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Identifying neonatal risk factors and predicting neonatal deaths in Georgia.

A predictive model which identifies 38% of the neonatal deaths by isolating only 11% of the births was formulated. It utilized existing vital records data for 230,585 single live births which occurred in Georgia for the period 1974-1976, to describe factors recorded on the birth certificate which are determinants of neonatal mortality on a statewide basis. Maternal age, race, premature birth, spontaneous abortion or stillbirth, complications related to pregnancy, complications not related to pregnancy, and type of birth (multiple gestation) were found to be statistically significant. It is proposed that private physicians evaluate patients on the basis of this model to facilitate estimates of risk of a neonatal death. In addition, public health physicians could utilize this model to make informed decisions in regard to the management of public health programs directed at the care of pregnant women.

Female↗

Long-term hyperalgesia induced by neonatal beta-endorphin and morphiceptin is blocked by neonatal Tyr-MIF-1.

Male rats were injected s.c. once daily during the first week of life with beta-endorphin (BE), morphiceptin, the antiopiate Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), or one of the two opiate peptides in combination Tyr-MIF-1. Pups treated with neonatal BE removed their tails from a series of increasingly hot water baths significantly faster than controls on day 9, confirming our earlier studies. In addition, we found that Tyr-MIF-1 blocked this effect of BE. At 4.5 months, latency to lick a hindpaw in the hot-plate test was significantly faster in groups given BE alone, morphiceptin alone, or the control vehicle than in any of the 3 groups given Tyr-MIF-1. At 6 months the two groups given opiate peptides alone showed faster tail-flick latencies than the controls and the groups given Tyr-MIF-1. These results indicated that the long-term nociceptive changes induced by the opiate peptides were opposite to those induced by Tyr-MIF-1. Mean tail-flick latencies of the groups on day 9 correlated well with hot-plate and tail-flick scores in adulthood, indicating that the effects of the peptides were persistent. The neonatal peptide treatments did not differentially affect the analgesia induced by the stress of footshock or warm-water swim. Rats given either of the opiate peptides alone tended to fall off a rotorod faster than those in the other groups. These results support the role of Tyr-MIF-1 as an antiopiate and further illustrate the long-term effects of neonatally administered peptides.

Animals↗

Neonatal exposure to a type-I pyrethroid (bioallethrin) induces dose-response changes in brain muscarinic receptors and behaviour in neonatal and adult mice.

This study shows that neonatal exposure to the insecticide bioallethrin has a dose-dependent effect on muscarinic cholinergic receptors (MAChR) in the neonatal mouse, leading to permanent changes in MAChR and in spontaneous behaviour in adult mice. Neonatal NMRI mice, given oral doses of either bioallethrin or the vehicle, once daily between the 10th and 16th postnatal day, were killed at the age of 17 days or 1 week after the spontaneous motor behaviour tests at 4 months. The MAChR were assayed in the cerebral cortex by using the antagonist quinuclidinyl benzilate ([3H]QNB) and the agonist carbachol. In the 17-day-old mice bioallethrin exposure elicited a significant dose-dependent increase in the specific [3H]QNB binding. The competition study showed that the proportion of low-affinity binding was significantly increased in the 17-day-old mice compared with controls. In the adult mouse there was a significant dose-dependent decrease in specific [3H]QNB binding. In these adult mice the behavioural variables 'locomotion' and 'total activity' showed significant (P < or = 0.01) dose-dependent increases at all doses up to and including 0.70 mg/kg b.wt.

Aging↗

Neonatal splenic suppressor cells in the chicken. I. In vivo suppression of the immune response to bovine serum albumin by normal and tolerized neonatal spleen cells.

The presence of active splenic suppressor cells in neonatal chickens, either normal or tolerant to bovine serum albumin (BSA), was examined by assessment of their effect on both primary and adoptively transferred secondary responses to BSA or sheep red blood cells (SRC). Both normal and BSA tolerized spleen cells were shown to be highly suppressive of secondary anti-BSA responses generated by specifically primed adult spleen cells in inert recipients. Suppression of the secondary anti-BSA response by normal spleen cells was slightly less effective than that seen with BSA tolerant spleen cells. Transfer of BSA tolerant spleen cells into normal recipients, followed by BSA challenge, prevented any significant primary anti-BSA response. In contrast, transfer of normal spleen cells into normal recipients, followed by BSA challenge, failed to show any suppression of the resulting primary response. Neither normal nor BSA tolerant neonatal spleen cells were capable of suppressing either primary or secondary responses to SRC. Thus, chickens tolerized to BSA have suppressor cells specific for the tolerizing antigen. We present evidence that both the tolerance associated suppressors and the suppressors detected in normal neonatal chickens are T cells.

Aging↗

Parathyroid hormone and neonatal calcium homeostasis: evidence for secondary hyperparathyroidism in the Asian neonate.

Calcium, 25-hydroxyvitamin D (25 OHD), and parathyroid hormone (PTH) concentrations were measured in 11 Asian and ten Caucasian pregnant women at parturition and in their respective newborns following a full term normal delivery. Maternal calcium and 25 OHD concentrations were significantly lower while PTH concentrations were significantly greater in Asians than those in Caucasians. There was a significant inverse relationship between calcium and PTH and the relationship between 25 OHD and PTH concentrations. Neonatal calcium and 25 OHD concentrations were also significantly lower and PTH concentrations significantly higher in Asians than those in Caucasians. There was a highly significant inverse correlation between neonatal calcium and PTH concentrations. Three of the 11 Asian babies had supranormal concentrations of PTH in their cord blood. We conclude that PTH participates in neonatal calcium homeostasis and Asian newborns have frequent secondary hyperparathyroidism.

Adult↗

Neonatal alcohol exposure alters suckling behavior in neonatal rat pups.

Prenatal alcohol exposure has been associated with a variety of suckling deficits in both humans and animals. In this study, the effect of neonatal alcohol exposure on suckling performance was examined in 15-day-old rat pups. Neonatal alcohol exposure has been used as a model to study the effects of alcohol exposure during a period equivalent to the human third trimester with respect to brain growth. Subjects were Long-Evans rats which had been artificially reared (AR) and fed through gastrostomy tubes from postnatal day (PN) 4-PN 12. The AR groups included two groups given ethanol doses of 6 g/kg/day or 4 g/kg/day and an isocaloric maltose-dextrin control group. A suckled control group raised by their natural mothers was also included to control for artificial rearing. Fifteen-day-old pups were individually placed with an anesthetized dam for a 1-h videotaped test session. Pups in the 6 g/kg alcohol group took longer to attach to the nipple and spent less time suckling than pups from all other treatment groups. Nipple-shifting behavior was disrupted in all artificially reared groups, but it was most severely affected in the 6 g/kg group. These findings suggest that neonatal alcohol exposure interferes with suckling performance and these altered behaviors may contribute to the postnatal growth deficits that have been reported following alcohol exposure in utero.

Animals↗

Passive immunotherapy in neonatal calves--I. Safety and potency of a J5 Escherichia coli hyperimmune plasma in neonatal calves.

A pair of studies designed to assess the clinical safety and potency of hyperimmune plasma administration was undertaken in neonatal calves. Bovine plasma from Holstein heifers hyperimmunized with a mutant Escherichia coli O111:B4 (J5) vaccine which had a geometric mean (GM) immunoglobulin G (IgG) ELISA titer of 3.5 x 10(4), was administered subcutaneously to < or = 2-day-old calves. In the first (study A) of two prospective trials, hyperimmune plasma was administered in two doses to colostrum-deprived (CD) (n = 7) and colostrum-fed (CF) (n = 16) neonatal dairy calves. Data were collected immediately before (0 h) and 6, 24, 48, 72, 96, 120 and 288 h after the first plasma administration. Total serum protein and serum IgG concentration elevated in both groups with a significant (p < 0.01) rise of E. coli J5-specific IgG from the corresponding baseline by 6 h post-plasma administration. In the second (study B) trial, calves (N = 75) allocated into three protocol groups received two doses of either the hyperimmune (TT) J5 plasma (n = 30) or the control (CT) plasma (n = 30), and the third group (NT) received no plasma (n = 15). Data were collected up to 96 h post-plasma administration. Serum IgG and J5 specific ELISA antibody titer increased significantly (p < 0.01) in TT calves compared to the other group calves. The endotoxin contents of the administered plasma were < or = 1 EU ml-1 by limulus amebocyte lysate (LAL) method and the collected physiological and hematological data values were similar in all groups in both trials. In addition, no immediate adverse reaction or death was observed in any phase of the plasma administration. The E. coli J5 hyperimmune bovine plasma, as prepared and administered to neonatal calves in the current trials, proved to be a safe and potent biomedical fluid.

Animals↗

Maternal diabetes and neonatal macrosomia. III. Neonatal body water estimates.

Body water estimates were obtained within 12 h of birth in 52 infants of non-diabetic mothers and 61 infants of diabetic mothers. Neonates were grouped as normally-grown or macrosomic. Total body water and extracellular water were estimated from antipyrine space and corrected bromide space, respectively. Intracellular water was assumed to be the difference between total and extracellular water. Infants of diabetic mothers, whether normally-grown or macrosomic, had markedly less mean total body water than normally-grown neonates of non-diabetic mothers. No effect of neonatal macrosomia or maternal diabetes on extracellular and intracellular water estimates could be detected with the techniques used. It is suggested that changes in total body water occur as a result of excessive fat accretion during fetal life.

Adipose Tissue↗

Prediction of lower developmental performances of healthy neonates by neonatal EEG-sleep measures.

Previous neurophysiologic studies from our laboratory have demonstrated altered EEG-sleep behavior at conceptional term ages in healthy preterm infant compared with a term cohort. Developmental assessments at 12 and 24 months of age of 16 children in each cohort were compared using MANOVA. Differences were detected on MANOVA between each cohort on Bayley mental and motor performance scores, while social skills (Vineland) and temperament (Carey) were similar. Healthy preterm infants had lower scores at 12 months of age (P < .0001) and 24 months (P < .04) than term infants before adjustment for prematurity. No group differences were observed after adjustment. For the combined cohort of 32 healthy neonates, specific neonatal EEG-sleep measures were included as predictor variables in regression analyses with Bayley mental scores as outcome variables. Lower Bayley mental scores at 12 and 24 months were associated with higher spectral EEG correlations, lower spectral EEG energies in the beta frequency ranges, fewer arousals per minute, lower rapid eye movements per minute, and shorter sleep latencies from awake state to active sleep. Significant associations were observed before adjustment for prematurity at both 12 and 24 months, and after adjustment at 12 months of age for lower spectral beta EEG energies. Lower socioeconomic class also correlated with lower developmental scores. Even in the absence of major neonatal illnesses, brain adaptation to prematurity influences later developmental outcome. Adjustment for "age equivalency" may be required up to at least 24 months of age even in a healthy preterm population.

Analysis of Variance↗

[Neonatal lupus: different clinical neonatal expression in siblings].

Neonatal Lupus Syndrome is a rare disease caused by placental passage of maternal autoantibodies. Pathogenesis is partially unknown and many clinical manifestations are possible. We report on newborn siblings who presented with different symptoms of Neonatal Lupus Syndrome. One patient presented with congenital heart block and another with hepatic and haematologic involvement. Cases of Neonatal Lupus among siblings are very rare, because of the high risk of pregnancy in affected women. Various clinical expressions may be explained by a different specificity of Anti-Ro autoantibodies among siblings. The reported cases are commented with regard to recent literature, trying to explain their pathogenesis.

Abortion, Spontaneous↗

Seasonal fluctuations in birth weight and neonatal limb length; does prenatal vitamin D influence neonatal size and shape?

BACKGROUND: Birth weight is known to fluctuate with season of birth, however, there is little information about seasonal variation in neonatal anthropometric measures. AIMS: The aim of this study was to examine seasonal fluctuations in birth weight and selected anthropometric measures. STUDY DESIGN AND SUBJECTS: The birth weight of singletons born after at least 37 weeks gestation was extracted from a perinatal register in south-east Queensland (n=350,171). Mean monthly birth weights for this period were examined. Based on a separate birth cohort, principal component analysis was undertaken on neonatal anthropometric measures (n=1233). Seasonality was assessed by (a) spectral analysis of time series data, (b) monthly and seasonal comparison of outcomes. RESULTS: Based on register data, birth weight displayed clear annual periodicity. Birth weight differed significantly when compared by month and season. Infants born in October were the heaviest (3484 g), while May-born infants were the lightest (3459 g; P=0.001). Based on the cohort anthropometric data, three components were identified related to (a) overall size, (b) limb length, and (c) head size and skin-fold thickness. Each of these components displayed significant seasonal variation. In particular, prominent seasonal fluctuations in limb length were identified, with peak limb length associated with winter/spring birth. CONCLUSION: Environmental factors that have regular seasonal fluctuation influence both the size and shape of neonates. Animal experiments suggest that prenatal hypovitaminosis D may underlie greater limb length. Because birth weight and limb length are associated with a broad range of important health outcomes, the seasonal exposures underlying these effects warrant further scrutiny from a public health perspective.

Birth Weight↗

Greater arousal and less attentiveness to face/voice stimuli by neonates of depressed mothers on the Brazelton Neonatal Behavioral Assessment Scale.

Neonates born to depressed (n=44) versus non-depressed (n=43) mothers were compared on individual items of the Brazelton Neonatal Behavioral Assessment Scale (NBAS). The neonates of depressed mothers received lower scores on orienting to the live face/voice stimulus and on the alertness items, suggesting they were less attentive. They also scored less optimally on the cuddliness and hand-to-mouth activity items, suggesting they were more aroused. These data lend support to the model that infants of depressed mothers are more aroused and less attentive.

Acoustic Stimulation↗

Neonatal vulnerability to ischemia and reperfusion: Cardioplegic arrest causes greater myocardial apoptosis in neonatal lambs than in mature lambs.

OBJECTIVES: Apoptosis is a mechanism for deletion of injured or obsolete cells that is distinct from necrosis and mediated by mitochondrial release of cytochrome c caspase activation. Because myocardial apoptosis is a part of normal fetal and postnatal maturation, we hypothesize that neonatal myocardium is more vulnerable to undergo myocardial apoptosis than mature myocardium after cardioplegic arrest. METHODS: Newborn and mature lambs (n = 5 in each group) underwent cardiopulmonary bypass, antegrade crystalloid hyperkalemic cardioplegic arrest for 60 minutes, and a 6-hour recovery period. Myocardium was examined by using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL), Western blotting, in vitro kinase assays, and fluorometric assays of the activity of caspases 3, 8, and 9. Myocardium from nonoperated control subjects (n = 5 in each age group) was also obtained. RESULTS: More TUNEL-positive nuclei were present in the newborn postcardioplegic myocardium (P =.04). Caspase 3, 8, and 9 activities were 1.6-fold, 1.5-fold, and 1.4-fold greater in the newborn postcardioplegic myocardium (P =.04, P =.01, and P =.01, respectively). The Bax/Bcl-2 ratio was higher in the newborn postcardioplegic myocardium (P =.04). Apoptosis signal-regulating kinase 1 activity and cleaved caspase 3 levels were higher in the newborn postcardioplegic myocardium (P =.02 and P =.009). Mitochondrial release of cytochrome c was greater in the newborn postcardioplegic myocardium (P =.009). CONCLUSIONS: The increased Bax/Bcl-2 ratio in the newborn myocardium suggests a proapoptotic state that is manifested by greater TUNEL staining, cytochrome c release, and cleavage of caspase 3. Increased apoptosis signal-regulating kinase 1 activity suggests greater oxidative stress, immature mechanisms to ameliorate oxidative stress, or both in the neonatal myocardium. Mitochondrial release of cytochrome c suggests that apoptosis-related mitochondrial dysfunction might contribute to early postoperative myocardial dysfunction in the neonate.

Animals↗

Prolactin, estradiol, and thyroid hormones in umbilical cord blood of neonates with and without hyaline membrane disease: a study of 405 neonates from midpregnancy to term.

Concentrations of prolactin (PRL), estradiol (E2), thyroxine (T4), triiodothyronine (T3), and reverse T3 in umbilical cord blood were measured by radioimmunoassay in neonates with (n = 60) and in a control group without (n = 345) hyaline membrane disease. Mean levels of all hormones assayed were not significantly different between the two groups at various stages of gestation. In the control group, gestational age correlated positively with PRL and inversely with reverse T3, whereas birth weight correlated positively with PRL, T4, and T3, but inversely with reverse T3 levels. Thus, larger, more mature neonates tended to have higher cord levels of PRL, T4, T3 and lower concentrations of reverse T3. The data also suggest that, in the premature neonate, various obstetric complications and exposure in utero to beta-mimetic drugs and glucocorticoids may be important determinants of the concentrations of E2 and thyroid hormone in cord blood.

Birth Weight↗

Neonatal ethanol withdrawal: characteristics in clinically normal, nondysmorphic neonates.

Although neonatal withdrawal syndrome is often noted in infants of narcotics addicts, ethanol withdrawal has been reported only among neonates with fetal alcohol syndrome. To examine the possibility that ethanol withdrawal occurs more widely and to identify its characteristics, the behavior of eight neonates born to women who drank a mean of 21 ounces of absolute alcohol per week during gestation was compared with that of two contrast groups: 15 infants whose mothers drank an equivalent amount but stopped in the second trimester, and 29 infants whose mothers never drank. None of the 52 infants had fetal alcohol syndrome, and all were in good health. Neurobehavioral evaluation 3 days postnatally compared the groups for the occurrence of characteristic signs of withdrawal from central nervous system depressants. Whereas there was no difference in the frequency of withdrawal symptoms among infants of mothers who never drank (mean 1.4) or of mothers who stopped drinking (mean 1.8), infants of mothers who continued to drink (mean 4.7) had significantly more tremors, hypertonia, restlessness, excessive mouthing movements, unconsolable crying, and reflex abnormalities. By interfering with state control and interactive behaviors, withdrawal could affect mother-infant bonding as well as the conditions that foster cognitive and social development.

Alcohol Drinking↗

Reappraisal of neonatal clavicular fracture: relationship between infant size and neonatal morbidity.

OBJECTIVE: To examine the extent of neonatal morbidity and its relation with infant size in newborns diagnosed with clavicular fracture after vaginal birth. METHODS: A retrospective case-control study was performed on all the infants diagnosed with clavicular fractures and born vaginally between July 1997 and June 2000. For each index case, a control matched for gestational age (within l week), birth weight (within 100 g), and delivered within the same 24-hour period (8 AM to 8 AM), was selected at random from the delivery suite registry. If a control could not be identified within the period, the search was extended to the previous or the following 24-hour period, and the birth weight criterion relaxed to within 250 g. The overall neonatal outcome was compared between the two groups and the morbidity was further analyzed according to whether the infants were large for gestational age (LGA) or not. RESULTS: Clavicular fracture, found in 1.6% (151 of 9540) of vaginal births, was associated with increased incidence of instrumental delivery (P =.001) and shoulder dystocia (P =.013). The associated morbidity were Erb palsy (P =.007), which was more often found in the LGA infants (P =.055), and cephalhematoma (P =.031), which was only found in the non-LGA infants (odds ratio 4.48, 95% confidence interval 1.23, 16.30). On multivariable analysis, clavicular fracture was excluded as a significant factor in these outcomes after adjusting for the effect of instrumental delivery and shoulder dystocia. CONCLUSION: Neonatal clavicular fracture is of little clinical significance, and it does not reflect quality of care.

Adult↗

Bedside application of the Neonatal Facial Coding System in pain assessment of premature neonates.

Assessment of infant pain is a pressing concern, especially within the context of neonatal intensive care where infants may be exposed to prolonged and repeated pain during lengthy hospitalization. In the present study the feasibility of carrying out the complete Neonatal Facial Coding System (NFCS) in real time at bedside, specifically reliability, construct and concurrent validity, was evaluated in a tertiary level Neonatal Intensive Care Unit (NICU). Heel lance was used as a model of procedural pain, and observed with n = 40 infants at 32 weeks gestational age. Infant sleep/wake state, NFCS facial activity and specific hand movements were coded during baseline, unwrap, swab, heel lance, squeezing and recovery events. Heart rate was recorded continuously and digitally sampled using a custom designed computer system. Repeated measures analysis of variance (ANOVA) showed statistically significant differences across events for facial activity (P < 0.0001) and heart rate (P < 0.0001). Planned comparisons showed facial activity unchanged during baseline, swab and unwrap, then increased significantly during heel lance (P < 0.0001), increased further during squeezing (P < 0.003), then decreased during recovery (P < 0.0001). Systematic shifts in sleep/wake state were apparent. Rise in facial activity was consistent with increased heart rate, except that facial activity more closely paralleled initiation of the invasive event. Thus facial display was more specific to tissue damage compared with heart rate. Inter-observer reliability was high. Construct validity of the NFCS at bedside was demonstrated as invasive procedures were distinguished from tactile. While bedside coding of behavior does not permit raters to be blind to events, mechanical recording of heart rate allowed for an independent source of concurrent validation for bedside application of the NFCS scale.

Facial Expression↗

Parenteral nutrition and immature neonates. Comparative study of neonates weighing under 1000 and 1000-1250 g at birth.

UNLABELLED: We studied the nutritional requirements of 53 neonates with a birth-weight of 1250 g or less and analysed the parenteral and enteral nutrition provided, the weight-gain curves, the incidence of prior pathology and complications. We compared those weighing under 1000 g at birth (n=25) with those weighing 1001-1250 g (n=28). All neonates received central parenteral nutrition at an average age of 42.3 h. The liquid requirements of the lower birth-weight group were significantly greater. No differences were found in the supply of glucose, proteins, lipids and calories until after the first 15 days of life, when the <1000 g group required a greater liquid and caloric intake. Parenteral nutrition was suspended earlier for the >1000 g group (32.6 vs. 48.1 days). Maximum weight loss (12.56%) for the two groups occurred at 5.23 days. No differences in weight gain (g/kg/day) between the groups were observed. The >1000 g group began enteral nutrition significantly earlier and presented greater tolerance. The incidence of complications (bronchopulmonary dysplasia, enterocolitis, nosocomial sepsis, Candidas A sepsis, osteopenia) was greater in the lower birth-weight group, as was that of hyaline membrane disease and mechanically assisted respiration. There were no differences in the incidence of intracraneal haemorrhage, ductus arteriosus, early sepsis, delayed intrauterine growth or hypoglucemia. CONCLUSIONS: The severity of the initial pathology and the greater incidence of complications among the lower birth-weight neonates (<1000 g) influenced both the need for parenteral nutrition and the reduced tolerance to enteral nutrition. Although the rate of weight gain was similar for the two groups, the <1000 g group required a longer period of parenteral nutrition.

Aging↗