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Revalidation of the Score for Neonatal Acute Physiology in the Vermont Oxford Network.

OBJECTIVES: Our specific objectives were (1) to document the performance of the revised Score for Neonatal Acute Physiology and the revised Score for Neonatal Acute Physiology Perinatal Extension in predicting death in the Vermont Oxford Network, compared with published normative values; (2) to determine whether this performance could be improved through recalibration of the weights for individual score items; (3) to determine the impact of including congenital anomalies in the predictive model; and (4) to compare performance against that of the Vermont Oxford Network risk adjustment, separately and in combination. METHODS: Fifty-eight Vermont Oxford Network centers collected data prospectively for the revised Score for Neonatal Acute Physiology in the first 12 hours after admission of infants in 2002. RESULTS: Data were collected for 10,469 infants, and analyses were undertaken for 9897 who met inclusion criteria. The median revised Score for Neonatal Acute Physiology was 5, and the mean birth weight was 1951 g. Recalibration of the revised Score for Neonatal Acute Physiology and revised Score for Neonatal Acute Physiology Perinatal Extension resulted in minimal changes in their discriminatory abilities. The Vermont Oxford Network risk adjustment performed similarly, compared with the revised Score for Neonatal Acute Physiology Perinatal Extension. CONCLUSIONS: Current score performance was similar to that observed previously, which suggests that the revised Score for Neonatal Acute Physiology and revised Score for Neonatal Acute Physiology Perinatal Extension have not decalibrated over the 7 years since the first cohort was assembled, despite advances in neonatal care during that period. Addition of congenital anomalies to the revised Score for Neonatal Acute Physiology Perinatal Extension improved discrimination significantly, particularly for infants with birth weights of >1500 g. The Vermont Oxford Network risk adjustment performed similarly, compared with the revised Score for Neonatal Acute Physiology Perinatal Extension.

Apgar Score↗

Evaluation of gastric pH and guaiac measurements in neonates receiving acid suppression therapy during extracorporeal membrane oxygenation.

STUDY OBJECTIVES: To assess gastric pH measurements, evaluate the frequency of guaiac-positive gastric aspirates, and characterize the appearance of gastric aspirates in neonates receiving acid suppression therapy during extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective, observational study. SETTING: Intensive care unit in a 225-bed tertiary care pediatric referral hospital. SUBJECTS: Thirteen neonates receiving ECMO. MEASUREMENTS AND MAIN RESULTS: Gastric pH measurements, guaiac test results, appearance of gastric aspirates, and ranitidine and antacid dosing were recorded. On ECMO day 1, mean+/-SD gastric pH was 4.3+/-2.8 in the five neonates whose pH was documented. Intravenous ranitidine 2.9+/-0.4 mg/kg/day was started in all neonates by ECMO day 2. Gastric pH was less than 4.0 in seven neonates; these low pH values accounted for only 10% of gastric pH measurements. The frequency of positive guaiac results in neonates with pH measurements below 4.0 was 27% compared with 41% for neonates with a gastric pH of 4.0 or greater (p=0.125). Guaiac tests were positive in 69 (42%) aspirates in 11 neonates. Of the guaiac-positive aspirates that had a corresponding pH measurement, 94% had a pH of 4.0 or greater. Guaiac-positive aspirates had evidence of bile (49%), antacid (17%), and blood (7%) in gastric fluid. In six patients, ranitidine dosages were increased to 3.9+/-0.6 mg/kg/day due to low pH and/or positive guaiac results. In two of these neonates, gastric pH remained below 4.0 in nine of 35 pH measurements despite increased ranitidine dosing. Guaiac results remained positive in all subsequent aspirates in five out of six of these neonates. No neonates developed clinically significant upper gastrointestinal bleeding (UGIB). CONCLUSIONS: Gastric pH is variable in neonates receiving histamine2-receptor antagonist and antacid therapy during ECMO, and gastric pH of 4.0 or greater does not decrease the frequency of guaiac-positive aspirates. Higher gastric pH measurements are confounded by duodenogastric reflux and the presence of blood and/or antacid in gastric fluid. Motility agents in combination with acid suppression therapy for prevention of UGIB may be necessary in this setting based on gastric pH measurements, appearance of gastric aspirates, and guaiac testing.

Antacids↗

Neonatal hypothermia on admission to a special care unit in Dar-es-Salaam, Tanzania: a cause for concern.

OBJECTIVE: To determine the prevalence and risk factors for hypothermia among neonates on admission to the Neonatal Care Unit. Hypothermia in newborn babies is a problem in tropical countries despite warm environmental conditions and it contributes to a high neonatal morbidity and mortality. METHODOLOGY: A study was undertaken to determine the prevalence of hypothermia and its association with early neonatal outcome among neonates admitted to the Neonatal Care Unit of Muhimbili Medical Centre. At admission all neonates were examined and axillary temperature recorded using a low-reading thermometer. Six-hourly temperature was taken in all infants. Those with a temperature below 36.5 degrees C were recruited as cases and those with normal temperature served as controls. These neonates were followed up for early neonatal outcome. RESULTS: Hypothermia on admission was found in 366 out of 1,632 babies (22.4%). In none of these was hypothermia recorded or reported as a reason for admission. Thirteen percent of the hypothermic neonates had severe hypothermia, with body temperature below 32 degrees C on admission. Hypothermia was significantly associated with deliveries from outside hospitals and with those who had operative or instrumental delivery in the same hospital. It was also associated with prematurity, low birth weight babies, time taken to transfer the baby and inadequate clothing after delivery. It was found that hypothermic infants had a three fold higher mortality and morbidity. These infants had a longer stay in the unit and had a higher post natal weight loss. There was no low-reading thermometer in the unit. CONCLUSION: It is concluded that there is cause for concern about hypothermia in the neonates at Muhimbili Medical Centre. Efforts should be made to sensitize and educate all levels of staff dealing with neonates, and low-reading thermometers should be part of the essential kit in the unit.

Chi-Square Distribution↗

Variations in early and intermediate neonatal outcomes for inborn infants admitted to a Canadian NICU and born of hypertensive pregnancies.

OBJECTIVE: To determine whether neonatal intensive care unit (NICU) outcomes vary by centre for inborn neonates of hypertensive pregnancies and, if so, whether that variation might be related to between-centre variations in obstetric practice. METHODS: The study comprised a prospective cohort of 13 505 singleton neonates admitted to 17 Canadian NICUs. Adjusting for potential confounders, we used multivariate regression to analyze the relation between centre of delivery and 6 dependent variables: (1) Apgar score < 7 at 5 minutes; (2) Score of Neonatal Acute Physiology-II (SNAP-II) score > or = 10; (3) neonatal death; (4) neonatal death or morbidity (owing to bronchopulmonary dysplasia [BPD], intraventricular hemorrhage [IVH], necrotizing enterocolitis [NEC], persistent ductus arteriosus [PDA], or periventricular leukomalacia [PVL]); (5) BPD alone; and (6) major neonatal morbidity (that is, at least one of IVH, PVL, NEC, or PDA). NICU practices known to influence these outcomes were included in the modelling for neonatal death and neonatal morbidity. In a sensitivity analysis for practice variation, antenatal steroid exposure was both included and excluded in each regression. RESULTS: For 5 of the 6 dependent variables, we identified between-centre variation that was not explained solely by variation in antenatal corticosteroid use. Adjusted odds ratios varied from 0.11 to 5.6 (the reference centre was the median rate of the adverse outcome). CONCLUSIONS: In the pregnancy hypertension setting, between-centre variations in practice are associated with variations in neonatal physiology and survival. For infants admitted to NICU, the obstetric management of hypertensive pregnancies appears to have an effect on both short- and medium-term neonatal outcomes, even after correction for NICU management.

Adrenal Cortex Hormones↗

[Standards for neonatal intensive care nursing: unit directed management standards].

The neonate has the right to quality nursing care and the Neonatal Intensive nursing care practitioner is professionally-ethically and personally liable for quality nursing care. The process of quality improvement is a structured, planned and purposeful action were standards are set and the nursing care is evaluated after which remedial steps are taken to improve quality nursing care. In this study the focus is on the first step in the quality assurance cycle:the setting of standards. The purpose of the study is to describe and formulate standards for Neonatal Intensive nursing care which can be utilised as an accreditation instrument for institutional selfevaluation to improve quality nursing care. Standards for Neonatal Intensive nursing care were developed and validated by utilising a three-phase research method. In phase one subjects for standards were identified by a panel of experts. The identification was done by means of a critical debate, after which a preliminary conceptual framework was formulated. During the second phase a literature control was done to refine the conceptual framework. It consisted of a conceptual framework pertaining to unitmanagement (article 1) and an conceptual framework pertaining to high incidency, high risk interactions in the Neonatal Intensive Care Unit. The conceptual framework pertaining to the high incidency, high risk interactions in the Neonatal Intensive Care Unit consisted of: assessment of the neonate preparedness for neonatal resuscitation mechanical ventilation humidification during ventilation physiotherapy and suctioning of the ventilated neonate weaning during mechanical ventilation ecstubation During the third phase, the standards were validated by means of a consencus debate. An accreditation instrument was developed for institutional selfevaluation to improve quality nursing care in the Neonatal Intensive Care Unit. The standards that were formulated consisted of standards for unitmanagement (article 1) and standards directed at high incidency, high risk interactions in the Neonatal Intensive Care Unit which is published in the second article in this series.

Accreditation↗

Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications.

CONTEXT: A neonatal behavioral syndrome linked to in utero serotonin reuptake inhibitor (SRI) exposure during the last trimester of pregnancy has been identified. The US Food and Drug Administration (FDA) and drug manufacturers have recently agreed to a class labeling change for SRIs, which include selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), to include information about potential adverse events in neonates exposed in utero. Integration of data about the neonatal behavioral syndrome into the management of pregnancy in women who take SRIs is a current challenge for physicians. OBJECTIVES: To review evidence regarding the SRI-related neonatal syndrome and to help clinicians guide their patients in a risk-benefit decision-making process. DATA SOURCES: We searched MEDLINE (1966-February 2005) and PsycINFO (1974-February 2005). All articles related to neonatal signs after in utero SRI exposure were acquired, as well as unpublished data on this topic from the FDA advisory committee meeting of June 2004. References cited in case reports and studies were reviewed. Foreign-language literature was included and translated to English. STUDY SELECTION AND DATA EXTRACTION: Studies were included if they had clearly identified maternal SRI exposure for a minimum of the final trimester of pregnancy through delivery and assessed neonatal outcomes. We identified 13 case reports describing a total of 18 cases. Nine cohort studies met criteria. When not included in the published article, relative risks and 95% confidence intervals (CIs) were computed from raw data and summary risk ratios and 95% CIs were determined with Mantel-Haenszel estimates. DATA SYNTHESIS: Compared with early gestational SRI exposure or no exposure, late SRI exposure carries an overall risk ratio of 3.0 (95% CI, 2.0-4.4) for a neonatal behavioral syndrome. The most SRI-related neonatal case reports involved fluoxetine and paroxetine exposures. Neonates primarily display central nervous system, motor, respiratory, and gastrointestinal signs that are usually mild and disappear by 2 weeks of age. Medical management has consisted primarily of supportive care in special care nurseries. A severe syndrome that consists of seizures, dehydration, excessive weight loss, hyperpyrexia, or intubation is rare in term infants (1/313 quantifiable cases). There have been no reported neonatal deaths attributable to neonatal SRI exposure. CONCLUSIONS: Available evidence indicates that in utero exposure to SRIs during the last trimester through delivery may result in a self-limited neonatal behavioral syndrome that can be managed with supportive care. The risks and benefits of discontinuing an SRI during pregnancy need to be carefully weighed for each individual patient. Development and validation of assessment methods and clinical management strategies are critical to advancing this research.

Female↗

Neurotoxicity of manganese chloride in neonatal and adult CD rats following subchronic (21-day) high-dose oral exposure.

The purpose of this study was to evaluate the relative sensitivity of neonatal and adult CD rats to manganese-induced neurotoxicity. Identical oral manganese chloride (MnCl(2)) doses (0, 25, or 50 mg kg(-1) body wt. day(-1)) were given to neonatal rats throughout lactation (i.e. from postnatal day (PND) 1 through 21) and to adult male rats for 21 consecutive days. The MnCl(2) doses administered to neonates were ca. 100-fold higher than those resulting from the consumption of an equivalent volume of rat's milk. Rats were assessed using similar behavioral and neurochemical evaluations. Several statistically significant changes occurred in Mn-exposed rats relative to control animals. Neonates given the high dose of MnCl(2) had reduced body weight gain. An increased pulse-elicited acoustic startle response amplitude was observed in neonates from both MnCl(2) treatment groups on PND 21. Increased striatal, hippocampal, hindbrain and cortical Mn concentrations were observed in all Mn-exposed neonates on PND 21. Increased hypothalamic and cerebellar Mn concentrations were also observed on PND 21 in neonates from the high-dose group only. Increased striatal, cerebellar and brain residue Mn concentrations were observed in adult rats from the high-dose group. Increased striatal dopamine and 3,4-dihydroxyphenylacetic acid levels were observed only in PND 21 neonates from the high-dose group. No treatment-related changes were observed in clinical signs, motor activity (assessed in neonates on PND 13, 17, 21 +/- 1 and in adults), passive avoidance (assessed in neonates on PND 20 +/- 1 and in adults) or neuropathology (assessed in PND 21 neonates only). The results of our experiment suggest that neonates may be at greater risk for Mn-induced neurotoxicity when compared to adults receiving similar high oral levels of Mn.

Animals↗

Impaired motility of neonatal PMN leukocytes: relationship to abnormalities of cell orientation and assembly of microtubules in chemotactic gradients.

To allow a further understanding of the pathogenesis of impaired stimulated locomotion by polymorphonuclear leukocytes (PMNs) in human neonates, we studied cellular orientation by neonatal PMNs in response to well-defined chemotactic gradients (Zigmond orientation chambers) and characterized the cytoplasmic microtubule (MT) complex of neonatal PMNs during cell orientation and movement. PMN suspensions obtained from 52 neonates demonstrated a diminished capacity to undergo orientation at all time intervals after exposure to gradients of N-formyl-methionyl-leucyl phenylalanine (f-Met-Leu-Phe) or C5a. Among responding (orienting) neonatal PMNs observed, only 70% (f-Met-Leu-Phe) or 59% (C5a) oriented accurately (toward chemotactic gradients) as compared to values of 96% (f-Met-Leu-Phe) or 92% (C5a) for adult controls. Furthermore, neonatal PMNs failed to alter their direction of orientation/migration when chemotactic gradients were reversed. Similar abnormalities were observed when 10-fold gradients of f-Met-Leu-Phe were employed over a concentration range between 10(-7) and 10(-11) M. Employing tubulin immunofluorescence, the cytoplasmic MT complex of-neonatal PMNs was assessed prior to and after cell exposure to uniform concentrations or gradients of chemotactic factors (CFs). MT assembly by neonatal PMNs studied under these experimental conditions was significantly diminished. Neonatal cell suspensions demonstrated 26 +/- 5 (f-Met-Leu-Phe) or 27 +/- 6 (C5a) MT/cell as compared to respective values of 36 +/- 6 or 35 +/- 5 for adult suspensions (P less than .001). MT lengths of neonatal PMNs increased from 6.7 +/- 1 micron (PBS) to 7.5 +/- 1 micron (f-Met-Leu-Phe) or 7.3 +/- 1 micron (C5a) as compared to values of 6.5 +/- 1 micron (PBS), 11.1 +/- 1 micron (f-Met-Leu-Phe), and 10.9 +/- 1 micron (C5a) for adult PMNs exposed to gradients or uniform concentrations of CFs (P less than .01 for both f-Met-Leu-Phe and C5a). Thus, the polymerized tubulin mass product of chemotactically stimulated neonatal PMNs (202 micron) was significantly (P less than .001) diminished as compared to adult PMNs (360 micron). As shown by a [3H]colchicine binding assay, impaired MT assembly could not be attributed to diminished cytoplasmic tubulin content of neonatal PMNs, which was comparable to adult PMNs.

Chemotaxis, Leukocyte↗

Neonatal morbidity and mortality in Nigeria.

A retrospective analysis of neonatal morbidity and mortality was conducted over a ten-year period (1981-1990) at a tertiary hospital in Ilesa, Nigeria, to determine the trends in neonatal morbidity and mortality in relation to places of delivery. 7,225 babies were admitted into the neonatal unit during the period wherein 3,232 (44.7%) were inborns and 3,993 (55.3%) outborns. Places of delivery of outborn babies were government hospitals/maternity centres (44.1%), home (28.5%), private hospitals/clinics (18.8%), and mission houses (8.7%). Major indications for admission among inborns were neonatal jaundice (45.6%), low birthweight (18.6%), birth asphyxia (14.2%), and neonatal infections (9.3%), while those for outborns were neonatal jaundice (39.5%), low birthweight (23.2%), neonatal infections (18.0%), neonatal tetanus (5.7%), birth asphyxia (4.8%). Overall mortality rate was 13.0%. It was higher in outborns than inborns (p < 0.001). Mortality was lowest in 1983 and peaked in 1987 and 1988. It was higher in outborns than inborns during the period (p < 0.001). Major causes of death were low birth weight (42.8%), neonatal jaundice (14.1%), neonatal tetanus (12.8%), infections (12.4%), and birth asphyxia (11.6%). In almost all cases, case fatality rates were higher among the outborns (p < 0.001). Similarly, mortality was higher in outborns than inborns in almost all the weight range. Among the outborns, mortality was highest in babies delivered at home and private hospitals. Improved access to neonatal medical and antenatal care will significantly reduce neonatal morbidity and mortality in Nigeria.

Cause of Death↗

GM-CSF augments the immunosuppressive capacity of neonatal spleen cells in vitro.

Addition of exogenous granulocyte-macrophage colony stimulating factor (GM-CSF) to cultures of adult murine spleen cells with sheep red blood cells (SRBC) results in an augmented plaque forming cell (PFC) response. The influence of GM-CSF on the ability of neonatal spleen cells to suppress the anti-SRBC plaque forming response of adult spleen cells was tested by adding GM-CSF to cultures of neonatal and adult spleen cells. The suppressive capacity of the neonatal spleen cells was augmented by exogenous GM-CSF. The augmented suppression of the neonatal spleen cells was dependent on a G-10 adherent population since the addition of GM-CSF to cultures containing G-10 passed neonatal spleen cells resulted in an augmented PFC response and not suppression. Neonatal splenic glass adherent cells were also capable of suppressing the response. Neonatal spleen cells or purified neonatal glass adherent spleen cells cultured in the presence of GM-CSF had markedly increased levels of PGE2 in the culture supernatant. Neonatal spleen cells cultured with GM-CSF had increased numbers of morphologically identifiable macrophages after 48 hr of culture. Both irradiation and G-10 passage of the neonatal spleen diminished the numbers of macrophages formed in response to GM-CSF, and both of these manipulations resulted in reversal of suppression in response to GM-CSF. Thus, the augmented suppressive capacity of neonatal spleen cells in response to GM-CSF is probably mediated by its ability to drive monocyte to macrophage differentiation as well as increase the suppressive capacity of the existing neonatal splenic macrophages by increasing their production of PGE2.

Animals↗

Flow behavior of neonatal and adult erythrocytes in narrow capillaries.

This study was designed to analyze the flow behavior of red blood cells (RBCs) in circular vessels with diameters of 3 to 6 microns by means of a mathematical model. According to this model, the RBC flow velocity is 1 mm/sec, RBCs assume axisymmetric shape, and the gap between the RBC and the vessel wall allows sufficient lubrication. The flow resistance depends on the surface area and volume of RBCs, the plasma viscosity, and the vessel diameter. Surface area and volume of RBCs from 10 term neonates and 10 adults were determined by means of a micropipet system and plasma viscosity was measured using a capillary viscometer. Neonatal RBCs had larger volumes (107 +/- 6 fl vs 90 +/- 4 fl) and surface areas (154 +/- 7 microns 2 vs 137 +/- 7 microns 2) than adult RBCs (P less than 0.005). Plasma viscosity was lower in neonates than in adults (1.04 +/- 0.10 cP vs 1.26 +/- 0.13 cP; P less than 0.005). The flow model leads to the following conclusions: During the passage of 3- to 6- microns vessels, the large neonatal RBCs are more elongated than the smaller adult RBCs. In vessels with diameters of less than 3.3 microns, the rear of neonatal RBCs becomes convex, whereas this critical vessel diameter is 3.1 microns for adult RBCs. If the cells are suspended in the same medium, neonatal RBCs require a 31% higher driving pressure than adult RBCs to achieve the necessary elongation for passing through a narrow capillary. However, both cell types require similar driving pressures, if the cells are suspended in the corresponding plasma. The tube/discharge hematocrit ratio of neonatal RBCs is 1 to 6% higher than that of adult cells. Relative viscosity of neonatal RBCs is approximately 7% higher compared with adult RBCs, whereas the blood viscosity (relative viscosity times plasma viscosity) is 12% less in neonates than in adults. We conclude that the large size of neonatal RBCs may cause impaired flow in narrow vessels with diameters below the critical value of 3.3 microns. In vessels with diameters of 3.3-6.0 microns, the disadvantage of the large size of neonatal RBCs appears to be completely compensated for by the lowr plasma viscosity in the neonate.

Adult↗

Analgesia and local anesthesia during invasive procedures in the neonate.

BACKGROUND: Preterm and full-term neonates admitted to the neonatal intensive care unit or elsewhere in the hospital are routinely subjected to invasive procedures that can cause acute pain. Despite published data on the complex behavioral, physiologic, and biochemical responses of these neonates and the detrimental short- and long-term clinical outcomes of exposure to repetitive pain, clinical use of pain-control measures in neonates undergoing invasive procedures remains sporadic and suboptimal. As part of the Newborn Drug Development Initiative, the US Food and Drug Administration and the National Institute of Child Health and Human Development invited a group of international experts to form the Neonatal Pain Control Group to review the therapeutic options for pain management associated with the most commonly performed invasive procedures in neonates and to identify research priorities in this area. OBJECTIVE: The goal of this article was to review and synthesize the published clinical evidence for the management of pain caused by invasive procedures in preterm and full-term neonates. METHODS: Clinical studies examining various therapies for procedural pain in neonates were identified by searches of MEDLINE (1980-2004), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2004), the reference lists of review articles, and personal files. The search terms included specific drug names, infant-newborn, infant-preterm, and pain, using the explode function for each key word. The English-language literature was reviewed, and case reports and small case series were discarded. RESULTS: The most commonly performed invasive procedures in neonates included heel lancing, venipuncture, IV or arterial cannulation, chest tube placement, tracheal intubation or suctioning, lumbar puncture, circumcision, and SC or IM injection. Various drug classes were examined critically, including opioid analgesics, sedative/hypnotic drugs, nonsteroidal anti-inflammatory drugs and acetaminophen, injectable and topical local anesthetics, and sucrose. Research considerations related to each drug category were identified, potential obstacles to the systematic study of these drugs were discussed, and current gaps in knowledge were enumerated to define future research needs. Discussions relating to the optimal design for and ethical constraints on the study of neonatal pain will be published separately. Well-designed clinical trials investigating currently available and new therapies for acute pain in neonates will provide the scientific framework for effective pain management in neonates undergoing invasive procedures.

Analgesia↗

Oxidative stress in neonates: evaluation using specific biomarkers.

Increased oxidative stress has been implicated in pathogenesis of serious diseases in neonates. We measured urinary levels of 8-hydroxy-2'-deoxyguanosine (a marker of oxidative DNA damage), acrolein-lysine adduct (a marker of lipid peroxidation and oxidative protein damage), and nitrite/nitrate (a marker of endogenous nitric oxide formation) in one-month-old neonates to examine the status of oxidative stress and its relationship to the degree of prematurity and clinical condition in neonates. Study subjects comprised three groups: healthy term neonates, clinically stable preterm neonates requiring no supplemental oxygen, and clinically sick preterm neonates requiring supplemental oxygen and ventilator support. Urinary levels of 8-hydroxy-2'-deoxyguanosine and acrolein-lysine adduct were significantly higher in sick preterm neonates than those of stable preterm and healthy term neonates. In the sick preterm group, neonates developing active retinopathy showed significantly higher levels of acrolein-lysine adduct than the other neonates without retinopathy. There were no significant differences in both urinary markers of oxidative stress between stable preterm and healthy term neonates. The urinary nitrite/nitrate levels were not significantly different among the three groups, suggesting no difference in endogenous nitric oxide formation. Collectively, these results provide evidence of augmentation of oxidative damage to DNA, lipids and proteins, especially in clinically sick preterm neonates.

8-Hydroxy-2'-Deoxyguanosine↗

Laryngeal mask airway: is the management of neonates requiring positive pressure ventilation at birth changing?

OBJECTIVE: To evaluate the impact of the laryngeal mask airway (LMA) on neonatal resuscitation policy. DESIGN: We analyzed retrospectively the records of neonates requiring positive pressure ventilation (PPV) at birth before (1996) and after (2000) the introduction of the LMA into our delivery suites. In addition, the outcome of neonates treated with the LMA was compared with that of neonates matched for gestational age and mode of delivery who were resuscitated using a face mask. RESULTS: During the year 2000, 95 out of 380 (25%) resuscitated neonates were treated with the LMA. The LMA was effective in 94 out of 95 (99%) of these infants. Over the same period, the percentage of neonates receiving tracheal intubation (TI) at birth (34%) was significantly reduced compared with the figure for 1996 (67%). There were no reported complications associated with the use of the LMA. Seventy-four out of the 95 neonates treated with the LMA were considered suitable for matching for gestational age and mode of delivery with 74 neonates treated with a face mask. No differences were found between the two groups for birth weight, Apgar scores, need for tracheal intubation, need for admission to the Neonatal Intensive Care Unit (NICU), primary diagnosis at discharge and primary outcomes. The LMA provided effective ventilation in four neonates in whom the face mask failed. CONCLUSIONS: The LMA is changing neonatal resuscitation practice in our Institution. Our data suggest that it is a safe and useful alternative method for respiratory support in neonates requiring PPV at birth, which merits further study.

Birth Weight↗

Maturation of human neonatal CD4+ and CD8+ T lymphocytes into Th1/Th2 effectors.

The increased susceptibility of neonates to infections has been ascribed to the immaturity of their immune system. More particularly, T cell-dependent responses were shown to be biased towards a Th2 phenotype. Our studies on the in vitro maturation of umbilical cord blood T cells suggest that the Th2 bias of neonatal response cannot be simply ascribed to intrinsic properties of neonatal T cells. Phenotypically, neonatal CD4+ T cells are more immature than their adult CD45RO-/RA+ naive counterparts and they contain a subset (10-20%) of CD45RO-/RA+ CD31- cells which is very low in adults and displays some unique functional features. The activation and maturation of neonatal CD4+ T cells is particularly dependent upon the strength of CD28-mediated cosignal which dictates not only the cytokine profile released upon primary activation but also the response to IL-12. Activation of adult as well as neonatal CD4+ T cells in the context of low CD28 costimulation yields to the production of low levels of only one cytokine, i.e. IL-2. In contrast, strong CD28 costimulation supports the production of high levels of type 1 (IL-2, IFN gamma and TNF beta) and low levels of type 2 (IL-4 and IL-13) cytokines by neonatal T cells. The low levels of naive T cell-derived IL-4 are sufficient to support their development into high IL-4/IL-5 producers by an autocrine pathway. The ability of IL-12 to prime neonatal CD4+ T cells for increased production of IL-4 (in addition to IFN gamma) is observed only when CD28 cosignal is minimal. Under optimal activation conditions (i.e. with anti-CD3/B7.1 or allogenic dendritic cells) the response and the maturation of neonatal and adult naive T cells are similar. Thus the Th2 bias of neonatal immune response cannot be simply ascribed to obvious intrinsic T cell defect but rather to particular conditions of Ag presentation at priming. Unlike CD4+ T cells, neonatal CD8+ T cells strictly require exogenous IL-4 to develop into IL-4/IL-5 producers. Most importantly, anti-CD3/B7-activated neonatal CD8 T cells coexpress CD4 as well as CCR5 and CXCR4 and are susceptible to HIV-1 infection in vitro.

Adult↗

Comparison study between induced and spontaneous term and preterm births of small-for-gestational-age neonates.

OBJECTIVE: To compare perinatal and maternal outcome between induced and spontaneous small-for-gestational-age (SGA) neonates at term and preterm deliveries. STUDY DESIGN: A cross-sectional study was designed and two groups were identified at each gestational age: study group - SGA neonates born after induction of labor, comparison group - SGA neonates born after spontaneous onset of labor. SGA was decoded as birth weight below 10th percentile. The population consisted of 367 consecutive SGA singleton preterm neonates (24-36 weeks' gestation) and 3921 term SGA neonates (37-42 weeks' gestation) delivered between 1990 and 1997. Patients with antepartum death and congenital anomalies were excluded from this study. RESULTS: The prevalence of SGA neonates among preterm deliveries was significantly higher than among term deliveries (9.3 versus 6.1%, P<0.001). The rate of induction of labor among preterm SGA deliveries was significantly higher than term SGA deliveries (17.7 versus 13.4%, P=0.002). The rates hypertensive disorders, suspected IUGR, placental abruption, cesarean section, chorioamnionitis and endometritis were significantly higher among preterm SGA than in term SGA. A multiple logistic regression analysis demonstrated that suspected IUGR, severe PIH (but not mild PIH), chronic hypertension and placental abruption were independent risk factors for induction of labor among preterm SGA neonates. In addition to these factors, oligohydramnios was considered to be an independent risk factor only among term SGA. No significant differences were found in the mean birthweight and post-partum death rates between the induced and spontaneous preterm and term SGA. The incidence of Apgar score < 7 at 5 min was significantly lower only among induced term SGA. CONCLUSIONS: Induction of labor in preterm SGA neonates is performed mainly due to maternal severe hypertension disorders. The indications for induction of labor among term SGA include maternal hypertensive disorders (mild or severe) as well as neonatal status, represented mainly by oligohydramnios. In addition, induction of labor in preterm or term SGA neonates does not change neonatal outcome. Moreover, since no evidence of improved neonatal outcome was demonstrated in either indicated group, preterm or term, the question of timing and indications for induction of labor should be discussed.

Adult↗

Neonatal hepatic drug elimination.

After the transition from in utero to newborn life, the neonate becomes solely reliant upon its own drug clearance processes to metabolise xenobiotics. Whilst most studies of neonatal hepatic drug elimination have focussed upon in vitro expression and activities of drug-metabolising enzymes, the rapid physiological changes in the early neonatal period of life also need to be considered. There are dramatic changes in neonatal liver blood flow and hepatic oxygenation due to the loss of the umbilical blood supply, the increasing portal vein blood flow, and the gradual closure of the ductus venosus shunt during the first week of life. These changes which may well affect the capacity of neonatal hepatic drug metabolism. The hepatic expression of cytochromes P450 1A2, 2C, 2D6, 2E1 and 3A4 develop at different rates in the postnatal period, whilst 3A7 expression diminishes. Hepatic glucuronidation in the human neonate is relatively immature at birth, which contrasts with the considerably more mature neonatal hepatic sulfation activity. Limited in vivo studies show that the human neonate can significantly metabolise xenobiotics but clearance is considerably less compared with the older infant and adult. The neonatal population included in pharmacological studies is highly heterogeneous with respect to age, body weight, ductus venosus closure and disease processes, making it difficult to interpret data arising from human neonatal studies. Studies in the perfused foetal and neonatal sheep liver have demonstrated how the oxidative and conjugative hepatic elimination of drugs by the intact organ is significantly increased during the first week of life, highlighting that future studies will need to consider the profound physiological changes that may influence neonatal hepatic drug elimination shortly after birth.

Animals↗

The incidence of morbidities in a cohort of neonates in rural Gadchiroli, India: seasonal and temporal variation and a hypothesis about prevention.

BACKGROUND: The incidence of morbidities among home-cared neonates in rural areas has not been studied. OBJECTIVES: To estimate the incidence of various neonatal morbidities and the associated risk of death in home-cared neonates in rural setting. To estimate the variation in the incidence of neonatal morbidities by season and by day of life. To identify the scope for prevention of morbidities and suggest a hypothesis. STUDY DESIGN: A prospective observational study nested in the first year of the field trial in rural Gadchiroli, India. Trained village health workers in 39 villages observed neonates at the time of birth and in subsequent eight home visits up to 28 days. We diagnosed 20 neonatal morbidities by using clinical definitions. The data were analyzed for the incidence, case fatality, and relative risk of death and for the seasonal and day-wise variation in the incidence of morbidities. RESULTS: We observed total 763 neonates in 1 year. The incidence of morbidities was a mean of 2.2 morbidities per neonate. The case fatality in 13 morbidities was >10%. Only 2.6% neonates were seen or treated by a physician, and 0.4% were hospitalized. Hypothermia, fever, upper respiratory symptoms, umbilical and skin infections, and conjunctivitis showed statistically significant seasonal variation. Although the morbidities were concentrated in the first week of life, new cases continued to appear throughout the neonatal period. Various morbidities showed different distribution of incidence during 1 to 28 days. CONCLUSIONS: A large burden of disease occurs in rural home-cared neonates, and many morbidities are associated with high case fatality. Some morbidities show strong seasonal and day-wise variation in incidence, indicating poor care at home. We hypothesize that changes in practices and better home-based care will prevent the seasonal and temporal increase in morbidities. Some morbidities may not be preventable and will need early detection and treatment. Therefore, frequent home visits by a health worker are necessary to identify sick neonates.

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