It is important to determine if rates of survival and major neurodevelopmental impairment in extremely low gestational age newborns (ELGANs; infants born at 23–27 weeks gestation) are changing over time.
Study infants were born at 23 to 27 weeks of gestation without congenital anomalies at a tertiary medical center between July 1, 1990 and June 30, 2000, to mothers residing in a thirteen-county region in North Carolina. Outcomes at one year adjusted age were compared for two epochs of birth: epoch 1, July 1, 1990 to June 30, 1995; epoch 2, July 1, 1995 to June 30, 2000. Major neurodevelopmental impairment was defined as cerebral palsy, Bayley Scales of Infant Development Mental Developmental Index more than two standard deviations below the mean, or blindness.
Survival of ELGANs, as a percentage of live births, was 67% [95% confidence interval: (61, 72)] in epoch 1 and 71% (65, 75) in epoch 2. Major neurodevelopmental impairment was present in 20% (15, 27) of survivors in epoch 1 and 14% (10, 20) in epoch 2. When adjusted for gestational age, survival increased [odds ratio 1.5 (1.0, 2.2), p = .03] and major neurodevelopmental impairment decreased [odds ratio 0.54 (0.31, 0.93), p = .02] from epoch 1 to epoch 2.
The probability of survival increased while that of major neurodevelopmental impairment decreased during the 1990's in this regionally based sample of ELGANs.
Objective To assess the impact of reorganisation of neonatal specialist care services in England after a UK Department of Health report in 2003.
Design A population-wide observational comparison of outcomes over two epochs, before and after the establishment of managed clinical neonatal networks.
Setting Epoch one: 294 maternity and neonatal units in England, Wales, and Northern Ireland, 1 September 1998 to 31 August 2000, as reported by the Confidential Enquiry into Stillbirths and Sudden Deaths in Infancy Project 27/28. Epoch two: 146 neonatal units in England contributing data to the National Neonatal Research Database at the Neonatal Data Analysis Unit, 1 January 2009 to 31 December 2010.
Participants Babies born at a gestational age of 27+0-28+6 (weeks+days): 3522 live births in epoch one; 2919 babies admitted to a neonatal unit within 28 days of birth in epoch two.
Intervention The national reorganisation of neonatal services into managed clinical networks.
Main outcome measures The proportion of babies born at hospitals providing the highest volume of neonatal specialist care (≥2000 neonatal intensive care days annually), having an acute transfer (within the first 24 hours after birth) and/or a late transfer (between 24 hours and 28 days after birth) to another hospital, assessed by change in distribution of transfer category (“none,” “acute,” “late”), and babies from multiple births separated by transfer. For acute transfers in epoch two, the level of specialist neonatal care provided at the destination hospital (British Association of Perinatal Medicine criteria).
Results After reorganisation, there were increases in the proportions of babies born at 27-28 weeks’ gestation in hospitals providing the highest volume of neonatal specialist care (18% (631/3495) v 49% (1325/2724); odds ratio 4.30, 95% confidence interval 3.83 to 4.82; P<0.001) and in acute and late postnatal transfers (7% (235) v 12% (360) and 18% (579) v 22% (640), respectively; P<0.001). There was no significant change in the proportion of babies from multiple births separated by transfer (33% (39) v 29% (38); 0.86, 0.50 to 1.46; P=0.57). In epoch two, 32% of acute transfers were to a neonatal unit providing either an equivalent (n=87) or lower (n=26) level of specialist care.
Conclusions There is evidence of some improvement in the delivery of neonatal specialist care after reorganisation. The increase in acute transfers in epoch two, in conjunction with the high proportion transferred to a neonatal unit providing an equivalent or lower level of specialist care, and the continued separation of babies from multiple births, are indicative of poor coordination between maternity and neonatal services to facilitate in utero transfer before delivery, and continuing inadequacies in capacity of intensive care cots. Historical data representing epoch one are available only in aggregate form, preventing examination of temporal trends or confounding factors. This limits the extent to which differences between epochs can be attributed to reorganisation and highlights the importance of routine, prospective data collection for evaluation of future health service reorganisations.
Objectives To compare changes in inequalities in sudden infant death syndrome with other causes of infant mortality and stillbirth in Scotland, 1985-2008.
Design Retrospective cohort study.
Setting Scotland 1985-2008, analysed by four epochs of six years.
Participants Singleton births of infants with birth weight >500 g born at 28-43 weeks’ gestation.
Main outcome measures Sudden infant death syndrome, other causes of postneonatal infant death, neonatal death, and stillbirth. Odds ratios expressed as the association across the range of seven categories of Carstairs deprivation score.
Results The association between deprivation and the risk of all cause stillbirth and infant death varied between the four epochs (P=0.04). This was wholly explained by variation in the risk of sudden infant death syndrome (P<0.001 for interaction). Among women living in areas of low deprivation, there was a sharp decline in the rate of sudden infant death syndrome from 1990 to 1993. Among women living in areas of high deprivation, there was a slower decline in sudden infant death syndrome rates between 1992 and 2004. Consequently, the odds ratio for the association between socioeconomic deprivation and sudden infant death syndrome increased from 2.04 (95% confidence interval 1.53 to 2.72) in 1985-90, to 7.52 (4.62 to 12.25) in 1991-6, and 9.50 (5.46 to 16.53) in 1997-2002 but fell to 1.78 (0.87 to 3.65) in 2002-8. The interaction remained significant after adjustment for maternal characteristics.
Conclusion The rate of sudden infant death syndrome declined throughout Scotland in the early 1990s. The decline had a later onset and was slower among women living in areas of high deprivation, probably because of slower uptake of recommended changes in infant sleeping position. The effect was to create a strong independent association between deprivation and sudden infant death syndrome where one did not exist before.
Rationale: Benefits of identifying risk factors for bronchopulmonary dysplasia in extremely premature infants include providing prognostic information, identifying infants likely to benefit from preventive strategies, and stratifying infants for clinical trial enrollment.
Objectives: To identify risk factors for bronchopulmonary dysplasia, and the competing outcome of death, by postnatal day; to identify which risk factors improve prediction; and to develop a Web-based estimator using readily available clinical information to predict risk of bronchopulmonary dysplasia or death.
Methods: We assessed infants of 23–30 weeks' gestation born in 17 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and enrolled in the Neonatal Research Network Benchmarking Trial from 2000–2004.
Measurements and Main Results: Bronchopulmonary dysplasia was defined as a categorical variable (none, mild, moderate, or severe). We developed and validated models for bronchopulmonary dysplasia risk at six postnatal ages using gestational age, birth weight, race and ethnicity, sex, respiratory support, and FiO2, and examined the models using a C statistic (area under the curve). A total of 3,636 infants were eligible for this study. Prediction improved with advancing postnatal age, increasing from a C statistic of 0.793 on Day 1 to a maximum of 0.854 on Day 28. On Postnatal Days 1 and 3, gestational age best improved outcome prediction; on Postnatal Days 7, 14, 21, and 28, type of respiratory support did so. A Web-based model providing predicted estimates for bronchopulmonary dysplasia by postnatal day is available at https://neonatal.rti.org.
Conclusions: The probability of bronchopulmonary dysplasia in extremely premature infants can be determined accurately using a limited amount of readily available clinical information.
bronchopulmonary dysplasia; prematurity; low-birth-weight infant
This report presents data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network on care of and morbidity and mortality rates for very low birth weight infants, according to gestational age (GA).
Perinatal/neonatal data were collected for 9575 infants of extremely low GA (22–28 weeks) and very low birth weight (401–1500 g) who were born at network centers between January 1, 2003, and December 31, 2007.
Rates of survival to discharge increased with increasing GA (6% at 22 weeks and 92% at 28 weeks); 1060 infants died at ≤ 12 hours, with most early deaths occurring at 22 and 23 weeks (85% and 43%, respectively). Rates of prenatal steroid use (13% and 53%, respectively), cesarean section (7% and 24%, respectively), and delivery room intubation (19% and 68%, respectively) increased markedly between 22 and 23 weeks. Infants at the lowest GAs were at greatest risk for morbidities. Overall, 93% had respiratory distress syndrome, 46% patent ductus arteriosus, 16% severe intraventricular hemorrhage, 11% necrotizing enterocolitis, and 36% late-onset sepsis. The new severity-based definition of bronchopulmonary dysplasia classified more infants as having bronchopulmonary dysplasia than did the traditional definition of supplemental oxygen use at 36 weeks (68%, compared with 42%). More than one-half of infants with extremely low GAs had undetermined retinopathy status at the time of discharge. Center differences in management and outcomes were identified.
Although the majority of infants with GAs of ≥24 weeks survive, high rates of morbidity among survivors continue to be observed.
extremely low gestation; very low birth weight; morbidity; death
To determine (1) the magnitude of clustering of bronchopulmonary dysplasia (36 weeks) or death (the outcome) across centers of the Eunice Kennedy Shriver National Institute of Child and Human Development National Research Network, (2) the infant-level variables associated with the outcome and estimate their clustering, and (3) the center-specific practices associated with the differences and build predictive models.
Data on neonates with a birth weight of <1250 g from the cluster-randomized benchmarking trial were used to determine the magnitude of clustering of the outcome according to alternating logistic regression by using pairwise odds ratio and predictive modeling. Clinical variables associated with the outcome were identified by using multivariate analysis. The magnitude of clustering was then evaluated after correction for infant-level variables. Predictive models were developed by using center-specific and infant-level variables for data from 2001 2004 and projected to 2006.
In 2001–2004, clustering of bronchopulmonary dysplasia/death was significant (pairwise odds ratio: 1.3; P < .001) and increased in 2006 (pairwise odds ratio: 1.6; overall incidence: 52%; range across centers: 32%–74%); center rates were relatively stable over time. Variables that varied according to center and were associated with increased risk of outcome included lower body temperature at NICU admission, use of prophylactic indomethacin, specific drug therapy on day 1, and lack of endotracheal intubation. Center differences remained significant even after correction for clustered variables.
Bronchopulmonary dysplasia/death rates demonstrated moderate clustering according to center. Clinical variables associated with the outcome were also clustered. Center differences after correction of clustered variables indicate presence of as-yet unmeasured center variables.
logistic models; infant; premature; predictive value of tests; clustering
The increased survival of infants born at extremely low birthweight (ELBW) has been associated with significant morbidity, including higher rates of neurodevelopmental disability. However, formalized testing to evaluate these problems is both time-consuming and costly. The revised Functional Status questionnaire (FS-II) was designed to assess caregivers’ perceptions of the functional status of children with chronic diseases.
We evaluated the reliability and validity of the FS-II for ELBW infants at 18 to 22 months corrected age using data from the US Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN). Exploratory factor analyses were conducted using data from the network’s first follow-up study of 1080 children born in 1993 to 1994 (508 males, 572 females [53%]), and results were confirmed using data from the next network follow-up of 4022 children born in 1995 to 2000 (1864 males, 2158 females [54%]).
Results suggest that a two-factor solution comprising measures of general health and independence is most appropriate for ELBW infants. These factors differed from those found among chronically ill children, and new, more appropriate scales are presented for screening ELBW survivors. Both scales demonstrated good internal consistency: Cronbach’s α=0.87 for general health and α=0.75 for independence. Construct validity of the scales was assessed by comparing mean scores on the scales according to scores on the Bayley Scales of Infant Development, second edition (BSID-II), and medical conditions.
As hypothesized, infants with greater functional impairments according to their BSID-II scores or medical conditions had lower scores on the general health and independence scales, supporting the validity of the scales.
Death remains a common event in the neonatal intensive care unit, and often involves limitation or withdrawal of life sustaining treatment.
To document changes in the causes of death and its management over the last two decades.
An audit of infants dying in the neonatal intensive care unit was performed during two epochs (1985–1987 and 1999–2001). The principal diagnoses of infants who died were recorded, as well as their apparent prognoses, and any decisions to limit or withdraw medical treatment.
In epoch 1, 132 infants died out of 1362 admissions (9.7%), and in epoch 2 there were 111 deaths out of 1776 admissions (6.2%; p<0.001). Approximately three quarters of infants died after withdrawal of life sustaining treatment in both epochs. There was a significant reduction in the proportion of deaths from chromosomal abnormalities, and from neural tube defects in epoch 2.
There have been substantial changes in the illnesses leading to death in the neonatal intensive care unit. These may reflect the combined effects of prenatal diagnosis and changing community and medical attitudes.
palliative care; withholding treatment; intensive care
Retinopathy of prematurity (ROP) significantly increased in New South Wales (NSW) from 1986 to 1994, but more recent data suggest that there has now been a decrease.
To study the incidence and treatment of severe ROP (stage ⩾3) in NSW and the Australian Capital Territory (ACT) from 1992 to 2002.
Data collected prospectively from the Neonatal Intensive Care Units' (NICUS) Data Collection over an 11‐year period in infants <30 weeks' gestation were divided into four epochs and analysed retrospectively. The incidence and treatment of severe ROP were compared for gestational ages ⩽24 weeks', 25–26 weeks' and 27–29 weeks' gestation over the four epochs.
In infants ⩽24 weeks' gestation the incidence of severe ROP and those treated increased significantly (stage ⩾3: from 17 (41.5%) to 41 (53.9%), p = 0.052; treated: from 8 (19.5%) to 25 (32.9%), p<0.05 (first and fourth epoch)). In infants 25–26 weeks' gestation the incidence of severe ROP decreased significantly whereas there was a non‐significant increase in those treated (stage ⩾3: from 55 (26.2%) to 46 (19.3%), p<0.05; treated: from 19 (9.0%) to 32 (13.4%)). In infants 27–29 weeks' gestation, there was no significant change in the incidence of severe ROP or those treated (stage ⩾3: from 30 (4.1%) to 17 (2.4%); treated: from 14 (1.9%) to 8 (1.1%)).
In infants ⩽24 weeks' gestation there has been a significant increase in severe ROP, and in infants <27 weeks' gestation the numbers treated for severe ROP increased.
retinopathy of prematurity; preterm infants; cryo‐therapy and laser therapy
Because of increased rates of respiratory complications, elective cesarean delivery is discouraged before 39 weeks of gestation unless there is evidence of fetal lung maturity. We assessed associations between elective cesarean delivery at term (37 weeks of gestation or longer) but before 39 weeks of gestation and neonatal outcomes.
We studied a cohort of consecutive patients undergoing repeat cesarean sections performed at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network from 1999 through 2002. Women with viable singleton pregnancies delivered electively (i.e., before the onset of labor and without any recognized indications for delivery before 39 weeks of gestation) were included. The primary outcome was the composite of neonatal death and any of several adverse events, including respiratory complications, treated hypoglycemia, newborn sepsis, and admission to the neonatal intensive care unit (ICU).
Of 24,077 repeat cesarean deliveries at term, 13,258 were performed electively; of these, 35.8% were performed before 39 completed weeks of gestation (6.3% at 37 weeks and 29.5% at 38 weeks) and 49.1% at 39 weeks of gestation. One neonatal death occurred. As compared with births at 39 weeks, births at 37 weeks and at 38 weeks were associated with an increased risk of the primary outcome (adjusted odds ratio for births at 37 weeks, 2.1; 95% confidence interval [CI], 1.7 to 2.5; adjusted odds ratio for births at 38 weeks, 1.5; 95% CI, 1.3 to 1.7; P for trend <0.001). The rates of adverse respiratory outcomes, mechanical ventilation, newborn sepsis, hypoglycemia, admission to the neonatal ICU, and hospitalization for 5 days or more were increased by a factor of 1.8 to 4.2 for births at 37 weeks and 1.3 to 2.1 for births at 38 weeks.
Elective repeat cesarean delivery before 39 weeks of gestation is common and is associated with respiratory and other adverse neonatal outcomes.
BACKGROUND AND OBJECTIVES:
Extremely low gestational age neonates are more likely than term infants to develop cognitive impairment. Few studies have addressed antenatal risk factors of this condition. We identified antenatal antecedents of cognitive impairment determined by the Mental Development Index (MDI) portion of the Bayley Scales of Infant Development, Second Edition (BSID-II), at 24 months corrected age.
We studied a multicenter cohort of 921 infants born before 28 weeks of gestation during 2002 to 2004 and assessed their placentas for histologic characteristics and microorganisms. The mother was interviewed and her medical record was reviewed. At 24 months adjusted age, children were assessed with BSID-II. Multinomial logistic models were used to estimate odds ratios.
A total of 103 infants (11%) had an MDI <55, and 99 infants (11%) had an MDI between 55 and 69. No associations were identified between organisms recovered from the placenta and developmental delay. Factors most strongly associated with MDI <55 were thrombosis of fetal vessels (OR 3.1; 95% confidence interval [CI] 1.2, 7.7), maternal BMI >30 (OR 2.0; 95% CI 1.1, 3.5), maternal education ≤12 years (OR 3.4; 95% CI 1.9, 6.2), nonwhite race (OR 2.2; 95% CI 1.3, 3.8), birth weight z score < −2 (OR 2.8; 95% CI 1.1, 6.9), and male gender (OR 2.7; 95% CI 1.6, 4.5).
Antenatal factors, including thrombosis of fetal vessels in the placenta, severe fetal growth restriction, and maternal obesity, convey information about the risk of cognitive impairment among extremely premature newborns.
prematurity; placenta; chorioamnionitis; fetal growth restriction; mental development
To evaluate the effect of antenatal indomethacin exposure on neurodevelopmental outcomes of premature infants.
A retrospective cohort study was performed to compare neurodevelopmental outcomes between premature infants exposed to antenatal indomethacin and infants unexposed to antenatal indomethacin. Inclusion criteria included all 23 – 29 weeks’ gestational age infants delivered between January, 1998 and December, 2002 and who had neurodevelopmental evaluation performed at 16–24 months corrected age. Out born infants and those with major congenital malformations or chromosomal problems were excluded. Continuous and categorical variables were analyzed using t-test and chi-square test, respectively.
87 infants met inclusion criteria. Of 87 infants, 29 infants were exposed to antenatal indomethacin (mean dose 267 mg and median duration 3 days) and 58 infants were unexposed to antenatal indomethacin. There were no significant differences between the two groups in clinical characteristics except for gestational age, mode of delivery and antenatal steroid exposure. There was no significant difference in major neurosensory abnormality (cerebral palsy and/or deafness and/or blindness); however the proportion of infants with sub-normal Bayley-Mental Developmental Index (MDI ≤ 70) and neurodevelopmental impairment (neurosensory abnormality and/or MDI ≤ 70) was significantly less in the group exposed to antenatal indomethacin compared to unexposed group. When controlled for confounders including antenatal steroids, antenatal indomethacin was not associated with MDI ≤ 70 (Odds ratio (OR) 0.44, 95% CI 0.12–1.5) and neurodevelopmental impairment (OR 0.4, 95% CI 0.13–1.2) using logistic regression. Subgroup analysis of 12 infants exposed to antenatal indomethacin within 48 hours of birth was not associated with neurodevelopmental impairment (OR 0.2, 95% CI 0.03–1.02) compared to unexposed group.
Antenatal indomethacin is not associated with abnormal neurodevelopmental outcome in infants ≤ 29 weeks gestational age.
Tocolysis; Antenatal Indomethacin; Neurodevelopment; Premature infants
Survival and outcomes for preterm infants with respiratory distress syndrome (RDS) have improved over the past 30 years. We conducted a study to assess the changes in perinatal care and delivery room management and their impact on respiratory outcome of very low birth weight newborns, over the last 15 years. A comparison between two epochs was performed, the periods before and after 2005, when early nasal continuous positive airway pressure (NCPAP) and Intubation-SURfactant-Extubation (INSURE) were introduced in our center. Three hundred ninety-five clinical records were assessed, 198 (50.1%) females, gestational age 29.1 weeks (22–36), and birth weight 1130 g (360–1498). RDS was diagnosed in 247 (62.5%) newborns and exogenous surfactant was administered to 217 (54.9%). Thirty-three (8.4%) developed bronchopulmonary dysplasia (BPD), and 92 (23%) were deceased. With the introduction of early NCPAP and INSURE, there was a decrease on the endotracheal intubation need and invasive ventilation (P < 0.0001), oxygen therapy (P = 0.002), and mortality (P < 0.0001). The multivariate model revealed a nonsignificant reduction in BPD between the two epochs (OR = 0.86; 95% CI 0.074–9.95; P = 0.9). The changes in perinatal care over the last 15 years were associated to an improvement of respiratory outcome and survival, despite a nonsignificant decrease in BPD rate.
The eyes of 177 very preterm (less than 33 weeks' gestation) infants, born between 1979 and 1982 and admitted to a neonatal intensive care unit, were examined as part of an ongoing follow-up study of neurodevelopmental outcome. Ocular pathology was diagnosed in 37 (21%) of the 177 infants: 14 (8%) had retinopathy of prematurity (ROP)--progressive in three--and nine (5%) infants had delayed visual maturation (DVM). The ocular pathology was permanent in 26 (15%) of the 177 infants. Refractive errors were the commonest problem and accounted for permanent sequelae in eight of the 14 infants with ROP and two of the nine with DVM. The presence or absence of ROP was related to a wide range of prospectively coded perinatal variables and to the results of routine neonatal ultrasound brain scans and neurodevelopmental follow-up assessments made in the first 18 months of life. As in previous studies, infants with ROP were of shorter gestation, lower birth weight, and required oxygen therapy for longer than unaffected infants, but the condition was only weakly associated with other indices of respiratory illness. In contrast, ROP was strongly associated with evidence of brain damage, often consistent with hypoxic ischaemic injury. We conclude that an underlying lesion in ROP may be hypoxic ischaemic damage to the retinal circulation.
To identify sensitive periods of postnatal growth for preterm infants relative to neurodevelopment at 18 months' corrected age.
PATIENTS AND METHODS:
We studied 613 infants born at <33 weeks' gestation who participated in the DHA for Improvement of Neurodevelopmental Outcome trial. We calculated linear slopes of growth in weight, length, BMI, and head circumference from 1 week of age to term (40 weeks' postmenstrual age), term to 4 months, and 4 to 12 months, and we estimated their associations with Bayley Scales of Infant Development, 2nd Edition, Mental (MDI) and Psychomotor (PDI) Development Indexes in linear regression.
The median gestational age was 30 (range: 2–33) weeks. Mean ± SD MDI was 94 ± 16, and PDI was 93 ± 16. From 1 week to term, greater weight gain (2.4 MDI points per z score [95% confidence interval (CI): 0.8–3.9]; 2.7 PDI points [95% CI: 1.2–.2]), BMI gain (1.7 MDI points [95% CI: 0.4–3.1]; 2.5 PDI points [95% CI: 1.2–3.9]), and head growth (1.4 MDI points [95% CI: −0.0–2.8]; 2.5 PDI points [95% CI: 1.2–3.9]) were associated with higher scores. From term to 4 months, greater weight gain (1.7 points [95% CI: 0.2–3.1]) and linear growth (2.0 points [95% CI: 0.7–3.2]), but not BMI gain, were associated with higher PDI. From 4 to 12 months, none of the growth measures was associated with MDI or PDI score.
In preterm infants, greater weight and BMI gain to term were associated with better neurodevelopmental outcomes. After term, greater weight gain was also associated with better outcomes, but increasing weight out of proportion to length did not confer additional benefit.
growth; motor development; cognitive development; preterm infants
Extremely low birth weight infants often require rehospitalization during infancy. Our objective was to identify at the time of discharge which extremely low birth weight infants are at higher risk for rehospitalization.
Data from extremely low birth weight infants in Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers from 2002–2005 were analyzed. The primary outcome was rehospitalization by the 18- to 22-month follow-up, and secondary outcome was rehospitalization for respiratory causes in the first year. Using variables and odds ratios identified by stepwise logistic regression, scoring systems were developed with scores proportional to odds ratios. Classification and regression-tree analysis was performed by recursive partitioning and automatic selection of optimal cutoff points of variables.
A total of 3787 infants were evaluated (mean ± SD birth weight: 787 ± 136 g; gestational age: 26 ± 2 weeks; 48% male, 42% black). Forty-five percent of the infants were rehospitalized by 18 to 22 months; 14.7% were rehospitalized for respiratory causes in the first year. Both regression models (area under the curve: 0.63) and classification and regression-tree models (mean misclassification rate: 40%–42%) were moderately accurate. Predictors for the primary outcome by regression were shunt surgery for hydrocephalus, hospital stay of >120 days for pulmonary reasons, necrotizing enterocolitis stage II or higher or spontaneous gastrointestinal perforation, higher fraction of inspired oxygen at 36 weeks, and male gender. By classification and regression-tree analysis, infants with hospital stays of >120 days for pulmonary reasons had a 66% rehospitalization rate compared with 42% without such a stay.
The scoring systems and classification and regression-tree analysis models identified infants at higher risk of rehospitalization and might assist planning for care after discharge.
logistic models; infant; premature; predictive value of tests
Decisions regarding whether to administer intensive care to extremely premature infants are often based on gestational age alone. However, other factors also affect the prognosis for these patients.
We prospectively studied a cohort of 4446 infants born at 22 to 25 weeks' gestation (determined on the basis of the best obstetrical estimate) in the Neonatal Research Network of the National Institute of Child Health and Human Development to relate risk factors assessable at or before birth to the likelihood of survival, survival without profound neurodevelopmental impairment, and survival without neurodevelopmental impairment at a corrected age of 18 to 22 months.
Among study infants, 3702 (83%) received intensive care in the form of mechanical ventilation. Among the 4192 study infants (94%) for whom outcomes were determined at 18 to 22 months, 49% died, 61% died or had profound impairment, and 73% died or had impairment. In multivariable analyses of infants who received intensive care, exposure to antenatal corticosteroids, female sex, singleton birth, and higher birth weight (per each 100-g increment) were each associated with reductions in the risk of death and the risk of death or profound or any neurodevelopmental impairment; these reductions were similar to those associated with a 1-week increase in gestational age. At the same estimated likelihood of a favorable outcome, girls were less likely than boys to receive intensive care. The outcomes for infants who underwent ventilation were better predicted with the use of the above factors than with use of gestational age alone.
The likelihood of a favorable outcome with intensive care can be better estimated by consideration of four factors in addition to gestational age: sex, exposure or nonexposure to antenatal corticosteroids, whether single or multiple birth, and birth weight. (ClinicalTrials.gov numbers, NCT00063063 and NCT00009633.)
This study aimed to assess early development in very low birth weight (VLBW) infants with mild intraventricular hemorrhage (IVH) or those without IVH and to identify the perinatal morbidities affecting early neurodevelopmental outcome.
Bayley Scales of Infant Development-II was used for assessing neurological development in 49 infants with a birth weight <1,500 g and with low grade IVH (≤grade II) or those without IVH at a corrected age of 12 months.
Among the 49 infants, 19 infants (38.8%) showed normal development and 14 (28.6%) showed abnormal mental and psychomotor development. Infants with abnormal mental development (n=14) were mostly male and had a longer hospitalization, a higher prevalence of patent ductus arteriosus (PDA) and bronchopulmonary dysplasia (BPD), and were under more frequent postnatal systemic steroid treatment compared with infants with normal mental development (n=35, P<0.05). Infants with abnormal psychomotor development (n=29) had a longer hospitalization and more associated PDA compared to infants with normal psychomotor development (n=20, P<0.05). Infants with abnormal mental and psychomotor development were mostly male and had a longer hospitalization and a higher prevalence of PDA and BPD compared to infants with normal mental and psychomotor development (n=19, P<0.05). Using multiple logistic regression analysis, a longer duration of hospitalization and male gender were found to be significant risk factors.
Approximately 62% of VLBW infants with low grade IVH or those without IVH had impaired early development.
Infant premature; Intracranial hemorrhages; Growth & development
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.
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.
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.
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.
Scores for Neonatal Acute Physiology; Extremely Low Gestational Age Newborns; Neurodevelopmental dysfunctions
The improvement in survival in premature infants associated with the evolution of mechanical ventilation has been accompanied by an increase in ventilator induced lung injury. High frequency ventilation has been shown to reduce the incidence of ventilator induced lung injury and hence chronic lung disease in the very low birth weight infant. The evolution in understanding how to best use high frequency ventilation in this population has prompted us to ask whether similar strategies to optimize lung volumes on conventional mechanical ventilation can minimize chronic lung disease in the neonate. We retrospectively reviewed the medical charts of 51 extremely low birth weight infants born in Kingston, Ontario in two epochs, 1990 to 1991 and 1999 to 2000, for ventilatory strategy and outcome. From our review, it is clear that surfactant therapy rapidly changes lung mechanics by improving pulmonary compliance and that lung damage may result if there are not changes in the ventilatory management to reflect the altered compliance. Early ventilation strategies during the apparently stable “honeymoon period” in a patient with respiratory distress syndrome (RDS) has significant implications on long term morbidity. In the era prior to the use of surfactant, 30% of infants died and 40% developed chronic lung disease (CLD). Immediately following the use of surfactant , mortality was reduced to 18%, however, the incidence of CLD increased to 78%. In the most recent era, following 10 years of experience with surfactant and mechanical ventilation, morbidity was 17% and CLD 21%. This study demonstrates that a particularly crucial time is in the immediate period following surfactant administration. The use of lower peak inspiratory pressure (PIP) and mean airway pressure (MAP) over the first 24 hours and an increase in the use of synchronous intermittent mandatory ventilation (SIMV) was associated with an improved outcome. The challenge remaining is to determine how to best utilize a conventional mode of ventilation to best optimize lung volume and protect the immature lung.
The hypothesis that the variability of physiological parameters may indicate pain or stress in the neonate was examined. Four parameters (heart rate, respiratory rate, transcutaneous oxygen tension, and carbon dioxide tension) were examined over a 2 minute epoch in response to a heel prick in an attempt to measure stress/pain in 35 preterm newborn infants (26-34 weeks' gestation) half of whom were receiving intensive care. The change in absolute values of these parameters did not discriminate a dummy procedure without prick from the actual procedure containing the prick (paired t test), but the variability of the parameters during an epoch showed significant discrimination. Three procedures were evaluated to reduce this distress using unpaired t test. The use of local anaesthetic cream was not successful. The components of the mixture cause vasoconstriction that would reduce blood flow to the heel and lead to more squeezing which is likely to be painful in the presence of tissue damage. A nurse comforting the infant with tactile and vocal stimulation was slightly helpful but the use of a spring loaded lance was most successful in reducing the distress. The use of spring loaded lances may be more humane for heel pricks.
To characterize early amplitude-integrated electroencephalogram (aEEG) and single-channel EEG (aEEG/EEG) in very preterm (VPT) infants for prediction of long-term outcome.
Forty-nine infants with median (range) gestational age of 25 (22–30) weeks.
Amplitude-integrated electroencephalogram/EEG recorded during the first 72 h and analysed over 0–12, 12–24, 24–48 and 48–72 h, for background pattern, sleep–wake cycling, seizures, interburst intervals (IBI) and interburst percentage (IB%). In total, 2614 h of single-channel EEG examined for seizures. Survivors were assessed at 2 years corrected age with a neurological examination and Bayley Scales of Infant Development-II. Poor outcome was defined as death or survival with neurodevelopmental impairment. Good outcome was defined as survival without impairment.
Thirty infants had good outcome. Poor outcome (n = 19) was associated with depressed aEEG/EEG already during the first 12 h (p = 0.023), and with prolonged IBI and higher IB% at 24 h. Seizures were present in 43% of the infants and associated with intraventricular haemorrhages but not with outcome. Best predictors of poor outcome were burst-suppression pattern [76% correctly predicted; positive predictive value (PPV) 63%, negative predictive value (NPV) 91%], IBI > 6 sec (74% correctly predicted; PPV 67%, NPV 79%) and IB% > 55% at 24 h age (79% correctly predicted; PPV 72%, NPV 80%). In 35 infants with normal cerebral ultrasound during the first 3 days, outcome was correctly predicted in 82% by IB% (PPV 82%, NPV 83%).
Long-term outcome can be predicted by aEEG/EEG with 75–80% accuracy already at 24 postnatal hours in VPT infants, also in infants with no early indication of brain injury.
Burst suppression; Cranial ultrasound; Interburst interval; Neurodevelopmental impairment; Seizure
Objective: To study neurodevelopmental outcome in a two year cohort of extremely low birthweight (ELBW) infants at 18 months corrected age, to compare the development of the ELBW infant subcohort with that of control children, and to find risk factors associated with unfavourable outcome.
Study design: All 211 surviving ELBW infants (birth weight < 1000 g) born in Finland in 1996–1997 were included in a national survey. The ELBW infants (n = 78) who were born and followed in Helsinki University Hospital belonged to a regional subcohort and were compared with a control group of 75 full term infants. A national follow up programme included neurological, speech, vision, and hearing assessments at 18 months of corrected age. Bayley infant scale assessment was performed on the subcohort and their controls at 24 months of age. Risk factors for unfavourable outcome were estimated using logistic and linear regression models.
Results: The prevalence of cerebral palsy was 11%, of all motor impairments 24%, of ophthalmic abnormalities 23%, and of speech delay 42%. No impairment was found in 42% of children, and 18% were classified as severely impaired. The prevalence of ophthalmic abnormalities decreased with increasing birth weight and gestational age, but the prevalence of other impairments did not. In the subcohort, a positive correlation was found between the date of birth and Bayley scores.
Conclusion: Ophthalmic abnormalities decreased with increasing birth weight and gestational age, but no other outcome differences were found between birthweight groups or in surviving ELBW infants born at 22–26 weeks gestation. The prognosis in the regional subcohort seemed to improve during the short study period, but this needs to be confirmed.
AIMS—To compare the
perinatal mortality and morbidity of infants with twin-twin transfusion
syndrome (TTTS) with those of gestation matched twin controls and to
assess the neurodevelopmental outcome of surviving twins with TTTS.
METHODS—A cohort of 17 consecutive pregnancies with TTTS was enrolled over three years
together with gestation matched twin pregnancies unaffected by TTTS.
Serial amnioreduction for the TTTS pregnancies was performed as
appropriate. Perinatal death and neonatal morbidities were recorded for
both the TTTS cohort and controls. The TTTS survivors had
neurodevelopmental follow up to at least 2 years of age.
RESULTS—In 12 of the
pregnancies, serial amniocenteses were performed, but, in five, the
infants were born before intervention. The mean gestational age at
delivery was 29.1 weeks (range 23-36). There were five intrauterine
deaths in the TTTS cohort and six neonatal deaths (survival 68%). In
the control group, there was one intrauterine death and five neonatal
deaths (survival 82%). Infants in the TTTS group had a greater
requirement for inotropes (p = 0.04) and a higher incidence of renal
failure (p = 0.005). Periventricular leucomalacia and cerebral
atrophy were seen in 17% of the TTTS group, but none of the controls
(p = 0.03). The 23 surviving TTTS infants were all followed up, with
22% having significant neurological morbidity: cerebral palsy and
global developmental delay.
TTTS have high perinatal mortality and neonatal morbidity, and long
term neurodevelopmental morbidity in survivors is high. Further
investigation into the pathogenesis and management of TTTS is required.
To compare continuous positive airway pressure (CPAP) vs. traditional mechanical ventilation (MV) at 24 h of age as predictors of neurodevelopmental (ND) outcomes in extremely low birth weight (ELBW) infants at 18-22 mo corrected gestational age (CGA).
Infants ≤ 1000g birth weight born from January 2000 through December 2006 at two hospitals at the Cincinnati site of the National Institute of Child Health and Human Development Neonatal Research Network were evaluated comparing CPAP (N = 198) vs. MV (N = 109). Primary outcomes included the Bayley Score of Infant Development Version II (BSID-II), presence of deafness, blindness, cerebral palsy, bronchopulmonary dysplasia and death.
Ventilatory groups were similar in gender, rates of preterm prolonged rupture of membranes, antepartum hemorrhage, use of antenatal antibiotics, steroids, and tocolytics. Infants receiving CPAP weighed more, were older, were more likely to be non-Caucasian and from a singleton pregnancy. Infants receiving CPAP had better BSID-II scores, and lower rates of BPD and death.
After adjusting for acuity differences, ventilatory strategy at 24 h of age independently predicts long-term neurodevelopmental outcome in ELBW infants.