Evolution of Hypogammaglobulinemia in Premature and Full-Term Infants

Abstract

There are few data in the literature reporting the evolution of hypogammaglobulinemia in premature and full-term infants during the first years of life. The aim of this study was to assess the clinical and immunological evolution of premature and full-term infants with hypogammaglobulinemia. We included 24 children (11 premature and 13 full-term infants), aged 0-36 months, with hypogammaglobulinemia. Fifteen (62.5%) children had an isolated reduction in IgG, 7 (29.2%) had a decrease in both IgG and IgA and 2 (8.3%) a reduction in IgG and IgM. Normalization of IgG serum levels occurred in the premature infants at a mean age of 7.2 months. FUll-term infants were divided into 3 groups based on age at normalization of IgG serum level: A) hypogammaglobulinemia with normalization within 12 months of life; B) with normalization within 36 months of life; C) normalization after 36 months. All the premature infants with hypogammaglobulinemia recovered, even though in the lower limits for age in the first years, while transient hypogammaglobulinemia observed in full-term infants has a different age of recovery. Immunoglobulins(Igs) G levels are physiologically lower in the first months of life, a condition that increases in premature infants in direct proportion to gestational age (1-2). In some infants, occasionally, adequate Ig synthesis may be abnormally delayed until 36 months of age, resulting in a prolonged reduction of Ig levels; this process is referred to as transient hypogammaglobulinemia of infancy (THI) (3).At present there are no clinical features or diagnostic tests that differentiate self-limiting hypogammaglobulinemia from permanent immune defects in young children. A definitive diagnosis of THI is only possible a posteriori, after normalization of IgG levels and the exclusion of other causes of hypogammaglobulinemia.The aim ofthis study is to appraise the clinical and immunological features of premature and full-term infants with a diagnosis of hypogammaglob ulinemi a and their subsequent evolution. MATERIALS AND METHODSThe study included 24 children (aged 0-36 months), consecutively referred to the Department of Pediatrics, Pediatrics Allergology and Immunology Center of Bologna University between January I, 2000 and December 31, 2008, with a diagnosis of hypogammaglobulinemia associated with other clinical symptoms. Hypogammaglobulinemia was considered if the infants showed values of one or more Ig isotypes below the "lower limit" «2 DS) of our pre-determined set of reference ranges per age (4).

Practice parameter for the diagnosis and management of primary immunodeficiency

“…This period of hypogammaglobulinemia can be associated with recurrent infections. [419][420][421][422] In one study 18 patients with THI were followed prospectively; IgG levels spontaneously corrected to Adapted from Orange et al 413 normal at a mean age of 27 months, with all patients reaching normal levels by 59 months. 423 The definitive diagnosis of THI can only be made after IgG (and in some cases IgA, IgM, or both) levels have corrected; before that, infants with a decreased IgG concentration have hypogammaglobulinemia of infancy that can become THI (Table E10).…”

“…Although most children with THI spontaneously recover their IgG values and have a benign clinical course, some of them do not recover and have SIGAD, CVID, or other forms of dysgammaglobulinemia. [419][420][421][422] Clinical manifestations of THI include bacterial sinopulmonary infections and other respiratory tract infections. THI is rarely associated with sepsis, meningitis, or invasive infections.…”

“…IgM levels, IgA levels, or both can also be transiently low; specific antibody production is usually preserved; and cellular immunity is intact. [419][420][421][422] Isolated transient deficiencies of IgA, IgG2, and SADs do exist but are not presently identified as a different form of antibody-like deficiency, as is THI (see also sections on SIGAD, IGGSD, and SAD). 425 Some authors stipulate that measurements should be repeated to eliminate misdiagnosis because of laboratory error.…”

“…Evaluation includes measurement of specific antibody production and enumeration of lymphocyte subsets by means of flow cytometry. [419][420][421][422] Most children have normal booster responses to protein vaccines and normal isohemagglutinin concentrations. Some patients have transient suppression of vaccine responses, which recover by the age of 3 to 4 years.…”

“…(C) Antibiotic prophylaxis should be the initial mode of preventive therapy for THI (see SS 16 and Table E7). 399,[419][420][421][422] If this fails or is not tolerated, some patients might benefit from IgG administration, particularly during seasons when respiratory illnesses are more frequent. 429 An increase in the patient's own IgG production can be monitored by keeping the IgG dose and infusion intervals constant; IgG production is clearly reflected by increasing IgG trough levels.…”