Increased incidence of hyperbilirubinaemia in 'unchallenged' glucose-6-phosphate dehydrogenase deficiency in term Saudi newborns.

The incidence of severe hyperbilirubinaemia was significantly higher among the G6PD-deficient Saudi infants born at term than in non-deficient babies (34% vs 9%) (p less than 0.005). No apparent offending factors were detected in either the babies or their mothers. All babies who developed hyperbilirubinaemia did so during the 1st week of life. The highest mean bilirubin level for all jaundiced G6PD-deficient babies was recorded on the 4th postnatal day. Although the incidence of severe hyperbilirubinaemia among our neonates was relatively high, only two of them (7%), a boy and a girl, required exchange transfusions. Five of 29 jaundiced babies with G6PD deficiency were readmitted after discharge because of significant jaundice. One required exchange transfusion. Since G6PD deficiency seems to be a relatively common cause of neonatal jaundice in Saudi newborns, early detection of this enzymopathy by cord blood screening is justified to avoid morbidity and deaths.     

Hyperbilirubinemia in healthy neonates with glucose-6-phosphate dehydrogenase deficiency

A cohort study was carried out to assess the association between glucose-6-phosphate dehydrogenase (G6PD) deficiency, diagnosed by quantitative enzyme assay, and neonatal hyperbilirubinemia, defined as serum total bilirubin >/=15 mg/dl, in the well-baby nursery of Chang Gung Children's Hospital. Among 42,110 inborn infants, 757 male (3.54%) and 326 female (1.57%) newborns were G6PD-deficient. Compared to the occurrence of hyperbilirubinemia in G6PD-normal newborns (1.41% in male, 1.44% in female) in the well-baby nursery, a significantly higher incidence was observed in both G6PD-deficient male (11.36%) and female (7.06%) newborns. Further analyses demonstrated that the enzyme activity of G6PD in G6PD-deficient male newborns with hyperbilirubinemia (1.56+/-1.37 U/g Hb) were significantly lower than the subjects without hyperbilirubinemia (2.01+/-1.7 U/g Hb). No significant difference was observed in G6PD-deficient female newborns with hyperbilirubinemia (6.91+/-2.76 U/g Hb) compared to those without hyperbilirubinemia (7.81+/-2.84 U/g Hb). These data suggest that the G6PD-deficient neonates are at increased risk for hyperbilirubinemia even in the nursery free from agents that can potentially cause hemolysis to G6PD-deficient red cells. The lower G6PD enzyme activity was associated with the neonatal hyperbilirubinemia in G6PD-deficient male neonates.     

Enzyme activity of glucose-6-phosphate dehydrogenase-deficient Malaysian neonates during the first 10 days of life

Objective: The objective of this study was to determine the degree of severity of enzyme deficiency in glucose-6-phosphate dehydrogenase (G6PD)-deficient Malaysian neonates as part of an effort to identify risk factors associated with severe hyperbilirubinaemia in G6PD-deficient infants.
Methodology: During this study, enzyme activity was measured in 53/59 (89.8%) hospital-diagnosed G6PD-deficient neonates (34 Malays, 12 Chinese, and seven other ethnic groups) born consecutively in the Kuala Lumpur Maternity Hospital. All neonates, except one, were males.
Results: The mean level of enzyme activity of the 52 males G6PD-deficient neonates (0.47 iu/g Hb, 95% confidence intervals: 0.37, 0.57) was less than 10% of that of normal Malaysian male neonates. The enzyme activity of the only female G6PD-deficient infant, at 1.11 iu/g Hb, was 12.5% of the mean G6PD enzyme activity of normal females.
Conclusion: Our results showed that G6PD deficiency in Malaysian neonates predominantly affects males and is usually severe.     

Neonatal jaundice and glucose-6-phosphate dehydrogenase deficiency in Basrah

In a study on a group of 186 newborn babies presenting with jaundice, erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency was detected in 95 (51%) of the patients. The incidence of severe hyperbilirubinaemia appeared to be much greater in G6PD-deficient infants (46%) than in infants who did not have the red cell defect (15%). No change was found in this association when ABO incompatibility was excluded. Phototherapy did not reduce the need for exchange transfusion, which was necessary in 27 babies. Eight babies developed kernicterus and one died. Early detection of G6PD deficiency and close surveillance of the affected newborns may be important in reducing the risk of severe neonatal jaundice and kernicterus associated with G6PD deficiency in Basrah.     

Screening for glucose-6-phosphate dehydrogenase deficiency as a preventive measure: prevalence among 1,286,000 Greek newborn infants.

We evaluated the Greek screening program for glucose-6-phosphate dehydrogenase (G6PD) deficiency, which was incorporated into the existing national phenyketonuria (PKU) screening program to identify infants with G6PD deficiency and eliminate the induction of acute hemolytic crisis by informing the families about the extrinsic factors that G6PD-deficient patients should avoid. Between 1977 and 1989, 1,286,000 infants were screened. The fluorescent spot test was used on samples extracted from dried blood spots. Abnormal fluorescence due to G6PD deficiency (severe or partial) was found in 3.14% of the samples (1 in 22 males and 1 in 54 females). The sensitivity of the test for homozygosity and hemizygosity was 100%. In heterozygosity the test identifies only subjects who have considerably diminished enzyme activity. The test is inexpensive when added to the PKU screening program ($0.90 US per test). We believe that screening a population for G6PD deficiency is justified if the incidence of the deficiency in the population is high and the clinical manifestations serious. The fluorescent spot test is recommended because it is reliable, easy to perform, and inexpensive. The test must be performed within a fortnight from sampling, and the cards must not be exposed to high temperature or humidity.     

Relationship between exposure to icterogenic agents, glucose-6-phosphate dehydrogenase deficiency and neonatal jaundice in Nigeria

In a study of the relationship between exposure to icterogenic agents, G-6-PD deficiency and severe neonatal jaundice (NNJ) (serum bilirubin greater than or equal to 205 mumol/l) in 234 Nigerian term male neonates, 106 infants with severe NNJ and 128 controls, it was found that 62.3% of the jaundiced infants and 13.3% of the infants without NNJ were G6PD deficient (p less than 0.01). The proportion of infants exposed to icterogenic agents in the two groups was very similar (p greater than or equal to 0.5). There was a strong association between exposure to icterogenic agents and NNJ in 83 G6PD deficient infants (p less than 0.01), but there was no association between exposure to icterogenic agents and NNJ in the whole group of 234 infants or in 151 infants with normal G6PD status. It is concluded that there is an association between genetically determined G-6-PD deficiency and exogenous agents in causing severe NNJ in Nigerian infants.     

Mutations of genes involved in the innate immune system as predictors of sepsis in very low birth weight infants

Mutations of genes involved in the innate immune system have been reported to be associated with an increased sepsis rate in adults. We determined the -159T mutation of the CD14 gene, the 896G mutation of the toll-like receptor 4 gene, the 3020insC mutation of the NOD2 gene (NOD2-3020insC), the IL-6 174G/C promoter polymorphism (IL6-174G/C), and the mannose-binding lectin genotype and their association to the subsequent development of neonatal sepsis in a large cohort of very low birth weight (VLBW) infants. Fifty (14%) of 356 VLBW infants developed blood culture-proven sepsis during their stay in the hospital. VLBW infants carrying the NOD2-3020insC allele (n =15) and the IL6-174G allele (n =121) had a significantly higher rate of blood culture-proven sepsis (33% and 19.8%, respectively) than VLBW infants without these genotypes (p = 0.046 and 0.035, respectively). In a multivariate logistic regression analysis, gestational age less than 28 wk (odds ratio, 3.2; 95% confidence interval, 1.7-6.0; p < 0.001) and the homozygous IL6-174G allele (odds ratio, 1.9; 95% confidence interval, 1.0-3.9; p = 0.039) were predictive for the development of sepsis, whereas the NOD2-3020insC allele was only of borderline significance (odds ratio, 3.2; 95% confidence interval, 1.0-10.4; p = 0.052). VLBW infants with repeated episodes of sepsis had higher frequencies of the NOD2-3020insC and IL6-174G allele. The increased sepsis rate of homozygous IL6-174G carriers was especially related to an increase in Gram-positive infections, and was not observed in VLBW infants who received prophylaxis with teicoplanin (frequency of Gram-positive sepsis in homozygous IL6-174G carriers without prophylaxis 16.5% versus 2.4% in homozygous IL6-174G carriers with prophylaxis; p = 0.033).     

Cytokine Responses of TNF-α, IL-6, and IL-10 in G6PD-Deficient Infants

G6PD-deficient adults are reported to be susceptible to severe infection, and decreased cytokine responses have been postulated as the underlying mechanism. However, investigating the association of G6PD deficiency and cytokine responses during infancy is lacking. The current study aims to determine whether cytokine responses of tumor necrosis factor ()-α, interleukins (IL)-6, and IL-10 are impaired in the G6PD-deficient infants. Upon agreements with informed consents, peripheral blood mononuclear cells (PBMCs) of enrolled infants were collected twice at 1 month and 1 year of age. PBMCs were then stimulated with toll-like receptor (TLR) agonists—including PAM3csk4 for TLR1–2, poly (I:C) for TLR3, and lipopolysaccharide for TLR4—to analyze the expression of TNF-α, IL-6, and IL-10. Males (P = .004) and phototherapy during neonatal period (P = .008) were more common among G6PD-deficient infants than G6PD-normal subjects. After the stimulation of TLR agonists, there was no significant difference in the expression of TNF-α, IL-6, and IL-10 between PBMCs of G6PD-deficient and -normal infants at both 1 month and 1 year of age. In conclusion, the clinical characteristics of G6PD-deficient infants are different from those of G6PD-normal subjects. The data suggest that the innate immune responses to TLR agonists in G6PD-deficienct infants are not different from those of G6PD-normal infants.     

Glucose-6-phosphate dehydrogenase status and neonatal jaundice.

Neonatal jaundice and its relationship to glucose-6-phosphate dehydrogenase (G6PD) status of healthy, term Chinese infants was evaluated in 220 G6PD-deficient infants, 26 intermediate infants who were observed for 3 weeks, and 116 normal (control) infants. Each infant was free of isoimmunisation, cephalhaematomas, or contusions. The mode of labour, method of delivery, and type of feeds had no appreciable effect on daily bilirubin levels. "Elevated" physiological jaundice was associated with normal and G6PD-deficient status; there was no increased haemolysis. G6PD-deficient status was associated with jaundice significantly raised especially in the first week of life, and prolonged beyond that of the "elevated" physiological jaundice. Significantly increased though mild haemolysis was observed. Close surveillance is therefore required for G6PD-deficient infants at least for the first week of life, the period of increased risk. With G6PD-intermediate infants, only the usual measures for normal infants are required.     

Diurnal fluctuation of leukocyte G6PD activity. A possible explanation for the normal neutrophil bactericidal activity and the low incidence of pyogenic infections in patients with severe G6PD deficiency in Israel

Acute hemolytic anemia associated with red blood cell (RBC) glucose-6-phosphate dehydrogenase (G6PD) deficiency is commonly encountered in the Mediterranean basin. Nevertheless, concomitant clinical evidence of white blood cell G6PD deficiency is extremely rare in Israel. This study sought to assess simultaneously levels of G6PD activity in polymorphonuclear leukocytes (PMN) and in red blood cells (RBC) of patients with G6PD deficiency, including full-term newborn infants. In PMN, the correlation between G6PD activity, hexose monophosphate shunt activity, and superoxide anion release was evaluated. In G6PD-deficient patients, a parallel and significantly decreased G6PD activity was found in neutrophils (range of activity 0-4.5 IU/10(6) PMN) and erythrocytes (range of activity 0-1.8 IU/g Hb), compared with healthy controls (5-23 IU/10(6) PMN and 2.4-6.4 IU/g Hb, respectively). A positive correlation was found in PMN between the levels of G6PD activity, hexose monophosphate (HMP) shunt activity, and superoxide anion release (p < 0.01). Nevertheless, all patients' bactericidal activity of neutrophils remained in the range of healthy controls. Although many episodes of acute hemolytic anemia were recorded, no increased incidence of pyogenic infections was observed in any group of patients investigated. Neutrophil and erythrocyte G6PD levels were re-assessed in some of these patients several times a day. A significant diurnal fluctuation of the enzyme activity was found. It is speculated that the patients produce fluctuating daily quantities of NADPH, sufficient to initiate the neutrophil respiratory burst and to achieve normal bactericidal activity, necessary to prevent the development of microbial infections.     

Bacterial profile of sepsis in a neonatal unit in south India

OBJECTIVE: To study the pattern of sepsis in a neonatal unit in south India and assess the influence of maternal factors on early onset sepsis (EOS). DESIGN: Prospective survey from 1995-1996. SETTING: Medical College Hospital. SUBJECTS: All inborn babies who had clinical signs of sepsis or were born to mothers with potential risk factors for infection were screened for sepsis. Neonatal septicemia was defined as a disease of infants who were younger than 1 month of age, were clinically ill, and had positive blood cultures. RESULTS: Among 13,367 live births in the study period, there were 131 episodes of neonatal septicemia among 125 newborn infants, 18 (14.4%) of whom died. Thirty (24%) had EOS (< or = 48 hours) and 95 (76%) had late onset sepsis (LOS) (> or = 48 hours). Sepsis occurred in 9.8 per 1000 livebirths and 4.4% of all nursery admissions. E. coli and E. fecalis were the predominant organisms causing EOS, while Klebsiella and E. fecalis were the predominant organisms in LOS. The mean gestational age (GA) and birth weight (BW) of babies with EOS was significantly higher than those with LOS. Maternal factors significantly associated with EOS were meconium staining of liquor and multiple vaginal examinations. CONCLUSIONS: The incidence of neonatal bacterial sepsis is 9.8 per 1000 livebirths. E. coli and Klebsiella were the most common organisms causing EOS and LOS, respectively. E. fecalis was also a major pathogen, both in EOS and LOS.     

Neonatal Hyperbilirubinemia in infants with G6PD c.563C > T Variant

ABSTRACT: BACKGROUND: There is a strong correlation between glucose-6-phosphate dehydrogenase (G6PD) deficiency and neonatal hyperbilirubinemia with a rare but potential threat of devastating acute bilirubin encephalopathy. G6PD deficiency was observed in 4-14% of hospitalized icteric neonates in Pakistan. G6PD c.563C > T is the most frequently reported variant in this population. The present study was aimed at evaluating the time to onset of hyperbilirubinemia and the postnatal bilirubin trajectory in infants having G6PD c.563C > T. METHODS: This was a case-control study conducted at The Aga Khan University, Pakistan during the year 2008. We studied 216 icteric male neonates who were re-admitted for phototherapy during the study period. No selection was exercised. Medical records showed that 32 were G6PD deficient while 184 were G6PD normal. Each infant was studied for birth weight, gestational age, age at the time of presentation, presence of cephalhematoma, sepsis and neurological signs, peak bilirubin level, age at peak bilirubin level, days of hospitalization, whether phototherapy or exchange blood transfusion was initiated, and the outcome. During hospital stay, each baby was tested for complete blood count, reticulocyte count, ABO and Rh blood type, direct antiglobulin test and quantitative G6PD estimation [by kinetic determination of G6PDH]. G6PDgenotype was analyzed in 32 deficient infants through PCRRFLP analysis and gene sequencing. RESULTS: G6PD variants c.563C > T and c.131 C > G were observed in 21 (65%) and three (9%) of the 32 G6PD deficient infants, respectively. DNA of eight (25%) newborns remained uncharacterized. In contrast to G6PD normal neonates, infants with c.563C > T variant had significantly lower enzyme activity (mean +/- 1SD; 0.3 +/- 0.2 U/gHb vs. 14.0 +/- 4.5 U/gHb, p < 0.001) experienced higher peak levels of total serum bilirubin (mean +/- 1SD; 16.8 +/- 5.4 mg/dl vs. 13.8 +/- 4.6 mg/dl, p = 0.008) which peaked earlier after birth (mean +/- 1SD 2.9 +/- 1.6 vs. 4.3 +/- 2.3 days, p = 0.007). No statistically significant difference was observed in mean weight, age at presentation, hemoglobin, reticulocyte count, TSH level, hospital stay or in the frequency of initiation of phototherapy or blood exchange between the two groups. CONCLUSIONS: We concluded that infants with G6PD c.563C > T variant developed jaundice earlier than infants with normal G6PD enzyme levels. Compared to G6PD normal infants, G6PD c.563C > T carrying infants had significantly low G6PD activity.     

Postoperative sepsis in infants below 6 months of age

Background  Sepsis is a threatening postoperative complication especially in small infants. Regarding the advances in perinatal medicine, its incidence is unknown to date. We aimed to investigate the incidence, risk factors, laboratory findings and outcome of postoperative sepsis in infants younger than 6 months old. Methods  We examined postoperative sepsis in babies below 6 months of age during a 4-year period at a tertiary pediatric institution. Results  The rate of postoperative sepsis was 6.9%. Laparotomy with enterotomy, thoracotomy and diaphragmatic hernia repair (P<0.05, respectively) as well as low postnatal age and long operation time (P<0.001, respectively) were correlated with the incidence of sepsis. Significant independent predictors for the development of sepsis were the presence of a central venous catheter and perioperative antibiotic treatment (P<0.001, respectively). Coagulase negative Staphylococci were the major infecting organism associated with postoperative sepsis, accounting for 53% of monomicrobial infections. Complete blood counts with differential were not different between infants with sepsis and controls, who had undergone the same surgical procedures. Outcome was favorable in all cases; however, the length of hospital stay was significantly longer in sepsis patients (P<0.05). Conclusions  Postoperative sepsis syndrome is a frequent complication in infants below 6 months of age and causes significant prolongation of hospital stay. Adequate prevention and therapeutic strategies warrant further prospective investigations.     

Early onset neonatal meningitis in Australia and New Zealand, 1992-2002

OBJECTIVES: To study the epidemiology of early onset neonatal bacterial meningitis (EONBM) in Australasia. DESIGN: Prospective surveillance study, 1992-2002, in 20 neonatal units in Australia and New Zealand. EONBM was defined as meningitis occurring within 48 hours of delivery. RESULTS: There were 852 babies with early onset sepsis, of whom 78 (9.2%) had EONBM. The incidence of early onset group B streptococcal meningitis fell significantly from a peak of 0.24/1000 live births in 1993 to 0.03/1000 in 2002 (p trend = 0.002). There was no significant change over time in the incidence of Escherichia coli meningitis. The rate of EONBM in very low birthweight babies was 1.09/1000 compared with the rate in all infants of 0.11/1000. The overall rate of EONBM was 0.41/1000 in 1992 and 0.06 in 2001, but this trend was not significant (p trend = 0.07). Case-fatality rates for EONBM did not change significantly with time. Birth weight <1500 g (odds ratio (OR) 7.2 (95% confidence interval (CI) 4.8 to 10.9)) and Gram negative bacillary meningitis (OR 3.3 (95% CI 2.2 to 4.9)) were significant risk factors for mortality. Sixty two percent of the 129 babies who died from early onset sepsis or suspected sepsis did not have a lumbar puncture performed. CONCLUSION: The incidence of early onset group B streptococcal meningitis has fallen, probably because of maternal intrapartum antibiotic prophylaxis, without a corresponding change in E. coli meningitis. Gram negative bacillary meningitis still carries a worse prognosis than meningitis with a Gram positive organism.     

新生儿细菌和真菌败血症的临床特征和住院费用比较

目的 分析比较革兰阳性菌(G+)、革兰阴性菌(G-)和真菌所致新生儿败血症的临床特征和住院费用.方法 对236 例新生儿败血症患儿的临床资料进行回顾性分析,包括G+ 菌败血症110 例,G-菌败血症68 例,真菌败血症58 例.结果 G+ 菌组足月儿占62%,G-菌组足月儿占38%,真菌组早产儿占86%,真菌组新生儿的胎龄、出生体重小于G+ 菌组和G-菌组(P-菌组、真菌组中多胎所占比例高于G+ 菌组(P-菌组胎膜早破>18 h、羊水Ⅲ度污染、早发型败血症的比例均高于G+ 菌组和真菌组(P+ 菌组起病症状为体温异常、脐炎或疱疹的患儿比例高于G-菌组和真菌组(P+ 菌组和G-菌组(P+ 菌组和G-菌组(P+ 菌组和G-菌组(P+ 菌组和G-菌组(P结论 G+菌败血症以足月儿为主;G-菌败血症多见于早发型;真菌败血症多见于早产儿和低出生体重儿,易发生呼吸暂停、血小板减少,且住院时间和住院费用高于细菌败血症.     

Efficacy of phototherapy in neonatal hyperbilirubinaemia associated with glucose-6-phosphate dehydrogenase deficient status

The efficacy of phototherapy in a group of 427 infants with hyperbilirubinaemia associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency and a comparable group of 3924 G6PD normal infants with non-haemolhtic hyperbilirubinaemia was evaluated. Phototherapy was highly effective in reducing bilirubin levels in both groups of infants, being significantly more effective in the group with normal G6PD status. Failure rate was very low (2.03/1000) in the group with normal G6PD status and nil in the G6PD deficient group. Bilirubin rebound after phototherapy was unremarkable with very few infants requiring a second exposure —4.68/1000 in the G6PD deficient group and 6.37/1000 in the G6PD normal group. All the babies tolerated phototherapy well. Phototherapy would therefore seem to be a simple and effective method for the management of severe jaundice associated with G6PD deficiency.     

Photooxidant injury to glucose-6-phosphate dehydrogenase-deficient erythrocytes with bilirubin as the sensitizer—an in vitro study

To evaluate the hypothesis that glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes are more prone to photooxidant injury with bilirubin as the sensitizer, we compared the malonyl dialdehyde (MDA) levels and haematocrit values in 11 G6PD-deficient samples with a bilirubin: albumin molar ratio of 1:2 (10mg% bilirubin, 2.5 g % albumin) photoexposed at 6 μW cm^-2nm^-2(420–460 nm), with 11 of control samples. Twelve hours after photoexposure the incremental changes in MDA levels (OD units) were higher in G6PD-deficient samples [mean (SE) = 0.230 (0.171) vs 0.075 (0.043), p > 0.01]. Antioxidant drugs may have a protective role while G6PD-deficient neonates undergo phototherapy.     

成都市54025例早产儿葡萄糖-6-磷酸脱氢酶缺乏症筛查结果及分子遗传学特征分析

目的 分析成都市早产儿葡萄糖-6-磷酸脱氢酶(glucose-6-phosphate dehydrogenase,G6PD)缺乏症筛查结果及基因突变分布情况,探讨早产儿人群G6PD筛查流程改进方案.方法 采用干血斑G6PD荧光分析法,对成都市2015年1月1日至2019年12月31日出生的54025例早产儿足跟血样本进...     

G6PD deficiency in newborn infants

Five hundred consecutive newborns were screened for erythrocytic G6PD deficiency in cord blood. The overall incidence of G6PD deficiency was found to be 2.80 percent. The incidence of G6PD deficiency was higher among males (3.77%) compared to females (1.44%). The incidence of erythrocytic G6PD deficiency was higher in Muslims (16.67%) compared to Hindus (2.63%). No definite relationship of erythrocytic G6PD deficiency was observed with consanguinity. Fifty per cent mothers of G6PD deficient newborns were also found to be G6PD deficient. Among brothers and sisters of G6PD deficient children the incidence of G6PD deficiency was 50.00 and 9.10 per cent respectively. There was no significant difference in the incidence of hyperbilirubinemia between erythrocytic G6PD deficient and non deficient newborns.     

Tumor necrosis factor alpha -- 308 polymorphism associated with increased sepsis mortality in ventilated very low birth weight infants

BACKGROUND: Sepsis commonly complicates the clinical course of critically ill very low birth weight infants, with as many as 30% developing hospital-acquired bacteremia. The tumor necrosis factor alpha (TNF-alpha) -- 308 G/A single nucleotide polymorphism (SNP) is associated with adverse outcome in septic adult patients. METHODS: One hundred seventy-three mechanically ventilated very low birth weight infants were genotyped for the TNF-alpha -- 308 G/A SNP. RESULTS: One hundred twenty (69%) infants were homozygous GG, 45 (26%) were heterozygous AG and 8 (5%) were homozygous AA; 2 of 120 (2%) infants developed early bacteremia in the GG group, and 1 of 53 (2%) developed early bacteremia in the AA/AG group (P = 0.919). One or more episodes of late bacteremia/fungemia developed in 59 of 120 (49%) infants with the GG genotype and 23 of 53 (43%) infants with the AG/AA genotype (P = 0.484). Endotracheal tube colonization rates were 65 of 120 (54%) for infants with the GG genotypes and 28 of 53 (53%) for infants with the AG/AA genotypes (P = 0.871). Nosocomial pneumonia developed in a similar number of infants in both genotype groups (9 of 120 infants vs. 3 of 53 infants; P = 0.461). Mortality from sepsis was 3 times greater in infants with the AA/AG genotypes than in those with the GG genotype (10%vs. 3%; P = 0.038). This difference in sepsis mortality was even greater when only bacteremic/fungemic infants are considered (4 of 59 infants vs. 6 of 23 infants; P = 0.026). CONCLUSIONS: These data suggest that the TNF-alpha -- 308 A allele does not affect the development of sepsis in ventilated premature infants but may increase mortality once sepsis develops.