Intensive care for extreme prematurity--moving beyond gestational age.

BACKGROUND: Decisions regarding whether to administer intensive care to extremely premature infants are often based on gestational age alone. However, other factors also affect the prognosis for these patients. METHODS: We prospectively studied a cohort of 4446 infants born at 22 to 25 weeks' gestation (determined on the basis of the best obstetrical estimate) in the Neonatal Research Network of the National Institute of Child Health and Human Development to relate risk factors assessable at or before birth to the likelihood of survival, survival without profound neurodevelopmental impairment, and survival without neurodevelopmental impairment at a corrected age of 18 to 22 months. RESULTS: Among study infants, 3702 (83%) received intensive care in the form of mechanical ventilation. Among the 4192 study infants (94%) for whom outcomes were determined at 18 to 22 months, 49% died, 61% died or had profound impairment, and 73% died or had impairment. In multivariable analyses of infants who received intensive care, exposure to antenatal corticosteroids, female sex, singleton birth, and higher birth weight (per each 100-g increment) were each associated with reductions in the risk of death and the risk of death or profound or any neurodevelopmental impairment; these reductions were similar to those associated with a 1-week increase in gestational age. At the same estimated likelihood of a favorable outcome, girls were less likely than boys to receive intensive care. The outcomes for infants who underwent ventilation were better predicted with the use of the above factors than with use of gestational age alone. CONCLUSIONS: The likelihood of a favorable outcome with intensive care can be better estimated by consideration of four factors in addition to gestational age: sex, exposure or nonexposure to antenatal corticosteroids, whether single or multiple birth, and birth weight. (ClinicalTrials.gov numbers, NCT00063063 [ClinicalTrials.gov] and NCT00009633 [ClinicalTrials.gov].).

Congenital diaphragmatic hernia in the preterm infant.

BACKGROUND: Congenital diaphragmatic hernia (CDH) remains a significant cause of death in newborns. With advances in neonatal critical care and ventilation strategies, survival in the term infant now exceeds 80% in some centers. Although prematurity is a significant risk factor for morbidity and mortality in most neonatal diseases, its associated risk with infants with CDH has been described poorly. We sought to determine the impact of prematurity on survival using data from the Congenital Diaphragmatic Hernia Registry (CDHR). METHODS: Prospectively collected data from live-born infants with CDH were analyzed from the CDHR from January 1995 to July 2009. Preterm infants were defined as <37 weeks estimated gestational age at birth. Univariate and multivariate logistic regression analysis were>performed. RESULTS: During the study period, 5,069 infants with CDH were entered in the registry. Of the 5,022 infants with gestational age data, there were 3,895 term infants (77.6%) and 1,127 preterm infants (22.4%). Overall survival was 68.7%. A higher percentage of term infants were treated with extracorporeal membrane oxygenation (ECMO) (33% term vs 25.6% preterm). Preterm infants had a greater percentage of chromosomal abnormalities (4% term vs 8.1% preterm) and major cardiac anomalies (6.1% term vs 11.8% preterm). Also, a significantly higher percentage of term infants had repair of the hernia (86.3% term vs 69.4% preterm). Survival for infants that underwent repair was high in both groups (84.6% term vs 77.2% preterm). Survival decreased with decreasing gestational age (73.1% term vs 53.5% preterm). The odds ratio (OR) for death among preterm infants adjusted for patch repair, ECMO, chromosomal abnormalities, and major cardiac anomalies was OR 1.68 (95% confidence interval [CI], 1.34-2.11). CONCLUSION: Although outcomes for preterm infants are clearly worse than in the term infant, more than 50% of preterm infants still survived. Preterm infants with CDH remain a high-risk group. Although ECMO may be of limited value in the extremely premature infant with CDH, most preterm infants that live to undergo repair will survive. Prematurity should not be an independent factor in the treatment strategies of infants with CDH.

Defining barriers in caring for seriously-ill children in a resource-limited setting: An observational study of 2 children's hospitals in Haiti

Background. According to the WHO 2007 country report, Haiti lags behind the Millennium Development Goal of reducing child mortality and maintains the highest under-5 mortality rate in the Western hemisphere. 3 Overall, few studies exist that seek to better grasp barriers in caring for a seriously ill child in a resource-limited setting and only a handful propose sustainable, effective interventions. ^ Objectives. The objectives of this study are to describe the prevalence of serious illnesses among children hospitalized at 2 children's hospitals in Port au Prince, to determine the barriers faced when caring for seriously ill children, and to report hospital outcomes of children admitted with serious illnesses. ^ Methods. Data were gathered from 2 major children's hospitals in Port au Prince, Haiti (Grace Children's Hospital [GCH] and Hopital d l'Universite d'Etat d'Haiti [HUEH]) using a triangulated approach of focus group discussions, physician questionnaires, and retrospective chart review. 23 pediatric physicians participated in focus group discussions and completed a self-administered questionnaire evaluating healthcare provider knowledge, self-efficacy, and perceived barriers relating to the care of seriously ill children in a resource-limited setting. A sample of 240 patient charts meeting eligibility criteria was abstracted for pertinent elements including sociodemographics, documentation, treatment strategies, and outcomes. Factors associated with mortality were analyzed using χ2 test and Fisher exact test [Minitab v.15]. ^ Results. The most common primary diagnoses at admission were gastroenteritis with moderate dehydration (35.5%), severe malnutrition (25.8%), and pneumonia (19.3%) for GCH, and severe malnutrition (32.6%), sepsis (24.7%), and severe respiratory distress (18%) for HUEH. Overall, 12.9% and 27% of seriously ill patients presented with shock to GCH and HUEH, respectively. ^ Shortage of necessary materials and equipment represented the most commonly reported limitation (18/23 respondents). According to chart data, 9.4% of children presenting with shock did not receive a fluid bolus, and only 8% of patients presenting with altered mental status or seizures received a glucose check. 65% of patients with meningitis did not receive a lumbar puncture due to lack of materials. ^ Hospital mortality rates did not differ by gender or by institution. Children who died were more likely to have a history of prematurity (OR 4.97 [95% CI 1.32-18.80]), an incomplete vaccination record (OR 4.05 [95% CI 1.68-9.74]), or a weight for age ≤3rd percentile (OR 6.1 [95% CI 2.49-14.93]. Case-fatality rates were significantly higher among those who presented with signs of shock compared with those who did not (23.1% vs. 10.7%, RR=2.16, p=0.03). Caregivers did not achieve shock reversal in 21% of patients and did not document shock reversal in 50% of patients. ^ Conclusions. Many challenges face those who seek to optimize care for seriously ill children in resource-limited settings. Specifically, in Haiti, qualitative and quantitative data suggest major issues with lack of supplies, pre-hospital factors, including malnutrition as a comorbidity, and early recognition and management of shock. A tailored intervention designed to address these issues is needed in order to prospectively evaluate improvements in child mortality in a high-risk population.^

The relationship between premature rupture of the membranes and sepsis in preterm neonates

This investigation was designed as a hospital-based, historical cohort study. The objective of the study was to determine the association between premature rupture of the membranes (PROM) and its duration on neonatal sepsis, infection, and mortality. Neonates born alive with gestational ages between 25 and 35 weeks from singleton pregnancies complicated by PROM were selected. Each of the 507 neonates was matched on gestational age, gender, ethnicity, and month of birth with a neonate without the complication of PROM.^ Data were abstracted from deliveries between January 1979 and December 1985 describing the mother's demographics, labor and delivery treatments and complications, the neonate's demographics, infection status, and medical care. The matched pairs analysis reveals a significant increase in risk of neonatal sepsis (RR = 3.5) and neonatal infection (RR = 2.4) among preterm births complicated by PROM, with a PROM exposure contributing an excess 4 to 5 cases of sepsis per 100 infants (RD = 0.04 for infection and RD = 0.05 for sepsis). Generally PROM remains an important risk factor for sepsis and infection when controlling for various other characteristics, and the risk difference remains constant.^ PROM was not significantly associated with neonatal mortality (RR = 1.02). There is an increase in risk difference for mortality associated with PROM among septic and infected infants, but it is not significant.^ A clear increase in risk of sepsis and infection from PROM occurs when durations of PROM are long (more than 48 hours), e.g., for sepsis the RR is 2.42 for short durations and RR is 6.0 for long durations. No such risk with long duration appears for neonatal mortality.^ This study indicates the importance of close observation of neonates with PROM for sepsis and infection so treatment can be initiated early. However, prematurity is the major risk for sepsis and the practice of early delivery to avoid prolonged durations of PROM does not alter the magnitude of risk. The greatest protection against these infection complications was provided when the neonate weighed over 1500 grams or had more than 33 weeks gestation. ^

Perinatal mortality and quality of care at the National Institute of Perinatology: A 3-year analysis

Quality of medical care has been indirectly assessed through the collection of negative outcomes. A preventable death is one that could have been avoided if optimum care had been offered. The general objective of the present project was to analyze the perinatal mortality at the National Institute of Perinatology (located in Mexico City) by social, biological and some available components of quality of care such as avoidability, provider responsibility, and structure and process deficiencies in the delivery of medical care. A Perinatal Mortality Committee data base was utilized. The study population consisted of all singleton perinatal deaths occurring between January 1, 1988 and June 30, 1991 (n = 522). A proportionate study was designed.^ The population studied mostly corresponded to married young adult mothers, who were residents of urban areas, with an educational level of junior high school or more, two to three pregnancies, and intermediate prenatal care. The mean gestational age at birth was 33.4 $\pm$ 3.9 completed weeks and the mean birthweight at birth was 1,791.9 $\pm$ 853.1 grams.^ Thirty-five percent of perinatal deaths were categorized as avoidable. Postnatal infection and premature rupture of membranes were the most frequent primary causes of avoidable perinatal death. The avoidable perinatal mortality rate was 8.7 per 1000 and significantly declined during the study period (p $<$.05). Preventable perinatal mortality aggregated data suggested that at least part of the mortality decline for amenable conditions was due to better medical care.^ Structure deficiencies were present in 35% of avoidable deaths and process deficiencies were present in 79%. Structure deficiencies remained constant over time. Process deficiencies consisted of diagnosis failures (45.8%) and treatment failures (87.3%), they also remained constant through the years. Party responsibility was as follows: Obstetric (35.4%), pediatric (41.4%), institutional (26.5%), and patient (6.6%). Obstetric responsibility significantly increased during the study period (p $<$.05). Pediatric responsibility declined only for newborns less than 1500 g (p $<$.05). Institutional responsibility remained constant.^ Process deficiencies increased the risk for an avoidable death eightfold (confidence interval 1.7-41.4, p $<$.01) and provider responsibility ninety-fivefold (confidence interval 14.8-612.1, p $<$.001), after adjustment for several confounding variables. Perinatal mortality due to prematurity, barotrauma and nosocomial infection, was highly preventable, but not that due to transpartum asphyxia. Once specific deficiencies in the quality of care have been identified, quality assurance actions should begin. ^

AMERICAN TRYPANOSOMIASIS (CHAGAS') DISEASE - A STUDY OF FETO-MATERNAL MORBIDITY AND MORTALITY

The possibility of a relationship between American Trypanosomiasis (Chagas') disease and pregnancy outcome was analyzed measuring feto-maternal morbidity and mortality in a sample of 604 pregnant women and their offspring seen at the Hospital Universitario de Maternidad y Neonatologia in Cordoba, Argentina during 1979.^ A cross-sectional, "case-comparison" investigation was employed to determine the degree of risk between having a reactive chagasic serologic test and a negative pregnancy outcome as determined by abortion, stillbirth, and infant death prior to one week of age. Patients were selected using a dichotomous, 0-1 scale with either the presence or the absence of a reactive Machado-Guerreiro complement fixation serologic blood test result.^ The data obtained were analyzed using appropriate statistical techniques for measuring the comparisons between the case and control groups under various demographic and socioeconomic variables such as, age, marital status, educational attainment, and residence. Similarly, additional biological variables of birth order, maternal and fetal complications, and prematurity were examined.^ From the analysis of the data obtained in this investigation, no definite conclusions can be reached regarding the risk of having an unsuccessful pregnancy outcome in the presence of a reactive serologic finding because the study design was a cross-sectional one and the number of events were too few for an adequate analysis. Notwithstanding these limitations, the results obtained, after statistical adjustments were employed, demonstrated that women with a reactive test result were older, were of a higher parity, and were less educated. Marital status and residence were not significant variables. The risk of pregnancy wastage, however, was almost twice as frequent in the reactive group as in the non-reactive group of women. Statistically significant differences in maternal morbidity involved two complications, polyhydramnios and varicosities of the lower extremities and vulva; while in the newborn, infection was higher in infants whose mothers exhibited a reactive serologic test result.^ In summary, what this research study has shown is the need for engaging in a larger, longitudinal study for an in-depth exploration of feto-maternal morbidity and mortality--an investigation that would corraborate or refute the findings of this study.^

INFANT MORTALITY IN THE MEXICAN AMERICAN COMMUNITY: AN ANALYSIS OF DIFFERENTIALS IN INFANT, NEONATAL, AND POSTNEONATAL MORTALITY BY ETHNICITY AND PARENTAL NATIVITY, 1974-75 SINGLE LIVE BIRTH COHORT, HARRIS COUNTY, TEXAS

The paradoxically low infant mortality rates for Mexican Americans in Texas have been attributed to inaccuracies in vital registration and idiosyncracies in Mexican migration in rural areas along the U.S.-Mexico border. This study examined infant (IMR), neonatal (NMR), and postneonatal (PNMR) mortality rates of Mexican Americans in an urban, non-border setting, using linked birth and death records of the 1974-75 single live birth cohort (N = 68,584) in Harris County, Texas, which includes the city of Houston and is reported to have nearly complete birth and death registration. The use of parental nativity with the traditional Spanish surname criterion made it possible to distinguish infants of Mexican-born immigrants from those of Blacks, Anglos, other Hispanics, and later-generation, more Anglicized Mexican Americans. Mortality rates were analyzed by ethnicity, parental nativity, and cause of death, with respect to birth weight, birth order, maternal age, legitimacy status, and time of first prenatal care.^ While overall IMRs showed Spanish surname rates slightly higher than Anglo rates, infants of Mexican-born immigrants had much lower NMRs than did Anglos, even for moderately low birth weight infants. However, among infants under 1500 grams, presumably unable to be discharged home in the neonatal period, Mexican Americans had the highest NMR. The inconsistency suggested unreported deaths for Mexican American low birth weight infants after hospital discharge. The PNMR of infants of Mexican immigrants was also lower than for Anglos, and the usual mortality differentials were reversed: high-risk categories of high birth order, high maternal age, and late/no prenatal care had the lowest PNMRs. Since these groups' characteristics are congruent with those of low-income migrants, the data suggested the possibility of migration losses. Cause of death analysis suggested that prematurity and birth injuries are greater problems than heretofore recognized among Mexican Americans, and that home births and "shoebox burials" may be unrecorded even in an urban setting.^ Caution is advised in the interpretation of infant mortality rates for a Spanish surname population of Mexican origin, even in an urban, non-border area with reportedly excellent birth and death registration. ^

Vitamin A supplementation in very low birth weight infants

PURPOSE: In United States, the percentage of Extremely Low Birth Weight (ELBW) born for year 2006 was 0.8% (approximately 32,000 babies) & Very Low Birth Weight (VLBW) 1.48% (1). ELBW babies account for nearly half (49%) of the infant mortality for United States. Very Low birth weight infants are at a significant risk for high mortality and morbidity due to their multi system involvement and predisposition to lung prematurity and impaired immune function. One of the common causes cited is Vitamin A deficiency (2, 3).The purpose of this study is to look at published literature on Vitamin A supplementation in very low birth weight (VLBW) infants. ^ RESEARCH DESIGN: Systematic review of literature of published articles meeting the pre-defined criteria. ^ PROCEDURE: Studies included in this review were those which looked at very low birth weight infants defined as birth weight<1500gms. All experimental studies were reviewed. Studies looking at the effect of Vitamin A supplementation in comparison with a placebo or by itself in varying dosing regimens as an intervention were reviewed. Vitamin A deficiency and its manifestations were of interest. We used key words such as "very low birth weight", "mortality", "Vitamin A", "retinol" and "supplementation" in our search. ^ RISKS & POTENTIAL BENEFITS: We do not see any potential risks associated with this study. The potential benefit is recommendation for future studies based on the review of literature available currently. ^ IMPORTANCE OF KNOWLEDGE THAT MAY REASONABLY BE EXPECTED TO RESULT: The systematic review of literature of all experimental studies in VLBW infants showed uniform correlation of parenteral Vitamin A dosing and high plasma concentrations achieved. The recommended dosage for use is 5000 IU 3 times/week given intramuscularly for 4 weeks to prevent CLD. Higher doses have not shown benefit, with a potential for toxicity, while lower doses are inadequate. There is no role of use of Vitamin A in closure of patent ductus arteriosus & reducing mortality. However, it is important to state that the number of studies done so far is limited with small sample sizes. There is a need in the future for experimental studies to ascertain the role of Vitamin A to improve outcomes in VLBW. Atleast, one more RCT should be conducted using the dosage recommended above to make this a standard practice.^

The effects of adequacy and content of prenatal care on birth outcomes in a high -risk Missouri population

The purpose of this observational study was investigation of the relationship between quantitative adequacy of prenatal care, specific prenatal care content and pregnancy outcome in a high risk Missouri population. A sample of 1484 women from three Missouri regions known to have high rates of low birth weight, infant mortality, and inadequate prenatal care rates participated in structured post-partum interviews. Approximately one-half of the sample had received adequate prenatal care and the other half inadequate prenatal care as determined by an index utilized by the Missouri Department of Health.^ Prenatal care content was assessed by reports of prenatal education in six different areas: Diet, smoking, alcohol, drug, preterm labor counseling, and advice on when to call the health provider if preterm labor was suspected by the woman. Low birth weight, in both term and preterm infants, were the two birth outcomes examined. A variety of maternal socio-demographic variables were also considered.^ The results of this study suggest that specific educational content, delivered during prenatal care, may have lessen the risk of giving birth to a preterm-low birth weight infant. Prenatal education for recognition of preterm labor, and advice on when to call the health provider if preterm labor was suspected were found to be associated with a decreased risk of preterm delivery. Specific educational content was not, however, associated with risk of term-low weight birth nor was quantitative adequacy of care associated with the risk of either term- or preterm-low birth weight.^ These findings reinforce a body of literature which stresses the importance of appropriate prenatal care in preventing preterm low birth weight. Additionally, the findings suggest interventions that may be specifically effective for prematurity prevention. ^