Showing papers in "Journal of Perinatology in 2005"

Amniotic fluid: not just fetal urine anymore.

Abstract: Amniotic fluid (AF) is a complex substance essential to fetal well-being. This article reviews recent discoveries and the current understanding of the origin and circulation of AF and its nutritive, protective, and diagnostic functions. Future directions for AF research are also discussed.

Definition of the clinical spectrum of kernicterus and bilirubin-induced neurologic dysfunction (BIND).

Abstract: Kernicterus, currently used to describe both the neuropathology of bilirubin-induced brain injury and its associated clinical findings, is a complex syndrome. The neurobiology of kernicterus, including the determinants and mechanisms of neuronal injury, is discussed along with traditional and evolving definitions ranging from classical kernicterus with athetoid cerebral palsy, impaired upward gaze and deafness, to isolated conditions, for example, auditory neuropathy or dys-synchrony (AN/AD), and subtle bilirubin-induced neurological dysfunction (BIND). The clinical expression of BIND varies with location, severity, and time of assessment, influenced by the amount, duration and developmental age of exposure to excessive free bilirubin. Although total serum bilirubin (TSB) is important, kernicterus cannot be defined based solely on TSB. For study purposes kernicterus may be defined in term and near-term infants with TSB > or = 20 mg/dl using abnormal muscle tone on examination, auditory testing diagnostic of AN/AD, and magnetic resonance imaging showing bilateral lesions of globus pallidus+/-subthalamic nucleus.

Neonatal and infant mortality in the ten years (1993 to 2003) of the Gadchiroli field trial: effect of home-based neonatal care.

Abstract: The field trial of HBNC in Gadchiroli, India, has completed the baseline phase (1993 to 1995), observational phase (1995 to 1996) and the 7 years of intervention (1996 to 2003). We measured the stillbirth rate (SBR), neonatal mortality rate (NMR), perinatal mortality rate (PMR), postneonatal mortality rate (PNMR) and the infant mortality rate (IMR) in the intervention area and the control area. The effect of HBNC on all these rates was estimated by comparing the change from baseline (1993 to 1995) to the last 2 years of intervention (2001 to 2003) in the intervention area vs in the control area. For other estimates, we made a before–after comparison of the rates in the intervention arm in the observation year (1995 to 1996) vs intervention years (1996 to 2003). We evaluated the effect on the cause-specific NMRs. By using the changes in the incidence and case fatality (CF) of the four main morbidities, we estimated the contribution of primary prevention and of the management of sick neonates. The proportion of deaths averted by different components of HBNC was estimated. The baseline population in 39 intervention villages was 39,312 and in 47 control villages it was 42,617, and the population characteristics and vital rates were similar. The total number of live births in 10 years (1993 to 2003) were 8811 and 9990, respectively. The NMR in the control area showed an increase from 58 in 1993 to 1995 to 64 in 2001 to 2003. The NMR in the intervention area declined from 62 to 25; the reduction in comparison to the control area was by 44 points (70%, 95% CI 59 to 81%). Early NMR decreased by 24 points (64%) and late NMR by 20 points (80%). The SBR decreased by 16 points (49%) and the PMR by 38 points (56%). The PNMR did not change, and the IMR decreased by 43 points (57%, 95% CI 46 to 68%). All reductions were highly significant (p<0.001) except for SBR it was <0.05. The cause-specific NMR (1995 to 1996 vs 2001 to 2003) for sepsis decreased by 90%, for asphyxia by 53% and for prematurity by 38%. The total reduction in neonatal mortality during intervention (1996 to 2003) was ascribed to sepsis management, 36%; supportive care of low birth weight (LBW) neonates, 34%; asphyxia management, 19%; primary prevention, 7% and management of other illnesses or unexplained, 4%. The HBNC package in the Gadchiroli field trial reduced the neonatal and perinatal mortality by large margins, and the gains were sustained at the end of the 7 years of intervention and were carried forward as improved survival through the first year of life. Most of the reduction in mortality was ascribed to sickness management, that is, management of sepsis, supportive care of LBW neonates and management of asphyxia, in that order, and a small portion to primary prevention.

Long-term programming effects of early nutrition -- implications for the preterm infant.

Abstract: The current focus of nutritional science has shifted from meeting needs to determining the biological effects that nutrition has on immediate and lifetime health. Of particular interest is the concept of programming, the idea that "a stimulus or insult during a critical or sensitive period of development can have long-term or lifetime effects on an organism." Evidence that early nutrition has such "programming" effects in animals is overwhelming. In humans, retrospective observations show a relationship between adult disease and size in early life, though it is difficult to prove nutritional cause from observational associations and therefore difficult to use such data to underpin health policy. However, the results of randomized intervention trials of early nutrition with long-term follow-up are emerging. These experimental studies show that nutrition in early life has a major impact on health into early adulthood, notably on cardiovascular disease risk, bone health and cognitive function. These new findings have major biological, social and medical implications and should increasingly underpin health practices.

Low birth weight and preterm births: etiologic fraction attributable to prenatal drug exposure.

Abstract: To determine the factors that would increase the likelihood of outcomes: low birth weight (LBW), preterm births and intrauterine growth restriction (IUGR). Secondary data analysis from a multi-center study. Risk factors for each outcome were derived from logistic regression models. Odds ratios (OR), 95% confidence intervals, and population-attributable risk proportions (PAR%) were estimated. Prenatal cocaine exposure increased the likelihood of LBW (OR: 3.59), prematurity (OR: 1.25), and IUGR (OR: 2.24). Tobacco, but not marijuana, significantly influenced these outcomes. Alcohol had an effect on LBW and IUGR. Etiologic fractions (PAR%) attributable to tobacco for LBW, prematurity, and IUGR were 5.57, 3.66, and 13.79%, respectively. With additional drug exposure including cocaine, estimated summary PAR% increased to 7.20% (LBW), 5.68% (prematurity), and 17.96% (IUGR). Disease burden for each outcome increases with each added drug exposure; however, etiologic fraction attributable to tobacco is greater than for cocaine.

Selective Serotonin Reuptake Inhibitor (SSRI) Use during Pregnancy and Effects on the Fetus and Newborn: A Meta-Analysis

Abstract: Selective serotonin reuptake inhibitors (SSRIs) are frequently used to treat depression during pregnancy and the postpartum period. These drugs are capable of crossing the placenta and being transferred to the newborn during lactation. This report reviews the available information regarding the effects of SSRIs on the fetus and newborn; including long-term neurodevelopmental outcomes.

Heat loss prevention for preterm infants in the delivery room.

Abstract: Preterm infants are prone to hypothermia immediately following birth. Among other factors, excessive evaporative heat loss and the relatively cool ambient temperature of the delivery room may be important contributors. Most infants 36.4°C. Placing infants <29 weeks gestation in polyurethane bags in the delivery room reduced the occurrence of hypothermia and increased their NICU admission temperatures. Maintaining warmer delivery rooms helped but was insufficient in preventing hypothermia in most of these vulnerable patients without the adjunctive use of the polyurethane bags.

The epidemiology of respiratory failure in neonates born at an estimated gestational age of 34 weeks or more

Abstract: The Epidemiology of Respiratory Failure in Neonates Born at an Estimated Gestational Age of 34 Weeks or More

Management of birth asphyxia in home deliveries in rural Gadchiroli: the effect of two types of birth attendants and of resuscitating with mouth-to-mouth, tube-mask or bag-mask.

Abstract: To evaluate the effect of home-based neonatal care on birth asphyxia and to compare the effectiveness of two types of workers and three methods of resuscitation in home delivery. In a field trial of home-based neonatal care in rural Gadchiroli, India, birth asphyxia in home deliveries was managed differently during different phases. Trained traditional birth attendants (TBA) used mouth-to-mouth resuscitation in the baseline years (1993 to 1995). Additional village health workers (VHWs) only observed in 1995 to 1996. In the intervention years (1996 to 2003), they used tube-mask (1996 to 1999) and bag-mask (1999 to 2003). The incidence, case fatality (CF) and asphyxia-specific mortality rate (ASMR) during different phases were compared. During the intervention years, 5033 home deliveries occurred. VHWs were present during 84% home deliveries. The incidence of mild birth asphyxia decreased by 60%, from 14% in the observation year (1995 to 1996) to 6% in the intervention years (p<0.0001). The incidence of severe asphyxia did not change significantly, but the CF in neonates with severe asphyxia decreased by 47.5%, from 39 to 20% (p<0.07) and ASMR by 65%, from 11 to 4% (p<0.02). Mouth-to-mouth resuscitation reduced the ASMR by 12%, tube–mask further reduced the CF by 27% and the ASMR by 67%. The bag–mask showed an additional decrease in CF of 39% and in the fresh stillbirth rate of 33% in comparison to tube–mask (not significant). The cost of bag and mask was $13 per averted death. Oxytocic injection administered by unqualified doctors showed an odds ratio of three for the occurrence of severe asphyxia or fresh stillbirth. Home-based interventions delivered by a team of TBA and a semiskilled VHW reduced the asphyxia-related neonatal mortality by 65% compared to only TBA. The bag–mask appears to be superior to tube–mask or mouth-to-mouth resuscitation, with an estimated equipment cost of $13 per death averted.

Follow-Up of Infants Exposed to Hydroxychloroquine Given to Mothers during Pregnancy and Lactation

Abstract: Objective To determine the effect of hydroxychloroquine treatment during pregnancy and lactation on babies of mothers affected by rheumatic diseases. Study design and methods A total of 40 infants born from mothers affected by rheumatic diseases and treated with hydroxychloroquine during pregnancy were enrolled in a prospective observational study. Main outcome measures at birth were incidence of prematurity, congenital malformations and neonatal infections. Of these babies, including 13 who were breast-fed, 24 were followed up during early infancy for visual function and neurodevelopmental outcome. Results Preterm delivery was the main complication (20.5%). No significant congenital malformations or neonatal infections were detected. All infants, including those who were breast-fed, had normal visual function and neurodevelopmental outcome. Conclusions Hydroxychloroquine treatment during gestation and lactation appeared to be safe. The relatively high incidence of preterm deliveries may reflect the maternal disease state.

Vernix Caseosa in Neonatal Adaptation

Abstract: To characterize vernix caseosa in newborn infants with respect to factors that influence vernix distribution on the skin surface, vernix effects on thermal stability, skin hydration, acid mantle development, and vernix antioxidant properties. Vernix distribution was determined for 430 infants. Thermal stability was assessed in parallel groups following vernix retention (n=66) and removal (n=64). The effects of vernix retention on skin hydration, pH, erythema, and dryness/scaling were determined. Samples were analyzed for vitamin E before and after UV exposure. Vernix distribution depended upon gestational age, delivery mode, gender, race, and meconium exposure. Retention had no effect on axillary temperatures. Skin hydration was significantly higher for vernix-retained skin. Skin pH and erythema were significantly lower with retention. Vitamin E levels were decreased by ultraviolet radiation. Vernix is a naturally occurring barrier cream with multiple salubrious effects, which support its retention on the skin surface at birth.

Validity of Hospital Discharge Data for Identifying Infants with Cardiac Defects

Abstract: To examine validity of the International Classification of Diseases, 9th Edition, Clinical Modification (ICD-9-CM) codes in discharge data for identifying infants with cardiac defects according to surveillance guidelines. Retrospective medical record review of infants born in 2001 at one hospital in Minneapolis, Minnesota. Infants were identified using ICD-9-CM codes from hospital discharge data, and keywords in medical records. Of 2697 children, ICD-9-CM codes identified 66 infants coded with cardiac defects; physician review confirmed 24 had cardiac defects. Only 35 of 85 (41.2%) ICD-9-CM codes accurately reflected the cardiac defect diagnoses. Additional case finding located four infants with five cardiac defects. Sensitivity of ICD-9-CM codes for identifying these infants was 0.857, predictive value positive was 0.364. ICD-9-CM codes from hospital discharge data identified most infants with cardiac defects, but many were false positives. ICD-9-CM codes were inaccurate for specific cardiac defects.

Surfactant administration by transient intubation in infants 29 to 35 weeks' gestation with respiratory distress syndrome decreases the likelihood of later mechanical ventilation: a randomized controlled trial.

Abstract: To assess, among premature infants with early respiratory distress syndrome (RDS), the effect of one dose of intratracheally administered surfactant followed by extubation to nasal continuous positive airway pressure (NCPAP) on subsequent mechanical ventilation (MV), when compared with NCPAP alone. Randomized, blinded trial in infants 29 to 35 weeks' gestation with mild-to-moderate RDS requiring supplemental oxygen and NCPAP. Infants were randomized to intubation, surfactant treatment, and immediate extubation (surfactant group N=52), or to no intervention (control group N=53). All infants were subsequently managed with NCPAP. Need for later MV was 70% in the control group and 50% in the surfactant group. Surfactant group subjects had lower inspired oxygen fraction (FiO2) after study intervention and were less likely to require subsequent surfactant. Overall surfactant use, duration of O2 therapy, length of stay, and bronchopulmonary dysplasia were unaffected. Among premature infants with mild-to-moderate RDS, transient intubation for surfactant administration reduces later MV.

Maternal infection and risk of cerebral palsy in term and preterm infants.

Abstract: We tested the hypothesis that term and preterm infants exposed to maternal infection at the time of delivery are at increased risk of developing cerebral palsy (CP). A population-based case–control study was conducted using Washington State birth certificate data linked to hospital discharge data. Cases (688) were children ≤6 years old, singleton births, hospitalized during 1987 to 1999 with an ICD-9 diagnosis code for CP. Controls were 3068 singleton birth infants randomly selected from birth records for the same years without CP-related hospitalizations. Infection information was available only for the birth hospitalization. Infants of women who had any infection during their hospitalization for delivery were at increased risk of CP (odds ratio (OR) 3.1, 95% confidence interval (CI) 2.3 to 4.2). This was observed for term deliveries (OR 1.8, 95% CI 1.1 to 2.8) and preterm deliveries (OR 2.3, 95% CI 1.3 to 4.2). Our results suggest that maternal infection is a risk factor for CP in both term and preterm infants.

Home-based neonatal care: summary and applications of the field trial in rural Gadchiroli, India (1993 to 2003).

Abstract: High levels of neonatal mortality and lack of access to neonatal health care are widespread problems in developing countries. A field trial of home-based neonatal care (HBNC) was conducted in rural Gadchiroli, India to develop and test the feasibility of a low-cost approach of delivering primary neonatal care by using the human potential available in villages, and to evaluate its effect on neonatal mortality. In the first half of this article we summarize various aspects of the field trial, presented in the previous 11 articles in this issue of the journal supplement. The background, objectives, study design and interventions in the field trial and the results over 10 years (1993 to 2003) are presented. Based on these results, the hypotheses are tested and conclusions presented. In the second half, we discuss the next questions: can it be replicated? Can this intervention become a part of primary health-care services? What is the cost and the cost-effectiveness of HBNC? The limitations of the approach, the settings where HBNC might be relevant and the management pre-requisites for its scaling up are also discussed. The need to develop an integrated approach is emphasized. A case for newborn care in the community is made for achieving equity in health care.

Work of Breathing During Nasal Continuous Positive Airway Pressure in Preterm Infants: A Comparison of Bubble vs Variable-Flow Devices

Abstract: To compare work of breathing and breathing asynchrony during bubble nasal continuous positive airway pressure (NCPAP) vs variable-flow (VF)-NCPAP in premature infants. We studied 18 premature infants of birth weight <1500 g who required NCPAP for mild respiratory distress. Each infant was studied on bubble and VF-NCPAP at 8, 6, 4, and 0 cmH2O. Tidal volumes were obtained by calibrated respiratory inductance plethysmography. Esophageal pressure estimated intrapleural pressure. Inspiratory and resistive work of breathing were calculated from pressure–volume data. Breathing asynchrony was assessed with phase angle. The results at all NCPAP levels were referenced to VF-NCPAP values at 8 cmH2O. Provision of NCPAP with either device decreased inspiratory work of breathing, tidal volume, and minute ventilation relative to NCPAP of 0 cmH2O. Bubble NCPAP did not decrease resistive work of breathing relative to 0 cmH2O. Resistive work of breathing (p=0.01), respiratory rate (p<0.03), and phase angle (p=0.002) were all greater with bubble compared to VF-NCPAP. The more labored and asynchronous breathing seen with bubble NCPAP may lead to higher failure rates over the long term than with VF-NCPAP.

Blood urea nitrogen concentration as a marker of amino-acid intolerance in neonates with birthweight less than 1250 g.

Abstract: Currently blood urea nitrogen (BUN) is commonly used as a marker of protein intolerance in very preterm infants. The purpose of this study was to evaluate the relationship between amino-acid intakes and BUN concentrations during the early neonatal period in preterm neonates. Retrospective review of BUN concentration data from 121 infants with birthweight ≤1250 g receiving exclusive parenteral nutrition over the first 72 hours of life. There were 136 separate BUN concentration values. Amino-acid intake range was 0 to 3.7 g kg−1 day−1 and nonprotein calorie intake range was 15 to 45 kcal kg−1 d−1. There was no correlation between BUN concentration and amino-acid intake (p=0.2 and r2=0.01). In parenterally nourished preterm neonates amino-acid intake is not correlated with BUN concentration in the first days of life. Therefore, limiting amino-acid intake based on BUN concentration is not warranted in this patient population.

Role of plasma B-type natriuretic peptide in screening for hemodynamically significant patent ductus arteriosus in preterm neonates.

Abstract: B-type natriuretic peptide (BNP) is a hormone secreted by the ventricles under hemodynamic stress and congestive failure. The objective of the present study was to evaluate whether BNP can be used as a valid screening test for the presence of a hemodynamically significant patent ductus arteriosus (hsPDA) in the preterm neonate. This was a prospective blinded study involving preterm neonates with birth weights ≤1500 g and gestational age ≤34 weeks. Each enrolled neonate underwent the initial echocardiogram for a clinical suspicion of patent ductus arteriosus (PDA) and BNP assay within 3 hours of each other. Those neonates who did not have a PDA or who were not treated underwent a repeat echo and BNP measurement 48 to 72 hours after the first echo. In patients who received treatment for a PDA, an echo and BNP were repeated 48 to 72 hours after completion of treatment. A total of 29 newborns with a median birth weight of 870 g (560 to 1325 g) and a median gestation of 26 weeks (24 to 31 weeks) were enrolled at a median age of 7 days (2 to 28 days). BNP levels were significantly higher in neonates with hsPDA (n=14) compared to those without (n=15) (508.5±618.2 vs 59.5±69.9 pg/ml, p<0.005). At a cutoff value of 70 pg/ml, BNP had a sensitivity of 92.9%, specificity of 73.3%, positive likelihood ratio of 3.5 and negative likelihood ratio of 0.09 for detection of hsPDA. BNP levels dropped significantly after medical or surgical closure of hsPDA (n=12), (404.9±159.2 to 25.1±4.1 pg/ml, p=0.03). Elevation of plasma BNP accurately detects the presence of hsPDA in premature infants. Successful closure is reflected by a corresponding decrease in BNP. At a cutoff of 70 pg/ml, BNP is a useful screening tool for diagnosis and for monitoring efficacy of treatment of hsPDA.

Experience with caspofungin in the treatment of persistent fungemia in neonates.

Abstract: To review our experience of caspofungin in the treatment of persistent candidemia in the neonatal intensive care unit. This was a retrospective chart review on 13 infants in whom caspofungin was added to conventional antifungals (amphotericin B and/or fluconazole or flucytosine) for the treatment of refractory candidemia. A total of 12 infants were preterm (gestational age, 24 to 28 weeks) and one was term; the median birth weight was 800 g (range, 530 to 5600 g). Candidemia (Candida albicans in five, C. parapsilosis in six, C. albicans and C. parapsilosis in one and C. tropicalis in one) persisted despite 6 to 30 days of conventional antifungal therapy. After the addition of caspofungin, sterilization of blood cultures was achieved in 11 infants at the median time of 3 days (range, 1 to 21 days). Adverse events included thrombophlebitis (one patient), hypokalemia (two patients) and elevation of liver enzymes (four patients). Three infants had a second episode of candidemia and seven patients died. Caspofungin may be an efficacious addition for treatment of candidemia refractory to conventional antifungal therapy. This drug should be further investigated in neonates.

Diagnosis and management of vein of galen aneurysmal malformations.

Abstract: Vein of Galen aneurysmal malformations (VGAM) are rare intracranial vascular anomalies typically found in children. The anatomic landmark of a VGAM is the presence of multiple arteriovenous shunts draining into a dilated median prosencephalic vein, an embryonic vessel normally absent at the adult stage. This article reviews the developmental anatomy, the clinical presentation, and the current management of VGAM.

Is home-based diagnosis and treatment of neonatal sepsis feasible and effective? Seven years of intervention in the Gadchiroli field trial (1996 to 2003).

Abstract: To further evaluate our earlier findings on the feasibility and effectiveness of home-based management of neonatal sepsis by analysing 7 years data (1996 to 2003) from the field trial in Gadchiroli, India. Neonates in 39 villages were monitored by trained village health workers (VHWs) from 1995 onwards. In 1996, we trained VHWs to diagnose sepsis by using a clinical algorithm and provide domiciliary treatment using intramuscular gentamicin and oral co-trimoxazole. Health records for all neonates were kept by the VHWs, checked by field supervisors, and computerized. Live births and neonatal deaths were recorded by an independent vital statistics collection system. We evaluated the feasibility and effectiveness of this approach. During September 1996 to March 2003, VHWs monitored 93% of all neonates in 39 villages (N=5268). As compared to 552 cases of sepsis diagnosed by computer algorithm, VHWs correctly diagnosed 492 cases (89%). Parents agreed to home-based treatment for the majority of infants (448, 91%), refused treatment in 31 (6.4%) cases, and hospitalized 13 infants (2.6%). VHWs treated 470 neonates with antibiotics, that is, 8.9% of all neonates in community. Of 552 cases diagnosed by computer, VHWs correctly treated 448 (81.2%) and gave unnecessary treatment to 22/470 (4.7%) of treated neonates. The case fatality (CF) was 6.9% in treated cases vs 22% in untreated or 16.6% in the pre-intervention period (p<0.001). Home-based treatment resulted in 67.2% reduction in %CF among preterm and a 72% reduction among LBW neonates. Home-based management of neonates with suspected sepsis is acceptable to most parents, safe, and effective in reducing sepsis case fatality by nearly 60%. With proper selection, training, and supervision of health workers, this method may be applicable in areas in developing countries where access to hospital care is limited.

The 4P's Plus screen for substance use in pregnancy: clinical application and outcomes.

Abstract: Determine the prevalence of substance use among pregnant women in five diverse communities utilizing the 4P's Plus© screen for alcohol, tobacco, and other drug use. Pregnant women enrolled in prenatal care clinics in five communities were screened for substance use with the 4P's Plus©. Those women with a positive screen underwent an assessment for substance use through a follow-up structured clinical interview conducted at the same prenatal visit. Among 7818 women in five communities, 2555 (32.7%) had a positive screen for substance use in pregnancy. Four of the communities conducted a follow-up assessment on all women with a positive screen (n=1548). Among these women, 717 (15% of the total population) had continued use after learning of the pregnancy. Overall, 21% of the pregnant women used alcohol prior to recognition of the pregnancy, and 11% continued use after knowledge of the pregnancy. Among the 512 women who continued to use alcohol, 2% were drinking daily, 7% were drinking 3 to 6 days per week, 27% were drinking 1 to 2 days per week, and 63% were drinking less than 1 day per week. The rates of marijuana use and other illicit drug use among the women were 7 and 2%, respectively, prior to knowledge of pregnancy and dropped to 3 and 1% after learning of the pregnancy. The 4P's Plus© identifies not only those pregnant women whose drinking or drug use is at a high enough level to impair daily functioning, but provides an opportunity for early intervention for the much larger group of women whose pregnancies are at risk from relatively small amounts of substance use.

Heat Loss Prevention: A Systematic Review of Occlusive Skin Wrap for Premature Neonates

Abstract: To systematically identify and synthesize investigations of the effectiveness of occlusive skin wrap for reducing heat loss in premature infants born at less than 36 weeks gestations. Systematic review. Three randomized controlled trials (RCT) and five historical controlled trials (HCT) were included. Meta-analysis shows wrapped infants had significantly higher admission temperatures than unwrapped infants (RCTs WMD 0.63°C, 95% confidence interval (CI) 0.38, 0.87; HCTs WMD 0.96°C, 95% CI 0.66, 1.27). A statistically significant difference in mortality was not found between wrapped and unwrapped infants in the RCTs (RR 0.72, 95% CI 0.36, 1.45) or the HCTs (RR 0.76, 95% CI 0.51, 1.13). The findings suggest that occlusive skin wrap prevents heat loss in premature infants. The meta-analysis lacked the power to provide definitive results regarding the effect of wrap on mortality.

Overview of surfactant replacement trials.

Abstract: Clinical trials have evaluated the overall efficacy of surfactant therapy, as well as the relative efficacy of different surfactant preparations, the optimal timing of administration and the optimal dosage. Surfactant therapy leads to significant clinical improvement in infants at risk for, or having, respiratory distress syndrome (RDS). Clinical trials that compared the effects of synthetic or animal-derived surfactant preparations to placebo or no therapy demonstrate that surfactant therapy lead to rapid improvement in oxygenation, decreased ventilator support, decreased risk of pneumothorax, and mortality. Earlier treatment, prophylactic treatment of infants at high risk of developing RDS, and selective re-treatment leads to improved clinical outcome as well. Currently available animal-derived surfactants are superior to non-protein-containing synthetic surfactants. Ongoing evaluation will determine if important differences in animal-derived products are noted. Future trials will evaluate third-generation surfactant products and further refine what constitutes optimal use of surfactant.

Amplitude-integrated EEG in preterm infants: maturation of background pattern and amplitude voltage with postmenstrual age and gestational age.

Abstract: Amplitude-integrated electroencephalogram (aEEG) is a single channel EEG recorded from two parietal electrodes. The objective of this study was to test the hypothesis that aEEG maturation follows postmenstrual age (PMA) irrespective of gestational age (GA). We recruited inborn infants with a GA <33 weeks and without evidence of neurologic anomaly. Serial aEEG recordings were assessed for: presence of continuous activity and mature sleep-wake cycling (SWC); low base voltage (V), that is, the lowest amplitude margin; high base V, that is, the most common amplitude margin; upper high V, that is, upper margin during highest activity; and span, that is, the difference between upper high and simultaneous high base V. Statistical analysis included logistic regression and repeated measures analysis of variance. We obtained 119 aEEG recordings in 31 preterm infants (GA 25 to 32 weeks; birth weight 600 to 1704 g, PMA 25 to 35 weeks). The frequency of mature SWC increased with PMA independent of GA, while the frequency of continuity increased with PMA and was higher in extremely preterm infants after correcting for PMA. Low base and high base V increased with PMA, while span and upper high V significantly decreased with PMA. In addition, high base V was higher in extremely preterm infants after correcting for PMA. In preterm infants aEEG matures predominantly with PMA. Our data suggest that some aspects of aEEG maturation are enhanced, rather than inhibited by extremely preterm birth. These data suggest that aEEG in preterm infants may need to be analyzed by comparing results with standards of similar PMA and GA.

A randomized-controlled trial of prophylactic hydrocortisone supplementation for the prevention of hypotension in extremely low birth weight infants.

Abstract: Extremely low birth weight (ELBW) infants are at risk for hypotension. Abnormal adrenal function may play a role in the pathogenesis of hypotension, and therefore, the administration of hydrocortisone (HC) may be an effective treatment for hypotension in some infants. However, the efficacy of prophylactic HC to prevent the use of vasopressors for a defined hypotensive state has not been studied. We conducted a randomized-controlled trial to determine the potential role on adrenal insufficiency in early neonatal hypotension and to determine the effectiveness of prophylactic HC in reducing treatment of hypotension in ELBW infants. Infants were assigned to receive either HC or placebo within the first 3 hours of life. Therapy was continued for 5 days. The presence of hypotension was based on an operational definition and treatment with vasopressors (VP) was standardized based on an a priori protocol. A total of 34 patients were enrolled. Baseline characteristics were similar between groups. Of the HC group 25% received VP at 24 hours of age compared to 44% of the placebo group. On day of life 2, only 7% of the HC group received VP compared to 39% of the placebo group (p<0.05). Prophylactic treatment with HC reduces the incidence of hypotension, defined by treatment with VP, among ELBW infants during the first 2 days of life. However, the mounting evidence that prophylactic administration of glucocorticoids in the first days of life is harmful to ELBW infants makes HC prophylaxis unwise until the efficacy of treatment relative to safety can be clearly established.

Reduction in red blood cell transfusions using a bedside analyzer in extremely low birth weight infants.

Abstract: Preterm infants typically experience heavy phlebotomy losses from frequent laboratory testing in the first few weeks of life. This results in anemia, requiring red blood cell (RBC) transfusions. We recently introduced a bedside point-of-care (POC) blood gas analyzer (iSTAT, Princeton, NJ) that requires a smaller volume of blood to replace conventional Radiometer blood gas and electrolyte analysis used by our neonatal intensive care unit (NICU). The smaller volume of blood required for sampling (100 vs 300–500 μl), provided an opportunity to assess if a decrease in phlebotomy loss occurred and, if so, to determine if this resulted in decreased transfusions administered to extremely low birth weight (ELBW) infants. We hypothesized that the use of the POC iSTAT analyzer that measures pH, PCO2, PO2, hemoglobin, hematocrit, serum sodium, serum potassium and ionized calcium would result in a significant decrease in the number and volume of RBC transfusions in the first 2 weeks of life. A retrospective chart review was conducted of all inborn premature infants with birth weights less than 1000 g admitted to the NICU that survived for 2 weeks of age during two separate 1-year periods. Blood gas analysis was performed by conventional laboratory methods during the first period (designated Pre-POC testing) and by the iSTAT POC device during the second period (designated post-POC testing). Data collected for individual infants included the number of RBC transfusions, volume of RBCs transfused, and the number and kind of blood testing done. There was no effort to change either the RBC transfusion criteria applied or blood testing practices. The mean (±SD) number of RBC transfusions administered in the first 2 weeks after birth was 5.7±3.74 (n=46) in the pre-POC testing period to 3.1±2.07 (n=34) in the post-POC testing period (p<0.001), a 46% reduction. The mean volume of RBC transfusions decreased by 43% with use of the POC analyzer, that is, from 78.4±51.6 ml/kg in the pre-POC testing group to 44.4±32.9 ml/kg in the Post-POC testing group (p<0.002). There was no difference between the two periods in the total number of laboratory blood tests done. Use of a bedside blood gas analyzer is associated with clinically important reductions in RBC transfusions in the ELBW infant during the first two weeks of life.

Reduced incidence of neonatal morbidities: effect of home-based neonatal care in rural Gadchiroli, India.

Abstract: We found a high burden of morbidities in a cohort of neonates observed in rural Gadchiroli, India. We hypothesised that interventions would reduce the incidence of neonatal morbidities, including the seasonal increase observed in many of them. This article reports the effect of home-based neonatal care on neonatal morbidities in the intervention arm of the field trial by comparing the early vs late periods, and the possible explanation for this effect. During 3 years (1995 to 1998), trained village-health-workers (VHWs) in 39 villages prospectively collected data by making home visits during pregnancy, home-delivery and during neonatal period. We estimated the incidence and burden of neonatal morbidities over the 3 years from these data. In the first year, the VHWs made home visits only to observe. From the second year, they assisted mothers in neonatal care and managed the sick neonates at home. Health education of mothers and family members, individually and in group, was added in the third year. We measured the coverage of interventions over the 3 years and evaluated maternal knowledge and practices on 21 indicators in the third year. The effect on 17 morbidities was estimated by comparing the incidence in the first year with the third year. The VHWs observed 763 neonates in the first year, 685 in the second and 913 in the third year. The change in the percent incidence of morbidities was (i) infections, from 61.6 to 27.5 (−55%; p<0.001), (ii) care-related morbidities (asphyxia, hypothermia, feeding problems) from 48.2 to 26.3 (−45%; p<0.001); (iii) low birth weight from 41.9 to 35.2 (−16%; p<0.05); (iv) preterm birth and congenital anomalies remained unchanged. The mean number of morbidities/100 neonates in the 3 years was 228, 170 and 115 (a reduction of 49.6%; p<0.001). These reductions accompanied an increasing percent score of interventions during 3 years: 37.9, 58.4 and 81.3, thus showing a dose–response relationship. In the third year, the proportion of correct maternal knowledge was 78.7% and behaviours was 69.7%. The significant seasonal increase earlier observed in the incidence of five morbidities reduced in the third year. The home-based care and health education reduced the incidence and burden of neonatal morbidities by nearly half. The effect was broad, but was especially pronounced on infections, care-related morbidities and on the seasonal increase in morbidities.

Procalcitonin as a Screening Test for Late-Onset Sepsis in Preterm Very Low Birth Weight Infants

Abstract: Procalcitonin as a Screening Test for Late-Onset Sepsis in Preterm Very Low Birth Weight Infants

Can oral sucrose reduce the pain and distress associated with screening for retinopathy of prematurity

Abstract: Infants undergoing eye exams to screen for retinopathy of prematurity (ROP) demonstrate physiologic and behavioral manifestations of pain and distress. Oral sucrose has analgesic properties that might reduce these effects. To determine the efficacy of oral sucrose in reducing the pain/distress of eye exams for ROP. A total of 32 infants about to undergo ROP screening exams received either oral sucrose [S] (N=16) or sterile water [C] (N=16) in a randomized, prospective and blinded fashion. Outcome measures included HR, RR, O2 saturation, BP, pain (premature infant pain profile) and percent of time spent crying during the eye exam. The groups were similar in GA (weeks) (28±1.6), BW (kg) (1.04±0.26), postnatal age (days) 50.8±20.3, and study weight (kg) 1.88±0.40). Both groups demonstrated significant increases in HR, BP, and pain score in response to the exam. Infants in both groups spent the majority of time actively crying during the exam ([S] 53±35% vs [C] 63±31%. Infants receiving [S] showed a small but significant drop in O2 saturation. No significant differences were seen between groups in physiologic or behavioral responses to the eye exam. Oral [S] was not effective in reducing pain/distress from the ROP screening exam. Alternative strategies should be considered to achieve adequate pain relief.