To investigate if the lack of gestational age correction may explain some of the school failure seen in ex-preterm infants.
A cohort study based on the Avon Longitudinal Study of Parents and Children (ALSPAC). The primary outcome was a low Key Stage 1 score (KS1) score at age 7 or having special educational needs (SEN). Exposure groups were defined as preterm (<37 weeks gestation, n = 722) or term (37–42 weeks, n = 11,268). Conditional regression models were derived, matching preterm to term infants on date of birth (DOB), expected date of delivery (EDD) or expected date of delivery and year of school entry. Multiple imputation was used to account for missing covariate data.
When matching for DOB, infants born preterm had an increased odds of a low KS1 score (OR 1.73 (1.45–2.06)) and this association persisted after adjusting for potential confounders (OR 1.57 (1.25–1.97)). The association persisted in the analysis matching for EDD (fully adjusted OR 1.53 (1.21–1.94)) but attenuated substantially after additionally restricting to those infants who entered school at the same time as the control infants (fully adjusted OR 1.25 (0.98–1.60)). A compatible reduction in the population attributable risk fraction was seen from 4.60% to 2.12%, and year of school entry appeared to modify the association between gestational age and the risk of a poor KS1 score (p = 0.029).
This study provides evidence that the school year placement and assessment of ex-preterm infants based on their actual birthday (rather than their EDD) may increase their risk of learning difficulties with corresponding school failure.
To assess performance of the WHO revised verbal autopsy tool for ascertaining the causes of still birth in comparison with reference standard cause of death ascertained by standardized clinical and supportive data.
All stillbirths at a tertiary hospital in Karachi, Pakistan were prospectively recruited into study from August 2006- February 2008. The reference standard cause of death was established by two senior obstetricians within 48 hours using the ICD coding system. Verbal autopsy interviews using modified WHO tool were conducted by trained health workers within 2- 6 weeks of still birth and the cause of death was assigned by second panel of obstetricians. The performance was assessed in terms of sensitivity, specificity and Kappa.
There were 204 still births. Of these, 80.8% of antepartum and 50.5% of intrapartum deaths were correctly diagnosed by verbal autopsy. Sensitivity of verbal autopsy was highest 68.4%, (95%CI: 46-84.6) for congenital malformation followed by obstetric complication 57.6%, (95%CI: 25-84.2). The specificity for all major causes was greater than 90%. The level of agreement was high (kappa=0.72) for anomalies and moderate (k=0.4) for all major causes of still birth, except asphyxia.
Our results suggest that verbal autopsy has reasonable validity in identifying and discriminating between causes of stillbirth in Pakistan. On the basis of these findings, we feel it has a place in resource constrained areas to inform strategic planning and mobilization of resources to attain Millennium Development Goals.
Male vulnerability in health and growth outcomes has often been reported in very low birth weight (VLBW) preterm neonates. On the basis of gender-difference theories, possible associations were explored between the levels of postnatal salivary testosterone/cortisol and the outcomes of neonatal health/growth.
This study used an exploratory and comparative research design. One-hundred-one mother–VLBW preterm neonate pairs were recruited from the neonatal intensive care unit (NICU) of a tertiary medical center in the Southeastern, US. Demographic information, health and growth variables of neonates, and pregnancy and labor variables of mothers were obtained from the medical record reviews and interviews of mothers. Saliva samples from each pair were collected between 9 and 60 days of age. The levels of testosterone and cortisol were determined by using an enzyme immunoassay methodology.
Linear regression analysis showed that neonatal health problems were positively associated with the levels of postnatal salivary testosterone and cortisol, while growth delays were positively associated with the levels of postnatal salivary testosterone after adjusting for the characteristics of neonates and mothers and day of saliva sampling. The salivary levels of testosterone and cortisol were higher in neonates than in mothers. A positive correlation between the levels of testosterone and cortisol was found in neonates and in mothers.
The level of postnatal salivary testosterone is a more reliable marker in assessing neonatal health and growth outcomes compared to salivary cortisol. Further research on both testosterone and cortisol measurements at various stages during the neonatal period may elucidate further these associations.
Salivary testosterone; Salivary cortisol; Neonatal health and growth
To determine in extremely low birth weight (ELBW) infants if elevated blood inteferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-18, tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGFβ) are associated with need for shunt following severe intraventricular hemorrhage (IVH), or with ventricular dilation following milder grades /no IVH.
Whole blood cytokines were measured on postnatal days 1, 3, 7, 14, and 21. Maximum IVH grade in the first 28d, and shunt surgery or ventricular dilation on subsequent ultrasound (28d -36 w PMA) were determined.
Of 902 infants in the NICHD NRN Cytokine study who survived to 36w/discharge, 3.1% had shunts. Of the 12% of infants with severe (Gr III–IV) IVH, 26% had a shunt associated with elevated TNF-α. None of the infants without IVH (69%) or with Gr I (12%) or II (7%) IVH received shunts, but 8.4% developed ventricular dilation, associated with lower IFN-γ and higher IL-18.
Statistically significant but clinically non-discriminatory alterations in blood cytokines were noted in infants with severe IVH who received shunts and in those without severe IVH who developed ventricular dilation. Blood cytokines are likely associated with brain injury but may not be clinically useful as biomarkers for white matter damage.
Infant; premature; Cytokines; Hydrocephalus; Intraventricular hemorrhage; Intracranial hemorrhage
To describe the staffing and availability of medical equipment and medications and the performance of procedures at health facilities providing maternal and neonatal care at African, Asian, and Latin American sites participating in a multicenter trial to improve emergency obstetric/neonatal care in communities with high maternal and perinatal mortality.
In 2009, prior to intervention, we surveyed 136 hospitals and 228 clinics in 7 sites in Africa, Asia, and Latin America regarding staffing, availability of equipment/ medications, and procedures including cesarean section.
The coverage of physicians and nurses/midwives was poor in Africa and Latin America. In Africa, only 20% of hospitals had full-time physicians. Only 70% of hospitals in Africa and Asia had performed cesarean sections in the last 6 months. Oxygen was unavailable in 40% of African hospitals and 17% of Asian hospitals. Blood was unavailable in 80% of African and Asian hospitals.
Assuming that adequate facility services are necessary to improve pregnancy outcomes, it is not surprising that maternal and perinatal mortality rates in the areas surveyed are high. The data presented emphasize that to reduce mortality in these areas, resources that result in improved staffing and sufficient equipment, supplies, and medication, along with training, are required.
emergency obstetric and neonatal care; developing countries; perinatal mortality
Risks of death are high when children with pneumonia also have severe acute malnutrition (SAM) as a co-morbidity. However, there is limited published information on risk factors of death from pneumonia in SAM children. We evaluated clinically identifiable factors associated with death in under-five children who were hospitalized for the management of pneumonia and SAM.
For this unmatched case-control design, SAM children of either sex, aged 0–59 months, admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) during April 2011 to July 2012 with radiological pneumonia were studied. The SAM children with pneumonia who had fatal outcome constituted the cases (n = 35), and randomly selected SAM children with pneumonia who survived constituted controls (n = 105).
The median (inter-quartile range) age (months) was comparable among the cases and the controls [8.0 (4.9, 11.0) vs. 9.7 (5.0, 18.0); p = 0.210)]. In logistic regression analysis, after adjusting for potential confounders, such as vomiting, abnormal mental status, and systolic hypotension (<70 mm of Hg) in absence of dehydration, fatal cases of severely malnourished under-five children with pneumonia were more often hypoxemic (OR = 23.15, 95% CI = 4.38–122.42), had clinical dehydration (some/severe) (OR = 9.48, 95% CI = 2.42–37.19), abdominal distension at admission (OR = 4.41, 95% CI = 1.12–16.52), and received blood transfusion (OR = 5.50, 95% CI = 1.21–24.99) for the management of crystalloid resistant systolic hypotension.
Conclusion and Significance
We identified hypoxemia, clinical dehydration, and abdominal distension as the independent predictors of death in SAM children with pneumonia. SAM children with pneumonia who required blood transfusion for the management of crystalloid resistant systolic hypotension were also at risk for death. Thus, early identification and prompt management of these simple clinically recognizable predictors of death and discourage the use of blood transfusion for the management of crystalloid resistant systolic hypotension may help reduce deaths in such population.
To implement a vital statistics registry system to register pregnant women and document birth outcomes in the Global Network for Women’s and Children’s Health Research sites in Asia, Africa, and Latin America.
The Global Network sites began a prospective population-based pregnancy registry to identify all pregnant women and record pregnancy outcomes up to 42 days post-delivery in more than 100 defined low-resource geographic areas (clusters). Pregnant women were registered during pregnancy, with 42-day maternal and neonatal follow-up recorded—including care received during the pregnancy and postpartum periods. Recorded outcomes included stillbirth, neonatal mortality, and maternal mortality rates.
In 2010, 72 848 pregnant women were enrolled and 6-week follow-up was obtained for 97.8%. Across sites, 40.7%, 24.8%, and 34.5% of births occurred in a hospital, health center, and home setting, respectively. The mean neonatal mortality rate was 23 per 1000 live births, ranging from 8.2 to 48.5 per 1000 live births. The mean stillbirth rate ranged from 13.7 to 54.4 per 1000 births.
The registry is an ongoing study to assess the impact of interventions and trends regarding pregnancy outcomes and measures of care to inform public health.
Maternal mortality; Neonatal mortality; Perinatal mortality; Pregnancy; Registry; Stillbirth
Improving the health and well-being of women and children has long been a common goal throughout the world. From 2005 to 2011, Suizhou City had an annual average of 22,405 pregnant and parturient women (1.04% of the population) and 98,811 children under 5 years old (4.57% of the population). Understanding the status of maternal and child health care in Suizhou City during such period can provide the local health administrative department valid scientific bases upon which to construct effective policies.
Various types of annual reports on maternal and child health care were collected and analyzed retrospectively.
Mortality rates for infants and children under 5 years showed a declining trend, while the rates of newborn home visiting, maternal health service coverage, and children health systematic management increased annually in Suizhou City from 2005 to 2011. The incidence of birth defect increased from 2.42‰ in 2005 to 3.89‰ in 2011. The maternal mortality ratio (MMR) fluctuated from 8.39/100,000 to 28.77/100,000, which was much lower than the national MMR (30.0/100,000 in 2010). The rates of hospitalized delivery and births attended by trained health personnel for pregnant women increased to more than 90% in the past five years.
The improvements in maternal and child health care work in Suizhou City are worthy of recognition. Thus, the government should continue to increase funding in these areas to promote the complete enhancement of the maternal and child health care system.
To assess the impact of emperic antifungal therapy of invasive candidiasis on subsequent outcomes in premature infants.
This was a cohort study of infants ≤1000 g birth weight cared for at Neonatal Research Network sites. All infants had at least 1 positive culture for Candida. Emperic antifungal therapy was defined as receipt of a systemic antifungal on the day of or the day before the first positive culture for Candida was drawn. We created Cox proportional hazards and logistic regression models stratified on propensity score quartiles to determine the effect of emperic antifungal therapy on survival, time to clearance of infection, retinopathy of prematurity, bronchopulmonary dysplasia, end-organ damage, and neurodevelopmental impairment (NDI).
136 infants developed invasive candidiasis. The incidence of death or NDI was lower for infants who received emperic antifungal therapy (19/38, 50%) compared with those who had not (55/86, 64%; odds ratio=0.27 [95% confidence interval 0.08–0.86]). There was no significant difference between the groups for any single outcome or other combined outcomes.
Emperic antifungal therapy was associated with increased survival without NDI. A prospective randomized trial of this strategy is warranted.
Candida; neonate; mortality; neurodevelopmental impairment
To test the hypothesis that preterm infants randomized to a low vs high O2 saturation target range have a higher incidence of intermittent hypoxemia.
A subcohort of 115 preterm infants with high resolution pulse oximetry enrolled in the Surfactant, Positive Pressure, and Oxygenation Randomized Trial were randomized to low (85%-89%) or high (91%-95%) O2 saturation target ranges. Oxygen saturation was monitored until 36 weeks postmenstrual age or until the infant was breathing room air without respiratory support for ≥72 hours.
The low target O2 saturation group had a higher rate of intermittent hypoxemia (≤80% for ≥10 seconds and ≤3 minutes) prior to 12 days and beyond 57 days of life (P < .05). The duration shortened (P < .0001) and the severity increased (P < .0001) with increasing postnatal age with no differences between target saturation groups. The higher rate of intermittent hypoxemia events in the low target group was associated with a time interval between events of <1 minute.
A low O2 saturation target was associated with an increased rate of intermittent hypoxemia events that was dependent on postnatal age. The duration and severity of events was comparable between target groups. Further investigation is needed to assess the role of intermittent hypoxemia and their timing on neonatal morbidity.
The objective of our study was to examine the relationship between brain injury and outcome following neonatal hypoxic–ischaemic encephalopathy treated with hypothermia.
Design and patients
Neonatal MRI scans were evaluated in the National Institute of Child Health and Human Development (NICHD) randomised controlled trial of whole-body hypothermia and each infant was categorised based upon the pattern of brain injury on the MRI findings. Brain injury patterns were assessed as a marker of death or disability at 18–22 months of age.
Scans were obtained on 136 of 208 trial participants (65%); 73 in the hypothermia and 63 in the control group. Normal scans were noted in 38 of 73 infants (52%) in the hypothermia group and 22 of 63 infants (35%) in the control group. Infants in the hypothermia group had fewer areas of infarction (12%) compared to infants in the control group (22%). Fifty-one of the 136 infants died or had moderate or severe disability at 18 months. The brain injury pattern correlated with outcome of death or disability and with disability among survivors. Each point increase in the severity of the pattern of brain injury was independently associated with a twofold increase in the odds of death or disability.
Fewer areas of infarction and a trend towards more normal scans were noted in brain MRI following whole-body hypothermia. Presence of the NICHD pattern of brain injury is a marker of death or moderate or severe disability at 18–22 months following hypothermia for neonatal encephalopathy.
Permanent ductal closure involves anatomic remodeling, in which transforming growth factor (TGF)-β appears to play a role. Our objective was to evaluate the relationship, if any, between blood spot TGF-β on day 3 and day 7 of life and patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. Prospective observational study involving ELBW infants (n = 968) in the National Institute of Child Health and Human Development Neonatal Research Network who had TGF-β measured on filter paper spot blood samples using a Luminex assay. Infants with a PDA (n = 493) were significantly more immature, had lower birth weights, and had higher rates of respiratory distress syndrome than those without PDA (n = 475). TGF-β on days 3 and 7 of life, respectively, were significantly lower among neonates with PDA (median 1,177 pg/ml [range 642–1,896]; median 1,386 pg/ml [range 868–1,913]) compared with others without PDA (median 1,334 pg/ml [range 760–2,064]; median 1,712 pg/ml [range 1,014–2,518 pg/ml]). The significant difference persisted when death or PDA was considered a composite outcome. TGF-β levels were not significantly different among subgroups of infants with PDA who were not treated (n = 51) versus those who were treated medically (n = 283) or by surgical ligation (n = 159). TGF-β was not a significant predictor of death or PDA (day 3 odds ratio [OR] 0.99, 95 % confidence interval [CI] 0.83–1.17; day 7 OR 0.88, 95 % CI 0.74–1.04) on adjusted analyses. Our results suggest that blood spot TGF-β alone is unlikely to be a reliable biomarker of a clinically significant PDA or its responsiveness to treatment.
Transforming growth factor; Patent ductus arteriosus; Preterm; Neonate
To assess the feasibility of a randomized placebo controlled trial (RCT) of blood pressure (BP) management for extremely preterm infants.
This was a prospective pilot RCT of infants 230/7 – 266/7 weeks gestation who had protocol-defined low BP in the first 24 postnatal hours. Enrolled infants were administered a study infusion (dopamine or placebo) and a study syringe medication (hydrocortisone or placebo).
Of the 366 infants screened, 119 (33%) had low BP, 58 (16%) met all entry criteria, and 10 (3%) were enrolled. 161 (44%) infants were ineligible because they received early indomethacin. Only 17% of eligible infants were enrolled. Problems with consent included insufficient time, parent unavailability, and physician unwillingness to enroll critically ill infants. Two infants were withdrawn from the study due to the potential risk of intestinal perforation with simultaneous administration of hydrocortisone and indomethacin.
This pilot RCT was not feasible due to low eligibility and consent rates. An RCT of BP management for extremely preterm infants may require a waiver of consent for research in emergency care. The frequent use of early indomethacin and the associated risk of intestinal perforation when used with hydrocortisone may limit future investigations to only inotropic medications.
Extremely preterm infant; hypotension; hydrocortisone; dopamine; informed consent
Methods are required to predict prognosis with changes in clinical course. Death or neurodevelopmental impairment in extremely premature neonates can be predicted at birth/admission to the ICU by considering gender, antenatal steroids, multiple birth, birth weight, and gestational age. Predictions may be improved by using additional information available later during the clinical course. Our objective was to develop serial predictions of outcome by using prognostic factors available over the course of NICU hospitalization.
Data on infants with birth weight ≤1.0 kg admitted to 18 large academic tertiary NICUs during 1998–2005 were used to develop multivariable regression models following stepwise variable selection. Models were developed by using all survivors at specific times during hospitalization (in delivery room [n = 8713], 7-day [n = 6996], 28-day [n = 6241], and 36-week postmenstrual age [n = 5118]) to predict death or death/neurodevelopmental impairment at 18 to 22 months.
Prediction of death or neurodevelopmental impairment in extremely premature infants is improved by using information available later during the clinical course. The importance of birth weight declines, whereas the importance of respiratory illness severity increases with advancing postnatal age. The c-statistic in validation models ranged from 0.74 to 0.80 with misclassification rates ranging from 0.28 to 0.30.
Dynamic models of the changing probability of individual outcome can improve outcome predictions in preterm infants. Various current and future scenarios can be modeled by input of different clinical possibilities to develop individual “outcome trajectories” and evaluate impact of possible morbidities on outcome.
logistic models; premature infant; predictive value of tests; prognosis
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
To determine whether resuscitation of infants who failed to develop effective breathing at birth increases survivors with neurodevelopmental impairment.
Infants unresponsive to stimulation who received bag and mask ventilation at birth in a resuscitation trial and infants who did not require any resuscitation were randomized to early neurodevelopmental intervention or control. Infants were evaluated by trained neurodevelopmental evaluators masked to both their resuscitation history and intervention group. The 12-month neurodevelopmental outcome data for both resuscitated and non-resuscitated infants randomized to the control groups are reported.
The study provided no evidence of a difference between the resuscitated (N = 86) and the non-resuscitated infants (N = 115) in the percentage of infants at 12 months with a mental developmental index < 85 on the Bayley Scales of Infant Development-II (primary outcome) (18% versus 12%; p = 0.22) and in other neurodevelopmental outcomes.
The overwhelming majority of infants who received resuscitation with bag and mask ventilation at birth have 12-month neurodevelopmental outcomes in the normal range. Longer follow-up is needed because of increased risk for neurodevelopmental impairments.
Resuscitation; intellectual disability; low and middle income countries; neonatal mortality; infant mortality; developmental outcome
Information on cytokine profiles in fungal sepsis (FS), an important cause of mortality in extremely low birthweight infants (ELBW), is lacking. We hypothesized that cytokine profiles in the 1st 21 days of life in ELBW with FS differ from those with bacterial sepsis (BS) or no sepsis (NS).
In a secondary analyses of the NICHD Cytokine study, three groups were defined - FS (≥1 episode of FS), BS (≥1 episode of BS without FS), and NS. Association between 11 cytokines assayed in dried blood spots obtained on days 0-1, 3±1, 7±2, 14±3, and 21±3 and sepsis group was explored.
Of 1066 infants, 89 had FS and 368 had BS. Compared to BS, FS was more likely to be associated with lower birthweight, vaginal delivery, patent ductus arteriosus, postnatal steroids, multiple central lines, longer respiratory support and hospital stay, and higher mortality (p<0.05). Analyses controlling for covariates showed significant group differences over time for IFN-γ, IL-10, IL-18, TGF-β and TNF-α (p<0.05).
Significant differences in profiles for IFN-γ, IL-10, IL-18, TGF-β and TNF-α in FS, BS or NS in this hypothesis-generating secondary study require validation in rigorously designed prospective studies and may have implications for diagnosis and treatment.
Pulmonary hypertension is associated with bronchopulmonary dysplasia in extremely low birth weight (ELBW) infants and contributes to morbidity and mortality. The objective was to determine the prevalence of pulmonary hypertension among ELBW infants by screening echocardiography and evaluate subsequent outcomes.
All ELBW infants admitted to a regional perinatal center were evaluated for pulmonary hypertension with echocardiography at 4 weeks of age and subsequently if clinical signs suggestive of right-sided heart failure or severe lung disease were evident. Management was at discretion of the clinician, and infants were evaluated until discharge from the hospital or pre-discharge death occurred.
One hundred forty-five ELBW infants (birth weight: 755 ± 144 g; median gestational age: 26 weeks [interquartile range: 24–27]) were screened from December 2008 to February 2011. Overall, 26 (17.9%) were diagnosed with pulmonary hypertension at any time during hospitalization (birth weight: 665 ± 140 g; median gestational age: 26 weeks [interquartile range: 24–27]): 9 (6.2%) by initial screening (early pulmonary hypertension) and 17 (11.7%) who were identified later (late pulmonary hypertension). Infants with pulmonary hypertension were more likely to receive oxygen treatment on day 28 compared with those without pulmonary hypertension (96% vs 75%, P < .05). Of the 26 infants, 3 died (all in the late group because of cor pulmonale) before being discharged from the hospital.
Pulmonary hypertension is relatively common, affecting at least 1 in 6 ELBW infants, and persists to discharge in most survivors. Routine screening of ELBW infants with echocardiography at 4 weeks of age identifies only one-third of the infants diagnosed with pulmonary hypertension. Further research is required to determine optimal detection and intervention strategies.
premature infant; bronchopulmonary dysplasia; pulmonary hypertension
Current guidelines, initially published in 1995, recommend antenatal corticosteroids for mothers with preterm labor from 24–34 weeks gestational age, but not before 24 weeks because of lack of data. However, many infants born before 24 weeks are provided intensive care now.
To determine if antenatal corticosteroids are associated with improvement in major outcomes in infants born at 22 and 23 weeks.
Design, Setting, Participants
Data for this cohort study were collected prospectively on 401–1000 gram inborn infants (N=10,541) of 22–25 weeks gestation born between 1993–2009 at 23 academic perinatal centers in the United States. Certified examiners unaware of exposure to antenatal corticosteroids performed follow-up examinations on 4,924 (86.5%) of the infants born in 1993–2008 who survived to 18–22 months. Logistic regression models generated adjusted odds ratios, controlling for maternal and neonatal variables.
Main Outcome Measures
Mortality and neurodevelopmental impairment at 18–22 months corrected age
Death or neurodevelopmental impairment at 18–22 months was lower for infants whose mothers received antenatal corticosteroids born at 23 weeks (antenatal corticosteroids, 83.4% vs no antenatal corticosteroids, 90.5%; adjusted odds ratio 0.58; 95% CI, 0.42–0.80), at 24 weeks (antenatal corticosteroids, 68.4% vs no antenatal corticosteroids, 80.3%; adjusted odds ratio 0.62; 95% CI, 0.49–0.78), and at 25 weeks (antenatal corticosteroids, 52.7% vs no antenatal corticosteroids, 67.9%; adjusted odds ratio 0.61; 95% CI, 0.50–0.74) but not at 22 weeks (antenatal corticosteroids, 90.2% vs no antenatal corticosteroids, 93.1%; adjusted odds ratio 0.80; 95% CI, 0.29–12.21). Death by 18–22 months, hospital death, death/intraventricular hemorrhage/periventricular leukomalacia, and death/necrotizing enterocolitis were significantly lower for infants born at 23, 24, and 25 weeks gestational age if the mothers had received antenatal corticosteroids but the only outcome significantly lower at 22 weeks was death/necrotizing enterocolitis (antenatal corticosteroids, 73.5% vs no antenatal corticosteroids, 84.5%; adjusted odds ratio 0.54; 95% CI, 0.30–0.97).
Among infants born at 23–25 weeks gestation, use of antenatal corticosteroids compared to non-use was associated with a lower rate of death or neurodevelopmental impairment at 18–22 months.
prematurity; infant mortality; neonatal intensive care; neurodevelopmental impairment; lung maturation; limits of viability
Ninety-eight percent of the 3.7 million neonatal deaths and 3.3 million stillbirths per year occur in developing countries, and evaluation of community-based interventions is needed.
Using a train-the-trainer model, local instructors trained birth attendants from rural communities in six countries (Argentina, Democratic Republic of Congo, Guatemala, India, Pakistan, and Zambia) in the World Health Organization Essential Newborn Care course (routine neonatal care, resuscitation, thermoregulation, breastfeeding, kangaroo care, care of the small baby, and common illnesses), and in a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program (in depth basic resuscitation), except in Argentina.
The Essential Newborn Care intervention was assessed with a before and after design (N=57, 643). The Neonatal Resuscitation Program intervention was assessed as a cluster randomized controlled trial (N=62,366). The primary outcome was 7-day neonatal mortality.
The 7-day follow-up rate was 99.2%. Following Essential Newborn Care training, there was no significant reduction from baseline in all-cause 7-day neonatal (RR 0.99; CI 0.81, 1.22) or perinatal mortality; there was a significant reduction in the stillbirth rate (RR 0.69; CI 0.54, 0.88; p<0.01). Seven-day neonatal mortality, stillbirth, and perinatal mortality were not reduced in clusters randomized to Neonatal Resuscitation Program training as compared with control clusters.
Seven-day neonatal mortality did not decrease following the introduction of Essential Newborn Care training of community-based birth attendants, although the rate of stillbirths was reduced following this intervention. Subsequent training in the Neonatal Resuscitation Program did not significantly reduce the mortality rates. (clinicaltrials.gov number, NCT00136708).
neonatal mortality; perinatal mortality; developing countries; health systems; effectiveness
To determine if selected pro-inflammatory and anti-inflammatory cytokines/mediators of inflammation reported to be related to development of cerebral palsy predict neurodevelopmental outcome in extremely low birth weight infants.
Infants with birth weights ≤ 1000 g (n=1067) had blood samples collected at birth and on days 3±1, 7±1, 14±3, and 21±3 to examine the association between cytokines and neurodevelopmental outcomes. The analyses were focused on five cytokines (IL-1β, IL-8, TNF-α, RANTES, and IL-2) reported to be most predictive of CP in term and late preterm infants.
IL-8 was higher on days 0–4 and subsequently in infants who developed CP compared with infants who did not develop CP in both unadjusted and adjusted analyses. Other cytokines (IL-12, IL-17, TNF-β, SIL-rα, MIP-1β) were found to be altered on days 0–4 in infants who developed CP.
CP in former preterm infants may, in part, have a late perinatal and/or early neonatal inflammatory origin.
To test the hypothesis that heart rate characteristics (HRC) monitoring improves neonatal outcomes.
Two-group, parallel, individually randomized controlled clinical trial of 3003 very low birth weight infants in 9 NICUs. In one group, HRC monitoring was displayed; in the other, it was masked. The primary outcome was number of days alive and ventilator-free in the 120 days after randomization. Secondary outcomes were mortality, number of ventilator days, NICU stay and antibiotic use.
Mortality was reduced in infants whose HRC monitoring was displayed, from 10.2% to 8.1% (HR = 0.78, 95% CI = 0.61 to 0.99, P = 0.04, number needed to monitor 48), and there was a trend toward increased days alive and ventilator-free (95.9 of 120 days compared to 93.6 in controls, P = 0.08). Mortality benefit was concentrated in infants with birth weight <1000g (HR=0.74, 95% CI 0.57 to 0.95, P=0.02, number needed to monitor 23). There were no significant differences in the other outcomes.
Heart rate characteristics monitoring can reduce mortality in very low birth weight infants.
Neonatal sepsis; sample entropy; predictive monitoring; heart rate variability
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
Preterm birth is a major cause of neonatal mortality, responsible for 28% of neonatal deaths overall. The administration of antenatal corticosteroids to women at high risk of preterm birth is a powerful perinatal intervention to reduce neonatal mortality in resource rich environments. The effect of antenatal steroids to reduce mortality and morbidity among preterm infants in hospital settings in developed countries with high utilization is well established, yet they are not routinely used in developing countries. The impact of increasing antenatal steroid use in hospital or community settings with low utilization rates and high infant mortality among premature infants due to lack of specialized services has not been well researched. There is currently no clear evidence about the safety of antenatal corticosteroid use for community-level births.
We hypothesize that a multi country, two-arm, parallel cluster randomized controlled trial to evaluate whether a multifaceted intervention to increase the use of antenatal corticosteroids, including components to improve the identification of pregnancies at high risk of preterm birth and providing and facilitating the appropriate use of steroids, will reduce neonatal mortality at 28 days of life in preterm newborns, compared with the standard delivery of care in selected populations of six countries. 102 clusters in Argentina, Guatemala, Kenya, India, Pakistan, and Zambia will be randomized, and around 60,000 women and newborns will be enrolled. Kits containing vials of dexamethasone, syringes, gloves, and instructions for administration will be distributed. Improving the identification of women at high risk of preterm birth will be done by (1) diffusing recommendations for antenatal corticosteroids use to health providers, (2) training health providers on identification of women at high risk of preterm birth, (3) providing reminders to health providers on the use of the kits, and (4) using a color-coded tape to measure uterine height to estimate gestational age in women with unknown gestational age. In both intervention and control clusters, health providers will be trained in essential newborn care for low birth weight babies. The primary outcome is neonatal mortality at 28 days of life in preterm infants.
ClinicalTrials.gov. Identifier: NCT01084096
Neonatal mortality; Antenatal corticosteroids; Implementation research; Preterm birth
Bone mineral deficiency continues to occur in extremely low birth weight (ELBW) infants despite formulas enriched in Ca and P.
This study tested whether extra enteral Ca supplementation increases bone mineral content (BMC) and prevents dolichocephalic head flattening and myopia in ELBW infants.
Infants 401–1000 birth weight receiving enteral feeds were randomized to receive feeds supplemented with Ca-gluconate powder, or pure standard feeds. Main outcome measures were the excretion of Ca and P by weekly spot urine measurements, the degree of dolichocephalic deformation (fronto-occipital to biparietal diameter ratio, FOD/BPD) at 36 weeks postmenstrual age and the BMC (by dual-energy x-ray absorptiometry) at discharge. Cycloplegic refraction was measured at 18–22 months corrected age.
Ninety-nine ELBW infants with a gestational age of 26 weeks (23–31) [Median (minimum-maximum)] were randomized at a postnatal age of 12 days (5–23) weighing 790g (440–1700). Urinary Ca excretion increased, P excretion decreased in the Ca supplemented group. Total body BMC was 89.9 ± 2.4 g (mean ± SE) in the supplemented group and 85.2 ± 2.6 g in the control group (p= 0.19). The FOD/BPD was 1.50 (1.13–1.69, mean ± SD) and 1.47 (1.18–1.64) in the supplemented and control groups, and the refraction 0.98 ± 1.23 and 1.40 ± 1.33 dpt. (p=0.68), respectively in 64 ELBW infants (79% of survivors) at 2-year-follow-up.
Extra enteral Ca supplementation did not change BMC, head shape or refraction. The decreased P excretion may reflect P deficiency in infants receiving extra Ca, preventing improved bone mineral accretion.
bone mineral content; bone mineral density; preterm infant; bioavailability; phosphorus