropsychological performance. Further investigation of the underlying mechanisms likely involves exploration of complex relationships between postnatal nutrition, growth hormone levels, body and brain development, and neuropsychological functioning.

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.

Intrauterine growth and neuropsychological performance in very low birth weight preschoolers.

In this study we examined the association between intrauterine growth, indexed either as a categorical variable or continuous dimension, and neuropsychological outcome, in a very low birth weight (VLBW) sample of 143 preschoolers. When the commonly used split at the 10th percentile rank was applied to classify intrauterine growth restriction (IUGR), we found that the growth restricted group (n = 25) exhibited significantly poorer performance in the global motor domain, but not on any other neuropsychological measure. In contrast, when adequacy of intrauterine growth was indexed by standardized birth weight, a continuous dimension, this early risk factor explained a unique portion of the variance in global cognitive abilities and visuospatial skills, as well as in global, fine, and gross motor skills. These findings are consistent with recent magnetic resonance imaging data disclosing global neurodevelopmental changes in the brains of preterm infants with IUGR. When cases classified with IUGR (<10th percentile) were excluded, the relationship between adequacy of intrauterine growth and global cognitive abilities remained significant despite range restriction. Hence, an association between appropriateness of intrauterine growth and global intellectual outcome may be observed even within the population of VLBW preschoolers with adequate standardized birth weight.

Neonatal respiratory dysfunction and neuropsychological performance at the preschool age: a study of very preterm infants with bronchopulmonary dysplasia.

OBJECTIVE: The neuropsychological outcome of chronic lung disease (CLD) in the very preterm (VP) infant may be determined by a process involving chronic hypoxia, with superimposed acute hypoxic episodes, in the developing brain. We wished to study the differences in quality of outcome between VP preschoolers with and without history of the most common form of CLD in the preterm infant, bronchopulmonary dysplasia (BPD). We also examined the strength of association between BPD severity and neuropsychological outcome, with degree of severity defined according to the National Institute of Child Health and Human Development (NICHD) National Heart, Lung and Blood Institute (NHLBI) Workshop categorical ranking scheme (Jobe & Bancalari, 2001) or in accord with dimensional views of severity of respiratory illness. METHOD: We evaluated the intellectual, language, and motor outcomes of 156, predominantly middle-class preschoolers with history of VP birth, with (n = 80) or without (n = 76) BPD. We used supplemental oxygen requirement or need for mechanical ventilation as indirect indexes of respiratory dysfunction. RESULTS: Following adjustment for potentially confounding sociodemographic variables and perinatal medical risk factors, we found no group differences in neuropsychological outcome based on categorical ranking of BPD severity. However, continuous measures of BPD severity accounted for a unique portion of the variance in fine motor performance (η²p = .05), while patent ductus arteriosus, a risk marker or antecedent of BPD, explained a unique portion of the variance in both receptive language (η²p = .048), and gross motor (η²p = .061) function. CONCLUSION: A significant, yet circumscribed, association was demonstrated between neonatal hypoxic risk, in the VP infant, and neuropsychological outcome assessed in the preschool years.

Extremely preterm infant mortality rates and cesarean deliveries in the United States.

OBJECTIVES: To estimate trends in infant mortality rates and cesarean delivery rates for extremely preterm infants born in the United States. METHODS: This national population-based study used public data from the Centers for Disease Control and Prevention to investigate extremely preterm infants born alive between 22 0/7 and 27 6/7 weeks of gestational age from 1999 to 2005. RESULTS: There were 177,552 extremely preterm infant births (fewer than 1% of all births) from 1999 to 2005. The number of annual extremely preterm births increased by 7% compared with a 4.5% increase for births at all gestations. During the study years, the extremely preterm infant mortality rate (percentage of infants who died in the first year) remained steady (range 33-34%; P=.22), whereas the cesarean delivery rate increased from 43% to 54% (P<.001). The infant mortality rate after cesarean delivery increased from 24% to 26% (P=.012). At each gestational age, the annual cesarean delivery rate increased over time (P<.001 for each), whereas gestational age-specific infant mortality rates were unchanged except for a 2% decline from 2004 to 2005 for infants born at 24 weeks of gestation (P=.01). CONCLUSION: A significant rise in the cesarean delivery rate in the United States from 1999 to 2005 for infants born at less than 28 weeks of gestation was not associated with an improvement in the infant mortality rate.

Early postnatal hypotension and developmental delay at 24 months of age among extremely low gestational age newborns.

OBJECTIVES: To evaluate in extremely low gestational age newborns, relationships between indicators of hypotension during the first 24 postnatal hours and developmental delay at 24 months of age. METHODS: The 945 infants in this prospective study were born at <28 weeks, were assessed for three indicators of hypotension in the first 24 postnatal hours, and were evaluated with the Bayley Mental Development Index (MDI) and Psychomotor Development Index (PDI) at 24 months corrected age. Indicators of hypotension included: (1) mean arterial pressure in the lowest quartile for gestational age; (2) treatment with a vasopressor; and (3) blood pressure lability, defined as the upper quartile for the difference between the lowest and highest mean arterial pressure. Logistic regression was used to evaluate relationships between hypotension and developmental outcomes, adjusting for potential confounders. RESULTS: 78% of infants in this cohort received volume expansion or vasopressor; all who received a vasopressor were treated with volume expansion. 26% had an MDI <70 and 32% had a PDI <70. Low MDI and PDI were associated with low gestational age, which in turn, was associated with receipt of vasopressor treatment. Blood pressure in the lowest quartile for gestational age was associated with vasopressor treatment and labile blood pressure. After adjusting for potential confounders, none of the indicators of hypotension were associated with MDI <70 or PDI <70. CONCLUSIONS: In this large cohort of extremely low gestational age newborns, we found little evidence that early postnatal hypotension indicators are associated with developmental delay at 24 months corrected gestational age.

One hundred consecutive infants born at 23 weeks and resuscitated.

We sought to delineate the in-hospital outcome for infants born alive and universally resuscitated at an estimated gestational age (GA) of 23(0)/(7) to 23(6)/(7) weeks and to document when and why death occurred. We performed a cohort study of prospectively collected data on 100 consecutive infants born alive at 23 weeks GA from June 16, 1990 through August 6, 2006. All deliveries were attended by a neonatologist and resuscitation was universally attempted. At the time of death, a primary cause was determined by the attending neonatologist. Forty infants survived and 60 died prior to hospital discharge. Survivors were more likely to have higher Apgar scores and be male gender. Ten infants could not be resuscitated and died in the delivery room. Twenty-eight other infants died in the first 4 days mainly from respiratory failure (10 from respiratory distress syndrome [RDS], 12 from RDS with interstitial emphysema, 5 from RDS with pulmonary hemorrhage). Twenty-two infants died after day 4 (8 from respiratory failure, 10 from necrotizing enterocolitis, and 4 from sepsis). In our experience, universal resuscitation at 23 weeks' estimated GA resulted in a survival rate of 40%.

Reader variability in the use of diagnostic terms to describe white matter lesions seen on cranial scans of severely premature infants: the ELGAN study.

PURPOSE: To evaluate reader variability of white matter lesions seen on cranial sonographic scans of extreme low gestational age neonates (ELGANs). METHODS: In 1,452 ELGANs, cranial sonographic scans were obtained in the first and second postnatal weeks, and between the third postnatal week and term. All sets of scans were read independently by two sonologists. We reviewed the use of four diagnostic labels: early periventricular leucomalacia, cystic periventricular leucomalacia, periventricular hemorrhagic infarction (PVHI), and other white matter diagnosis, by 16 sonologists at 14 institutions. We evaluated the association of these labels with location and laterality of hyperechoic and hypoechoic lesions, location of intraventricular hemorrhage, and characteristics of ventricular enlargement. RESULTS: Experienced sonologists differed substantially in their application of the diagnostic labels. Three readers applied early periventricular leucomalacia to more than one fourth of all the scans they read, whereas eight applied this label to ≤5% of scans. Five applied PVHI to ≥10% of scans, while three applied this label to ≤5% of scans. More than one third of scans labeled cystic periventricular leucomalacia had unilateral hypoechoic lesions. White matter abnormalities in PVHI were more extensive than in periventricular leucomalacia and were more anteriorly located. Hypoechoic lesions on late scans tended to be in the same locations, regardless of the diagnostic label applied. CONCLUSIONS: Experienced sonologists differ considerably in their tendency to apply diagnostic labels for white matter lesions. This is due to lack of universally agreed-upon definitions. We recommend reducing this variability to improve the validity of large multicenter studies.

Extreme prematurity and neuropsychological outcome in the preschool years.

With the increasing survival of extremely preterm (EP) birth infants in the surfactant era, the longer-term outcome of infants born at the threshold of viability has become a vital topic of study. The goal of this investigation was twofold. First, while taking into account the influence of sociodemographic confounds, we wished to investigate neuropsychological outcome differences between two groups of EP preschoolers: 23-24 weeks (n = 20), and 25-26 weeks' (n = 21) gestation at delivery. Second, we wished to explore whether, within the population of EP preschoolers, gestational maturity accounts for a unique portion of the variance in neuropsychological outcome, over and above the variance explained by ante-, peri-, and neonatal complications, or treatment factors. The findings revealed group differences, ranging from .70 to .80 of a standard deviation in general intellectual abilities, nonverbal intelligence, and global motor performance, in favor of the more mature EP group. Additionally, gestational maturity was found to explain a unique portion of the variance in global intellectual and motor abilities. These findings are interpreted from the perspective that gestational age is an index of the vulnerability of the central nervous system to disruption of developmentally regulated processes.

Clinical report--Antenatal counseling regarding resuscitation at an extremely low gestational age.

The anticipated delivery of an extremely low gestational age infant raises difficult questions for all involved, including whether to initiate resuscitation after delivery. Each institution caring for women at risk of delivering extremely preterm infants should provide comprehensive and consistent guidelines for antenatal counseling. Parents should be provided the most accurate prognosis possible on the basis of all the factors known to affect outcome for a particular case. Although it is not feasible to have specific criteria for when the initiation of resuscitation should or should not be offered, the following general guidelines are suggested. If the physicians involved believe there is no chance for survival, resuscitation is not indicated and should not be initiated. When a good outcome is considered very unlikely, the parents should be given the choice of whether resuscitation should be initiated, and clinicians should respect their preference. Finally, if a good outcome is considered reasonably likely, clinicians should initiate resuscitation and, together with the parents, continually reevaluate whether intensive care should be continued. Whenever resuscitation is considered an option, a qualified individual, preferably a neonatologist, should be involved and should be present in the delivery room to manage this complex situation. Comfort care should be provided for all infants for whom resuscitation is not initiated or is not successful.

Cranial ultrasound lesions in the NICU predict cerebral palsy at age 2 years in children born at extremely low gestational age.

Our prospective cohort study of extremely low gestational age newborns evaluated the association of neonatal head ultrasound abnormalities with cerebral palsy at age 2 years. Cranial ultrasounds in 1053 infants were read with respect to intraventricular hemorrhage, ventriculomegaly, and echolucency, by multiple sonologists. Standardized neurological examinations classified cerebral palsy, and functional impairment was assessed. Forty-four percent with ventriculomegaly and 52% with echolucency developed cerebral palsy. Compared with no ultrasound abnormalities, children with echolucency were 24 times more likely to have quadriparesis and 29 times more likely to have hemiparesis. Children with ventriculomegaly were 17 times more likely to have quadriparesis or hemiparesis. Forty-three percent of children with cerebral palsy had normal head ultrasound. Focal white matter damage (echolucency) and diffuse damage (late ventriculomegaly) are associated with a high probability of cerebral palsy, especially quadriparesis. Nearly half the cerebral palsy identified at 2 years is not preceded by a neonatal brain ultrasound abnormality.

Observer variability assessing US scans of the preterm brain: the ELGAN study.

BACKGROUND: Neurosonography can assist clinicians and can provide researchers with documentation of brain lesions. Unfortunately, we know little about the reliability of sonographically derived diagnoses. OBJECTIVE: We sought to evaluate observer variability among experienced neurosonologists. MATERIALS AND METHODS: We collected all protocol US scans of 1,450 infants born before the 28th postmenstrual week. Each set of scans was read by two independent sonologists for the presence of intraventricular hemorrhage (IVH) and moderate/severe ventriculomegaly, as well as hyperechoic and hypoechoic lesions in the cerebral white matter. Scans read discordantly for any of these four characteristics were sent to a tie-breaking third sonologist. RESULTS: Ventriculomegaly, hypoechoic lesions and IVH had similar rates of positive agreement (68-76%), negative agreement (92-97%), and kappa values (0.62 to 0.68). Hyperechoic lesions, however, had considerably lower values of positive agreement (48%), negative agreement (84%), and kappa (0.32). No sonologist identified all abnormalities more or less often than his/her peers. Approximately 40% of the time, the tie-breaking reader agreed with the reader who identified IVH, ventriculomegaly, or a hypoechoic lesion in the white matter. Only about 25% of the time did the third party agree with the reader who reported a white matter hyperechoic lesion. CONCLUSION: Obtaining concordance seems to be an acceptable way to assure reasonably high-quality of images needed for clinical research.