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PubMed2002

Neonatal organ system injury in acute birth asphyxia sufficient to result in neonatal encephalopathy.

OBJECTIVE: To identify the proportion of major organ system injury in cases of acute intrapartum asphyxia that result in neonatal encephalopathy. METHODS: A prospectively maintained database was cross-referenced using medical record coding to identify diagnoses of acute intrapartum asphyxia, acute birth asphyxia, or neonatal encephalopathy over a 6-year period. An acute intrapartum asphyxial antecedent was validated with emphasis on excluding long-standing or chronic conditions where injury likely occurred before presentation. Injury pattern was evaluated using routinely available laboratory and imaging tests. RESULTS: Forty-six cases of acute peripartum asphyxia sufficient to result in the diagnosis of neonatal encephalopathy were identified. Clinical central nervous system injury resulting in encephalopathy was present in 100% of cases as it was an entry criteria; of these, 49% had electroencephalogram and 40% had imaging studies diagnostic of acute injury. Liver injury based on elevated aspartate transaminase or alanine transaminase levels occurred in 80%. Heart injury, as defined by pressor or volume support beyond 2 hours of life or elevated cardiac enzymes, occurred in 78%. Renal injury, defined by an elevation of serum creatinine to greater than 1.0 mg/dL, persistent hematuria, persistent proteinuria, or clinical oliguria, occurred in 72%. An elevation in nucleated red blood cell counts exceeding 26 per 100 white blood cells occurred in 41%. CONCLUSION: Using common diagnostic tests as markers of acute asphyxial injury, we noted that multiple organs suffer damage during an acute intrapartum asphyxial event sufficient to result in a neonatal encephalopathy.

Adult↗
PubMed2003

Impaired CD40-signalling in Langerhans' cells from murine neonatal draining lymph nodes: implications for neonatally induced cutaneous tolerance.

Cutaneous tolerance to antigens may be induced in mice through application of antigen during the first few days following birth. The mechanism governing this neonatally induced tolerance remains uncertain. We employed a contact hypersensitivity model to analyse dendritic cell (DC) function and the expression of classical and non-classical lymphocyte populations within the neonate. Examination of draining lymph node DC after antigenic challenge of the skin revealed these DC to be significantly deficient in their ability to stimulate antigen-specific T cell proliferation. Co-stimulatory molecule (CD40, CD80 and CD86) expression of these cells was deficient in comparison to adult DC, and functional tests revealed these cells to possess a critical absence of CD40 signalling. A numerical analysis of classical and non-classical lymphocyte expression demonstrated that while the neonatal spleen is devoid of T cells, the lymph nodes have a normal repertoire of T, B, gammadelta and CD4+CD25+ lymphocytes but an increased expression of natural killer (NK) cells. This study indicates that functionally deficient DC are likely contributors to neonatally induced cutaneous tolerance.

Animals↗
PubMed2002

Neurological and perceptual-motor outcome at 5 - 6 years of age in children with neonatal encephalopathy: relationship with neonatal brain MRI.

OBJECTIVE: The aims of this study were 1) to determine the incidence of minor neurological dysfunction and perceptual-motor difficulties in children aged 5-1/2 -- 6-1/2, who had been born full-term but presented with neonatal encephalopathy (NE) and low Apgar scores and 2) to examine the relationships between the presence/absence of these difficulties with neonatal brain MRI. PARTICIPANTS AND METHODS: Sixty-eight full-term infants with one minute Apgar scores less than or equal to 5 and neurological abnormalities during the first 48 hours after birth were included in the study. All children had a neonatal MRI brain scan. Surviving infants were assessed between the age of 5 and 6 years using the Touwen Examination, the Movement ABC and the WPPSI-R. RESULTS: Fifteen of the 68 infants (22 %) died in the neonatal period. Of the 53 surviving infants, 19 (36 %) had cerebral palsy. The remaining 34 were considered normal at 2 years of age but, when assessed at school age, 8 (15 %) had minor neurological dysfunction and/or perceptual-motor difficulties, 1 (2 %) had only cognitive impairment and 25 (47 %) were normal. The outcome largely reflected the pattern of lesions on brain imaging. While 83 % of those with a normal outcome had normal scans or minimal white matter lesions, 80 % of those with minor neurological dysfunction and/or perceptual-motor difficulties had mild or moderate basal ganglia or more marked white matter lesions. CONCLUSION: Continued surveillance is recommended for children with apparently normal outcome at two years of age after NE, particularly when abnormalities are detected on brain MRI.

Age Factors↗
PubMed1985

Prognostic value of neonatal CT scans in asphyxiated term babies: low density score compared with neonatal neurological signs.

Twenty-five asphyxiated term babies were investigated in order to evaluate the prediction of their neurodevelopmental outcome by means of computerized tomography (CT) as compared to neurological symptoms during the neonatal period. Low density (LD) areas, thought to represent hypoxicischaemic lesions, were assessed quantitatively by means of a LD score based on the extent and degree of LD, the total score ranging from 0-36. Neonatal scans were defined according to the time span elapsed between asphyxia and CT as (1) early CT (day 1-7, n = 15), and (2) intermediate CT (day 9-23: n = 14; day 29: n = 1). The newborns were classified according to the neonatal neurological findings as having mild (n = 8, 32%), moderate (n = 9, 36%), and severe (n = 8, 32%) encephalopathy, following the definition of Sarnat and Sarnat (1976). Among the twenty-two survivors, the follow-up (mean age 19.2 +/- 6.0 mts) revealed fourteen (56%) with normal outcome, two (8%) with transient neurodevelopmental anomalies during the first year, and nine (36%) with permanent abnormalities such as cerebral palsy and/or retardation (mainly global) and/or epilepsy. Early CT scans had no predictive value. Intermediate CT, however, showed distinct variations of LD areas which resulted in an LD score well correlated with the later outcome. In particular, a LD score below 14 characterized every baby who developed normally; a prediction not possible in a reliable way be means of neonatal neurological signs. For all abnormal children, the score correlated with the severity of the later neurodevelopmental disorder, except for one with the latest intermediate CT (day 29).

Asphyxia Neonatorum↗
PubMed2002

Prevention of neonatal group B streptococcal disease: A combined intrapartum and neonatal protocol.

OBJECTIVE: We sought to assess the efficacy of a clinical protocol to reduce the incidence of early-onset neonatal group B Streptococcus (GBS) infection. STUDY DESIGN: We assessed neonatal sepsis from GBS and other organisms with use of a before-after study design to evaluate the effects of implementation of combined intrapartum antimicrobial prophylaxis given selectively to mothers with GBS risks and penicillin G given to all neonates. RESULTS: In 1994, early-onset GBS infection developed in 31 of 13,887 live births (2.2/1000), 13 preterm and 18 term cases. After implementation of the prophylaxis protocol (1995), 6 of 13,527 live births had early-onset GBS (0.4/1000) (P <.001). There were no preterm (P =.0004) and 6 term GBS cases (P =.02). The efficacy continued through 1999 (0.5/1000) without an increase in neonatal infections from other bacteria. CONCLUSION: Combined maternal and infant antimicrobial prophylaxis can significantly and safely reduce rates of early-onset GBS infection in both preterm and term infants.

Algorithms↗
PubMed2003

Use of biomarkers of sub-clinical infection, nutrition and neonatal maturity to interpret plasma retinol in Nigerian neonates.

Using the World Health Organization criterion, the prevalence of sub-clinical vitamin A deficiency can be assessed using plasma retinol concentrations <0.7 micromol/l. However, plasma retinol can be depressed by infection; thus, the use of this criterion alone may overestimate deficiency. In the present study, we investigated the usefulness of the acute-phase proteins (APP) alpha1-antichymotrypsin (ACT) and alpha1-acid glycoprotein (AGP), plasma carotenoids and anthropometric and gestational indices to interpret plasma retinol in the blood of 192 apparently healthy Nigerian neonates collected randomly during days 1-20 postpartum. The mean weight (2.64 kg) and length (0.458 m) of the neonates and plasma concentrations (geometric mean, micromol/l) of retinol (0.54), alpha-carotene (0.072), ss-carotene (0.076) and lutein (0.080) were low. The prevalence of vitamin A deficiency was 72 %, indicating a severe public health problem. Babies who were of low birth weight (P<0.003) or premature and low birth weight (P<0.023) had significantly lower retinol concentrations than full-term normal weight babies. Thirty-two neonates had abnormal ACT and forty-four abnormal AGP concentrations. Positive correlations between retinol and ACT (r 0.186, P=0.05) and AGP (r 0.31, P=0.0001) during days 1-5 may be due to the increasing plasma retinol from maternal milk and a coincidental increasing capacity to synthesise APP. Subsequently, negative correlations between retinol and ACT (r -0.28, P=0.02) and AGP (r -0.29, P=0.018) from day 6 onwards reflected the continuing increase in plasma retinol, but no further increase in the APP. Overall, weight, ACT, lutein and age explained 30 % of the variance in retinol, but lutein was the most significant (r(2) 0.18, P<0.0001). Hence, the distribution of plasma retinol concentrations in this group of neonates was more strongly linked with nutrition (via the surrogate marker lutein) than infection.

Biomarkers↗
PubMed1998

Acute neonatal respiratory distress in Italy: a one-year prospective study. Italian Group of Neonatal Pneumology.

A prospective multicentre 12-month survey of neonatal respiratory disorders in 63 537 Italian infants was performed to evaluate the incidence of acute neonatal respiratory disorders and of the main related complications. A total of 1427 developed respiratory disorders (2.2%), 208 of whom died (14.6%). The incidence of respiratory distress syndrome was 1.16%, with a case fatality rate (CFR) of 24%; that of transient tachypnoea was 0.93%, with a CFR of 1.3%. The rates of meconium aspiration syndrome, persistent pulmonary hypertension and pneumonia were 0.06%, 0.02% and 0.07%, with CFRs of 10.3%, 38.5% and 21.7%, respectively. The occurrences of the main complications in affected newborns were: bronchopulmonary dysplasia 5.6%, necrotizing enterocolitis 1.7%, patent ductus arteriosus 9.8%, 3 degrees and 4 degrees grade intraventricular haemorrhage 6.8% and air leak 4.9%. It was concluded that the incidence of acute neonatal respiratory disorders and the main related complications was lower than that reported two decades ago and that the CFR of acute neonatal respiratory disorders had increased. These results may be the consequences of (i) progress in the management of high-risk pregnancies, (ii) an increased number of viable infants with extremely low birth weight and (iii) diffusion of antenatal treatment with corticosteroids which, in this series, seemed to reduce the morbidity but not the mortality in the high-risk infants.

Acute Disease↗
PubMed1959

The nature of the immunologic inadequacy of neonatal rabbits. II. Antibody formation by neonatal splenic cells transferred to adult recipients.

It has been shown that cells from neonatal rabbits are capable of producing considerable amounts of antibody after exposure to antigen in vitro and transfer to x-radiated adult recipients. This suggests that the immunological inadequacy of these neonates is not dependent primarily upon the lack of cells capable of antibody formation. Both in vitro sensitized neonatal lymphoid cells and in vivo sensitized adult lymphoid cells made much more antibody after transfer to x-rayed adult recipients than to neonatal recipients. Possible reasons for and significance of these observations are pointed out in the discussion.

Animals↗
PubMedDate not supplied

Role of intravenous immunoglobulin in prevention of late-onset infection in low-birth-weight neonates. The Neonatal IVIG Study Group.

As a result of inadequate placental transport of maternal IgG, preterm neonates of less than 32 weeks' gestation, especially those with birth weights less than 1,500 g, are profoundly hypogammaglobulinemic at birth, a condition that worsens during the first several weeks of life. This hypogammaglobulinemia is believed to contribute to their high frequency of late-onset sepsis, with its accompanying morbidity and mortality. Animal studies suggest that human immunoglobulin prepared for intravenous use (IVIG) improves host defense against pathogens that cause neonatal infections, but studies of IVIG in human neonates have been inconclusive because of the small numbers of infants included, lack of suitable controls, use of clinical rather than strict microbiologic definition of sepsis, and performance only in a single hospital outside the United States. A double-blind, randomized, placebo-controlled multicenter trial in the United States is in progress to determine the efficacy of IVIG in the prevention of late-onset infections in infants with birth weights between 500 and 1,750 g. Infants are infused with 500 mg of IVIG/kg or albumin-saline placebo at 3-7 days of age, 7 days later, and every 14 days for five doses. Efficacy parameters include mortality, number of proved infectious episodes (bacterial, fungal, or viral), and infection-related morbidity. Definitive guidelines for the possible use of prophylactic IVIG in low-birth-weight neonates should result from this evaluation of 500 to 700 infants in the United States.

Agammaglobulinemia↗
PubMed1988

Neonatal neurobehavioral examination. A new instrument for quantitative analysis of neonatal neurological status.

A new neonatal neurobehavioral examination (NNE) was designed in response to the need for a more quantitative assessment of neonatal neurological status. The NNE consists of 27 items divided into three sections: 1) tone and motor patterns, 2) primitive reflexes, and 3) behavioral responses. Each section consists of 9 items scored on a three-point scale. Fifty-four healthy full-term infants were examined at 2 days of age and demonstrated total NNE scores ranging from 70 to a maximum possible score of 81 (X = 76, s = 1.03). Mean section scores for these infants ranged from 25.3 to 26.6 (s = .59-1.79). Intertester agreement was 88% by item and 95% by total score in each section. Two hundred ninety-eight high-risk infants were then examined at 37 to 40 weeks conceptional age (gestational age plus chronological age) or at discharge from the neonatal intensive care unit, whichever occurred first. Total NNE mean scores for high-risk infants fell into discrete clusters by conceptional age at the time of examination (37-42 weeks, mean score = 66.5; 34-36 weeks, mean score = 60.7; less than 34 weeks, mean score = 51.1). Similar clustering occurred for the three section scores. Highly significant differences existed between the three conceptional age groups for total scores and section scores. No clinically significant score differences were associated with severity of illness or gestational age at birth. The results of this study suggest that the NNE easily and reliably assesses infants' neonatal neurobehavioral status at a given conceptional age. Additional studies are in progress to determine the value of the NNE in predicting subsequent developmental disabilities.

Child Behavior↗
PubMed1989

Perinatal risk factors in birth asphyxia: relationship of obstetric and neonatal complications to neonatal mortality in 16,365 consecutive live births.

Over a period of one year, 16,365 consecutively live born neonates were prospectively studied for evidence of birth asphyxia using the requirement of greater than one minute of positive pressure ventilation for identifying infants suffering from birth asphyxia. Asphyxia occurred in 2.8% of all neonates. Multivariate analysis of high risk factors associated with increased risk of asphyxia showed that low birth weight was the most significant predictor of asphyxia: asphyxia occurred in 68% of infants of less than 1,000 g birth weight and decreased to 1.2% in infants of 3-4 kg birth weight. Perinatal risk factors associated with a higher incidence of asphyxia include: postmaturity, birth weight (less than or equal to 2.5 kg) and with the presence of maternal and/or obstetric complications. The impact of asphyxia on neonatal mortality was most pronounced in more mature infants and the mortality was increased 3 fold in infants of less than 34 week gestation and greater than 27 fold for infants greater than 38 week gestation. Of the asphyxiated neonates, intrauterine growth retardation, fetal macrosomia, hypothermia, hyaline membrane disease, seizures, hypoglycemia and hyponatremia were significantly associated with an increased risk of death.

Adolescent↗
PubMed1992

Melatonin concentration in the umbilical artery and vein in human preterm and term neonates and neonates with acute fetal distress.

In order to assess the existence of a rhythmic secretion of melatonin (aMT) in newborns and whether this rhythm is affected by neonatal stress, we studied 112 newborns classified in three groups: normal babies delivered at term, preterm infants born before the 38th week, and babies with fetal distress. Melatonin was measured by RIA in the umbilical artery and vein at the time of birth. Melatonin levels in umbilical arterial and venous blood showed a diurnal rhythm in all groups. Melatonin levels in umbilical cord artery and vein were closely related. Nocturnal melatonin levels were increased in newborns with acute fetal distress in comparison with normal term and preterm neonates. These results suggest that (1) a rhythm of aMT secretion exists in newborns, although it cannot be determined whether this rhythm is of maternal or fetal origin and (2) neonatal stress (acute fetal distress) increases aMT production during the night in comparison with normal term and preterm neonates.

Acute Disease↗
PubMed1987

Doppler studies in the growth retarded fetus and prediction of neonatal necrotising enterocolitis, haemorrhage, and neonatal morbidity.

In 82 consecutive cases of intrauterine growth retardation managed by established criteria fetal Doppler studies identified 29 fetuses with absence of end diastolic frequencies in the fetal aorta. These same fetuses were significantly more growth retarded (p less than 0.001) and had an earlier gestational age at delivery (p less than 0.001) than those with end diastolic frequencies present. A subgroup of these cases was analysed in more detail to examine the prognostic value of this phenomenon for the neonate. Two groups of neonates of equivalent gestational age and with a birth weight below 2000 g were compared. There were 26 neonates with absent end diastolic frequencies (group 1) and 20 with end diastolic frequencies (group 2) in the fetal aorta. Those in group 1 were more likely to suffer perinatal death (p less than 0.05), necrotising enterocolitis (p less than 0.01), and haemorrhage (p less than 0.05). Only 4 (15%) of the babies in group 1 had an uncomplicated neonatal period compared with 15 (75%) in group 2 (p less than 0.001). The circulatory changes identified in these cases may provide a more sensitive measure of critical fetal compromise than current techniques and thus allow the clinician to deliver the fetus before irreversible tissue damage has occurred.

Adult↗
PubMed2000

Role of alveolar macrophages in innate immunity in neonates: evidence for selective lipopolysaccharide binding protein production by rat neonatal alveolar macrophages.

As the first line of defense against inhaled substances, alveolar macrophages (AM) play a crucial role in maintaining lung homeostasis. This is achieved via phagocytosis of foreign material and the secretion of a wide range of mediator molecules, including those involved in neutrophil recruitment. Neonates are known to manifest increased susceptibility to lung infections, and we hypothesize that this may be due in part to a deficiency in the function of AM. We report here that although recruitment of neutrophils into the respiratory tract of newborn animals in response to Moraxalla catarrhalis exposure is greatly delayed and diminished, AM from newborn animals have greater phagocytic capacity when compared with those from adult animals. Additionally, newborn AM respond normally to lipopolysaccharide (LPS) via production of a variety of chemokines, including macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, monocyte chemotactic protein-1, gro/ cytokine-induced neutrophil chemoattractant, MIP-2, and tumor necrosis factor-alpha. We have also demonstrated an LPS inducible expression of messenger RNA for LPS binding protein (LBP) in neonatal AM that was not observed in AM from adult animals or in peritoneal macrophages. We speculate that local production of LBP by AM may be a significant factor in the neonatal immunologic response to infections, providing a compensatory mechanism for the deficiency in specific neonatal immunity during this period of development when the newborn is being exposed to a range of potentially pathogenic materials for the first time.

Animals↗
PubMed1987

Neonatal intussusception associated with neonatal small left colon syndrome.

A newborn infant with intestinal obstruction resulting from intussusception associated with neonatal small left colon syndrome is described. Differences between neonatal and infantile intussusception are detailed. Chronic loose intussusception in utero is proposed as one cause of the neonatal small left colon syndrome. Consideration should be given to doing a rectal biopsy and a sweat chloride test to differentiate neonatal small left colon syndrome from Hirschsprung's disease and cystic fibrosis, respectively, when the clinical diagnosis is not readily apparent.

Adult↗
PubMed2006

Expression of LGR7 and LGR8 by neonatal porcine uterine tissues and transmission of milk-borne relaxin into the neonatal circulation by suckling.

Estrogen receptor-dependent organizational events between birth [postnatal day (PND) 0] and PND 14 affect development and function of porcine uterine tissues. Observations that uterotrophic effects of relaxin (RLX) in neonatal gilts were inhibited by the antiestrogen ICI 182,780 suggested that a RLX signaling system, capable of cross-talk with the estrogen receptor, evolves during a critical period for uterine programming (PND 0-14). Objectives were to determine 1) effects of age and estrogen exposure from birth on porcine uterine RLX/insulin-like 3 receptor (LGR7/LGR8) expression and 2) whether milk serves as a natural source of RLX in neonatal pigs. Uterine LGR7/LGR8 expression, detected by RT-PCR and in situ hybridization on PND 0, 7, and 14, was predominantly stromal for LGR7, myometrial for LGR8, and increased with age and after treatment with estradiol valerate (50 microg/kg body weight x d) from birth. Stromal expression of LGR7 was also detected immunohistochemically. Milk RLX concentrations declined (P < 0.001) from 17.3 +/- 1.4 ng/ml (lactation d 0) to 1.7 +/- 0.3 ng/ml (lactation d 14). RLX, present in the serum of nursing pigs on PND 0 and 1, was undetectable before nursing and in neonates fed RLX-free milk replacer for 12 h. Thus, a developmentally regulated, estrogen-sensitive LGR7 and LGR8 receptor system is present in the porcine uterus at birth and may be activated by milk-borne RLX delivered into the circulation during the first 48 h of postnatal life. Maternal lactocrine contributions to the neonatal hormonal milieu could affect the developmental programming of uterine and other somatic tissues.

Animals↗
PubMed2002

Longitudinal study of plasma pregnenolone and 17-hydroxypregnenolone in full-term and preterm neonates at birth and during the early neonatal period.

Pregnenolone (Preg) and 17-hydroxypregnenolone (17OH-Preg) are marker steroids that are elevated in the 3beta-hydroxysteroid-dehydrogenase-II deficiency form of congenital adrenal hyperplasia. The aim of this study was to establish normative data for both steroids in healthy preterm (28-33 and 34-37 wk gestation) and full-term infants, because reference values for the early neonatal period do not exist. At delivery, the main source of Preg is the placenta, because the highest levels were found in the retroplacental space (median, 141.31 nmol/liter), with no significant difference between preterm and full-term pregnancies. The fetal adrenals provide most of the circulating 17OH-Preg in full-term neonates, as demonstrated by a marked arteriovenous gradient in cord blood (40.96 nmol/liter vs. 10.77 nmol/liter). 17OH-Preg levels in the umbilical arteries were significantly lower in premature infants than in full-term infants (8.06 nmol/liter vs. 40.96 nmol/liter). During the first 2 postnatal weeks, Preg concentrations showed a rapid and significant fall in early preterm infants [95.78 nmol/liter (0 h) to 36.69 nmol/liter (d 14)] as well as in full-term infants [66.62 nmol/liter (0 h) to 14.81 nmol/liter (d 6)]. In addition, a significant fall in 17OH-Preg levels was found in full-term neonates [40.96 nmol/liter (0 h) to 11.32 nmol/liter (d 6)]. After 12 h, significantly higher levels for Preg and 17OH-Preg were found in early preterm infants (98.01 nmol/liter and 69.13 nmol/liter), compared with full-term neonates (36.29 nmol/liter and 28.55 nmol/liter, P < 0.05), reflecting the increased fetocortical activity as a response to the stress of delivery in the prematures. With these longitudinal data, it is now possible to confirm or exclude the diagnosis of 3beta-hydroxysteroid-dehydrogenase-II deficiency within the first postnatal week.

17-alpha-Hydroxypregnenolone↗
PubMed1991

Preventability of neonatal cold injury and its contribution to neonatal mortality.

When the body temperature of a small neonate falls below 35 degrees C, lassitude can be noted; severe derangements of cardiovascular, renal, hepatic, immunological, and hematological systems may also occur depending in part on the duration and severity of hypothermia. Diagnosis requires a low-reading thermometer, lacking which the diagnosis can be suspected, but most often is missed. Fatal cases of diagnosed cold injury commonly have terminal pneumonia or sepsis. Prevention involves identification and home visits to high-risk infants; intensive care of those with the diagnosis at Soroka Hospital Medical Center has reduced the case-fatality rate from 30% in 1971 to 3% in 1988-1989. During the same period in our region, the proportion of neonatal deaths occurring in winter months of December, January, and February has dropped from 55 to 27%. The expected proportion is 25%. We hypothesize that excess neonatal mortality during winter months, especially due to pneumonia and sepsis or sudden infant death syndrome (SIDS) is an indicator of missed cold injury syndrome. A preliminary evaluation was made form U.S. data by state, provided by the National Center for Health Statistics, which records no fatalities from cold injury during 1986. Contrasted with this are 26 cold injury deaths in Israel for 1977-1980. In the U.S., though, excess winter neonatal deaths in 1986 from SIDS, pneumonia, and sepsis are reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Cold Temperature↗