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ROLE OF INTRAVENOUS IMMUNOGLOBULIN IN NEONATAL SEPSIS
Sunita Sreedhar*, Anagha Jayakar**
*Senior Resident; **Professor, Neonatology Unit, Department of Paediatrics, TN Medical College and BYL Nair Hospital, Dr. AL Nair Road, Mumbai 400 008.
A prospective case control study was conducted over two years to evaluate the impact of intravenous immunoglobulin (IVIG) on the outcome of neonatal sepsis and to evaluate the role of prophylactic IVIG in the prevention of neonatal sepsis. The incidence of sepsis among newborn in the present study was 28.9/1000 livebirths which was higher than that reported from developed countries and in other studies from India. This study did not find any statistically significant decrease in mortality with the use of IVIG irrespective of the gestational age and birth weight.INTRODUCTION
Neonatal sepsis is a clinical syndrome characterised by systemic signs of infection accompanied by bacteraemia in the first month of life.1 In neonates, maternal, environmental and host factors determine the risk of sepsis on exposure to a pathogen. As the early signs may be nonspecific, a high degree of suspicion and some overtreatment is necessary to reduce its mortality and morbidity.
Management included attention to temperature, feeding, hydration and prevention of hypoglycaemia. Mainstay of treatment is antibiotics. Additional supportive management may include the use of blood transfusion, fresh frozen plasma, inotropic support, IVIG, exchange transfusion, granulocyte and fibronectin transfusion, haematopoietic factors etc. The role of prophylactic interventions to prevent infections is as yet unclear.
AIM
The present study aims to evaluate the impact of IVIG if any, on the outcome of neonatal sepsis. An attempt was also made in a few cases to evaluate the role of IVIG as a prophylactic measure to prevent neonatal sepsis in preterms.
MATERIAL AND METHODS
A prospective case control study was conducted in the NICU of our institution over 2 years to evaluate the supportive role of IVIG in the management of neonatal sepsis. The babies were evaluated for maternal and foetal risk factors and clinical features of sepsis. Cases were those who received IVIG and controls were those who could not be given IVIG due to financial constraints. Both groups were closely followed for any improvement, deterioration or new signs. Investigations included complete haemogram, peripheral smear and blood culture in all cases and cerebrospinal fluid examination, X-ray chest and ultrasonography of skull when clinically indicated. Cases were given IVIG in the dose of 500 mg/kg weekly.
RESULTS
In the present study 92 babies were cases and 43 were controls. Incidence of neonatal sepsis was 28.9/1000 live births. Comparing the mortality of 39.1% and 32.5% of cases and controls respectively, there was no statistically significant difference, based on both the gestational age and the birth weight. Of the 92 cases, 23 received exchange transfusion for hyperbilirubinaemia but among them there was no statistically significant decrease in mortality in those patients given only IVIG compared to others who received IVIG with exchange transfusion. There was no change in risk of death in those given IVIG compared to the others. Among the 10 patients who were given IVIG prophylactically, all developed clinical features of sepsis showing that IVIG in the present study did not prevent sepsis.
DISCUSSION
Immune serum globulin used intramuscularly was tried in neonatal sepsis as early as 1963.[2,3] This required deep IM injections which were painful and had a highly variable systemic absorption and required several days for tissue levels to equilibrate. The development of a safe and effective IV preparation has overcome these difficulties and has renewed interest in its use.
Among the studies done on IVIG use as an adjunct to therapy, that of Sidiropoulos et al[4] showed a significant decrease in mortality in preterms, while that of Friedman et al[5] showed no statistically significant difference. A multicentre placebo controlled trial by Weisman et al[6] showed significant decrease in mortality in the 1st 7 days, while the survival at 56 days had not improved significantly. In this study, we did not find any significant decrease in mortality in those who received IVIG in addition to the standard treatment.
Among the studies done on IVIG use as prophylaxis against neonatal sepsis, those of Kinney et al[7], Kueser et al,[8] and Faranoff et al[9] found no effect, while Magny et al[10] found that the difference was not statistically significant. Chirico et al[11] suggested that IVIG may be effective as prophylaxis only in VLBW. Many studies[12-17] found that IVIG as prophylaxis significantly reduced the number of infective episodes. In the present study IVIG was used as prophylaxis in only 10 patients and was not found to be useful. However, as the numbers were small, this aspect requires further evaluation.
Mathur et al[18] found that exchange transfusion with fresh whole blood, in patients with neutropenia, improves survival and increases polymorph count and function. In our study the mortality in the group which received exchange transfusion was lower than the average mortality, but the difference was not statistically significant.
Hence the present study did not find any significant impact of IVIG on the outcome of neonatal sepsis or any role in prophylaxis.
Gestational
age in weeks
(IVIG given)
N = 92
--------------------------
No. Mortality No.
(%)
(IVIG not given)
N = 43
-------------------------
No. Mortality No.
(%)
< 34 51 26 (50.9) 11 7 (63.6) 34-37 25 8 (32) 18 5 (27.8) Full term 16 2 (12.5) 14 2 (14.3) Total 92 36 (39.1) 43 14 (32.5) The overall mortality among the cases and controls was 39.1% and 32.5% respectively, but the difference was not statistically significant (P > 0.05) in both preterms and full terms.
Birth weight
-------------------------------
No. Mortality No.
(%)
-------------------------------
No. Mortality No.
(%)
VLBW (< 1.5 kg) 46 24 (52.2) 8 4 (50) LBW (< 2.5 kg) 36 10 (27.7) 26 9 (34.6) > 25 kg 10 2 (20) 9 — Total 92 36 (39.1) 43 14 (32.5)
No. of cases Mortality No (%) Exchange transfusionwith IVIG 23 5 (21.7) IVIG 92 36 (39.1)
Weight
al ageNo.
CasesELBW VLBW LBW < 31 < 34 Birth (< 1 kg) (< 1.5 kg) (< 2.5 kg) wks wks Leak/pv asphyxia 10 2 5 3 5 5 1 3 There was no statistically significant difference in mortality between cases and controls based on birth weight.
The Table shows the outcome of babies who received IVIG alone in comparison with those who received exchange transfusion in addition.
It was observed that the mortality was reduced when exchange transfusion was used in addition to IVIG, but the difference was not statistically significant.
This Table shows gestational age and weight wise distribution and risk factors in neonates given IVIG as prophylaxis.
All the 10 patients developed clinical features of sepsis showing that, prophylactic IVIG had no role in prevention of neonatal sepsis.
Study Relative risk Present study 1.0 Sidiropoulos[4] 2.7 Haque[19] 3.6 Friedman[5] 3.4 Weisman et al[8] 2.1 This table shows comparison of the present study with other studies. This Table shows that there was no change in risk of death in those given IVIG in the present study.
REFERENCES
- Mathur NB. Neonatal sepsis. Indian Pediatr 1996; 33 : 663-74.
- Amer J, Ott E, Ibbott FA, et al. The effect of monthly gamma globulin administration on mortality and morbidity from infection in premature infants during first year. Pediatrics 1963; 32 : 4-9.
- Steen JA. Gamma globulin in preventing infections in premature infants. Arch Pediatrics 1960; 77 : 291-94.
- Boehme U, Sidiropoulos, Muralt GV, et al. Immunoglobulin supplementation in prevention and treatment of neonatal sepsis. Pediatr Infect Dis J 1986; 5 : S193-95.
- Friedman CA, Wender, Temple DM, et al. IVIG as adjunct therapy for severe group B streptococcal disease in the newborn. Am J Perinatol 1989; 6 : 453-56.
- Weisman LE, Stoll BJ, Kueser TJ, et al. Intravenous immune globulin therapy for early onset sepsis in premature neonates. J Pediatr 1992; 121 : 431-43.
- Kinney J, Mundorf L, Gleason C, et al. Efficacy and pharmacokinetics of intravenous immune globulin administration to high-risk neonates. AJDC 1991; 145 : 1233-38.
- Weisman LE, Stoll BJ, Kuecer TJ, et al. Intravenous immune globulin prophylaxis of late onset sepsis in premature neonates. J Pediatr 1994; 125 : 129-35.
- Fanaroff AA, Korones SB, Wright LL, et al. A controlled trial of intravenous immune globulin to reduce nosocomial infections in very low birth weight infants. N Engl J Med 1994; 330 : 1107-13.
- Magny JF, Oury CB, Brault D, et al. Intravenous immunoglobulin therapy for prevention of infection in high risk premature infants - Reports of a multicenter, double-blind study. Pediatrics 1991; 88 : 437-42.
- Chirico G, Rondini G, Plebani A, et al. Intravenous gammaglobulin therapy for prophylaxis of infection in high-risk neonates. J Pediatr 1987; 110 : 437-42.
- Haque KN, Zaidi MH, Haque SK, et al. Intravenous immunoglobulin for prevention of sepsis in preterm and low birth weight infants. Pediatr Infect Dis J 1986; 5 : 622-25.
- Conway SP, Gillies DRN, Docherty A. Neonatal infection in premature infants and use of human immunoglobulin. Arch Dis Child 1987; 62 : 1252-56.
- Stabile A, Sopo SM, Romanelli V, et al. Intravenous immunoglobulin for prophylaxis of neonatal sepsis in premature infants. Arch Dis Child 1988; 63 : 441-43.
- Clapp DW, Kleigman RM, Baley JE, et al. Use of intravenously administered immune globulin to prevent nosocomial sepsis in low birth weight infants : Report of a pilot study. J Pediatr 1988; 115 : 973-78.
- Baker CJ, Melish ME, Hall RT, et al. and the multi center group for study of immune globulin in neonates. Intravenous immune globulin for the prevention of nosocomial infection in low birth weight neonates. N Engl J Med 1992; 327 : 213-19.
- Atici A, Satar M, Karabay A, et al. Intravenous immunoglobulin for prophylaxis of nosocomial sepsis. Indian J Pediatr 1996; 63 : 517-21.
- Mathur NB, Subramanium BKM, Sharma YK, et al. Exchange transfusion in neutropenic septicemic neonates - Effects on granulocyte function. Acta Pediatr 1993; 82 : 939-43.
- Haque KN, Zaidi MH, Bahakim H. IgM-enriched intravenous immunoglobulin therapy in neonatal sepsis. AJDC 1988; 142 : 1293-96.
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