Severe hemolysis with normal blood count in a glucose-6-phosphate dehydrogenase deficient neonate.

A premature glucose-6-phosphate dehydrogenase (G-6-PD) deficient neonate was readmitted for exponential rise in the plasma bilirubin concentration to 33.0 mg dl(-1). Blood carboxyhemoglobin (2.8% of total hemoglobin, >threefold normal value) confirmed the presence of hemolysis; however, hematological indices were unchanged from the birth hospitalization. Serum unbound bilirubin, although present, was probably at a concentration insufficient to cause bilirubin encephalopathy. In G-6-PD deficient neonates, severe hemolysis may occur in the absence of hematological changes typical of a hemolytic process.

Procalcitonin in preterm infants during the first few days of life: introducing an age related nomogram.

OBJECTIVE: To determine normal concentrations of procalcitonin in preterm infants shortly after birth and to assess its accuracy in detecting bacterial infection. METHODS: Blood samples of 100 preterm infants were prospectively drawn during the first 4 days of life for determination of procalcitonin concentration. Infants were classified into four groups according to their sepsis status. RESULTS: Mean (SD) gestational age and birth weight were 32 (2.9) weeks and 1682 (500) g respectively. A total of 283 procalcitonin concentrations from healthy infants were plotted to construct nomograms of physiologically raised procalcitonin concentration after birth, stratified by two groups to 24-30 and 31-36 weeks gestation. The peak 95th centile procalcitonin concentration was plotted at 28 hours of age; values return to normal after 4 days of life. Only 12 infants were infected, and 13 of their 16 procalcitonin concentrations after birth were higher than the 95th centile, whereas samples taken at birth were lower. In a multivariable analysis, gestational age, premature rupture of membrane, and sepsis status influenced procalcitonin concentration independently, but maternal infection status did not. CONCLUSIONS: The suggested neonatal nomograms of preterm infants are different from those of term infants. Procalcitonin concentrations exceeding the 95th centile may be helpful in detecting congenital infection, but not at birth.

Neonatal bilirubin production-conjugation imbalance: effect of glucose-6-phosphate dehydrogenase deficiency and borderline prematurity.

OBJECTIVE: To evaluate relations between production and conjugation of bilirubin in the pathophysiology of jaundice in glucose-6-phosophate dehydrogenase (G6PD) deficient neonates. METHODS: Term and borderline premature (35-37 weeks gestational age), healthy, male, G6PD deficient neonates were studied close to the beginning of the 3rd day. Blood carboxyhaemogobin corrected for inspired CO (COHbc; an index of bilirubin production) and serum total conjugated bilirubin (TCB; a reflection of bilirubin conjugation) were measured in simultaneously drawn blood samples by gas chromatography and reverse phase high performance liquid chromatography respectively. A bilirubin production-conjugation index comprising COHbc/TCB was determined; a high index reflects imbalance between the bilirubin production and conjugation processes. COHbc and TCB individually and the production-conjugation index were studied in relation to serum total bilirubin (STB) concentration. RESULTS: Fifty one G6PD deficient neonates were sampled at 51 (8) hours. COHbc values did not correlate with STB (r=0.22, p=0.15). TCB did correlate inversely with STB (r=-0.42, p=0.004), and there was a positive correlation between the production-conjugation index and STB (r=0.45, p=0.002). The production-conjugation index (median (interquartile range)) was higher in the premature (n=8) than term neonates (2.31 (2.12-3.08) v 1.05 (0.53-1.81), p=0.003). This difference was the result of changes in TCB. CONCLUSIONS: The data show that jaundice in G6PD deficient neonates is the result of an imbalance between production and conjugation of bilirubin with a tendency for inefficient bilirubin conjugation over increased haemolysis in its pathogenesis. Borderline premature infants are at special risk of bilirubin production-conjugation imbalance.

Parental education and the WHO neonatal G-6-PD screening program: a quarter century later.

Neonatal screening for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in any population with a male frequency >3-5%, combined with parental education regarding the dietary, environmental and sepsis-related triggers for hemolysis was recommended by the WHO (World Health Organization) Working Group in 1989. As the aim of identifying G-6-PD deficiency in the newborn period is to avert or detect extreme hyperbilirubinemia developing at home, before the development of kernicterus, the parental role in identifying evolving icterus was considered integral to any screening program. Now, a quarter century after publication of this report, severe bilirubin neurotoxicity associated with G-6-PD deficiency continues to be encountered worldwide. Screening programs have not been universally introduced but several national or regional maternal child health programs have implemented neonatal G-6-PD screening. Some reports detail the role of parental education, based on the above mentioned principles, through a variety of audio-visual materials. The paucity of randomized controlled trials or validated evidence to demonstrate the effectiveness of the contribution of parental education fails to meet the ideal testable evidence-based approach. However, our review of the cumulative experience and evidence currently available does supply certain information reflecting a positive impact of screening programs combined with parental input. We propose that the current information is sufficient to continue to support and apply the Working Group's recommendations. In order not to waste unnecessary time available, data may be used in lieu of randomized trials to continue to recommend screening programs, as suggested, in high-risk regions. If the incidence of kernicterus associated with G-6-PD deficiency is to be diminished, G-6-PD screening in combination with parental explanation may be one instance in which the consensus approach suggested by the WHO Working Group, rather than reliance on (nonexistent) evidence-based studies, should continue to be practiced.

Predischarge bilirubin screening in glucose-6-phosphate dehydrogenase-deficient neonates.

OBJECTIVE: To assess the validity of predischarge serum bilirubin values in determining or predicting hyperbilirubinemia in glucose-6-phosphate dehydrogenase (G-6-PD)-deficient neonates, and to facilitate appropriate discharge planning. METHODS: Serum total bilirubin values were determined between 44 and 72 hours of life in a cohort of term, healthy neonates at high-risk for G-6-PD deficiency but with no other risk factors for hyperbilirubinemia. Percentile-based bilirubin nomograms were constructed for G-6-PD-deficient infants and normal infants according to age at sampling. The incidence of hyperbilirubinemia (serum bilirubin value > or =256 micromol/L [15 mg/dL]) for each group was determined according to the percentiles for that group. RESULTS: In both G-6-PD-deficient neonates (n = 108) and control neonates (n = 215) with serum bilirubin values <50th percentile for age, the incidence of hyperbilirubinemia was low in the G-6-PD-deficient neonates, with no measurable incidence in the controls. The incidence of hyperbilirubinemia became clinically consequential, and significantly higher in the G-6-PD-deficient groups, when the percentiles were > or =50: for those in the 50% to 74% range the incidence was moderate (23%) for the G-6-PD-deficient and small (7%) for the control infants (relative risk, 3.29; 95% confidence interval, 1.01-10.67). Among those infants > or =75th percentile, 82% of the G-6-PD-deficient infants, compared with 25% of the control infants, were either already hyperbilirubinemic at the time of screening or subsequently developed hyperbilirubinemia (relative risk, 3.23; 95% confidence interval, 1.99-5.24). CONCLUSIONS: Timed, predischarge serum bilirubin screening can be used to identify G-6-PD-deficient neonates at low, intermediate, or high-risk of developing severe neonatal hyperbilirubinemia, and thus offer a selective approach to the discharge and follow-up surveillance of these infants.

Comparative measurements of phototherapy: a practical guide.

Increasing the dose of administered phototherapy has been shown to increase the rate of bilirubin decrement up to a saturation point beyond which no further increases in bilirubin degradation are observed. This study provides irradiance measurements which can be used to interpret phototherapy dose-response and saturation data clinically and to determine an optimal phototherapy lamp combination for maximal bilirubin degradation.

Continuous versus multiple rapid infusions of indomethacin: effects on cerebral blood flow velocity.

OBJECTIVE: Therapeutic administration of indomethacin for patent ductus arteriosus (PDA) closure has been documented to decrease cerebral blood flow velocity which may be harmful to the vulnerable premature neonate. We have therefore compared the effects of administering indomethacin by rapid injection versus slow, continuous indomethacin infusion at the same total therapeutic dose on middle cerebral artery (MCA) systolic and diastolic flow velocity, resistance index, and cerebral blood flow (as reflected by the integrated area under the curve). METHODS: Premature neonates (< 1750 g) documented echocardiographically to have a PDA were randomized to receive indomethacin either by three rapid injection doses or by continuous intravenous infusion over the ensuing 36 hours, providing an equivalent total dose. Echocardiograms and transcranial color flow mapping of the MCA flow velocity were measured at baseline and serially following initiation of therapy in both groups. Effects on cerebral blood flow velocity are presented. RESULTS: Eighteen infants [rapid injection-1.2 +/- 0.3 kg (n = 9) and continuous-1.1 +/- 0.2 kg (n = 9)] were studied. In the rapid injection treated infants decreased flow velocity in the MCA as manifested by abrupt, significant decreases in systolic (to 70 +/- 8% baseline) and diastolic (to 65 +/- 13% baseline) flow velocity and area under the curve (to 60 +/- 10% of baseline) were evident by 4 minutes and progressed to 30 minutes after treatment initiation. These changes were not observed in the group treated with continuous indomethacin. Both therapeutic modalities were equally successful in closing the ductus, although the numbers are too small to definitively determine therapeutic efficacy. CONCLUSIONS: Slow, continuous infusion eliminated the decrease in cerebral flow velocity and appears to be effective in closing the PDA.

Neonatal hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient heterozygotes.

OBJECTIVES: We assessed the incidence of hyperbilirubinemia, defined as serum total bilirubin >/=15 mg/dL (256 micromol/L), in a cohort of Sephardic Jewish female neonates at risk for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency with especial emphasis on the heterozygotes. We studied the roles of hemolysis by blood carboxyhemoglobin (COHb) determinations and of the variant promoter of the gene for the bilirubin-conjugating enzyme uridine 5'-diphosphate glucuronosyltransferase 1 (UGT1A1) seen in Gilbert's syndrome in the pathogenesis of the hyperbilirubinemia. METHODS: Consecutively born, healthy, term, female neonates were screened for G-6-PD deficiency and observed clinically with serum bilirubin evaluations as indicated for hyperbilirubinemia. On day 3, blood was sampled for COHb, total hemoglobin (tHb), and a mandatory serum bilirubin determination. COHb, determined by gas chromatography, was expressed as percentage of tHb and corrected for inspired carbon monoxide (COHbc). DNA was analyzed for the G-6-PD Mediterranean563T mutation and for the variant UGT1A1 gene. RESULTS: The cohort included 54 G-6-PD-deficient heterozygotes, 19 deficient homozygotes, and 112 normal homozygotes. More heterozygotes (12/54, 22%; relative risk: 2.26; 95% CI: 1.07-4.80) and deficient homozygotes (5/19, 26.3%; relative risk: 2.68; 95% CI: 1.05-6.90) developed hyperbilirubinemia, than did normal homozygotes (11/112, 9.8%). Third-day serum bilirubin values that were obtained from 144 neonates were significantly higher in both heterozygotes (11.2 +/- 3. 7 mg/dL [192 +/- 64 micromol/L]) and G-6-PD-deficient homozygotes (12.0 +/- 3.0 mg/dL [206 +/- 52 micromol/L]) than in the G-6-PD normal homozygotes (9.4 +/- 3.4 mg/dL [160 +/- 58 micromol/L). In contrast, COHbc values were higher only in G-6-PD-deficient homozygotes (0.74% +/- 0.14%) and not in heterozygotes (0.69% +/- 0. 19%, not statistically significant), compared with control values (0. 63% +/- 0.19%). High COHbc values were not a prerequisite for the development of hyperbilirubinemia in any of the G-6-PD genotypes. A greater incidence of hyperbilirubinemia was found among the G-6-PD-deficient heterozygotes, who also had the variant UGT1A1 gene, in both heterozygous (6/20, 30%) and homozygous (4/8, 50%) forms, than was found in their counterparts with the normal UGT1A1 gene (2/26, 7.7%). This effect was not seen in the G-6-PD normal homozygote group. A color reduction screening test for G-6-PD deficiency identified only 20.4% (11/54) of the heterozygotes. CONCLUSIONS: We showed that G-6-PD-deficient heterozygotes, categorically defined by DNA analysis, are at increased risk for neonatal hyperbilirubinemia. The screening test that was used was unable to detect most heterozygotes. Increased bilirubin production was not crucial to the development of hyperbilirubinemia, but presence of the variant UGT1A1 gene did confer increased risk.

Antenatal presentation of carnitine palmitoyltransferase II deficiency.

Carnitine palmitoyl transferase (CPT) II deficiency is usually manifested around puberty by exercise induced myoglobinuria. Two Ashkenazi Jewish sibs with the rare antenatal form of CPTII deficiency are reported. On the 5th gestational month periventricular calcifications and markedly enlarged kidneys were found in both of them. The activity of CPTII in lymphocytes was undetectable and both sibs were homozygous for the 1237delAG mutation. Because of the serious consequences of homozygosity for this mutation, genotype determination of all Ashkenazi patients with the adolescent form of CPTII deficiency is warranted.

Plasma thromboxane and pulmonary artery pressure in neonates treated with extracorporeal membrane oxygenation.

To examine whether neonates with persistent pulmonary hypertension are subject to a thromboxane-mediated exacerbation of their pulmonary hypertension during extracorporeal membrane oxygenator therapy (a form of partial cardiopulmonary bypass), we performed serial measurements of plasma thromboxane B2 and pulmonary artery pressure before, during, and after extracorporeal membrane oxygenation. Pulmonary artery pressure was high before extracorporeal membrane oxygenation, did not increase after the start of this therapy, but began to decrease after 48 hours of extracorporeal membrane oxygenation. During the course of extracorporeal membrane oxygenation, mean pulmonary artery pressure decreased by 50% and mean plasma thromboxane B2 levels decreased by 70%. In addition, serial plasma thromboxane B2 levels were significantly correlated with pulmonary artery pressures in individual infants with a primary diagnosis of meconium aspiration (r = 0.965 to 0.723). We speculate that the decrease in pulmonary artery pressure and plasma thromboxane B2 levels over time may reflect resolution of acute lung injury and that thromboxane B2 may play a role in regulating pulmonary artery pressure in infants with meconium aspiration.

Plasma prostanoids in neonatal extracorporeal membrane oxygenation. Influence of meconium aspiration.

Thromboxane B2 may be a mediator of neonatal persistent pulmonary hypertension. Elevated levels of plasma thromboxane and prostacyclin have been described previously in hypoxic newborn infants with neonatal pulmonary hypertension. We measured serial plasma levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha (stable metabolite of prostacyclin) in 21 newborn infants with severe respiratory failure and pulmonary hypertension who required extracorporeal membrane oxygenation support. We sought to study (1) the evolution of plasma prostanoids in pulmonary hypertensive infants treated with extracorporeal membrane oxygenation and (2) whether different pulmonary hypertensive diagnostic subgroups have distinctive prostanoid profiles. Our data indicated that infants with meconium aspiration had significantly lower levels of plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha while receiving extracorporeal membrane oxygenation than did infants with persistent pulmonary hypertension but no meconium aspiration. Levels of all infants decreased progressively as extracorporeal membrane oxygenation support continued.

Plasma prostanoids in neonates with pulmonary hypertension treated with conventional therapy and with extracorporeal membrane oxygenation.

Thromboxane may be a mediator of pulmonary hypertension in the neonate. Acute thromboxane-mediated pulmonary hypertension has been described in sheep receiving extracorporeal membrane oxygenation, which raises concerns about a potential thromboxane-mediated exacerbation of pulmonary hypertension in human neonates with severe pulmonary hypertension who are treated with extracorporeal membrane oxygenation. We measured plasma levels of thromboxane, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha in infants with pulmonary hypertension, some of whom were treated medically and some of whom were treated with extracorporeal membrane oxygenation. Plasma levels of all three prostanoids were elevated in infants with pulmonary hypertension and decreased with time, whether the neonates were treated with extracorporeal membrane oxygenation or with medical management alone. In infants treated with extracorporeal membrane oxygenation, we collected samples simultaneously from preoxygenator sites, postoxygenator sites, and umbilical artery catheter. We could demonstrate no significant difference in plasma prostanoid levels across the oxygenator. In two patients, plasma thromboxane and prostaglandin F2 alpha levels measured shortly after a platelet transfusion were distinctly higher in the umbilical artery catheter than in venous samples.

Comparative tolerability of pharmacological treatments for patent ductus arteriosus.

The ductus arteriosus is a vascular channel which, although vital to the fetal circulation, rapidly becomes unnecessary and even deleterious after birth. As such, it is 'preprogrammed' to constrict within the first few hours of life. In infants born prematurely this natural closure is often delayed and/or ineffective. In this review, we summarise the current knowledge of the delicately orchestrated control of normal ductal closure, with emphasis on the role of various biochemical mediators. The major focus of this review, however, is on pharmacological approaches designed to prevent and/or treat the persistently patent ductus arteriosus (PDA) which often fails to constrict spontaneously in the premature infant. The standard treatment regimen is based on the administration of 3 doses of the nonselective cyclo-oxygenase inhibitor, indomethacin. We begin by examining, from the vantage point of the ductus, the use of this indomethacin as a tocolytic. It seems that antenatal administration of indomethacin can cause transient, reversible ductus constriction which renders the post-treatment ductus resistant to subsequent closure, both natural and therapeutic. We then review some of the pros and cons associated with the prophylactic administration of indomethacin. Although prophylactic indomethacin is aimed primarily at preventing intraventricular haemorrhages in premature neonates, it does tend to reduce the risk of PDA as well. We then describe some novel therapeutic approaches to effect ductal closure with indomethacin, including the use of continuous infusions to minimise toxic vasoconstrictive phenomena and the use of prolonged maintenance dose to prevent PDA recurrences. Finally we discuss some of the newer agents described more recently which play a role in closing the persistently patent ductus over the next decade. Most prominent of these is ibuprofen which some studies have shown to have less undesirable vasoconstrictive adverse effects. Studies which compare the use of ibuprofen to indomethacin are summarised.

Prostanoid inhibition and group B hemolytic streptococci (GBS) induced neutropenia in newborn piglets.

GBS (Group B Hemolytic Streptococci) cause pulmonary hypertension with associated neutropenia. We investigated whether there is a correlation between the neutropenia of sepsis and GBS-induced pulmonary vasoconstriction, through study of the effects of inhibiting pulmonary vasoconstriction on the neutropenia of GBS in newborn piglets. Fifteen piglets were infused with GBS. After one hour, animals were given either a thromboxane inhibitor (DAZ), a combined cyclooxygenase/lipoxygenase inhibitor, BW755C, or placebo. With GBS infusion, WBC and PMN counts dropped steadily, from similar baselines, to 2250 +/- 570, 3300 +/- 500 and 5400 +/- 1100 cells/mm3 respectively (p less than 0.05; DAZ and BW vs. placebo). PMN's dropped similarly to 710 +/- 320, 2390 + 1240 and 3130 +/- 1050 cells/mm3 respectively (p less than 0.05; DAZ vs. BW and placebo). The drop in WBC's predominantly resulted from proportional decreases in PMN's (DAZ: r = 0.98; BW: r = 0.88; placebo r = 0.93). Compared to GBS alone, DAZ reduced pulmonary vasoconstriction, but exacerbated the granulocytopenia. BW755C similarly reduced pulmonary hypertension: however, it ameliorated the exacerbation of GBS induced neutropenia described above. These data imply that there is no direct correlation between GBS induced granulocytopenia and pulmonary hypertension.

Lipoxygenase and cyclooxygenase blockade by BW755C does not prevent the secondary phase of septic pulmonary hypertension.

The infusion of Group B beta hemolytic streptococci (GBS) in newborn animals generates a dual phase pulmonary hypertensive response. The initial, acute phase responds to cyclooxygenase or thromboxane inhibition, and appears to be thromboxane mediated. The second phase is characterized by a more moderate rise in pulmonary vascular resistance, accompanied by an increase in microvascular permeability. It has been speculated that this phase may be leukotriene mediated. In an attempt to clarify this, we have studied and compared the effects of the thromboxane synthetase inhibitor, Dazmegrel (DAZ), and the combined cyclooxygenase/lipoxygenase inhibitor, BW755C, on the cardiopulmonary hemodynamics of the secondary phase of GBS induced pulmonary hypertension in newborn piglets. Ten piglets were infused with GBS, and all animals developed a significant increase in pulmonary artery pressure (to 39 +/- 5 and 36 +/- 5 mmHg for DAZ and BW755C animals respectively). After one hour of GBS, either DAZ or BW755C was administered. Data were collected for another two hours following drug administration. GBS infusion was continued throughout. Both DAZ and BW755C were associated with transient, acute reductions in pulmonary artery pressure (to 22 +/- 5 and 22 +/- 8 mmHg, respectively). However, after 60 minutes, PAP again began to rise in both groups (PAP 30 +/- 5 and 30 +/- 11 mmHg respectively by 240 minutes). There were no differences between the groups at any time. These data do not support a significant role for lipoxygenase products in mediating the secondary phase of septic pulmonary hypertension.

Patent ductus arteriousus in the premature neonate: current concepts in pharmacological management.

In utero, the ductus arteriosus shunts deoxygenated blood away from the pulmonary artery and towards the placental circulation where foetal gas exchange occurs. As a result of an intricately intertwined network of both physiological and biochemical changes, this vessel constricts rapidly after birth. Deoxygenated blood is diverted away from the placenta and through the lungs now vital for gas exchange. Premature closure of the ductus in utero can cause pulmonary hypertension and even death. Conversely, failure to close after birth can exacerbate respiratory distress, precipitate congestive heart failure and increase the risk of subsequent intestinal ischaemia leading to necrotising enterocolitis, bronchopulmonary dysplasia, renal hypoperfusion and/or cerebral ischaemia. In this review we summarise current knowledge of the delicately orchestrated control of the ductus arteriosus, focusing on the role of cyclo-oxygenase isoforms on prostaglandin production, on the interaction between prostaglandins and oxygen, and on the effects of these on ductal patency. We also seek to describe some of the standard and nonstandard therapeutic approaches available to the clinician when natural closure fails, reviewing alternative protocols for indomethacin administration and comparing indomethacin treatment with newer approaches such as ibuprofen. In summary, we will follow the course of this unique blood vessel as it is transformed over several hours from an organ absolutely vital to survival into programmed obsolescence.

Neonatal screening for glucose-6-phosphate dehydrogenase deficiency: sex distribution.

Eight hundred and six newborn infants at high risk for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency were screened; 30.2% of the boys and 10.4% of the girls had severe G-6-PD deficiency. Surprisingly, 14% of the enzyme deficient girls had a father from a low risk ethnic group. Girls of high risk mothers should be screened for G-6-PD deficiency regardless of paternal origin.

Neonatal bilirubin production, reflected by carboxyhaemoglobin concentrations, in Down's syndrome.

AIM: To determine whether increased bilirubin production, reflected by blood carboxyhaemoglobin (COHb) values, is responsible for hyperbilirubinaemia in cases of Down's syndrome with no obvious cause for excessive jaundice. METHODS: Blood was sampled on the third day of life for COHb, total haemoglobin (tHb), and serum total bilirubin, from 19 consecutively born neonates with Down's syndrome (a subset of 34 term babies), who had developed hyperbilirubinaemia (serum bilirubin >/= 256 micromol), and from 32 term controls. COHb, measured by gas chromatography, was corrected for inspired CO (COHbc) and expressed as a percentage of tHb. RESULTS: Significantly more of the Down's syndrome subset developed hyperbilirubinaemia than the controls (10/19 (52%) vs 7/32 (22%), relative risk 2.4, 95% confidence intervals (CI) 1.10 to 5.26). Third day serum bilirubin values (mean (SD)) were higher in the Down's syndrome neonates than in controls (214 +- 63 micromol/l vs 172 +- 54 micromol/l, respectively, p=0.015). Mean (SD) COHbc values were significantly higher in the Down's syndrome neonates than in controls (0.92 +- 0. 24% vs 0.63 +- 0.17%; p<0.0001). However, Down's syndrome neonates who became hyperbilirubinaemic had similar COHbc values to those who did not (0.87 +- 0.26% and 0.95 +- 0.23%, respectively). These values contrast with those of the controls, in whom a significant increase in COHbc was associated with hyperbilirubinaemia (0.74 +- 0. 15% vs 0.60 +- 0.16%, respectively; p<0.05). tHb values were similar in both groups. CONCLUSIONS: Down's syndrome neonates had a greater risk of hyperbilirubinaemia, and higher COHbc values, than controls. However, excessive bilirubin production could not be exclusively responsible for the hyperbilirubinaemia. By inference, decreased bilirubin elimination probably plays a greater part in its pathogenesis than in controls. Down's syndrome neonates may have abnormal erythropoiesis, leading to increased haem turnover.

Glucose-6-phosphate dehydrogenase activity in male premature and term neonates.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) activity is higher in term neonates than in adults. Some studies have suggested that activity may be even higher in preterm infants. OBJECTIVES: To determine if G6PD activity is higher in preterm than term neonates, and whether higher activity would interfere with diagnosis of G6PD deficiency in premature infants. METHODS: G6PD activity was determined in the first 48 hours after delivery in male premature, term, and near term infants. G6PD deficient neonates were separated, and the remaining premature infants compared with healthy, male, G6PD normal, near term and term neonates. RESULTS: Ninety four premature infants (mean (SD) gestational age 31.9 (3.8) weeks (range 23-36)) were studied. In four, G6PD activity was 0.8-1.8 U/g haemoglobin (Hb), which is clearly in the deficient range with no overlap into the normal range. G6PD activity in the remaining premature infants was significantly higher than in 24 near term and term neonates (gestational age > or = 37 weeks) (14.2 (4.6) v 12.0 (3.8) U/g Hb). Further analysis showed that significance was limited to those born between 29 and 32 weeks gestation, in which group G6PD activity was significantly higher than in those born before 29 weeks gestation, at 33-36 weeks gestation, and > or = 37 weeks gestation. CONCLUSIONS: G6PD activity is higher in premature infants born between 29 and 32 weeks gestation than in term neonates. This did not interfere with diagnosis of G6PD deficiency.

Effect of vitamin K1 on glucose-6-phosphate dehydrogenase deficient neonatal erythrocytes in vitro.

AIM: To determine whether vitamin K1, which is routinely administered to neonates, could act as an exogenous oxidising agent and be partly responsible for haemolysis in glucose-6-phosphat-dehydrogenase (G-6-PD). METHODS: G-6-PD deficient (n = 7) and control (n = 10) umbilical cord blood red blood cells were incubated in vitro with a vitamin K1 preparation (Konakion). Two concentrations of Vitamin K1 were used, both higher than that of expected serum concentrations, following routine injection of 1 mg vitamin K1. Concentrations of reduced glutathione (GSH) and methaemoglobin, indicators of oxidative red blood cell damage, were determined before and after incubation, and the mean percentage change from baseline calculated. RESULTS: Values (mean (SD)) for GSH, at baseline, and after incubation with vitamin K1 at concentrations of 44 and 444 microM, respectively, and percentage change from baseline (mean (SD)) were 1.97 + 0.31 mumol/g haemoglobin, 1.89 +/- 0.44 mumol/g (-4.3 +/- 13.1%), and 1.69 +/- 0.41 mumol/g (-14.5 +/- 9.3%) for the G-6-PD deficient red blood cells, and 2.27 +/- 0.31 mumol/g haemoglobin, 2.09 +/- 0.56 mumol/g (-7.2 +/- 23.2%), and 2.12 +/- 0.38 mumol/g (-6.0 + 14.1%) for the control cells. For methaemoglobin (percentage of total haemoglobin), the corresponding values were 2.01 +/- 0.53%, 1.93 +/- 0.37% (-0.6 +/- 17.4%) and 2.06 +/- 0.43% (5.7 +/- 14.2%) for the G-6-PD deficient red blood cells, and 1.56 +/- 0.74%, 1.70 +/- 0.78% (12.7 +/- 21.9%), and 1.78 +/- 0.71% (20.6 +/- 26.8%) for the control red blood cells. None of the corresponding percentage changes from baseline was significantly different when G-6-PD deficient and control red blood cells were compared. CONCLUSIONS: These findings suggest that G-6-PD deficient red blood cells are not at increased risk of oxidative damage from vitamin K1.