Cost estimation alongside a multi-regional, multi-country randomized trial of antenatal ultrasound in five low-and-middle-income countries.

BACKGROUND: Improving maternal health has been a primary goal of international health agencies for many years, with the aim of reducing maternal and child deaths and improving access to antenatal care (ANC) services, particularly in low-and-middle-income countries (LMICs). Health interventions with these aims have received more attention from a clinical effectiveness perspective than for cost impact and economic efficiency. METHODS: We collected data on resource use and costs as part of a large, multi-country study assessing the use of routine antenatal screening ultrasound (US) with the aim of considering the implications for economic efficiency. We assessed typical antenatal outpatient and hospital-based (facility) care for pregnant women, in general, with selective complication-related data collection in women participating in a large maternal health registry and clinical trial in five LMICs. We estimated average costs from a facility/health system perspective for outpatient and inpatient services. We converted all country-level currency cost estimates to 2015 United States dollars (USD). We compared average costs across countries for ANC visits, deliveries, higher-risk pregnancies, and complications, and conducted sensitivity analyses. RESULTS: Our study included sites in five countries representing different regions. Overall, the relative cost of individual ANC and delivery-related healthcare use was consistent among countries, generally corresponding to country-specific income levels. ANC outpatient visit cost estimates per patient among countries ranged from 15 to 30 USD, based on average counts for visits with and without US. Estimates for antenatal screening US visits were more costly than non-US visits. Costs associated with higher-risk pregnancies were influenced by rates of hospital delivery by cesarean section (mean per person delivery cost estimate range: 25-65 USD). CONCLUSIONS: Despite substantial differences among countries in infrastructures and health system capacity, there were similarities in resource allocation, delivery location, and country-level challenges. Overall, there was no clear suggestion that adding antenatal screening US would result in either major cost savings or major cost increases. However, antenatal screening US would have higher training and maintenance costs. Given the lack of clinical effectiveness evidence and greater resource constraints of LMICs, it is unlikely that introducing antenatal screening US would be economically efficient in these settings--on the demand side (i.e., patients) or supply side (i.e., healthcare providers). TRIAL REGISTRATION: Trial number: NCT01990625 (First posted: November 21, 2013 on https://clinicaltrials.gov ).

Association of haemoglobin levels in the first trimester and at 26-30 weeks with fetal and neonatal outcomes: a secondary analysis of the Global Network for Women's and Children's Health's ASPIRIN Trial.

OBJECTIVE: Limited data are available from low- and middle-income countries (LMICs) on the relationship of haemoglobin levels to adverse outcomes at different times during pregnancy. We evaluated the association of haemoglobin levels in nulliparous women at two times in pregnancy with pregnancy outcomes. DESIGN: ASPIRIN Trial data were used to study the association between haemoglobin levels measured at 6+0 -13+6  weeks and 26+0 -30+0  weeks of gestation with fetal and neonatal outcomes. SETTING: Obstetric care facilities in Pakistan, India, Kenya, Zambia, The Democratic Republic of the Congo and Guatemala. POPULATION: A total of 11 976 pregnant women. METHODS: Generalised linear models were used to obtain adjusted relative risks and 95% CI for adverse outcomes. MAIN OUTCOME MEASURES: Preterm birth, stillbirth, neonatal death, small for gestational age (SGA) and birthweight <2500 g. RESULTS: The mean haemoglobin levels at 6+0 -13+6  weeks and at 26-30 weeks of gestation were 116 g/l (SD 17) and 107 g/l (SD 15), respectively. In general, pregnancy outcomes were better with increasing haemoglobin. At 6+0 -13+6  weeks of gestation, stillbirth, SGA and birthweight <2500 g, were significantly associated with haemoglobin of 70-89 g/l compared with haemoglobin of 110-129 g/l The relationships of adverse pregnancy outcomes with various haemoglobin levels were more marked at 26-30 weeks of gestation. CONCLUSIONS: Both lower and some higher haemoglobin concentrations are associated with adverse fetal and neonatal outcomes at 6+0 -13+6  weeks and at 26-30 weeks of gestation, although the relationship with low haemoglobin levels appears more consistent and generally stronger. TWEETABLE ABSTRACT: Both lower and some higher haemoglobin concentrations were associated with adverse fetal and neonatal outcomes at 6-13 weeks and 26-30 weeks of gestation.

Routine antenatal ultrasound in low- and middle-income countries: first look - a cluster randomised trial.

OBJECTIVE: Ultrasound is widely regarded as an important adjunct to antenatal care (ANC) to guide practice and reduce perinatal mortality. We assessed the impact of ANC ultrasound use at health centres in resource-limited countries. DESIGN: Cluster randomised trial. SETTING: Clusters within five countries (Democratic Republic of Congo, Guatemala, Kenya, Pakistan, and Zambia) METHODS: Clusters were randomised to standard ANC or standard care plus two ultrasounds and referral for complications. The study trained providers in intervention clusters to perform basic obstetric ultrasounds. MAIN OUTCOME MEASURES: The primary outcome was a composite of maternal mortality, maternal near-miss mortality, stillbirth, and neonatal mortality. RESULTS: During the 24-month trial, 28 intervention and 28 control clusters had 24 263 and 23 160 births, respectively; 78% in the intervention clusters received at least one study ultrasound; 60% received two. The prevalence of conditions noted including twins, placenta previa, and abnormal lie was within expected ranges. 9% were referred for an ultrasound-diagnosed condition, and 71% attended the referral. The ANC (RR 1.0 95% CI 1.00, 1.01) and hospital delivery rates for complicated pregnancies (RR 1.03 95% CI 0.89, 1.20) did not differ between intervention and control clusters nor did the composite outcome (RR 1.09 95% CI 0.97, 1.23) or its individual components. CONCLUSIONS: Despite availability of ultrasound at ANC in the intervention clusters, neither ANC nor hospital delivery for complicated pregnancies increased. The composite outcome and the individual components were not reduced. TWEETABLE ABSTRACT: Antenatal care ultrasound did not improve a composite outcome that included maternal, fetal, and neonatal mortality.

A prospective cause of death classification system for maternal deaths in low and middle-income countries: results from the Global Network Maternal Newborn Health Registry.

OBJECTIVE: To describe the causes of maternal death in a population-based cohort in six low- and middle-income countries using a standardised, hierarchical, algorithmic cause of death (COD) methodology. DESIGN: A population-based, prospective observational study. SETTING: Seven sites in six low- to middle-income countries including the Democratic Republic of the Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. POPULATION: All deaths among pregnant women resident in the study sites from 2014 to December 2016. METHODS: For women who died, we used a standardised questionnaire to collect clinical data regarding maternal conditions present during pregnancy and delivery. These data were analysed using a computer-based algorithm to assign cause of maternal death based on the International Classification of Disease-Maternal Mortality system (trauma, termination of pregnancy-related, eclampsia, haemorrhage, pregnancy-related infection and medical conditions). We also compared the COD results to healthcare-provider-assigned maternal COD. MAIN OUTCOME MEASURES: Assigned causes of maternal mortality. RESULTS: Among 158 205 women, there were 221 maternal deaths. The most common algorithm-assigned maternal COD were obstetric haemorrhage (38.6%), pregnancy-related infection (26.4%) and pre-eclampsia/eclampsia (18.2%). Agreement between algorithm-assigned COD and COD assigned by healthcare providers ranged from 75% for haemorrhage to 25% for medical causes coincident to pregnancy. CONCLUSIONS: The major maternal COD in the Global Network sites were haemorrhage, pregnancy-related infection and pre-eclampsia/eclampsia. This system could allow public health programmes in low- and middle-income countries to generate transparent and comparable data for maternal COD across time or regions. TWEETABLE ABSTRACT: An algorithmic system for determining maternal cause of death in low-resource settings is described.

Global Network for Women's and Children's Health Research: probable causes of stillbirth in low- and middle-income countries using a prospectively defined classification system.

OBJECTIVE: We sought to classify causes of stillbirth for six low-middle-income countries using a prospectively defined algorithm. DESIGN: Prospective, observational study. SETTING: Communities in India, Pakistan, Guatemala, Democratic Republic of Congo, Zambia and Kenya. POPULATION: Pregnant women residing in defined study regions. METHODS: Basic data regarding conditions present during pregnancy and delivery were collected. Using these data, a computer-based hierarchal algorithm assigned cause of stillbirth. Causes included birth trauma, congenital anomaly, infection, asphyxia, and preterm birth, based on existing cause of death classifications and included contributing maternal conditions. MAIN OUTCOME MEASURES: Primary cause of stillbirth. RESULTS: Of 109 911 women who were enrolled and delivered (99% of those screened in pregnancy), 2847 had a stillbirth (a rate of 27.2 per 1000 births). Asphyxia was the cause of 46.6% of the stillbirths, followed by infection (20.8%), congenital anomalies (8.4%) and prematurity (6.6%). Among those caused by asphyxia, 38% had prolonged or obstructed labour, 19% antepartum haemorrhage and 18% pre-eclampsia/eclampsia. About two-thirds (67.4%) of the stillbirths did not have signs of maceration. CONCLUSIONS: Our algorithm determined cause of stillbirth from basic data obtained from lay-health providers. The major cause of stillbirth was fetal asphyxia associated with prolonged or obstructed labour, pre-eclampsia and antepartum haemorrhage. In the African sites, infection also was an important contributor to stillbirth. Using this algorithm, we documented cause of stillbirth and its trends to inform public health programs, using consistency, transparency, and comparability across time or regions with minimal burden on the healthcare system. TWEETABLE ABSTRACT: Major causes of stillbirth are asphyxia, pre-eclampsia and haemorrhage. Infections are important in Africa.

Early postnatal hypotension is not associated with indicators of white matter damage or cerebral palsy in extremely low gestational age newborns.

OBJECTIVE: To evaluate, in extremely low gestational age newborns (ELGANs), relationships between indicators of early postnatal hypotension and cranial ultrasound indicators of cerebral white matter damage imaged in the nursery and cerebral palsy diagnoses at 24 months follow-up. STUDY DESIGN: The 1041 infants in this prospective study were born at <28 weeks gestation, were assessed for three indicators of hypotension in the first 24 postnatal hours, had at least one set of protocol cranial ultrasound scans and were evaluated with a structured neurological exam at 24 months corrected age. Indicators of hypotension included: (1) lowest mean arterial pressure (MAP) in the lowest quartile for gestational age; (2) treatment with a vasopressor; and (3) blood pressure lability, defined as the upper quartile of the difference between each infant's lowest and highest MAP. Outcomes included indicators of cerebral white matter damage, that is, moderate/severe ventriculomegaly or an echolucent lesion on cranial ultrasound and cerebral palsy diagnoses at 24 months gestation. Logistic regression was used to evaluate relationships among hypotension indicators and outcomes, adjusting for potential confounders. RESULT: Twenty-one percent of surviving infants had a lowest blood pressure in the lowest quartile for gestational age, 24% were treated with vasopressors and 24% had labile blood pressure. Among infants with these hypotension indicators, 10% percent developed ventriculomegaly and 7% developed an echolucent lesion. At 24 months follow-up, 6% had developed quadriparesis, 4% diparesis and 2% hemiparesis. After adjusting for confounders, we found no association between indicators of hypotension, and indicators of cerebral white matter damage or a cerebral palsy diagnosis. CONCLUSION: The absence of an association between indicators of hypotension and cerebral white matter damage and or cerebral palsy suggests that early hypotension may not be important in the pathogenesis of brain injury in ELGANs.

Bronchopulmonary dysplasia and inflammatory biomarkers in the premature neonate.

Bronchopulmonary dysplasia (BPD) is the most common, serious sequela of premature birth. Inflammation is a major contributor to the pathogenesis of BPD. Often initiated by a pulmonary fetal inflammatory response, lung inflammation is exacerbated by mechanical ventilation and exposure to supplemental oxygen. In response to these initiators of injury, a complex interaction occurs between proteins that attract inflammatory cells (ie, chemokines), proteins that facilitate the transendothelial migration of inflammatory cells from blood vessels (ie, adhesion molecules), proteins that promote tissue damage (ie, pro-inflammatory cytokines and proteases), and proteins that modulate the process (eg, anti-inflammatory cytokines, binding proteins and receptor antagonists). In addition, during recovery from inflammatory injury, growth factors and other substances that control normal lung growth and mediate repair influence subsequent lung structure. In this review, we discuss the role of each aspect of the inflammatory process in the development of BPD. This discussion will include data from measurements of biomarkers in samples of fluid aspirated from the airways of human infants relevant to each phase of inflammation. Despite their limitations, these measurements provide some insight into the role of inflammation in the development of BPD and may be useful in identifying infants at risk for the disease.

Growth and neurodevelopment at 16 to 24 months of age for infants born with gastroschisis.

OBJECTIVE: To examine growth, neurodevelopment and morbidity in infants with gastroschisis. STUDY DESIGN: We enrolled all infants with gastroschisis treated at the North Carolina Children's Hospital from March 2003 through June 2005. Neonatal data were collected. Medical history, growth and neurodevelopment were assessed at 16 to 24 months. RESULT: Of 24 infants, 17 completed follow-up. Weight and length were below the 10th percentile for five and six infants, respectively. Three infants scored less than 85 on the Bayley Scales of Infant Development, second edition. Small for gestational age (SGA) infants were smaller and had lower neurodevelopmental scores. Fourteen experienced continued bowel dysfunction; nine were rehospitalized. CONCLUSION: One-third of infants with gastroschisis experience growth delay. Infants who are SGA are at higher risk, suggesting that postnatal growth may be influenced by fetal phenomena, and may not be modifiable. Neurodevelopment is not delayed. Continued bowel dysfunction is common.

Reduced serum amino acid concentrations in infants with necrotizing enterocolitis.

OBJECTIVE: To determine whether premature infants who have necrotizing enterocolitis (NEC) have deficiencies in glutamine (GLN) and arginine (ARG), which are essential to intestinal integrity. STUDY DESIGN: A 4-month prospective cohort study of serum amino acid and urea levels in premature infants was done. Serum amino acid and urea levels were measured by high-pressure liquid chromatography and enzymatic methods, respectively, on samples obtained on days of life 3, 7, 14, and 21. RESULTS: Infants in the control (n = 32) and NEC groups (n = 13) were comparable for birth weight, gestational age, and Apgar scores. NEC began on mean day of life 14.5 (95% CI, day of life 11 to 18). Median values of GLN were 37% to 57% lower in the NEC group on days 7, 14, and 21 compared with those in the control group (P <.05). On days 7 and 14, median values of ARG, GLN, alanine, lysine, ornithine, and threonine were decreased 36% to 67% (P <.05) in the NEC group. Total nonessential amino and total essential amino acids were 35% to 50% lower in the NEC group on days 7 and 14 (P <.05). Infants in the NEC group had significant reductions in GLN and ARG 7 days before the onset of NEC. CONCLUSIONS: Infants who have NEC have selective amino acid deficiencies including reduced levels of GLN and ARG that may predispose to the illness.

Risk factors for chronic lung disease in the surfactant era: a North Carolina population-based study of very low birth weight infants. North Carolina Neonatologists Association.

OBJECTIVE: To identify risk factors for chronic lung disease (CLD) in a population-based cohort of very low birth weight infants, born in an era of surfactant usage. We specifically investigated the effects of antenatal steroids, nosocomial infection, patent ductus arteriosus (PDA), fluid management, and ventilator support strategies. METHODS: Data were prospectively collected on 1244 infants born in North Carolina in 1994 with birth weights 500 to 1500 g, and treated at 1 of the 13 intensive care nurseries across the state. The outcome of interest was CLD, defined as dependency on supplemental oxygen at 36 weeks' postmenstrual age. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were estimated with logistic regression models. RESULTS: Among 865 survivors to 36 weeks' postmenstrual age, 224 (26%) had CLD. Nosocomial infection (OR: 2.0; 95% CI: 1.4-3.3), fluid intake on day 2 (OR: 1.06 per 10 mL increase; 95% CI: 1.01-1.11), and the need for ventilation at 48 hours of life (OR: 2.2; 95% CI: 1.3-3.7) were associated with an increased risk of CLD. Among infants ventilated at 48 hours, nosocomial infection (OR: 1.64; 95% CI: 1.02-2.62) and PDA (OR: 1.9; 95% CI: 1.2-3.1) were associated with an increased risk. No association was found with antenatal steroid receipt or increased levels of ventilator support. CONCLUSION: This analysis suggests that with widespread use of surfactant, nosocomial infection, PDA, and water balance persist as risk factors for CLD.

Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial.

BACKGROUND: Inhaled nitric oxide improves oxygenation and lessens the need for extracorporeal-membrane oxygenation in full-term neonates with hypoxaemic respiratory failure and persistent pulmonary hypertension, but potential adverse effects are intracranial haemorrhage and chronic lung disease. We investigated whether low-dose inhaled nitric oxide would improve survival in premature neonates with unresponsive severe hypoxaemic respiratory failure, and would not increase the frequency or severity of intracranial haemorrhage or chronic lung disease. METHODS: We did a double-blind, randomised controlled trial in 12 perinatal centres that provide tertiary care. 80 premature neonates (gestational age < or = 34 weeks) with severe hypoxaemic respiratory failure were randomly assigned inhaled nitric oxide (n=48) or no nitric oxide (n=32, controls). Our primary outcome was survival to discharge. Analysis was by intention to treat. We studied also the rate and severity of intracranial haemorrhage, pulmonary haemorrhage, duration of ventilation, and chronic lung disease at 36 weeks' postconceptional age. FINDINGS: The two groups did not differ for baseline characteristics or severity of disease. Inhaled nitric oxide improved oxygenation after 60 min (p=0.03). Survival at discharge was 52% in the inhaled-nitric-oxide group and 47% in controls (p=0.65). Causes of death were mainly related to extreme prematurity and were similar in the two groups. The two groups did not differ for adverse events or outcomes (intracranial haemorrhage grade 2-4, 28% inhaled nitric oxide and 33% control; pulmonary haemorrhage 13% and 9%; chronic lung disease 60% and 80%). INTERPRETATION: Low-dose inhaled nitric oxide improved oxygenation but did not improve survival in severely hypoxaemic premature neonates. Low-dose nitric oxide in the most critically ill premature neonates does not increase the risk of intracranial haemorrhage, and may decrease risk of chronic lung injury.

Population-based study of chronic lung disease in very low birth weight infants in North Carolina in 1994 with comparisons with 1984. The North Carolina Neonatologists Association.

OBJECTIVE: To assess the pulmonary outcomes of very low birth weight (VLBW) infants in North Carolina in 1994 and to compare rates of survival and chronic lung disease (CLD) between 1994 and 1984 (see reference 2). METHODS: Data were collected prospectively by collaborators from all 13 neonatal intensive care units in North Carolina to determine survival and pulmonary outcomes of infants with birth weights of 500 to 1500 g. State vital statistics data were used to confirm completeness of the sample. CLD was defined as oxygen or ventilator therapy at 36 weeks' postmenstrual age (PMA). For comparisons with the 1984 cohort, survival and pulmonary outcomes of infants defined to be at risk for CLD (ventilated >48 hours and survived 30 days) were recorded at 30 days, 3 months, and 6 months of postnatal age. RESULTS: Outcome data were available for 1413 (92%) of the in-state VLBW live births. Of VLBW infants, 224 (15%) died before 48 hours of age. The overall rate of CLD in 1994 at 36 weeks' PMA was 25%. Rates by birth weight group were 57% for 500 to 750 g birth weight (BW), 41% for 751 to 1000 g BW, 19% for 1001 to 1250 g BW, and 8% for 1251 to 1500 g BW. Infants who received ventilator therapy for >48 hours accounted for 89% of the CLD cases. The CLD rate at 36 weeks' PMA in infants weighing 751 to 1500 g was 37% for those ventilated >48 hours versus 5% for those ventilated <48 hours (OR: 7.1; 95% CI: 4.4-11.3). Overall survival in 1994 was significantly higher for infants than in 1984 (78% vs 74%), most notably in infants 500 to 750 g BW (37% vs 24%), and 751 to 1000 g BW (82% vs 65%). When compared with 1984, the CLD rates in those infants defined to be at risk were significantly higher in 1994 at 30 days (68% vs 54%) and at 3 months (24% vs 15%) of postnatal age. For at-risk infants in 1994, there were fewer infants on the ventilator, but more infants on oxygen alone at all measured time points compared with 1984. CONCLUSION: Survival of VLBW infants has improved since 1984. Ventilator therapy for >48 hours remains a significant risk factor for CLD. The incidence of CLD has increased from 1984 to 1994 but has shifted from ventilator to oxygen therapy. bronchopulmonary dysplasia, epidemiology, infant, low birth weight, intensive care units, neonatal statistics, infant mortality, prospective studies.

Effect of initial nitric oxide concentration on outcome in infants with persistent pulmonary hypertension of the newborn.

A randomized nonblinded comparison of two treatment groups was performed to determine whether treatment of infants with persistent pulmonary hypertension of the newborn using a continuous 6-ppm dose of inhaled nitric oxide (iNO) changes the likelihood of death or utilization of extracorporeal membrane oxygenation (ECMO) when compared to infants treated with 20 ppm iNO for 4 h followed by 6 ppm. Twenty-nine infants with a gestational age >/=34 weeks and a diagnosis of persistent pulmonary hypertension of the newborn were enrolled during the 3- year study period. The relative risk (20/6 vs. 6 ppm) for treatment with ECMO was 3.11 (p = 0.02), for death it was 2.80 (p = 0.32), and for either death or ECMO it was 3.42 (p = 0. 006). There was no apparent advantage of treatment with a higher dosage of iNO at the initiation of therapy in the reduction of death or utilization of ECMO. These data suggest that a continuous lower dose of iNO results in a comparable improvement in oxygenation as a short exposure of higher dose iNO at the initiation of therapy.

The effect of a neonatal telecardiology system on respiratory therapy in very low birthweight infants.

Factors in the U.S. healthcare system have shifted the site of care of many newborns to hospitals where subspecialty services are unavailable. This study examines whether a more rapid turn-around of echocardiogram interpretations and availability of interactive video during neonatal consultations reduces the morbidity of very low birthweight (VLBW) infants. The two groups (n = 21 and n = 28) were similar on the basis of known risk factors. A composite index of respiratory therapy intensivity and duration was used to measure the utilization of respiratory therapies. The index was similar in both groups, 89.6 +/- 12.6 before versus 89.5 +/- 13.0 with telemedicine. These results show little evidence of a reduction in RT utilization.

Effect of telemedicine on health outcomes in 87 infants requiring neonatal intensive care.

OBJECTIVE: This is an evaluation of a telemedicine system for the rapid interpretation of neonatal echocardiograms from a regional, level III neonatal intensive care unit (NICU). The use of telemedicine to support the cardiology needs of NICUs is increasing. However, there is very little published objective information regarding health outcomes or costs resulting from such telemedicine systems. The primary hypothesis tested was that the utilization of a telemedicine system for the interpretation of neonatal echocardiograms reduces the intensive care length of stay of low birthweight (LBW) infants. STUDY DESIGN: All infants who were admitted to neonatal intensive care at New Hanover Regional Medical Center during the first six months of the system were studied by the use of echocardiograms. They were compared with infants who were born in the same period of the previous year. The outcome measures were the intensive care length of stay, rate of transfer to academic medical centers, and mortality rate. RESULTS: A statistically non-significant reduction of 5.4 days in the intensive care length of stay (LOS) of low birthweight infants was observed (p = 0.37). The cost per echocardiogram transmitted was calculated at $33 compared to previous method of sending videotapes via overnight courier. CONCLUSIONS: While the sample size was inadequate to demonstrate improvements in health outcomes, the magnitude of the change and the low costs of the system suggest that this intervention is practical for obtaining rapid diagnostic and treatment support. Larger studies are warranted to confirm these findings and determine whether faster diagnosis and earlier initiation of treatment improve health outcomes of newborn infants.

Double-blind evaluation of developmental and health status to age 2 years of infants weighing 700 to 1350 grams treated prophylactically at birth with a single dose of synthetic surfactant or air placebo.

In a previously published article, we reported results of a two-center study of outcome to 28 days of 385 infants with birth weights from 700 to 1350 gm who were assigned randomly to receive a single 5 ml/kg intratracheal dose of either synthetic surfactant or air placebo. Infants treated with surfactant had a higher rate of survival to 28 days without bronchopulmonary dysplasia than did control subjects given an air placebo. The present study assessed survivors in early childhood to determine neurodevelopmental outcome and late morbidity. Two hundred fifty-eight surviving infants from both centers were evaluated at 1-year adjusted age; medical histories were obtained, standard physical and neurologic examinations were performed, and Bayley Scales of Infant Development were administered. Ophthalmologic examinations were performed at various times between 28 days and 1-year adjusted age. At 2-years adjusted age, 118 infants from one center were reevaluated with the same procedures and also had hearing and speech evaluations. Neither the 1-year assessment of the entire population nor the 2-year assessment of the one center's cohort revealed physical or neurodevelopmental differences between treatment groups. We conclude that administration of a single prophylactic dose of synthetic surfactant to premature infants with birth weights from 700 to 1350 grams results in improved survival rates to 28 days without bronchopulmonary dysplasia and is not associated with adverse health or neurodevelopmental effects at 1-year or 2-years adjusted age.

Administration of granulocyte colony-stimulating factor to neutropenic low birth weight infants of mothers with preeclampsia.

Nine low birth weight infants with neutropenia born to mothers with preeclampsia were treated with granulocyte-colony stimulating factor, 10 micrograms/kg intravenously, within 24 hours of birth and at 24-hour intervals for a maximum of three doses if neutropenia persisted. The absolute neutrophil count increased significantly in eight of the nine infants within 6 hours, and neutrophilia was sustained for at least 72 hours after administration of a single dose of granulocyte-colony stimulating factor.

The incidence and effects of motion sickness among medical attendants during transport.

Motion sickness is a common and often debilitating problem. The purpose of this study was to determine the incidence and effects of the motion sickness syndromes, the Nausea and Sopite Syndromes, among medical transport personnel. Members of the Transport Teams of the University of North Carolina Hospitals completed a questionnaire to identify a history of susceptibility to motion sickness. An additional questionnaire evaluated each individual for symptoms of motion sickness during transport. The Digit Span Test portion of the Mini-Mental Status Examination (DST-MMSE) was used to evaluate cognitive function after transport. Control data on each subject were obtained by testing during nontransport shifts. The Nausea Syndrome was observed during transport in 46% of subjects; 65% experienced symptoms consistent with the Sopite Syndrome. Pretransport surveys were predictive of the Nausea Syndrome, but not of the Sopite Syndrome. The Nausea Syndrome was related to subjective assessments of the severity of motion experienced; the Sopite Syndrome did not correlate with the severity of motion. The DST-MMSE scores after transport were significantly lower than scores during nontransport periods in 85% of personnel. We conclude that transport personnel are susceptible to motion sickness manifested by both the Nausea Syndrome and the Sopite Syndrome. The presence of motion sickness is associated with a significant decline in performance on tests of attention and concentration.

Effect of L-arginine infusion on infants with persistent pulmonary hypertension of the newborn.

Nitric oxide (NO) is thought to be a primary mediator of the reduction in pulmonary vascular resistance which occurs in the newborn period. L-arginine is the precursor for the formation of nitric oxide in the pulmonary endothelium. Low serum arginine levels have been reported in infants with persistent pulmonary hypertension of the newborn (PPHN). We infused a single L-arginine dose of 500 mg/kg over 30 min to 5 consecutive infants with PPHN. Ninety minutes after infusion we observed an associated rise in PaO2 of 37 to 84 mm Hg and, in 4 of 5 infants, a reduction in oxygenation index (OI) of 33-50% over the 5-hour period following infusion. Infusion was not associated with adverse effects. These observations suggest that L-arginine administration may be an effective therapeutic alternative in infants with PPHN.