To evaluate maternal and neonatal risk factors associated with post-neonatal intensive care unit (NICU) discharge mortality among ELBW infants.
This is a retrospective analysis of extremely low birth weight (<1,000 g) and <27 weeks' gestational age infants born in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network sites from January 2000 to June 2007. Infants were tracked until death or 18–22 months corrected age. Infants who died between NICU discharge and the 18–22 month follow-up visit were classified as post-NICU discharge mortality. Association of maternal and infant risk factors with post-NICU discharge mortality was determined using logistic regression analysis. A prediction model with six significant predictors was developed and validated.
5,364 infants survived to NICU discharge. 557 (10%) infants were lost to follow-up, and 107 infants died following NICU discharge. Post-NICU discharge mortality rate was 22.3 per 1000 ELBW infants. In the prediction model, African-American race, unknown maternal health insurance, and hospital stay ≥120 days significantly increased risk, and maternal exposure to intra-partum antibiotics was associated with decreased risk of post-NICU discharge mortality.
We identified African-American race, unknown medical insurance and prolonged NICU stay as risk factors associated with post-NICU discharge mortality among ELBW infants.
extremely preterm infants; discharge; mortality; predictive model
Data are limited on the impact of methicillin-resistant Staphylococcus aureus (MRSA) on morbidity and mortality among very low birth weight (VLBW) infants with S aureus (SA) bacteremia and/or meningitis (B/M).
Neonatal data for VLBW infants (birth weight 401–1500 g) born January 1, 2006, to December 31, 2008, who received care at centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were collected prospectively. Early-onset (≤72 hours after birth) and late-onset (>72 hours) infections were defined by blood or cerebrospinal fluid cultures and antibiotic treatment of ≥5 days (or death <5 days with intent to treat). Outcomes were compared for infants with MRSA versus methicillin-susceptible S aureus (MSSA) B/M.
Of 8444 infants who survived >3 days, 316 (3.7%) had SA B/M. Eighty-eight had MRSA (1% of all infants, 28% of infants with SA); 228 had MSSA (2.7% of all infants, 72% of infants with SA). No infant had both MRSA and MSSA B/M. Ninety-nine percent of MRSA infections were late-onset. The percent of infants with MRSA varied by center (P < .001) with 9 of 20 centers reporting no cases. Need for mechanical ventilation, diagnosis of respiratory distress syndrome, necrotizing enterocolitis, and other morbidities did not differ between infants with MRSA and MSSA. Mortality was high with both MRSA (23 of 88, 26%) and MSSA (55 of 228, 24%).
Few VLBW infants had SA B/M. The 1% with MRSA had morbidity and mortality rates similar to infants with MSSA. Practices should provide equal focus on prevention and management of both MRSA and MSSA infections among VLBW infants.
Staphylococcus aureus; methicillin resistant; infant; newborn
We sought to determine if a center’s approach to care of premature infants at the youngest gestational ages (22–24 weeks’ gestation) is associated with clinical outcomes among infants of older gestational ages (25–27 weeks’ gestation).
Inborn infants of 401 to 1000 g birth weight and 22 0/7 to 27 6/7 weeks’ gestation at birth from 2002 to 2008 were enrolled into a prospectively collected database at 20 centers participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Markers of an aggressive approach to care for 22- to 24-week infants included use of antenatal corticosteroids, cesarean delivery, and resuscitation. The primary outcome was death before postnatal day 120 for infants of 25 to 27 weeks’ gestation. Secondary outcomes were the combined outcomes of death or a number of morbidities associated with prematurity.
Our study included 3631 infants 22 to 24 weeks’ gestation and 5227 infants 25 to 27 weeks’ gestation. Among the 22- to 24-week infants, use of antenatal corticosteroids ranged from 28% to 100%, cesarean delivery from 13% to 65%, and resuscitation from 30% to 100% by center. Centers with higher rates of antenatal corticosteroid use in 22- to 24-week infants had reduced rates of death, death or retinopathy of prematurity, death or late-onset sepsis, death or necrotizing enterocolitis, and death or neurodevelopmental impairment in 25- to 27-week infants.
This study suggests that physicians’ willingness to provide care to extremely low gestation infants as measured by frequency of use of antenatal corticosteroids is associated with improved outcomes for more-mature infants.
low-birth weight infant; NICUs; treatment; patient outcome assessment
We compared neurodevelopmental outcomes at 18 to 22 months' corrected age of infants born with extremely low birth weight at an estimated gestational age of <25 weeks during 2 periods: 1999–2001 (epoch 1) and 2002–2004 (epoch 2).
PATIENTS AND METHODS:
We conducted a multicenter, retrospective analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Perinatal and neonatal variables and outcomes were compared between epochs. Neurodevelopmental outcomes at 18 to 22 months' corrected age were evaluated with neurologic exams and Bayley Scales of Infant Development II. Logistic regression analyses determined the independent risk of epoch for adverse outcomes.
Infant survival was similar between epochs (epoch 1, 35.4%, vs epoch 2, 32.3%; P = .09). A total of 411 of 452 surviving infants in epoch 1 and 405 of 438 surviving infants in epoch 2 were evaluated at 18 to 22 months' corrected age. Cesarean delivery (P = .03), surgery for patent ductus arteriosus (P = .004), and late sepsis (P = .01) were more common in epoch 2, but postnatal steroid use was dramatically reduced (63.5% vs 32.8%; P < .0001). Adverse outcomes at 18 to 22 months' corrected age were common in both epochs. Moderate-to-severe cerebral palsy was diagnosed in 11.1% of surviving infants in epoch 1 and 14.9% in epoch 2 (adjusted odds ratio [OR]: 1.52 [95% confidence interval (CI): 0.86–2.71]; P = .15), the Mental Developmental Index was <70 in 44.9% in epoch 1 and 51% in epoch 2 (OR: 1.30 [95% CI: 0.91–1.87]; P = .15), and neurodevelopmental impairment was diagnosed in 50.1% of surviving infants in epoch 1 and 58.7% in epoch 2 (OR: 1.4 [95% CI: 0.98–2.04]; P = .07).
Early-childhood outcomes for infants born at <25 weeks' estimated gestational age were unchanged between the 2 periods.
extremely preterm; neurodevelopmental; outcome; cerebral palsy; Bayley Scales of Infant Development II
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
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.
The heptavalent pneumococcal-CRM197 conjugate vaccine (PCV-7) has been incompletely studied in very-low-birth-weight (VLBW, ≤1500 grams) infants.
To assess PCV-7 immunogenicity in VLBW, premature infants. We hypothesized that the frequency of post-vaccine antibody concentrations ≥0.15 µg/mL would vary directly with birth weight.
This was a multi-center observational study. Infants 401–1500 grams birth weight and <32 0/7 weeks gestation, stratified by birth weight, were enrolled from 9 NICHD Neonatal Research Network centers. Infants received PCV-7 at 2, 4 and 6 months after birth and had blood drawn 4–6 weeks following the third dose. Antibodies against the 7 vaccine serotypes were measured by enzyme-linked immunosorbent assay.
Of 369 enrolled infants, 244 completed their primary vaccine series by 8 months and had serum obtained. Subjects were 27.8 ± 2.2 (mean ± standard deviation) weeks gestation and 1008 ± 282 grams birth weight. Twenty-six percent had bronchopulmonary dysplasia and 16% had received postnatal glucocorticoids. Infants 1001–1500 grams birth weight were more likely than those 401–1000 grams to achieve antibody concentrations ≥0.15 µg/mL against the least two immunogenic serotypes (6B: 96% v. 85%, P = 0.003 and 23F: 97% v. 88%, P = 0.009). In multiple logistic regression analysis, lower birth weight, postnatal glucocorticoid use, lower weight at blood draw and Caucasian race were each independently associated with antibody concentrations <0.35 µg/mL against serotypes 6B and/or 23F.
When compared with larger premature infants, infants weighing ≤1000 grams at birth have similar antibody responses to most, but not all, PCV-7 vaccine serotypes.
Infant, premature; infant, very low birth weight; pneumococcal vaccines; immunization; vaccines
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
Individuals with Down syndrome (DS) are at increased risk of several morbidities with lifelong health consequences. Little is known about mortality or morbidity risks in early infancy among very-low-birth-weight (VLBW) infants with DS. Our objective was to compare survival and neonatal morbidities between VLBW infants with DS and VLBW infants with other non-DS chromosomal anomalies, other non-chromosomal birth defects, and VLBW infants without major birth defects.
Data were collected prospectively for infants weighing 401-1500 grams born and/or cared for at one of the study centers participating in the NICHD Neonatal Research Network from 1994 through 2008. Risk of death and morbidities including patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), late onset sepsis (LOS), retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD), were compared between VLBW infants with DS and infants in the other groups.
Infants with DS were at increased risk of death (adjusted relative risk [RR] 2.47, 95% confidence interval [CI] 2.00-3.07), PDA, NEC, LOS, and BPD relative to infants with no birth defects. Decreased risk of death (RR 0.40, 95% CI 0.31-0.52) and increased risks of NEC and LOS were observed when comparing infants with DS to infants with other non-DS chromosomal anomalies. Relative to infants with non-chromosomal birth defects, infants with DS were at increased risk of PDA and NEC.
The increased risk of morbidities among VLBW infants with DS provides useful information for counseling parents and for caretakers in anticipating the need for enhanced surveillance for prevention of these morbidities.
neonatal mortality; neonatal morbidity; preterm infants; Down syndrome; trisomy 21
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
Delayed cord clamping may be beneficial in very preterm and low birth weight infants.
A randomized unmasked controlled trial
The study was performed in three centers of the NICHD Neonatal Research Network
Delayed cord clamping in very preterm and very low birth weight infants will result in an increase in hematocrit at 4 hours of age.
Infants with a gestational age of 24-28 weeks were randomized into early (< 10 seconds) or delayed (30-45 seconds) cord clamping. The primary outcome was venous hematocrit at 4 hours of age. Secondary outcomes included delivery room management, selected neonatal morbidities and the need for blood transfusion during the infants’ hospital stay.
Thirty three infants were randomized: 17 to the immediate cord clamping (ICC, cord clamped at 7.9 ± 5.2 seconds, m±SD) and 16 to the delayed cord clamping (DCC, cord clamped at 35.2 ± 10.1 seconds) group. The hematocrit was higher in the DCC group (45 ± 8 versus 40 ± 5%, p<0.05). The frequency of events during delivery room resuscitation was almost identical between the two groups. There was no difference in hourly mean arterial blood pressure during the first 12 hours of life, there was a trend in the difference in the incidence of selected neonatal morbidities, hematocrit at 2, 4 and 6 weeks as well as the need for transfusion, but none of the differences was statistically significant
A higher hematocrit is achieved by delayed cord clamping in very low birth weight infants suggesting effective placental transfusion.
For newborn infants in intensive care units, the morbidity and mortality from infection continues to be a major burden despite advances in neonatal care. Infants are at risk for early onset, late onset, as well as hospital acquired infections. Research studies are needed to optimize timely diagnosis and treatment, and develop patient-specific and system-wide strategies to prevent perinatal and neonatal infections. To address the knowledge gaps that preclude optimal, evidence-based care in this critical field, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) organized a workshop in August 2008. In this paper we provide a summary of the discussions, focusing on major knowledge gaps, and prioritized suggestions for research in this area.
infant; infection; newborn; sepsis
Objectives: To compare mortality and death or major morbidity (DOMM) among infants <25 weeks estimated gestational age (EGA) born during two post-surfactant era time periods.
Study design and patients: Comparative cohort study of very low birthweight (501–1500 g) infants <25 weeks EGA in the NICHD Neonatal Research Network born during two post-surfactant era time periods (group I, 1991–1994, n = 1408; group II, 1995–1998, n = 1348). Perinatal and neonatal factors were compared, and group related mortality and DOMM risk were evaluated.
Results: Mortality was higher for group I (63.1% v 56.7%; p = 0.0006). Antenatal steroids (ANS) and antenatal antibiotics (AABX), surfactant (p<0.0001), and bronchopulmonary dysplasia (p = 0.0008) were more prevalent in group II. In a regression model that controlled for basic and delivery factors only, mortality risk was greater for group I than for group II (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2 to 1.7); the addition of AABX and surfactant, or ANS (OR 0.97, 95% CI 0.79 to 1.2) to the model appeared to account for this difference. There was no difference in DOMM (86.8% v 88.4%; p = 0.2), but risk was lower for group I in regression models that included ANS (OR 0.70, 95% CI 0.52 to 0.94).
Conclusion: Survival to discharge was more likely during the more recent period because of group differences in ANS, AABX, and surfactant. However, this treatment shift may reflect an overall more aggressive management approach. More consistent application of treatment has led to improving survival of <25 week EGA infants during the post-surfactant era, but possibly at the cost of greater risk of major in-hospital morbidities.
To compare the risk-adjusted incidence of death or neuro-developmental impairment at 18–22 months corrected age, between twin and singleton extremely low birth weight infants.
Twin gestation is independently associated with increased risk of death or adverse neuro-developmental outcomes at 18–22 months corrected age in extremely low birth weight infants.
Retrospective study of inborn extremely low birth weight infants (BW 401– 1000g) admitted to NICHD Neonatal Research Network units between 1997 and 2005, who either died or had follow-up data available at 18–22 months corrected age. Neuro-developmental impairment (NDI), the primary outcome variable, was defined as the presence of any one of the following: moderate or severe cerebral palsy, severe bilateral hearing loss needing amplification, bilateral blindness, Bayley Mental Developmental Index or Psychomotor Developmental Index of less than 70. Death was included with NDI as a composite outcome since it is a competing variable. Results were compared for both twins, twin A, twin B, same sex twins, unlike sex twins and singleton infants. Logistic regression analysis was done to control for demographic and clinical factors that were different among the groups.
The cohort of infants who either died or were assessed for NDI consisted of 7,630 singleton infants and 1,376 twins. Logistic regression adjusting for clinical and socio-demographic risk factors showed an increased risk of death or NDI for twins as a group when compared with the singletons (OR-1.39, 95% CI- 1.19–1.63). On analyzing twin A and B separately as well, risk of death or NDI was increased in both twin A (OR-1.32, 95% CI- 1.09–1.59) and for twin B (OR-1.47, 95% CI- 1.21–1.78), when compared with singleton infants.
Twin gestation in ELBW infants is associated with an independent increased risk of death or NDI at 18–22 months corrected age, compared to ELBW singleton gestation infants. Both first and second born twins are at increased risk of death or NDI when compared to singleton ELBW infants.
twins; neuro-developmental impairment; extremely low birth weight infants
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.
Guidelines for prevention of group B streptococcal (GBS) infection have successfully reduced early onset (EO) GBS disease. Study results suggest that Escherichia coli is an important EO pathogen.
To determine EO infection rates, pathogens, morbidity, and mortality in a national network of neonatal centers.
Infants with EO infection were identified by prospective surveillance at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Network centers. Infection was defined by positive culture results for blood and cerebrospinal fluid obtained from infants aged ≤72 hours plus treatment with antibiotic therapy for ≥5 days. Mother and infant characteristics, treatments, and outcomes were studied. Numbers of cases and total live births (LBs) were used to calculate incidence.
Among 396 586 LBs (2006–2009), 389 infants developed EO infection (0.98 cases per 1000 LBs). Infection rates increased with decreasing birth weight. GBS (43%, 0.41 per 1000 LBs) and E coli (29%, 0.28 per 1000 LBs) were most frequently isolated. Most infants with GBS were term (73%); 81% with E coli were preterm. Mothers of 67% of infected term and 58% of infected preterm infants were screened for GBS, and results were positive for 25% of those mothers. Only 76% of mothers with GBS colonization received intrapartum chemoprophylaxis. Although 77% of infected infants required intensive care, 20% of term infants were treated in the normal newborn nursery. Sixteen percent of infected infants died, most commonly with E coli infection (33%).
In the era of intrapartum chemoprophylaxis to reduce GBS, rates of EO infection have declined but reflect a continued burden of disease. GBS remains the most frequent pathogen in term infants, and E coli the most significant pathogen in preterm infants. Missed opportunities for GBS prevention continue. Prevention of E coli sepsis, especially among preterm infants, remains a challenge.
neonatal sepsis; group B streptococcal disease; Escherichia coli infection
Clinical experience of phototherapy for non-haemolytic hyperbilirubinaemia in 3999 infants in Kandang Kerbau Hospital, Singapore, is documented. Phototherapy was most effective in extremely preterm infants with very low birth weight (gestation less than or equal to 32 weeks, birth weight less than or equal to 1500 g) and least effective in full term infants with very low birth weight (gestation greater than or equal to 37 weeks, birth weight less than or equal to 1500 g) and large preterm infants (gestation less than 37 weeks, birth weight greater than 2270 g). Overall, phototherapy was effective in almost all the infants, with a failure rate of only 2.00/1000 infants. No characteristic features common to all the failures could be detected. The bilirubin rebound was usually mild; repeat phototherapy was required in only 30 infants (7.50/1000), with the response to the second exposure comparable to that to the first. No infant required a third exposure. All the infants tolerated phototherapy well, none developing any illness that could be attributed to the treatment. This clinical experience shows that phototherapy for the treatment of nonhaemolytic hyperbilirubinaemia is effective and safe.
Introduction: Advances in technology have resulted in increasing survival rates for premature infants. Oxygen therapy is commonly used in neonatal units as part of respiratory support. The number of premature infants in our institution surviving with severe (stage ≥3) retinopathy of prematurity (ROP) prompted a review of oxygen therapy as a contributing factor. Prolonged exposure to high concentrations of oxygen may cause irreversible damage to the eyes of very-low-birth-weight preterm infants and is a potential cause of blindness.
Objective: We developed strategies to reduce incidence of severe ROP requiring laser surgery in premature infants.
Methods: We studied 37 preterm infants who were born at a gestational age of <32 weeks, with a birth weight of <1500 g, receiving supplemental oxygen, and had been admitted to our neonatal intensive care unit. Infants received oxygen via mechanical ventilator, nasal continuous positive airway pressure (CPAP), or intranasal (I/N) and titration of oxygen was based on each infant's measured oxygen saturation (Spo2). For each infant, we monitored the Spo2 trend, Spo2 alarm limit, and the percentage of time that the alarm limit was set incorrectly. We implemented a Spo2 targeting protocol and developed an algorithm for titrating fraction of inspired oxygen (Fio2).
Results: After phase 1 of implementation, the percentage of time that Spo2 readings were >95% was reduced to between 20% and 50%. However, our findings raised concern regarding the wide fluctuation of Spo2 readings because of inconsistency in Fio2 titration, which can contribute to deviation from the optimal target range. Accordingly, we developed an algorithm for titrating Fio2 aimed at maintaining each infant's Spo2 within the optimal target range. After phase 2 of implementation, the percentage of Spo2 readings >95% was markedly reduced to between 0% and 15%. The incidence of infants with severe ROP requiring laser surgery decreased from 5 to 1.
Conclusions: A change in clinical practice aimed at maintaining oxygen within the target range to avoid a high Spo2 was associated with a significant decrease in the incidence of both severe ROP and the need for laser surgery, thus reducing hospital costs and length of hospital stays for premature infants.
The potential negative impact of early blood oxygenation on development of specific cognitive and motor outcomes in children born at very low birth weight (VLBW; 1000 − 1500g) has not been examined even though these infants are exposed to varying durations and amounts of oxygen as part of their neonatal care. While this is the largest group of preterm infants, they receive much less research attention than extremely low birth weight infants (ELBW < 1000g).
Although neonatologists are questioning the routine use of oxygen therapy for all neonates, research has focused primarily on the more medically fragile ELBW infants. To date there are no systematic studies available to guide decision making for oxygen supplementation for a large segment of the preterm infant population. The aim of the present study was to determine if there is an association between blood oxygenation in the first four hours of life and specific cognitive and motor skills in preterm infants with acute respiratory disorders but no severe intracranial insult using a selected cohort from a longitudinal study children recruited in 1991 and 1992 designed to examine the role of biological immaturity as defined by gestational age and parenting in development. From this cohort, 55 children had acute respiratory disorders without severe intracranial insult. Of these, 35 children had at least one partial pressure of oxygen obtained from arterial blood (PaO2) during the first four hours of life as part of their clinical care. Higher early PaO2 values were associated with lower impulse control and attention skills in the elementary school age period. Models that examined for relations between PaO2 values that also included birth weight and parenting quality across the first year of life revealed that higher PaO2 remained associated with impulse control but not attention skills. Birth weight was not associated with any outcomes. These results suggest that hyperoxia may be a risk factor for developmental problems that are not expressed until school age.
very low birth weight; acute respiratory disorders; child development
the differences in short term outcome of very low birthweight infants
attributable to sex.
METHODS—Boys and girls
weighing 501-1500 g admitted to the 12 centres of the National
Institute of Child Health and Human Development Neonatal Research
Network were compared. Maternal information and perinatal data were
collected from hospital records. Infant outcome was recorded at
discharge, at 120 days of age if the infant was still in hospital, or
at death. Best obstetric estimate based on the last menstrual period,
standard obstetric factors, and ultrasound were used to assign
gestational age in completed weeks. Data were collected on a cohort
that included 3356 boys and 3382girls, representing all inborn births
from 1 May 1991 to 31 December 1993.
boys was 22% and that for girls 15%. The prenatal and perinatal data
indicate few differences between the sex groups, except that boys were
less likely to have been exposed to antenatal steroids (odds ratio
(OR) = 0.80) and were less stable after birth, as reflected in a
higher percentage with lower Apgar scores at one and five minutes and
the need for physical and pharmacological assistance. In particular,
boys were more likely to have been intubated (OR = 1.16) and to have
received resuscitation medication (OR = 1.40). Boys had a higher risk
(OR > 1.00) for most adverse neonatal outcomes. Although pulmonary
morbidity predominated, intracranial haemorrhage and urinary tract
infection were also more common.
differences in short term morbidity and mortality persist between the sexes.
Improved survival of preterm infants, beneficial effects of trophic feeding and limited data on timing management of enteral feeding for very low birth weight preterm infants requires more researches to determine the exact starting time and increased volumes. This study aims to compare early (<48 h) versus late (>72h) trophic feeding with respect to important neonatal outcomes.
In a cohort study from September 2007 to October 2008, a total of 170 preterm infants (1000-1500 gram, 26-31 weeks) consisting of 125 who received trophic feeding enterally within the first 48 hours of birth (early group) and 45 fed enterally after 72 h0urs (late group), without major congenital birth defects and severe asphyxia entered the study. Bolus feeding was started in both groups at 1-2 cc/kg every 4-6 hours of human milk or preterm infant formula and was advanced 1-2 cc/kg/day if tolerated along with parenteral nutrition. Feeding intolerance, possibility of necrotizing entrocolitis (NEC), episodes of sepsis, body weight, length of NICU stay, and duration of parenteral nutrition were assessed serially.
There were no statistically significant differences in the clinical and maternal characteristics of infants in the two groups. The time to gain birth weight (13.75±5.21 vs 20.53±6.31 (P < 0.001)), duration of parenteral nutrition (9.26±4.572 days vs 14.11±6.415 days (P < 0.001)), hospital stay (12.14±8.612 vs 21.11±1.156 (P < 0.001)) were significantly shorter in early compared to late feeding group; none of the two groups experienced a high incidence of late onset sepsis (P = 0.73). There was 1 case of confirmed NEC in every group.
The benefits of early trophic feeding shown by this study strongly support its use for the preterm infants without adding to complications.
Trophic Feeding; Preterm Infant; Very Low Birth Weight Infant; Parenteral Nutrition
Extremely low birth weight twins have a higher rate of death or neurodevelopmental impairment than singletons. Higher-order extremely low birth weight multiple births may have an even higher rate of death or neurodevelopmental impairment.
Extremely low birth weight (birth weight 401–1000 g) multiple births born in participating centers of the Neonatal Research Network between 1996 and 2005 were assessed for death or neurodevelopmental impairment at 18 to 22 months' corrected age. Neurodevelopmental impairment was defined by the presence of 1 or more of the following: moderate to severe cerebral palsy; mental developmental index score or psychomotor developmental index score less than 70; severe bilateral deafness; or blindness. Infants who died within 12 hours of birth were excluded. Maternal and infant demographic and clinical variables were compared among singleton, twin, and triplet or higher-order infants. Logistic regression analysis was performed to establish the association between singletons, twins, and triplet or higher-order multiples and death or neurodevelopmental impairment, controlling for confounding variables that may affect death or neurodevelopmental impairment.
Our cohort consisted of 8296 singleton, 2164 twin, and 521 triplet or higher-order infants. The risk of death or neurodevelopmental impairment was increased in triplets or higher-order multiples when compared with singletons (adjusted odds ratio: 1.7 [95% confidence interval: 1.29–2.24]), and there was a trend toward an increased risk when compared with twins (adjusted odds ratio: 1.27 [95% confidence: 0.95–1.71]).
Triplet or higher-order births are associated with an increased risk of death or neurodevelopmental impairment at 18 to 22 months' corrected age when compared with extremely low birth weight singleton infants, and there was a trend toward an increased risk when compared with twins.
extremely low birth weight; triplets; neurodevelopmental outcomes
The objective of this study was to determine the (1) incidence of short bowel syndrome in very low birth weight (<1500 g) infants, (2) associated morbidity and mortality during initial hospitalization, and (3) impact on short-term growth and nutrition in extremely low birth weight (<1000 g) infants.
Infants who were born from January 1, 2002, through June 30, 2005, and enrolled in the National Institute of Child Health and Human Development Neonatal Research Network were studied. Risk factors for developing short bowel syndrome as a result of partial bowel resection (surgical short bowel syndrome) and outcomes were evaluated for all neonates until hospital discharge, death, or 120 days. Extremely low birth weight survivors were further evaluated at 18 to 22 months’ corrected age for feeding methods and growth.
The incidence of surgical short bowel syndrome in this cohort of 12 316 very low birth weight infants was 0.7%. Necrotizing enterocolitis was the most common diagnosis associated with surgical short bowel syndrome. More very low birth weight infants with short bowel syndrome (20%) died during initial hospitalization than those without necrotizing enterocolitis or short bowel syndrome (12%) but fewer than the infants with surgical necrotizing enterocolitis without short bowel syndrome (53%). Among 5657 extremely low birth weight infants, the incidence of surgical short bowel syndrome was 1.1%. At 18 to 22 months, extremely low birth weight infants with short bowel syndrome were more likely to still require tube feeding (33%) and to have been rehospitalized (79%). Moreover, these infants had growth delay with shorter lengths and smaller head circumferences than infants without necrotizing enterocolitis or short bowel syndrome.
Short bowel syndrome is rare in neonates but has a high mortality rate. At 18 to 22 months’ corrected age, extremely low birth weight infants with short bowel syndrome were more likely to have growth failure than infants without short bowel syndrome.
short bowel syndrome; preterm; necrotizing enterocolitis; nutrition
Over the last two decades, improvements in medical care have been associated with a significant increase and better outcome of very preterm (VP, < 32 completed gestational weeks) and very low birth weight (VLBW, < 1500 g) infants. Only a few publications analyse changes of their short-term outcome in a geographically defined area over more than 10 years. We therefore aimed to investigate the net change of VP- and VLBW infants leaving the hospital without major complications.
Our population-based observational cohort study used the Minimal Neonatal Data Set, a database maintained by the Swiss Society of Neonatology including information of all VP- and VLBW infants. Perinatal characteristics, mortality and morbidity rates and the survival free of major complications were analysed and their temporal trends evaluated.
In 1996, 2000, 2004, and 2008, a total number of 3090 infants were enrolled in the Network Database. At the same time the rate of VP- and VLBW neonates increased significantly from 0.87% in 1996 to 1.10% in 2008 (p < 0.001). The overall mortality remained stable by 13%, but the survival free of major complications increased from 66.9% to 71.7% (p < 0.01). The percentage of infants getting a full course of antenatal corticosteroids increased from 67.7% in 1996 to 91.4% in 2008 (p < 0.001). Surfactant was given more frequently (24.8% in 1996 compared to 40.1% in 2008, p < 0.001) and the frequency of mechanical ventilation remained stable by about 43%. However, the use of CPAP therapy increased considerably from 43% to 73.2% (p < 0.001). Some of the typical neonatal pathologies like bronchopulmonary dysplasia, necrotising enterocolitis and intraventricular haemorrhage decreased significantly (p ≤ 0.02) whereas others like patent ductus arteriosus and respiratory distress syndrome increased (p < 0.001).
Over the 12-year observation period, the number of VP- and VLBW infants increased significantly. An unchanged overall mortality rate and an increase of survivors free of major complication resulted in a considerable net gain in infants with potentially good outcome.
To compare incision-to-delivery intervals and related maternal and neonatal outcomes by skin incision in primary and repeat emergent cesarean deliveries.
From 1999 to 2000, a prospective cohort study of all cesarean deliveries was conducted at 13 hospitals comprising the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Maternal–Fetal Medicine Units Network. This secondary analysis was limited to emergent procedures, defined as those performed for cord prolapse, abruption, placenta previa with hemorrhage, nonreassuring fetal heart rate tracing, or uterine rupture. Incision-to-delivery intervals, incision-to-closure intervals, and maternal outcomes were compared by skin-incision type (transverse compared with vertical) after stratifying for primary compared with repeat singleton cesarean delivery. Neonatal outcomes were compared by skin-incision type.
Of the 37,112 live singleton cesarean deliveries, 3,525 (9.5%) were performed for emergent indications of which 2,498 (70.9%) were performed by transverse and the remaining 1,027 (29.1%) by vertical incision. Vertical skin incision shortened median incision-to-delivery intervals by 1 minute (3 compared with 4 minutes, P<.001) in primary and 2 minutes (3 compared with 5 minutes, P<.001) in repeat cesarean deliveries. Total median operative time was longer after vertical skin incision by 3 minutes in primary (46 compared with 43 minutes, P<.001) and 4 minutes in repeat cesarean deliveries (56 compared with 52 minutes, P<.001). Neonates delivered through a vertical incision were more likely to have an umbilical artery pH of less than 7.0 (10% compared with 7%, P=.02), to be intubated in the delivery room (17% compared with 13%, P=.001), or to be diagnosed with hypoxic ischemic encephalopathy (3% compared with 1%, P<.001).
In emergency cesarean deliveries, neonatal delivery occurred more quickly after a vertical skin incision, but this was not associated with improved neonatal outcomes.
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