Maternal magnesium therapy, neonatal serum magnesium concentration and immediate neonatal outcomes.

OBJECTIVE: The fetus is exposed to magnesium administered to the pregnant mother. However, there is controversy regarding magnesium-related neonatal adverse outcomes, largely driven by a limited understanding of the factors that influence neonatal serum magnesium concentrations and associated outcomes. The objective of this study was to examine the relationship between antenatal maternal magnesium dose and serum concentrations, neonatal serum magnesium concentration and immediate neonatal outcomes. STUDY DESIGN: A retrospective study was conducted at a community-based teaching hospital. Neonatal serum magnesium concentrations within 48 h of birth were used to stratify magnesium-exposed neonates into three groups: group 1: <2.5 mg dl-1, group 2: ⩾2.5 to <4.5 mg dl-1, and group 3:⩾4.5 mg dl-1. Immediate neonatal outcomes were compared between the three groups. Total maternal magnesium dose and serum magnesium concentrations before the delivery were correlated with neonatal serum magnesium concentrations and outcomes. RESULTS: Of the 304 mother-baby dyads between 24 and 34 weeks gestation, 237 received antenatal magnesium. Neonatal serum magnesium concentration was 3.14±0.83 mg dl-1 in exposed and 1.96±0.42 mg dl-1 in unexposed neonates (P<0.001). Compared with group 2, neonates had higher odds of grade 3 or 4 intraventricular hemorrhage in group 1 (adjusted odds ratio (AOR) 5.95 (95% confidence interval (CI) 1.05 to 33.66)) and group 3 (AOR 8.42 (95% CI 1.35 to 52.54)). Group 3 neonates also had increased odds of periventricular leukomalacia (AOR: 5.37 (95% CI 1.02 to 28.28) compared with group 2 neonates. Predictors of neonatal serum magnesium concentrations included maternal magnesium dose (r=0.66, P<0.0001), duration of therapy (r=0.70, P<0.0001) and serum concentration (r=0.72, P<0.001). CONCLUSION: The between-group differences highlight that there is a therapeutic range of neonatal serum magnesium concentrations for neuroprotective effects of antenatal magnesium sulfate, while concentrations outside of this range may be associated with adverse neonatal outcomes. Further studies are needed to determine the optimal dose and duration of maternal magnesium to minimize adverse neonatal outcomes.

Sudden versus gradual pressure wean from Nasal CPAP in preterm infants: a randomized controlled trial.

OBJECTIVE: In preterm infants, nasal continuous positive airway pressure (NCPAP) is widely used for treatment of respiratory distress syndrome. However, the strategies for successfully weaning infants off NCPAP are still not well defined and there remains considerable variation between the methods. The objective of this study is to determine whether gradual weaning of NCPAP pressure is more successful than sudden weaning off NCPAP to room air. STUDY DESIGN: A randomized controlled trial was conducted in a level 3 neonatal intensive care unit on 70 preterm neonates who were born between 26 and 32 weeks gestation and required NCPAP for at least 48 h. When infants were stable on NCPAP at 0.21 FiO2 and 5 cm H2O positive end expiratory pressure, neonates were randomized to the gradual wean group (reduction in pressure by 1 cm every 8 h until 3 cm H20 was reached) or to sudden wean group (one time NCPAP removal to room air). The primary outcome was a success at the first trial to wean to room air. Secondary outcomes were a number of trials, and weight and postmenstrual age (PMA) at the time of successful wean. Total number of days on NCPAP and length of stay (LOS) in the hospital were also compared between the groups. RESULTS: Of the 70 infants included in the study, 35 were randomized to sudden group and 33 infants to gradual group (2 excluded for protocol deviation). In sudden and gradual groups, 14 and 22 infants, respectively, were weaned successfully in the first attempt (P=0.03). The infants were successfully weaned at 32.7±1.7 weeks versus 33.1±2.4 weeks (P=0.39) PMA and at a weight of 1651±290 g versus 1589±398 g (P=0.46) in the sudden and gradual groups, respectively. The total number of days on NCPAP was 27±19 days versus 32±24 days (P=0.38) and LOS was 63±25 days versus 63±22 days (P=0.99) in the sudden and gradual groups, respectively. CONCLUSIONS: Gradual weaning method was more successful as compared to sudden weaning method in the initial trial off NCPAP. There was no difference in the PMA, weight at the time of successful wean, total days on NCPAP and LOS between the two groups.

Limb girdle weakness responding to salbutamol: an Indian family with DOK7 mutation.

BACKGROUND: Congenital Myasthenic Syndromes (CMS) are heterogeneous genetic diseases. CASE CHARACTERISTICS: Two siblings presented with progressive limb girdle weakness without significant fluctuations or ocular muscle weakness. Repetitive nerve stimulation showed a decremental response and there was no response to pyridostigmine therapy. OUTCOME: A trial of salbutamol produced a remarkable, consistent improvement. Mutation in exon 5 of the DOK7 gene was found in both siblings. MESSAGE: Patients with congenital myasthenic syndrome with DOK 7 mutation benefit remarkably with salbutamol.

UGT1A1 gene variants and clinical risk factors modulate hyperbilirubinemia risk in newborns.

OBJECTIVE: To study the contribution of UGT1A1 gene variants and clinical risk factors in modulating hyperbilirubinemia risk in newborns. STUDY DESIGN: Seven UGT1A1 gene variants and clinical risk factors were studied in 113 hyperbilirubinemia cases and 218 control newborns. Hyperbilirubinemia was defined as the total serum bilirubin levels >95th percentile of the American Academy of Pediatrics nomogram. The study population included term (37 to 41 weeks) newborns below 2 weeks of age. RESULT: UGT1A1 gene variants, namely, c.211G>A, g.-3279T>G, TATA box polymorphism and CAT insertion were identified as independent molecular risk factors for neonatal hyperbilirubinemia, whereas c.686C>A, c.1091C>T and c.1456T>G were not detected in study cohort. Among clinical risk factors, excessive weight loss, sepsis and ABO incompatibility emerged as independent risk factors. Co-expression of UGT1A1 variants and clinical risk factors further accentuated the risk of neonatal hyperbilirubinemia. CONCLUSION: Multiple risk factors, whether genetic or clinical, are instrumental in modulating hyperbilirubinemia risk in newborns. Disordered bilirubin conjugation through interactions of UG1TA1 gene variants contributes to the clinical phenotype of neonatal hyperbilirubinemia.

Randomised controlled trial of thiopental for intubation in neonates.

AIMS: To determine the effects of premedication with thiopental on heart rate, blood pressure, and oxygen saturation during semi-elective nasotracheal intubation in neonates. METHODS: A randomised, placebo controlled, non-blinded study design was used to study 30 neonates (mean birthweight 3.27 kg) requiring semi-elective nasotracheal intubation. The babies were randomly allocated to receive either 6 mg/kg of thiopental (study group) or an equivalent volume of physiological saline (control group) one minute before the start of the procedure. Six infants were intubated primarily and 24 were changed from orotracheal to a nasotracheal tube. The electrocardiogram, arterial pressure wave, and transcutaneous oxygen saturation were recorded continuously 10 minutes before, during, and 20 minutes after intubation. Minute by minute measurements of heart rate, heart rate variability, mean blood pressure (MBP) and transcutaneous oxygen saturation (SpO(2)) were computed. The differences for all of these between the baseline measurements and those made during and after intubation were determined. Differences in the measurements made in the study and the control groups were compared using Student's t test. RESULTS: During intubation, heart rate increased to a greater degree (12.0 vs -0.5 beats per minute, p < 0.03) and MBP increased to a lesser degree (-2.9 vs 4.4 mm Hg; p < 0.002) in the infants who were premedicated with thiopental. After intubation only the changes in MBP differed significantly between the two groups (-3.8 vs 4.6 mm Hg; p < 0.001). There were no significant changes in the oxygen saturation between the two groups during or after intubation. The time taken for intubation was significantly shorter in the study group (p < 0.04). CONCLUSIONS: The heart rate and blood pressure of infants who are premedicated with thiopental are maintained nearer to baseline values than those of similar infants who receive no premedication. Whether this lessening of the acute drop in the heart rate and increase in blood pressure typically seen during intubation of unmedicated infants is associated with long term advantages to the infants remains to be determined.

Spontaneous correction of the malpositioned percutaneous central venous line in infants.

Malpositioning of the percutaneously placed central venous line (PCVL) or percutaneously inserted central catheter (PICC) in infants is not a rare occurrence. It has been occasionally observed that these lines spontaneously correct themselves. This prospective study was done to study the incidence of malposition and spontaneous correction. Using a modification of the standard method, 187 catheters were placed with 98.9 % success. Seven of these were initially malpositioned. All seven corrected themselves within a day when left in and used as a peripheral intravenous line. In many centers malpositioned catheters are taken out and replaced, which imposes great stress on the critically ill infant. Our study suggests that to avoid this stress the catheter should be left in place, since spontaneous correction may occur.

Serum and growth factor induction of Na(+)-K(+)-ATPase subunit mRNAs in Clone 9 cells: role of protein kinase C.

In a previous study, we found that addition of serum to confluent Clone 9 cells, a nontransformed rat liver cell line, increased the abundance of mRNA alpha 1 and mRNA beta 1 at 3 h by 2- and 2.7-fold, respectively [Bhutada et al. Am. J. Physiol. 258 (Cell Physiol. 27): C1044-C1050, 1990]. We now report that exposure of these cells to 160 nM 12-O-tetradecanoylphorbol 13-acetate (TPA) for 6 h increases mRNA alpha 1 and mRNA beta 1 by 1.7 +/- 0.2- and 2.1 +/- 0.3-fold, respectively. Incubation in the presence of 160 nM TPA for 24 h reduced high-affinity phorbol dibutyrate-binding sites [dissociation constant (Kd) = 5 nM; maximum binding (Bmax) = 1.2 pmol/mg protein] to undetectable levels. In such cells, exposure to 10% serum for 6 h still resulted in two- and fourfold increment in mRNA alpha 1 and mRNA beta 1 abundances, respectively, while further addition of TPA to these protein kinase C (PKC)-depleted cells resulted in no change in the subunit mRNA abundances. The increments in mRNA alpha 1 content in response to 10% serum and 160 nM TPA at 6 h were additive, whereas the increments in mRNA beta 1 were not. The following agents increased mRNA alpha 1 and mRNA beta 1 abundance in both control and PKC-depleted cells: epidermal growth factor, platelet-derived growth factor, basic fibroblast growth factor, insulin, dexamethasone, and hypothyroid calf serum. In contrast, N6,2'-O-dibutyryl-adenosine 3',5'-cyclic monophosphate and aldosterone had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Dexamethasone markedly induces Na,K-ATPase mRNA beta 1 in a rat liver cell line.

Exposure of Clone 9 cells, a "nontransformed" rat liver cell line, to 10(-8) M dexamethasone resulted at 3 h in 1.8 +/- 0.2- and 40 +/- 5-fold increases in mRNA alpha 1 and mRNA beta 1 content, respectively, an effect that was not mimicked by 10(-8) M aldosterone. The increments in mRNA alpha 1 and mRNA beta 1 abundances in total cell RNA were half-maximal at 5 x 10(-9) M dexamethasone and persisted for more than 24 h. Na,K-ATPase activity, however, increased only slightly (by 9%) at 24 h. The induction of mRNA beta 1 by dexamethasone was not prevented by the presence of cycloheximide. mRNA beta 1 abundance increased earlier in the nuclear RNA pool (becoming apparent within 45 min) than in the cytoplasmic RNA pool, consistent with a precursor-product relationship. Moreover, putative pre-mRNA beta 1 bands of approximately 4,600 and approximately 12,000 nucleotides accumulated in the nRNA pool after 1 h of exposure to dexamethasone. Incubation in the presence of dexamethasone for 3 h enhanced the incorporation of [3H]uridine into total cell mRNA alpha 1 and mRNA beta 1 by 1.3- and 12-fold, respectively. In nuclear run-on assays, however, transcription of mRNA alpha 1 and mRNA beta 1 was not altered after 30 min of exposure to 10(-8) M dexamethasone. The abundance of mRNA beta 1 in rat liver also increased markedly (greater than 30-fold) in rats treated with the hormone for 6 h. We conclude that dexamethasone causes an induction of Na,K-ATPase subunit mRNAs, an effect that is markedly greater for mRNA beta 1 than for mRNA alpha 1. The increases in subunit mRNA content, however, are associated with, at most, a small increase in Na,K-ATPase activity, suggesting that the increments in mRNA abundances, especially that of mRNA beta 1, do not play a determining role in the regulation of Na,K-ATPase activity in these cells.

Induction of Na(+)-K(+)-ATPase subunit mRNAs by cycloheximide in a rat liver cell line.

Exposure of confluent Clone 9 cells to 40 microM cycloheximide (CHX), a concentration sufficient to inhibit leucine incorporation by 95% within 5 min, coordinately increased the abundances of Na(+)-K(+)-ATPase subunit mRNAs, mRNA alpha 1 and mRNA beta 1. The CHX-induced increases in mRNA alpha 1 and mRNA beta 1 abundances were, respectively, 1.8- and 1.9-fold at 40 min and 3.0- and 3.3-fold at 6 h. Augmented subunit mRNA contents were also observed after exposure to other protein synthesis inhibitors including 100 microM anisomycin and 100 microM emetine. Upon removal of CHX, the rate of leucine incorporation returned to control values within 1 h, but mRNA alpha 1 and mRNA beta 1 content decreased only slowly and were still elevated at 24 h at 1.7- and 1.8-fold the respective control values. Despite the persistence of increased levels of the subunit mRNAs and normalization of the rate of leucine incorporation, Na(+)-K(+)-ATPase activity was unchanged at 3, 6, 24, and 48 h after removal of CHX. In cells "depleted" of protein kinase C (PKC) activity after a 24-h preincubation in the presence of 160 nM 12-O-tetradecanoylphorbol-13-acetate (TPA), mRNA alpha 1 and mRNA beta 1 abundances were still inducible by CHX. It is concluded that exposure of Clone 9 cells to CHX and other inhibitors of protein synthesis results in increased abundances of Na(+)-K(+)-ATPase subunit mRNAs independently of PKC activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Induction of Na(+)-K(+)-ATPase and its subunit mRNAs by serum in a rat liver cell line.

Addition of serum to confluent Clone 9 cells increased the protein, RNA, and DNA content per plate of cells; the increments became manifest within 3-6 h and were sustained for the 48-h duration of study. After the addition of serum, Na(+)-K(+)-ATPase activity was stimulated 1.25- and 1.45-fold at 6 and 12 h, respectively. In cells preincubated in the absence of serum for 24 h, addition of serum increased the abundances of Na(+)-K(+)-ATPase subunit mRNAs, mRNA alpha 1 and mRNA beta, coordinately by approximately 2- and 2.7-fold at 3 h, an effect that preceded the stimulation of Na(+)-K(+)-ATPase activity. The serum-induced increments in subunit mRNA abundances were further enhanced by the combined presence of serum and cycloheximide; mRNA alpha 1 and mRNA beta abundances were also augmented by cycloheximide alone (approximately 2.5- and 9.2-fold at 6 h, respectively). In cells incubated in the absence of serum, the half-lives of mRNA alpha 1 and mRNA beta, estimated from decrements in their abundances after the addition of actinomycin D, were 12 and 10 h, respectively. These data demonstrate that serum enhances Na(+)-K(+)-ATPase subunit mRNA abundance and enzyme activity in Clone 9 cells. Comparison of the estimated half-lives of Na(+)-K(+)-ATPase subunit mRNAs with the observed increments in their abundances at 3 h suggests that the serum-induced increases in mRNA alpha 1 and mRNA beta abundances are in large part due to enhanced synthesis of these mRNAs.