Iowa Neonatology Handbook: Infection

Immunoglobulin Therapy

Chetan A. Patel MD and Edward F. Bell, MD
Peer Review Status: Internally Peer Reviewed

Maternal IgG is the major source of fetal and neonatal IgG; hence, the antibody profile of the neonate is dependent on the profile of antibodies in the maternal circulation. Since significant transfer of maternal IgG across the placenta to the fetus does not begin until the 32nd week of gestation, VLBW (<1500 g) infants are born with relatively low levels of IgG compared with full-term infants. Furthermore, in all infants, serum immunoglobulin levels decline further after birth. In term infants, the postnatal physiologic trough occurs at 4 - 6 months of age, but serum IgG levels usually remain above 400 mg/dl. Preterm infants can have levels as low as 60 mg/dl by 3 months of age.

Infectious diseases are a significant cause of morbidity and mortality among preterm infants. The risk of neonatal sepsis is 4 to 10 times higher among infants < 2500 g than in term infants. The incidence of sepsis is gestational age dependent, infection rates reported as high as 50% in infants <1000 g. The survival of low birth weight infants has improved greatly in recent years. But the care of these infants involves procedures (endotracheal intubation, catheters, lines, broad-spectrum antibiotics) that increase their risk of nosocomial infection.

Together, the increased risk factors for sepsis and the relative quantitative and qualitative IgG deficiency in preterm infants (that increases with postnatal age) provide a rationale for intravenous immunoglobulin (IVIG) therapy as a means for prophylaxis and treatment of neonatal sepsis. However, clinical studies have failed to substantiate consistently a beneficial effect of prophylactic use of IVIG in reducing the incidence of hospital-acquired infections in VLBW infants (Baker 1992; Fanaroff, 1994). A meta-analysis of studies done does however suggest a demonstrable benefit of prophylactic IVIG in preventing sepsis in LBW newborns (Jensen, 1997).

Recent evidence suggests that the use of immunoglobulin may be appropriate in the following group of infants. The use of IVIG must be cleared by the attending physician. This list and the references below are not meant to be comprehensive.

I. Prophylaxis to prevent nosocomial infections in preterm infants with BW < 750 g: IVIG 500 mg/kg IV over 3 - 4 hours (@ 10 ml/kg volume), starting the first week of life and every 2 weeks as long as the infant has an indwelling IV line (maximum of 5 doses).

Whenever possible, administer doses on Mondays to reduce cost by allowing multiple infants to be treated from the same vial of IVIG.

Further rationale for prophylatic use of IVIG and the results of several large clinical trials are described in the references cited at the end of this section.

II. Treatment for infants with proven early-onset neonatal sepsis (esp. with Group B strep infection or with accompanying neutropenia): IVIG 500 mg/kg IV over several hours.

The immunoglobulins serve both a therapeutic role (enhancing humoral immunity and clearing the organism) as well as a prophylactic role in helping to prevent superimposed infections. Shortening the bacteremic phase may also limit damage from secondary immune or nonimmune factors contributing to the shock-like state. Total IgG titers in treated, septic neonates remain elevated for ª 10 days. Meta-analysis of the effectiveness of IVIG in the treatment of early-outset sepsis shows that the addition of IVIG to standard therapies increases the survival nearly six-fold (Jensen 1997).

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