Birth attendants as perinatal verbal autopsy respondents in low- and middle-income countries: a viable alternative?

OBJECTIVE: To assess the feasibility of using birth attendants instead of bereaved mothers as perinatal verbal autopsy respondents. METHODS: Verbal autopsy interviews for early neonatal deaths and stillbirths were conducted separately among mothers (reference standard) and birth attendants in 38 communities in four developing countries. Concordance between maternal and attendant responses was calculated for all questions, for categories of questions and for individual questions. The sensitivity and specificity of individual questions with the birth attendant as respondent were assessed. FINDINGS: For early neonatal deaths, concordance across all questions was 94%. Concordance was at least 95% for more than half the questions on maternal medical history, birth attendance and neonate characteristics. Concordance on any given question was never less than 80%. Sensitivity and specificity varied across individual questions, more than 80% of which had a sensitivity of at least 80% and a specificity of at least 90%. For stillbirths, concordance across all questions was 93%. Concordance was 95% or greater more than half the time for questions on birth attendance, site of delivery and stillborn characteristics. Sensitivity and specificity varied across individual questions. Over 60% of the questions had a sensitivity of at least 80% and over 80% of them had a specificity of at least 90%. Overall, the causes of death established through verbal autopsy were similar, regardless of respondent. CONCLUSION: Birth attendants can substitute for bereaved mothers as verbal autopsy respondents. The questions in existing harmonized verbal autopsy questionnaires need further refinement, as their sensitivity and specificity differ widely.

An alternative strategy for perinatal verbal autopsy coding: single versus multiple coders.

OBJECTIVE: To determine the comparability between cause of death (COD) by a single physician coder and a two-physician panel, using verbal autopsy. METHODS: The study was conducted between May 2007 and June 2008. Within a week of a perinatal death in 38 rural remote communities in Guatemala, the Democratic Republic of Congo, Zambia and Pakistan, VA questionnaires were completed. Two independent physicians, unaware of the others decisions, assigned an underlying COD, in accordance with the causes listed in the chapter headings of the International classification diseases and related health problems, 10th revision (ICD-10). Cohen's kappa statistic was used to assess level of agreement between physician coders. RESULTS: There were 9461 births during the study period; 252 deaths met study enrolment criteria and underwent verbal autopsy. Physicians assigned the same COD for 75% of stillbirths (SB) (K = 0.69; 95% confidence interval: 0.61-0.78) and 82% early neonatal deaths (END) (K = 0.75; 95% confidence interval: 0.65-0.84). The patterns and proportion of SBs and ENDs determined by the physician coders were very similar compared to causes individually assigned by each physician. Similarly, rank order of the top five causes of SB and END was identical for each physician. CONCLUSION: This study raises important questions about the utility of a system of multiple coders that is currently widely accepted and speculates that a single physician coder may be an effective and economical alternative to VA programmes that use traditional two-physician panels to assign COD.

Detection and quantitation of gallid herpesvirus 1 in avian samples by 5' Taq nuclease assay utilizing Minor Groove Binder technology.

A 5' Taq nuclease assay utilizing Minor Groove Binder technology and targeting the thymidine kinase gene of gallid herpesvirus 1 (GaHV-1) was designed and optimized for use in diagnosing avian infectious laryngotracheitis. The assay was specific for GaHV-1 in that it did not react with other avian viral or bacterial pathogens. The detection limit was 1.0x10(-2) median tissue culture infectious dose per reaction or 90 target copies per reaction. Fifteen out of 41 diagnostic samples from sick birds reacted in the assay, five of which produced a typical alphaherpesvirus cytopathic effect (CPE) on chicken kidney (CK) cells. Sequencing, using amplicons generated by a polymerase chain reaction with primers flanking the 5' Taq nuclease amplicon, confirmed the presence of GaHV-1 in six samples (two producing alphaherpesvirus CPE on CK cells, three not producing alphaherpesvirus CPE, and one that was not inoculated onto CK cells). Tracheal swabs taken from 18 healthy broilers did not react in the assay. The ability of the assay to determine viral load in samples was demonstrated. Overall the assay is suitable for the rapid diagnosis of infectious laryngotracheitis.

Using verbal autopsy to ascertain perinatal cause of death: are trained non-physicians adequate?

OBJECTIVES: To develop a standardized verbal autopsy (VA) training program and evaluate whether its implementation resulted in comparable knowledge required to classify perinatal cause of death (COD) by physicians and non-physicians. METHODS: Training materials, case studies, and written and mock scenarios for this VA program were developed using conventional VA and ICD-10 guidelines. This program was used to instruct physicians and non-physicians in VA methodology using a train-the-trainer model. Written tests of cognitive and applied knowledge required to classify perinatal COD were administered before and after training to evaluate the effect of the VA training program. RESULTS: Fifty-three physicians and non-physicians (nurse-midwives/nurses and Community Health Workers [CHW]) from Pakistan, Zambia, the Democratic Republic of Congo, and Guatemala were trained. Cognitive and applied knowledge mean scores among all trainees improved significantly (12.8 and 28.8% respectively, P < 0.001). Cognitive and applied knowledge post-training test scores of nurse-midwives/nurses were comparable to those of physicians. CHW (high-school graduates with 15 months or less formal health/nursing training) had the largest improvements in post-training applied knowledge with scores comparable to those of physicians and nurse-midwives/nurses. However, CHW cognitive knowledge post-training scores were significantly lower than those of physicians and nurses. CONCLUSIONS: With appropriate training in VA, cognitive and applied knowledge required to determine perinatal COD is similar for physicians and nurses-midwives/nurses. This suggests that midwives and nurses may play a useful role in determining COD at the community level, which may be a practical way to improve the accuracy of COD data in rural, remote, geographic areas.

Periodontal disease and adverse birth outcomes: a study from Pakistan.

OBJECTIVE: Periodontal disease may increase the risk of adverse birth outcomes; however, results have been mixed. Few studies have examined periodontal disease in developing countries. We describe the relationship between periodontal disease and birth outcomes in a community setting in Pakistan. STUDY DESIGN: This was a prospective cohort study. Enrollment occurred at 20-26 weeks of gestation. A study dentist performed the periodontal examination to assess probing depth, clinical attachment level, gingival index, and plaque index. Outcomes included stillbirth, neonatal death, perinatal death, < 32 weeks preterm birth, 32-36 weeks preterm birth, and low birthweight and are presented for increasing periodontal disease severity by quartiles. RESULTS: Dental examinations and outcome data were completed for 1152 women: 81% of the women were multiparous, with a mean age of 27 years; 33% of the women had no education. Forty-seven percent of the women had dental caries; 27% of the women had missing teeth, and 91% of the women had had no dental care in the last year. Periodontal disease was common: 76% of the women had > or = 3 teeth with a probing depth of > or = 3 mm; 87% of the women had > or = 4 teeth with a clinical attachment level of > or = 3 mm; 56% of the women had > or = 4 teeth with a plaque index of 3; and 60% of the women had > or = 4 teeth with a gingival index of 3. As the measures of periodontal disease increased from the 1st to 4th quartile, stillbirth and neonatal and perinatal death also increased, with relative risks of approximately 1.3. Early preterm birth increased, but the results were not significant. Late preterm birth and low birthweight were not related to measures of periodontal disease. CONCLUSION: Pregnant Pakistani women have high levels of moderate-to-severe dental disease. Stillbirth and neonatal and perinatal deaths increased with the severity of periodontal disease.

Pasteurella multocida detection by 5' Taq nuclease assay: a new tool for use in diagnosing fowl cholera.

A 5' Taq nuclease assay utilising minor groove binder technology and targeting the 16S rRNA gene was designed to detect Pasteurella multocida (the causative agent of fowl cholera) in swabs collected from poultry. The assay was first evaluated using pure cultures. The assay correctly identified four P. multocida taxonomic type strains, 18 P. multocida serovar reference strains and 40 Australian field isolates (17 from poultry, 11 from pigs and 12 from cattle). Representatives of nine other Pasteurella species, 26 other bacterial species (18 being members of the family Pasteurellaceae) and four poultry virus isolates did not react in the assay. The assay detected a minimum of approximately 10 cfu of P. multocida per reaction. Of 79 poultry swabs submitted to the laboratory for routine bacteriological culture, 17 were positive in the 5' Taq nuclease assay, but only 10 were positive by culture. The other 62 swabs were negative for P. multocida by both 5' Taq nuclease assay and culture. The assay is suitable for use in diagnosing fowl cholera, is more rapid than bacteriological culture, and may also have application in diagnosing P. multocida infections in cattle and pigs.

Association between early postnatal weight loss and death or BPD in small and appropriate for gestational age extremely low-birth-weight infants.

OBJECTIVE: To examine the association between weight loss during the first 10 days of life and the incidence of death or bronchopulmonary dysplasia (BPD) in small for gestational age (SGA) and appropriate for gestational age (AGA) extremely low-birth-weight infants. DESIGN/METHODS: This is a retrospective analysis of a cohort of ELBW (birth weight <1000 g) infants from the NICHD Neonatal Research Network's database. The cohort consisted of 9461 ELBW infants with gestational age of 24-29 weeks, admitted to Network's participating centers during calendar years 1994-2002 and surviving at least 72 h after birth. The cohort was divided into two groups, 1248 SGA (with birth weight below 10th percentile for gestational age) and 8213 AGA (with birth weight between 10th and 90th percentile) infants. We identified infants with or without weight loss during the first 10 days of life, which we termed as 'early postnatal weight loss' (EPWL). Univariate analyses were used to predict whether EPWL was related to the primary outcome, death or BPD, within each birth weight/gestation category (SGA or AGA). BPD and death were also analyzed separately in relation to EPWL. Logistic regression analysis was done to evaluate the risk of death or BPD in SGA and AGA groups, controlling for maternal and neonatal demographic and clinical factors found to be significant by univariate analysis. RESULTS: SGA ELBW infants had a lower prevalence of EPWL as compared with AGA ELBW infants (81.2 vs 93.7%, respectively, P<0.001). In AGA infants, univariate analysis showed that death or BPD rate was lower in the group of infants with EPWL compared with infants without EPWL (53.4 vs 74.3%, respectively, P<0.001). The BPD (47.2 vs 64%, P<0.001) and death (13.8 vs 32.9%, P<0.001) rate were similarly lower in the EPWL group. The risk-adjusted odds ratios (ORs) showed that EPWL was associated with lower rate of death or BPD (OR 0.47, 95% CI: 0.37-0.60). In SGA infants, on univariate analysis, a similar association between EPWL and outcomes was seen as shown in AGA infants: death or BPD (55.9 vs 75.2%, P<0.001), BPD rate (48.3 vs 62.1%, P=0.002) and rate death (19 vs 40.8%, P<0.001) for those with or without EPWL, respectively. Multiple logistic regression showed that as in AGA ELBW infants, EPWL was associated with lower risk for death or BPD (OR 0.60, 95% CI: 0.41-0.89) among SGA infants. CONCLUSIONS: SGA infants experienced less EPWL when compared with their AGA counterparts. EPWL was associated with a lower risk of death or BPD in both ELBW AGA and SGA infants. These data suggest that clinicians who consider the association between EPWL and risk of death or BPD should do so independent of gestation/birth weight status.

Maternal and neonatal outcomes of hospital vaginal deliveries in Tibet.

INTRODUCTION: To determine the outcomes of vaginal deliveries in three study hospitals in Lhasa, Tibet Autonomous Region (TAR), People's Republic of China (PRC), at high altitude (3650 m). METHODS: Prospective observational study of 1121 vaginal deliveries. RESULTS: Pre-eclampsia/gestational hypertension (PE/GH) was the most common maternal complication 18.9% (n=212), followed by postpartum hemorrhage (blood loss > or = 500 ml) 13.4%. There were no maternal deaths. Neonatal complications included: low birth weight (10.2%), small for gestational age (13.7%), pre-term delivery (4.1%) and low Apgar (3.7%). There were 11 stillbirths (9.8/1000 live births) and 19 early neonatal deaths (17/1000 live births). CONCLUSION: This is the largest study of maternal and newborn outcomes in Tibet. It provides information on the outcomes of institutional vaginal births among women delivering infants at high altitude. There was a higher incidence of PE/GH and low birth weight; rates of PPH were not increased compared to those at lower altitudes.

The use of chlorhexidine to reduce maternal and neonatal mortality and morbidity in low-resource settings.

Of the 4 million neonatal deaths and 500,000 maternal deaths that occur annually worldwide, almost 99% are in developing countries and one-third are associated with infections. Implementation of proven interventions and targeted research on a select number of promising high-impact preventative and curative interventions are essential to achieve Millennium Development Goals for reduction of child and maternal mortality. Feasible, simple, low-cost interventions have the potential to significantly reduce the mortality and severe morbidity associated with infection in these settings. Studies of chlorhexidine in developing countries have focused on three primary uses: 1) intrapartum vaginal and neonatal wiping, 2) neonatal wiping alone, and 3) umbilical cord cleansing. A study of vaginal wiping and neonatal skin cleansing with chlorhexidine, conducted in Malawi in the 1990s suggested that chlorhexidine has potential to reduce neonatal infectious morbidity and mortality. A recent trial of cord cleansing conducted in Nepal also demonstrated benefit. Although studies have shown promise, widespread acceptance and implementation of chlorhexidine use has not yet occurred. This paper is derived in part from data presented at a conference on the use of chlorhexidine in developing countries and reviews the available evidence related to chlorhexidine use to reduce mortality and severe morbidity due to infections in mothers and neonates in low-resource settings. It also summarizes issues related to programmatic implementation.

Changes in mortality and morbidities among infants born at less than 25 weeks during the post-surfactant era.

OBJECTIVES: To compare mortality and death or major morbidity (DOMM) among infants <25 weeks estimated gestational age (EGA) born during two post-surfactant era time periods. STUDY DESIGN AND PATIENTS: Comparative cohort study of very low birthweight (501-1500 g) infants <25 weeks EGA in the NICHD Neonatal Research Network born during two post-surfactant era time periods (group I, 1991-1994, n=1408; group II, 1995-1998, n=1348). Perinatal and neonatal factors were compared, and group related mortality and DOMM risk were evaluated. RESULTS: Mortality was higher for group I (63.1% v 56.7%; p=0.0006). Antenatal steroids (ANS) and antenatal antibiotics (AABX), surfactant (p<0.0001), and bronchopulmonary dysplasia (p=0.0008) were more prevalent in group II. In a regression model that controlled for basic and delivery factors only, mortality risk was greater for group I than for group II (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2 to 1.7); the addition of AABX and surfactant, or ANS (OR 0.97, 95% CI 0.79 to 1.2) to the model appeared to account for this difference. There was no difference in DOMM (86.8% v 88.4%; p=0.2), but risk was lower for group I in regression models that included ANS (OR 0.70, 95% CI 0.52 to 0.94). CONCLUSION: Survival to discharge was more likely during the more recent period because of group differences in ANS, AABX, and surfactant. However, this treatment shift may reflect an overall more aggressive management approach. More consistent application of treatment has led to improving survival of <25 week EGA infants during the post-surfactant era, but possibly at the cost of greater risk of major in-hospital morbidities.

Cocaine exposure is associated with subtle compromises of infants' and mothers' social-emotional behavior and dyadic features of their interaction in the face-to-face still-face paradigm.

Prenatal cocaine and opiate exposure are thought to subtly compromise social and emotional development. The authors observed a large sample of 236 cocaine-exposed and 459 nonexposed infants (49 were opiate exposed and 646 nonexposed) with their mothers in the face-to-face still-face paradigm. Infant and maternal behaviors were microanalytically coded. No opiate-exposure effects were detected. However, mothers of cocaine-exposed infants showed more negative engagement than other mothers. The cocaine-exposed dyads also showed higher overall levels of mismatched engagement states than other dyads, including more negative engagement when the infants were in states of neutral engagement. Infants exposed to heavier levels of cocaine showed more passive-withdrawn negative engagement and engaged in more negative affective matching with their mothers than other infants. Although effect sizes were small, cocaine exposure, especially heavy cocaine exposure, was associated with subtly negative interchanges, which may have a cumulative impact on infants' later development and their relationships with their mothers.

Development of the sex difference in neuron numbers of the superior cervical ganglion: effects of transection of the cervical sympathetic trunk.

The number of superior cervical ganglion (SCG) neurons does not differ for males and females on the day of birth, but by 15 days, after most of the normal neuron death has occurred, males have significantly more neurons than females. This difference persists in the adult. The present study was undertaken to determine whether the presence of afferent input to the SCG is required for the development of this sex difference. Bilateral transection of the cervical sympathetic trunk, which deafferents the SCG neurons, or a sham operation was performed on male and female Sprague Dawley rats on the day of birth. Numbers of neurons were counted in SCGs of animals sacrificed on either postnatal day 4 or 15, before or after normal development of the SCG sex difference. At 4 days, the number of SCG neurons in sham-operated males and females were not different, but by 15 days, females had lost a significant number of neurons, whereas the males had not. Transection of the cervical sympathetic trunk led to a significant loss of over 6,000 SCG neurons by postnatal day 4 in both males and females. Whereas some of this loss is due to axotomy of caudally projecting SCG neurons, at least half of the neuron loss is due to removal of the afferent input. At 15 days, sham-operated males had significantly more SCG neurons than did sham-operated females, but the gender difference was not significant in animals with neonatally deafferented ganglia. Thus, the normal development of the gender difference in SCG neuron numbers requires an intact afferent input.

Time of cell origin and cell death in the avian dorsal motor nucleus of the vagus.

Cessation of cell proliferation and cell death were studied in the dorsal motor nucleus of the vagus of the chick embryo, hatching, and adult. Most of the cells comprising the nucleus (94%) complete their final DNA synthesis on days 2 and 3 of incubation. There is a caudo-rostral gradient in the cessation of proliferation, with the caudalmost cells withdrawing from the cell cycle slightly in advance of the middle and rostral cells. Cell death in the dorsal motor nucleus results in a 21% loss of cells between days 8 and 12, and 37% loss by hatching. A caudo-rostral gradient was also present with respect to cell death, with more delayed and gradual cell loss occurring in the rostral region. The timing and spatial pattern of cell death may be related to the asynchronous innervation of the several targets of the nucleus.

Quantitative study of primary sensory neurone populations of three species of elasmobranch fish.

In order to assess the ability of sharks and rays to sense pain, the proportion of myelinated versus unmyelinated sensory fibres in the dorsal roots and the diameter spectrum of cells in the dorsal root ganglia of three species of elasmobranch fish were ascertained. Electron micrographs were used to count the numbers of myelinated and unmyelinated fibres in montages of whole dorsal roots of the long-tailed stingray (Himantura sp.), the shovelnose ray (Rhinobatus battilum), and small specimens of the black-tip shark (Carcharhinus melanopterus). The diameters of dorsal root ganglion cells in each species were measured by using the light microscope. Less than 1% of the dorsal root axons in the long-tailed stringray and a large specimen of the shovelnose were unmyelinated, whereas in smaller shovelnose rays and in the small black-tipped sharks, from 14% to 38% of axons were unmyelinated. Unmyelinated fibres differed from those in mammalian nerves in that there was a one-to-one association of the fibre with a Schwann cell. We conclude from these observations that myelination was incomplete in the black-tipped sharks and the smaller specimens of the shovelnose rays. The distribution of the diameter of cells of the dorsal root ganglia of these species was unimodal, resembling the diameter range that has been reported for the somata of myelinated fibres in the cat. We interpret these results as indications that sharks and rays lack the neural apparatus essential for the sensation of pain and we suggest that, to these life forms, the perception of pain might have little relevance to survival.

Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes.

OBJECTIVES: In the era before widespread use of inhaled nitric oxide, to determine the prevalence of persistent pulmonary hypertension (PPHN) in a multicenter cohort, demographic descriptors of the population, treatments used, the outcomes of those treatments, and variation in practice among centers. STUDY DESIGN: A total of 385 neonates who received >/=50% inspired oxygen and/or mechanical ventilation and had documented evidence of PPHN (2D echocardiogram or preductal or postductal oxygen difference) were tracked from admission at 12 Level III neonatal intensive care units. Demographics, treatments, and outcomes were documented. RESULTS: The prevalence of PPHN was 1.9 per 1000 live births (based on 71 558 inborns) with a wide variation observed among centers (.43-6.82 per 1000 live births). Neonates with PPHN were admitted to the Level III neonatal intensive care units at a mean of 12 hours of age (standard deviation: 19 hours). Wide variations in the use of all treatments studied were found at the centers. Hyperventilation was used in 65% overall but centers ranged from 33% to 92%, and continuous infusion of alkali was used in 75% overall, with a range of 27% to 93% of neonates. Other frequently used treatments included sedation (94%; range: 77%-100%), paralysis (73%; range: 33%-98%), and inotrope administration (84%; range: 46%-100%). Vasodilator drugs, primarily tolazoline, were used in 39% (range: 13%-81%) of neonates. Despite the wide variation in practice, there was no significant difference in mortality among centers. Mortality was 11% (range: 4%-33%). No specific therapy was clearly associated with a reduction in mortality. To determine whether the therapies were equivalent, neonates treated with hyperventilation were compared with those treated with alkali infusion. Hyperventilation reduced the risk of extracorporeal membrane oxygenation without increasing the use of oxygen at 28 days of age. In contrast, the use of alkali infusion was associated with increased use of extracorporeal membrane oxygenation (odds ratio: 5.03, compared with those treated with hyperventilation) and an increased use of oxygen at 28 days of age. CONCLUSIONS: Hyperventilation and alkali infusion are not equivalent in their outcomes in neonates with PPHN. Randomized trials are needed to evaluate the role of these common therapies.

Longitudinal growth of hospitalized very low birth weight infants.

BACKGROUND: The interpretation of growth rates for very low birth weight infants is obscured by limited data, recent changes in perinatal care, and the uncertain effects of multiple therapies. OBJECTIVES: To develop contemporary postnatal growth curves for very low birth weight preterm infants and to relate growth velocity to birth weight, nutritional practices, fetal growth status (small- or appropriate-for-gestational-age), and major neonatal morbidities (chronic lung disease, nosocomial infection or late-onset infection, severe intraventricular hemorrhage, and necrotizing enterocolitis). DESIGN: Large, multicenter, prospective cohort study. METHODS: Growth was prospectively assessed for 1660 infants with birth weights between 501 to 1500 g admitted by 24 hours of age to 1 of the 12 National Institute of Child Health and Human Development Neonatal Research Network centers between August 31, 1994 and August 9, 1995. Infants were included if they survived >7 days (168 hours) and were free of major congenital anomalies. Anthropometric measures (body weight, length, head circumference, and midarm circumference) were performed from birth until discharge, transfer, death, age 120 days, or a body weight of 2000 g. To obtain representative data, nutritional practices were not altered by the study protocol. RESULTS: Postnatal growth curves suitable for clinical and research use were constructed for body weight, length, head circumference, and midarm circumference. Once birth weight was regained, weight gain (14.4-16.1 g/kg/d) approximated intrauterine rates. However, at hospital discharge, most infants born between 24 and 29 weeks of gestation had not achieved the median birth weight of the reference fetus at the same postmenstrual age. Gestational age, race, and gender had no effect on growth within 100-g birth weight strata. Appropriate-for-gestational age infants who survived to hospital discharge without developing chronic lung disease, severe intraventricular hemorrhage, necrotizing enterocolitis, or late onset-sepsis gained weight faster than comparable infants with those morbidities. More rapid weight gain was also associated with a shorter duration of parenteral nutrition providing at least 75% of the total daily fluid volume, an earlier age at the initiation of enteral feedings, and an earlier age at achievement of full enteral feedings. CONCLUSIONS: These growth curves may be used to better understand postnatal growth, to help identify infants developing illnesses affecting growth, and to aid in the design of future research. They should not be taken as optimal. Randomized clinical trials should be performed to evaluate whether different nutritional management practices will permit birth weight to be regained earlier and result in more rapid growth, more appropriate body composition, and improved short- and long-term outcomes.

Streptozyme test for antibodies to group A streptococcal antigens.

The ability of the Streptozyme test to identify significant antibody rises in 46 patients with streptococcal pharyngitis was comparable to, but no greater than, that of the antistreptolysin O or antideoxyribonuclease B test and inferior to that of the combined use of both the antistreptolysin O and antideoxyribonuclease B tests. Serum specimens were also simultaneously analyzed with three different lots of Streptozyme reagent. Lot-to-lot variation in the reagent resulted in a significant difference in antibody titer for 18 (19%) of the 92 sera tested. Differences among the three lots also produced variation in determining whether a significant rise in titer had occurred from the acute phase to the convalescent phase serum for a given patient. These observations raise concerns about the standardization of the Streptozyme reagent and document the need for precise identification and quantitation of the streptococcal antigens used in this product.

Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants. The National Institute of Child Health and Human Development Neonatal Research Network.

BACKGROUND: Septicemia is a major antecedent of morbidity and mortality in very low birth weight (501- to 1500-g) infants. Our purpose was to determine prospectively the incidence, clinical presentation, laboratory features, risk factors, morbidity and mortality associated with late onset septicemia in infants 501 to 1500 g. METHODS: Clinical data were prospectively collected for 2416 infants enrolled in a multicenter trial to determine the efficacy of intravenous immunoglobulin in preventing nosocomial infections. Septicemia was confirmed by positive blood culture in 395 symptomatic infants. Multivariate analyses of factors associated with septicemia were performed. RESULTS: Sixteen percent of VLBW infants developed septicemia at a median age of 17 days. Factors associated with septicemia by logistic regression included male gender, lower gestational age and birth weight and decreased baseline serum IgG concentrations. Increasing apnea (55%), feeding intolerance, abdominal distension or guaiac-positive stools (43%), increased respiratory support (29%), lethargy and hypotonia (23%) were the dominant presenting features of septicemia. An abnormal white blood cell count (46%), unexplained metabolic acidosis (11%) and hyperglycemia (10%) were the most common laboratory indicators. Septicemic infants, compared with nonsepticemic infants, had significantly increased mortality (21% vs. 9%), longer hospital stay (98 vs. 58 days) and more serious morbidity, including severe intraventricular hemorrhage, bronchopulmonary dysplasia and increased ventilator days (P < 0.001). CONCLUSIONS: Late onset septicemia is common in very low birth weight infants, and the rate is inversely proportional to gestational age and birth weight. Septicemia is more common in males and those with low initial serum IgG values. A set of clinical signs (apnea, bradycardia, etc.) and laboratory values (leukocytosis, immature white blood cells and neutropenia) increase the probability of late onset sepsis, but they have poor positive predictive value.

Central and autonomic nervous systems' signs associated with in utero exposure to cocaine/opiates.

In summary, we found that the prevalence of CNS/ANS signs was significantly higher in the infants exposed to cocaine and/or opiates than in nonexposed infants. However, the prevalence of a large number of these signs was less than 5%. The prevalence rates of these signs are lower when exposure involved cocaine only; thus, their assessment has limited clinical utility.

Prenatal and perinatal risk and protective factors for neonatal intracranial hemorrhage. National Institute of Child Health and Human Development Neonatal Research Network.

OBJECTIVE: To identify prenatal and perinatal risk and protective factors for grade III and IV intracranial hemorrhage (ICH) in 4795 singleton infants (weight, < or = 1500 g). METHOD: Prenatal and perinatal risk and protective factors for ICH were examined initially by univariate analysis and adjusted for year of birth, followed by multivariate logistic regression analysis that adjusted simultaneously for the effects of year of birth and prenatal and perinatal characteristics. SETTING: Seven tertiary care neonatal-perinatal centers. RESULTS: By univariate analysis, African-American race, prenatal care, older maternal age, hypertension or preeclampsia, antenatal steroid administration, cesarean section delivery, increasing birth weight, increasing gestational age, and female gender of the infant were protective prenatal or perinatal factors. Antepartum hemorrhage, the presence of labor, and breech presentation were perinatal factors that were associated with an increased risk of ICH. By using staged logistic regression, a model of combined prenatal and perinatal characteristics that influenced grade III and IV ICH was developed. Significant protective factors against ICH included a complete course of antenatal steroid therapy, African-American maternal race, female gender of the infant, hypertension or preeclampsia with no antepartum hemorrhage, increasing gestational age, and increasing birth weight. CONCLUSION: Antenatal steroid administration is a therapeutic intervention that is associated with a decreased risk for neonatal grade III and IV ICH.