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Regulation of growth hormone (GH) secretion by GH-releasing factor, somatostatin, and insulin-like growth factor I in ovine fetal and neonatal pituitary cells in vitro.

Serum GH concentrations in the ovine fetus are much higher than those in the neonate, and the maximal GH response induced by GRF is 5-fold greater in the fetus than in the neonate. To clarify these in vivo observations further, we studied the effects of GRF, somatostatin (SRIF), and insulin-like growth factor I (IGF-I) on primary cultures of fetal and neonatal ovine pituitary cells. GH secretion from fetal ovine pituitary cells increased from 148 +/- 34 to 950 +/- 130 ng/10(5) cells.3 h in response to 1 nM GRF, whereas GH secretion from neonatal pituitary cells rose from 113 +/- 26 to 1221 +/- 129 ng/10(5) cells.3 h, a significantly greater response (P less than 0.001). This greater GRF-induced GH response in neonatal than fetal cells differs from the response in vivo and suggests that the increased in vivo response in the fetus is not due to inherently increased sensitivity of pituitary cells to GRF. SRIF (10 nM) decreased maximal GRF-induced GH secretion by 37 +/- 3% in fetal cells compared with 59 +/- 8% in neonatal cells (P less than 0.01). This may explain in part the decreased in vivo sensitivity to SRIF in the ovine fetus compared to that in the neonatal lamb. In fetal pituitary cells, 10 nM GRF increased ovine (o) GH mRNA from 100 +/- 14% to 145 +/- 40%, SRIF decreased oGH mRNA to 84 +/- 3%, and GRF and SRIF in combination increased fetal oGH mRNA to 126 +/- 24%. Values in neonatal pituitary cell cultures were similar (control, 100 +/- 17%; GRF, 132 +/- 6%, SRIF, 85 +/- 15%; GRF plus SRIF, 105 +/- 26%). Pretreating fetal cells with 100 nM IGF-I for 3 days reduced GRF-stimulated GH secretion from 1049 +/- 38 to 232 +/- 8 ng/10(5) cells.3 h (P less than 0.001). Similarly, IGF-I pretreatment of neonatal cells reduced GRF-stimulated GH secretion from 810 +/- 18 to 419 +/- 16 ng/10(5) cells.3 h (P less than 0.001). The mean secreted IGF-I was 0.58 U/ml (36 nM) in culture medium from neonatal cells and was unchanged by incubation for 3 days with 5 micrograms/ml hGH. Secreted IGF-I in medium from fetal cells was 0.87 U/ml (54 nM) without GH and 0.81 U/ml (51 nM) after incubation with human GH. IGF-I mRNA was present in neonatal pituitary and brain.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Elevated umbilical cord ghrelin concentrations in small for gestational age neonates.

Ghrelin has orexigenic effects. It is present in umbilical cord plasma in full-term neonates, raising the prospect that ghrelin plays a role in fetal and neonatal energy balance. We measured ghrelin in small (SGA), appropriate (AGA), and large (LGA) for gestational age neonates and evaluated whether ghrelin levels are modulated by neonatal insulin and glucose concentrations. Plasma concentrations of ghrelin, insulin, and glucose were measured in cord blood sampled at birth in 123 SGA, AGA, and LGA neonates (gestational age, 24-41 wk) born to mothers with and without diabetes. Ghrelin was detected in samples from all infants. Its concentration was 40% higher in SGA neonates (mean +/- SD, 2436 +/- 657 pg/ml) compared with AGA (1738 +/- 380) and LGA (1723 +/- 269) neonates. There was a positive correlation between ghrelin and gestational age in AGA/LGA (r = 0.23; P < 0.05) and a negative correlation in SGA (r = -0.67; P < 0.005) neonates. Therefore, the difference in ghrelin between SGA and AGA/LGA neonates decreases with advancing gestational age. Birth weight z-score, maternal hypertension, and glucose concentrations were significant determinants of ghrelin concentrations. In conclusion, SGA neonates present with higher umbilical cord ghrelin plasma concentrations than AGA/LGA neonates. Ghrelin may play a physiological role in fetal adaptation to intrauterine malnutrition.

Anthropometry↗

Neonatal antibody titers against varicella-zoster virus in relation to gestational age, birth weight, and maternal titer.

OBJECTIVE: Varicella-zoster virus (VZV) can cause severe disease in premature neonates. The fetus receives protective maternal VZV-immunoglobulin G (IgG) mainly in the third trimester of pregnancy. Therefore, premature neonates are considered at risk for VZV infection. Administration of varicella-zoster immunoglobulin (VZIG) within 96 hours after exposure effectively prevents severe illness in susceptible patients. The objectives of this study were to define the major determinants of the neonatal VZV-IgG titer and to determine the half-life of transplacentally acquired VZV-IgG. Guidelines provided by the Centers for Disease Control and Prevention for the use of VZIG in (premature) neonates were evaluated. METHODS: VZV-IgG titers were measured in sera of 221 neonates and 43 mothers using a quantitative enzyme-linked immunosorbent assay. In 27 neonates, VZV-IgG titers were followed for up to 14 weeks. RESULTS: In a linear regression model, the maternal antibody titer was the major determinant of the neonatal titer (beta = 0.89); gestational age was only of minor importance (beta = 0.18). The median half-life of VZV-IgG in neonates was 25.5 days (range: 14.6-76.0 days). In the first weeks of life, major fluctuations of the VZV-IgG titer occurred in >50% of the neonates. The predictive value of Centers for Disease Control and Prevention guidelines for identification of neonates who should receive VZIG in case of exposure to VZV was poor: positive and negative predictive values were 0.80 and 0.43, respectively. CONCLUSIONS: The neonatal VZV-IgG titer is predominantly predicted by the maternal VZV-IgG titer, whereas birth weight and gestational age are much less predictive than previously reported.

Antibodies, Viral↗

Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less.

OBJECTIVE: Ductus arteriosus (DA) closure occurs within 96 hours in >95% of neonates >1500 g in birth weight (BW). The prevalence and postnatal age of spontaneous ductal closure in neonates < or =1000 g in BW (extremely low birth weight [ELBW] neonates) remain unclear, as does the incidence of failure to close with indomethacin. Therefore, we prospectively examined the prevalence, postnatal age, and clinical variables associated with spontaneous DA closure, occurrence of persistent patent DA, and indomethacin failure in ELBW neonates. METHODS: Neonates delivered at Parkland Memorial Hospital from February 2001 through December 2003 were studied. Those with congenital heart defects or death <10 days postnatally were excluded. Echocardiograms were performed 48 to 72 hours postnatal and every 48 hours until 10 days postnatally. RESULTS: We studied 122 neonates with BW of 794 +/- 118 (SD) g and estimated gestational age (EGA) of 26 +/- 2 weeks. Spontaneous permanent DA closure occurred in 42 (34%) neonates at 4.3 +/- 2 days postnatally, with 100% closure by 8 days. These neonates were more mature, less likely to have received antenatal steroids or have hyaline membrane disease (HMD; 52% vs 79%), and more likely to be growth restricted (31% vs 5%) and delivered of hypertensive women. Using regression analysis, EGA and absence of antenatal steroids and HMD predicted ductal closure. Ten (8%) neonates with early DA closure reopened and required medical/surgical closure. Eighty neonates had persistent patent DA; 7 were surgically ligated, and 5 remained asymptomatic, with 4 of 5 closing after 10 days postnatally. Sixty-eight (85%) received indomethacin at 6.2 +/- 4 days postnatally; 41% failed therapy and had no distinguishing characteristics. CONCLUSIONS: Spontaneous permanent DA closure occurs in >34% of ELBW neonates and is predicted by variables related to maturation, for example, EGA and an absence of HMD, whereas indomethacin failure could not be predicated.

Ductus Arteriosus↗

Neonatal myasthenia gravis and the role of agalactosyl IgG.

Neonatal autoimmune diseases are thought to be due to the transfer of maternal autoantibodies. However, there is a puzzling lack of correlation between maternal autoantibody titres and disease in the neonate. So far, no factor reliably predictive of neonatal disease has been found. Agalactosyl IgG is a variable feature of normal IgG. Preliminary studies indicated that the percentage of agalactosyl IgG is lower in the serum of normal neonates, than in the serum of the mother at delivery. Since raised % agalactosyl IgG is often associated with autoimmune disease we sought to determine whether this relationship holds true in a neonatal autoimmune disease. We measured the % agalactosyl IgG in paired maternal-cord sera from patients with myasthenia gravis, some of whom had offspring with neonatal myasthenia gravis. We found that the percentage of agalactosyl IgG was significantly higher in affected than in unaffected neonates. Moreover % agalactosyl IgG was higher in sera of affected neonates than in serum from their mothers, while unaffected infants of mothers with myasthenia had %Gal(0) lower than their mothers, mimicking the normal situation. This suggests that in affected neonates a high proportion of the IgG is synthesised by the baby itself rather than derived from the mother. This agrees with previous evidence based on the presence of idiotypes not found in the mother which implied that the neonates with neonatal myasthenia gravis produce their own autoantibodies.

Age Factors↗

Maternal autoantibody triggers de novo T cell-mediated neonatal autoimmune disease.

Although human maternal autoantibodies may transfer transient manifestation of autoimmune disease to their progeny, some neonatal autoimmune diseases can progress, leading to the loss of tissue structure and function. In this study we document that murine maternal autoantibody transmitted to progeny can trigger de novo neonatal pathogenic autoreactive T cell response and T cell-mediated organ-specific autoimmune disease. Autoantibody to a zona pellucida 3 (ZP3) epitope was found to induce autoimmune ovarian disease (AOD) and premature ovarian failure in neonatal, but not adult, mice. Neonatal AOD did not occur in T cell-deficient pups, and the ovarian pathology was transferable by CD4(+) T cells from diseased donors. Interestingly, neonatal AOD occurred only in pups exposed to ZP3 autoantibody from neonatal days 1-5, but not from day 7 or day 9. The disease susceptibility neonatal time window was not related to a propensity of neonatal ovaries to autoimmune inflammation, and it was not affected by infusion of functional adult CD4(+)CD25(+) T cells. However, resistance to neonatal AOD in 9-day-old mice was abrogated by CD4(+)CD25(+) T cell depletion. Finally, neonatal AOD was blocked by Ab to IgG-FcR, and interestingly, the disease was not elicited by autoantibody to a second, independent native ZP3 B cell epitope. Therefore, a new mechanism of neonatal autoimmunity is presented in which epitope-specific autoantibody stimulates de novo autoimmune pathogenic CD4(+) T cell response.

Administration, Oral↗

Comparison of urinary iodine excretion in neonates and their mothers in Isfahan, Iran.

OBJECTIVE: To determine the urinary iodine excretion of neonates (28 days of age or younger) and their mothers in Isfahan, a centrally located city in Iran, in 1997 after 8 years of iodized salt distribution in an effort to ameliorate iodine deficiency. METHODS: Through a cross-sectional study and by means of convenient sampling, 146 mother-neonate pairs were selected among neonates born in Shahid Sadoughi Hospital in Isfahan. In order to eliminate the effect of povidone-iodine on breast milk and urinary iodine, Savlon antiseptic solution was used in normal vaginal delivery and on the umbilical cord. Normal values of urinary iodine concentration for the mothers and their neonates were > or = 10.0 microg/dL and >5.0 microg/dL, respectively. The data were analyzed and compared by the Student t test and Pearson correlation coefficient in SPSS software. P values <0.05 were considered statistically significant. RESULTS: In only 3% of the neonates and 14% of the mothers, urinary iodine excretion was below the normal range. No mother or neonate had severe iodine deficiency. In 2% of the mothers and 2% of the neonates, mild iodine deficiency was found. The mean urinary iodine concentration of neonates whose mothers were iodine deficient was significantly lower than that of neonates whose mothers were iodine sufficient (17.34 +/- 7.83 microg/dL versus 22.21 +/- 7.57 microg/dL; P<0.01). A direct significant correlation was noted between the urinary iodine excretion of neonates and that of their mothers (r = 0.37; P<0.01). CONCLUSION: The urinary iodine excretion in mothers paralleled the urinary iodine concentration of their neonates. If urinary iodine concentration is considered an index of total body iodine content, this study demonstrated that prolonged iodized salt intake has minimized the occurrence of iodine deficiency in Isfahan.

Cross-Sectional Studies↗

Determinants of neonatal mortality at Wesley Guild Hospital, Ilesa, Nigeria.

BACKGROUND: More than 10 million under five children die each year of preventable and easily treatable conditions in developing countries. Of these, eight million are infants, half of whom are newborns in their first month of life. A high proportion of babies die in their first month of life, many of them during their first week. The objective of this study is to assess sociodemographic and other determinants of neonatal mortality in Wesley Guild Hospital (WGH), Ilesa, Nigeria. METHODS: This is a record review of 235 neonatal deaths reported at WGH from January 01 2001 to December 31 2003. Similarly, records of equal number of neonates (235) admitted to the same hospital during the same period but who were discharged alive was also reviewed for comparison. Four hundred and seventy records were reviewed. The two groups were matched for age, sex and within a 7-day period of admission. Information was collected with the aid of predesigned schedule from the patients' case notes, death registers and discharge summaries in the Records Department of the hospital. Information collected included the bio-data of the mothers, birth weight of neonates, estimated gestational age at delivery, age at death or discharge, date of admission, duration of the illness and date of discharge. Others included mode and place of delivery, maternal booking status and complications of pregnancy and birth. Data were analyzed using descriptive and inferential statistics by computer software, Epi-Info 2002. RESULTS: Teenage pregnancy, low birth weights (LBW), prematurity and neonatal tetanus were positively associated with neonatal death. Unbooked mothers, deliveries at missions and homes and low socioeconomic status were also positively associated with neonatal death (P < 0.05 in all cases). There was no statistically significant association between the sex of neonate, parity of mother and complications in pregnancy with neonatal death (P > 0.05 in all cases). CONCLUSION: The major determinants of neonatal deaths were teenage pregnancy, prematurity, LBW, poverty and lack of skilled attendance at delivery. Addressing the basic determinants of neonatal mortality will improve newborn survival and health and this will significantly reduce mortality among under five children in developing countries.

Adolescent↗

Multicenter randomized placebo controlled trial of therapy with intravenous immunoglobulin in decreasing mortality due to neonatal sepsis.

OBJECTIVE: To determine whether therapy with intravenous immunoglobulin G (IVIG) would decrease mortality in neonatal sepsis. SETTING: Three tertiary care neonatal intensive care units in the city of Bangalore. METHODS: All neonates admitted to the Neonatal Intensive Care Units with the clinical diagnosis of sepsis and having at least C-reactive protein and one other rapid diagnostic criteria positive were enrolled. Neonates with a birth weight of less than 1000 g and those with any major congenital malformation were excluded. The neonates were randomized to receive 1 g/kg of IVIG on three consecutive days or an equivalent amount of placebo. The rest of the treatment including antibiotics and supportive care was as per the treating physician's decision. The main outcome variable was survival. RESULTS: The trial was carried out over a period of 8 months and recruited 58 neonates. Seven neonates who qualified but did not receive either IVIG or placebo were taken into a separate control group, and one baby who received only one dose of IVIG was excluded from the analysis. Twenty-five neonates were enrolled into the IVIG arm and 25 in the placebo arm. The neonates in the therapy and placebo groups were comparable in terms of birth weight (2144+/-675 g vs. 2072+/-682 g), gestation (37.0+/-3.56 vs. 35.8+/-3.52 weeks), sex distribution, duration of stay, and number requiring ventilation. The placebo group had a significantly higher number of babies with positive blood culture. Seven babies in each group died (p>0.05). There was no significant benefit in using IVIG (OR 1.0; 95% CI 0.25-4.07) (p = 0.74). CONCLUSION: In the sample studied therapy with IVIG did not reduce mortality in neonatal sepsis

Female↗

Platelet and platelet-derived microparticle surface factor V/Va binding in whole blood: differences between neonates and adults.

Platelet-derived microparticles (PDMP) appear to play a major role in the generation of procoagulant activity. In this study, we describe a novel flow cytometric method that allows direct evaluation of the procoagulant activity of PDMP and platelets in the physiological milieu of whole blood. The percent PDMP generated in response to calcium ionophore A23187 and calcium was increased in preterm neonates (67.5+/-3.4%, mean +/- S.E.M., n = 8, p <0.05) and term neonates (67.2+/-2.7%, n = 7, p<0.05) compared with adults (49.5+/-3.4%, n = 13). However, in preterm neonates A23187/calcium-induced binding of factor V/Va to PDMP and platelets (22.8+/-5.6 fluorescence units) was markedly reduced (p <0.05) compared to term neonates (58.2+/-7.2) and adults (50.6+/-6.3). In preterm blood, A23187/calcium-induced binding of factor V/Va to PDMP and platelets returned to adult levels when: a) adult plasma, rather than autologous preterm neonatal plasma, was added; or b) factor V, but not factor VIII, was added to autologous preterm neonatal plasma. In summary: 1) We have developed a flow cytometric method for the direct detection of procoagulant PDMP and platelets in whole blood. 2) Compared to adults and term neonates, PDMP and platelets of preterm neonates bound markedly less factor V/Va (reflecting reduced procoagulant activity), because of a relative lack of factor V in preterm neonates. 3) This procoagulant defect in PDMP and platelets may contribute to the propensity of preterm neonates, but not term neonates, to intraventricular hemorrhage. 4) The percent PDMP does not necessarily reflect the degree of procoagulant activity of PDMP or platelets.

Adult↗

[Effect of natural surfactant on mortality and morbidity in neonates with a birth weight below 1500 grams].

OBJECTIVE OF STUDY: Evaluation of the natural surfactant in treatment of the respiratory distress syndrome (RDS) on the mortality and morbidity of neonates with a birth weight lower than 1500 g. TYPE OF STUDY: Retrospective analysis of data. SETTING: Department:perinatological centre, Institute for Mother and Child, Prague. METHOD: A total of 442 neonates with birth weights under 1500 g were evaluated. During period I/1994-XII/1998 271 neonates were analyzed (Group A). The results of the total neonatal mortality and morbidity were compared with results of care provided to 171 patients during I/1989-XII/1993 before introduction of the surfactant. Surfactant therapy was used in 134 patients of group A (9%) with RDS who met the standard indication criteria. The initial surfactant dose (Alveofact R Boehringer Ingelheim, GFR) depended on the ventilation parameters and was 50 mg/kg and in severe forms of RDS 100 mg/kg. The total cumulative dose did not exceed 200 mg/kg. The data were assembled in a database used in the Institute for the Care of Mother and Child and evaluated using the statistical programme EpiInfo (CDC, USA). RESULTS: In the group of neonates with a birth weight lower than 1000 g 110 neonates in group A were evaluated and 61 in group B. Surfactant was administered to 77 infants of the treated group (70%). Statistically significant differences were recorded: in the total mortality (A: 29 vs. B: 79%, p < 0.0001, the number of neonates who died during UPV (A: 32% vs. B: 80%, p < 0.0001), incidence of PVH-IVH grade I-IV (A: 29% vs. B: 67%, p < 0.0001). In the group of neonates with a birth weight of 1000 to 1499 g 161 children were evaluated in group A and 110 in group B. Alveofact was administered to 57 neonates of the treated group (35%). Statistically significant differences were recorded: in the total mortality (A: 4%, vs. B: 31%, p < 0.0001), the number of neonates who died during UBPV (A: 7% vs. B: 45%, p < 0.0001), incidence of perintraventricular grade I-IV (A: 11% vs. B: 35%, p < 0.0001), incidence of patent ductus arteriosus (A: 6% vs. B: 15%, p < 0.02), incidence of pneumothorax (A: 7% vs. B: 18%, p < 0.01) and in the incidence of posthaemorrhagic hydrocephalus (A: 2% vs. B: 11%, p < 0.01). There was a statistically significant difference in the incidence of BPD to the disadvantage of group A (A: 16% vs. B: 8%, p < 0.01). CONCLUSION: The study confirmed the favourable effect of the introduction of surfactant in the treatment of RDS and on the general mortality and morbidity of neonates with a birth weight below 1500 g.

Czech Republic↗

Shorter PFA-100 closure times in neonates than in adults: role of red cells, white cells, platelets and von Willebrand factor.

UNLABELLED: In neonates, despite poor platelet function in various in vitro tests, closure times (CTs) in PFA-100 measurements are shorter than in adults. Neonates have a higher polymeric von Willebrand factor (vWF). They also have a higher haematocrit and higher white blood cell count than adults. which may interfere with the evaluation of platelet and vWF function by means of the PFA-100 in neonates. To assess the role of different blood constituents on neonatal CTs, red blood cell, platelet and white blood cell counts in cord blood were modified. These modifications did not provide any evidence that the difference in number between adult and neonatal blood cells was responsible for shorter neonatal CTs. In further experiments, platelets and/or vWF were inhibited by means of abciximab and anti-vWF antibody, and mixing experiments with neonatal platelet-rich and platelet-poor plasma were performed. The results showed that short cord blood PFA-100 CTs were caused by a constituent of neonatal platelet-poor plasma, probably the neonatal high multimeric vWF. CONCLUSION: This study demonstrates that CTs in neonates are dependent on the same components, platelets and vWF, as in adults, making it likely that the PFA-100 can be used in neonates in the same way as in adults to investigate platelet and vWF function.

Abciximab↗

Neonatal herpes simplex virus infection presenting with fever alone.

OBJECTIVE: Unlike bacterial infections, herpes simplex virus (HSV) infections are rarely considered as the diagnosis in neonates less than 1 month of age who present with fever alone. We wanted to determine the proportion of neonates with HSV who presented with fever alone and to compare that with the proportion of neonates with bacterial infection who presented with fever alone over the same period of time at our institution. STUDY DESIGN/METHODS: We retrospectively reviewed all neonatal medical records from March 1995 to February 1997 with a discharge diagnosis of HSV infection and all laboratory reports of a positive assay for HSV. We reviewed the medical records of neonates with a discharge diagnosis of bacterial infection over the same period of time. We excluded neonates who were afebrile, whose fever source was evident on physical examination, or who were immunocompromised. RESULTS: Eighteen neonates were diagnosed with an HSV infection over the 2-year period. One presented with fever alone. Twenty-seven of 113 neonates who presented with fever alone had a bacterial infection; 2 of these babies had meningitis. CONCLUSION: The proportion of neonates with HSV infection who presented with fever alone was comparable to that of neonates with bacterial meningitis who presented with fever alone at our institution. Testing and empirically treating for HSV infection might be warranted in febrile neonates with negative bacterial cultures.

Bacteremia↗

Significance of high and normal neonatal nucleated red blood cell count in small-for-gestational-age newborns.

The objective of this study was to evaluate the obstetrical and neonatal outcome in small-for-gestational age (SGA) and appropriate-for-gestational-age (AGA) fetuses with normal and elevated neonatal nucleated red blood cell counts. Therefore the nucleated red blood cell count was assessed immediately after birth in 906 neonates delivered at our institution and the perinatal and neonatal data were compared. Postnatally, infants were classified as SGA if they had a birth weight for given gestational age below the 10th percentile. Neonates were allocated to four groups according to their nucleated red blood cell count: SGA neonates with normal and high nucleated red blood cell count and appropriate-for-gestational-age newborns (AGA) with normal and high nucleated red blood cell count. Statistical analysis included the Mann-Whitney U-Test, Student's t-test, chi2 analysis of variance and stepwise regression analysis. SGA newborns with high nucleated red blood cell count had a significantly lower birth weight, a lower gestational age at delivery, lower arterial and venous pH values, lower Apgar scores at 1 min, 5 min and 10 min as well as lower base excess values compared to the other groups. They had to be transferred significantly more often and stayed longer in the neonatal intensive care unit. Three cases of intraventricular hemorrhage, four cases of necrotizing enterocolotis and two neonatal deaths occurred all in the SGA group with high neonatal nucleated red blood cell counts. Neonatal outcomes of SGA and AGA newborns with normal nucleated red blood cell counts were comparable. Our data do therefore underline the possible value of neonatal nucleated red blood cell counts to differentiate the healthy small-for-gestational age newborn from the truely growth retarded newborn.

Apgar Score↗

Controversies regarding neonatal seizure recognition.

Recognition and classification of neonatal seizures remain problematic, particularly when clinicians rely only on clinical criteria. Physicians should utilize synchronized video-EEG-polygraphic recordings to correlate suspicious behaviors with electrographic seizures, to help limit misdiagnosis and overtreatment of either normal or abnormal nonepileptic behaviors. Since neonatal seizures, particularly status epilepticus, predict an increased risk for later epilepsy and other neurological sequelae, accurate diagnoses are needed for aggressive antiepileptic drug use in the NICU, as well as family counseling and anticipatory medical care after discharge. Neurophysiological documentation of neonatal seizures also must be integrated with an appreciation of pathophysiological mechanisms responsible for brain lesions that cause seizures. Maternal-fetal-placental diseases, as well as genetic vulnerabilities may be responsible for seizures long before diagnosis in the newborn period. Alternatively, the severity of seizures in neonates with perinatal asphyxia or other etiologies may be independently associated with brain injury. Seizures in the newborn are one of the few, neonatal neurological emergencies. While prompt diagnostic and therapeutic plans are necessary, unresolved medical issues continue to challenge the physician's evaluation of the newborn with suspected seizures (table I) [1-3]. Recognition of the seizure state remains the foremost challenge to overcome. Clinical and electroencephalographic manifestations of neonatal seizures vary dramatically from those of older children. This generalization is underscored by the brevity and subtlety of the clinical repertoire of the newborn's neurological examination. Environmental restrictions surrounding the sick infant in an intensive care setting, including confinement within an isolette, intubation and attachment to multiple catheters limit accessibility. Medication alters arousal and muscle tone, which further limit the clinician's ability to consider these clinical neurological signs as surrogate markers of underlying brain disorders. Brain injury from antepartum factors may later be expressed as neonatal seizures, as part of a postnatal, encephalopathic clinical picture which may only be precipitated by stress during the intrapartum and neonatal periods [4]. Alternatively, medical conditions during parturition or after birth may cause seizures, with coincident injury. For medication options to effectively treat seizures, new agents need to be designed for specific etiologies, timing of injury, and the unique cellular/molecular organization of the immature brain. This review addresses the challenges and controversies regarding neonatal seizure recognition in the context of current clinical practices. Experimental models of neonatal seizures elucidate the pathophysiological mechanisms and adverse consequences of seizures on brain development. Since 20% to 50% of children with neonatal seizures experience later epilepsy, diagnostic accuracy is essential [5, 6], particularly for the newborn who suffers a prolonged seizure state.

Brain↗

[Neonatal neurology decision-making starting from systematic reviews of Cochrane Collaboration].

INTRODUCTION: Cochrane Collaboration (CC) provides growing and readily accessible resource to help that decision-making care is based on detailed, critical, and current reviews of the best available evidence. There are many clinical questions for which there is no good evidence on which to base clinical practice. AIM: To analyse the bibliometric characteristics of the systematic reviews (SR) about neonatal neurology published in Neonatal CC. MATERIALS AND METHODS: Bibliometric analysis of The Cochrane Database Systematic Reviews in Neonatal CC, Issue 1, 2004 (n = 169 SR). The dependent variable registered in each SR was subject area of study (mainly neurology subject area) and the rest of variables were considered independent: authors (number and country), dates (late review and update), characteristics of included clinical trials (number and type), characteristics of the newborns included (number and gestational age), reviewer's conclusions and potential conflicts of interest. RESULTS: Neurology was the third most important subject area in Neonatal CC (13 SR), after the subject area of respiratory (73 SR) and gastroenterology-nutrition (26 RS). We identified three selective clusters of secondary investigation in neonatal neurology SR: intraventricular haemorrhage (4 SR), perinatal asphyxia (4 SR) and opiate withdrawal syndrome (2 SR). The number of clinical trials (median 4), patients (median 193), update (46%), sufficient conclusion (54%) and potential conflicts of interest (8 %) in each SR is similar to the rest of SR in Neonatal CC; the only difference we found is less preterm infants (15%) in this SR. All the SR are about interventions for the treatment or prevention of diseases, and we don't found any review about diagnostic tests. CONCLUSIONS: At the moment, the neonatal neurology SR published in Neonatal CC are infrequent and almost half of them the reviewer's conclusions are insufficient for inferring probable effects in clinical practice. Many therapies in neonatal neurology persist without supportive evidence, and some common therapies may actually be harmful, and these are the conclusions found in SR about intraventricular haemorrhage. We detected no SR about important neuropediatric themes in neonatal period: hypoxic-ischemic encephalopathy, periventricular leukomalacia, neonatal seizures, hypotonia, etc.

Bibliometrics↗

[Neonatal mortality in a regional perinatal hospital in Merida, Yucatan, 1995-2004 I. Analysis of the gross, specific rates].

OBJECTIVE: To evaluate the neonatal mortality and the specific neonatal mortality rates by groups of birthweight and gestacional age, at the Ignacio García Téllez National Medical Center which is a reference tertiary perinatal center of the Social Security Mexican Institute for the Yucatan Peninsula, along the period of 1995-2004. MATERIAL AND METHODS: A cohort of 46,297 live newborns was studied with birtweight of 500 grams or more, that were discharged between January 1st 1995 and December 31st 2004. Birthweight, gestational age, length of hospitalization, condition at discharge were captured in a data base. Triennial analysis of mortality was done. RESULTS: The proportion of neonates with birthweight <2,500 g increased and 19% neonates <1,000 g 50%, the increment was 21% for preterm neonates, 46% for immature, and 40% for those extremely immature. The early neonatal mortality rate diminished from 7.0 to 6.9, the late mortality from 3.0 to 2.2, the neonatal from 10.0 to 9.2/1,000 live newborn, the survival increased 232% in neonates with birthweight between 500-749 g, 25% between 750-999 g, 5.8% between 1,000-1,249 g, 8.2% between 1,250-1,499 g. The neonatal mortality decreased 31.8% from the expected, because the adjusted neonatal mortality rate was 13.5 compared with the observed 9.2/1,000 live newborn. CONCLUSIONS: There was a significant increase of the survival with lesser birthweight and gestational age, although it was not reflected in the brut neonatal mortality rate because there was an increase of the risk population.

Birth Weight↗

[Pharmacokinetic and clinical studies of cefotiam in mature neonates].

Pharmacokinetic and clinical studies on cefotiam (CTM) in mature neonates were carried out. The results were summarized as follows: The serum peak level of CTM after intravenous bolus injection at a single dose of 10 mg/kg was found at 15 minutes after the injection. The serum peak level was 32.9 micrograms/ml in a 1 day-old neonate and it was 17.7 micrograms/ml in a 4 day-old neonate. Serum levels at 6 hours after injection were 4.5 micrograms/ml and 0.7 microgram/ml for the 1 day-old and the 4 day-old, respectively. Half-lives were 2.1 and 1.2 hours in the 1 and 4 day-old neonates, respectively. Serum peak levels of CTM at 15 minutes after intravenous bolus injection at a single dose of 20 mg/kg were 40.9 micrograms/ml in a 1 day-old neonate and 36.5 micrograms/ml in a 5 day-old neonate. Serum levels of CTM at 6 hours were 8.0 micrograms/ml in the 1 day-old neonate and 2.3 micrograms/ml in the 5 day-old neonate. Half-lives were 2.5 and 1.5 hours in the 1 and 5 day-old neonates, respectively. With each dosage, the younger showed extended half-lives. A dose-response relationship was observed. In 2 cases of 2 day-old neonates given CTM 20 mg/kg by 30-minute intravenous drip infusion, the mean peak concentration at the termination of the infusion was 25.1 micrograms/ml. Even after 6 hours the concentration was found at 8.7 micrograms/ml. Half-lives were 2.9 and 3.7 hours. Urinary excretion rates of CTM in 1 to 5 day-old neonates were as low as about 20% in any of cases subjected to a 10 mg/kg intravenous bolus injection, a 20 mg/kg intravenous bolus injection a 20 mg/kg 30-minute intravenous drip infusion. It was possible to evaluate the efficacy of CTM in only 1 case of pneumonia. CTM was clinically and bacteriologically effective in this case. No abnormal clinical symptoms and findings were observed in all of the 5 cases.

Cefotaxime↗