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Bacterial Infection in the Fetus and Newborn Arch Dis Child: first published as 10.1136/adc.46.245.1 on 1 February 1971. Downloaded from Review Article Archives of Disease in Childhood, 1971, 46, 1. Bacterial Infection in the Fetus and Newborn PAMELA A. DAVIES From the Neonatal Research Unit, Hammersmith Hospital, London The significance of potentially harmful influences years is illustrated by the fact that a request for a on the fetus and newborn may be judged in two Medlars search of the literature from 1963 to the ways. A direct effect on perinatal mortality is the middle of 1969 resulted in the retrieval of 17,147 more easily measured; while subtle damage at a relevant items. The computer rebelled at the size period of very rapid growth may have lasting effects, of this 'print-out' so relieving the writer of a 'read- not always immediately obvious, on the ultimate out' which would have extended into senescence. size and function of organs in survivors. Bacterial Those interested will therefore be deprived of a infection continues to exert an influence in both complete coverage ofthe problem, and subjected to a ways in the perinatal period, for the impact of personal and language bias. Much reliance has antibiotic and chemotherapeutic drugs has been been placed on previous review articles, so that less dramatic than at other ages, and humoral and often, and most regrettably, earlier original work copyright. cellular defence mechanisms may differ qualitatively goes unacknowledged. and quantitatively. It is difficult to assess the true extent of this The Defence Mechanisms of the Host problem from the recent literature, largely because The inflammatory response. The inflam- criteria for diagnosis are often inexact. It is not matory response produced by the host is usually always clear for instance whether septicaemia has considered the most fundamental of his defence been diagnosed on blood culture taken from peri- mechanisms. Freund (1931) showed how young pheral veins, or from the umbilical vein which may and adult rabbits reacted differently to intra- http://adc.bmj.com/ give false positive results (Lipsitz and Cornet, 1960). cutaneous injections of virulent organisms. An Even the morbid anatomist's interpretation of his extensive local inflammation occurred in the adults, necropsy material is dependent to some extent on while the newborn young failed to develop this and the clinician's diagnostic efforts, as inflammatory died with bacteraemia. In the human infant, the change may be minimal when death has been rapid inflammatory exudate in the first days of life has from profound bacterial toxaemia. Previous estim- been studied by several workers (Eitzman and ates of bacterial infection among stillbirths range Smith, 1959; Prindull, 1968; Bullock et al., 1969), from 3-15%, and among neonatal deaths from using a modification of the skin window cover-slip on September 26, 2021 by guest. Protected 10-20% (Claireaux, 1958), and there may well be technique of Rebuck and Crowley (1955). As in racial and geographical variations dependent on the adult, all have found polymorphonuclear social and economic conditions. Even allowing for leucocytes predominating in the early cellular the fact that neonatal infection is now being sought response, with mononuclear cells increasing more energetically, McCracken and Shinefield after a 6-hour period. This shift to mono- (1966) suggest a recent increase in the mortality nuclear cells is however less rapid and exten- from septicaemia and meningitis. Thus, it may be sive in the newborn. Prindull (1968) has pertinent to review the various aspects of bacterial pointed out another difference: in the presence of a and host defence at a time when the fetus can no raised eosinophil count in the blood, these cells are longer be considered inviolate from marauding also seen on the skin cover-slip preparation in the Man, and when increasing technical expertise is newborn, but not in the adult. He concludes being lavished on infants who make an untimely exit that newly born infants are unable to concentrate from the uterus. their inflammatory cells selectively at the site of The growing interest in this subject in recent inflammation. Arch Dis Child: first published as 10.1136/adc.46.245.1 on 1 February 1971. Downloaded from 2 Pamela A. Davies Immunoglobulins. The ontogenesis of tears, and supposed that the latter could be immunoglobulins has recently been reviewed by associated with antigenic stimulation from organic Adinolfi and Wood (1969). There is good evidence dust particles in the atmosphere; IgA in the tears that both IgG and IgM are synthesized by the fetus appeared significantly earlier however in both in small amounts, mainly in the spleen, from the normal and low birthweight infants if they deve- 20th week of gestation onwards. IgE is present in loped an infective conjunctivitis. small amounts in cord sera at birth, and as there is The relative paucity of IgM present in the normal no correlation between maternal and fetal levels, the newborn compared with the adult is generally held supposition is that it too is synthesized in utero. to be responsible for his known susceptibility to IgD on the other hand is absent in cord blood, and Gram-negative infections (Gitlin, Rosen, and so, very frequently, is IgA. Synthesis of these two Michael, 1963), though Cohen and Norins (1968) classes starts gradually after birth, though in the have recently demonstrated some antibodies reactive presence of a suitable antigenic stimulus during with Gram-negative bacteria in the IgG class. pregnancy, both IgA and IgM concentrations may However a quick increase in IgM synthesis, be considerably raised in the cord blood. However perhaps associated with bacterial colonization of the maternally derived IgG, the only class to cross the gut, occurs after birth, though it may be slower in placenta, constitutes the bulk of the healthy infant's infants of very low gestational age (Berg, 1968). serum immunoglobulin at birth, gradually dis- As Adinolfi and Wood (1969) point out, there are appearing over the first weeks of life. several studies testifying to the newborn's ability to The transfer occurs largely in the last trimester of produce antibody titres comparable to the adult's pregnancy, and Hobbs and Davis (1967) were able following both natural and artificial challenges. to show a linear relation between the logarithm of Synthesis of IgG proceeds less quickly after birth IgG concentrations and gestational age, levels at than that of IgM; and they cite animal and human the very low gestations falling below 100 mg/ evidence suggesting that the passively acquired 100 ml. Gusdon (1969) demonstrated concentra- maternal antibody may result in some suppression tions consistently about 200 mg/100 ml higher than of immune response. Similarly Hobbs, Hughes, copyright. the previous authors, with no significant increase and Walker (1968), reporting raised levels of IgA after 33 weeks of gestation, when maternal and and IgM at birth in infants who had undergone infant values became similar. Presumably diff- intrauterine transfusions, demonstrated that these erences in the racial composition of groups (Hardy same children had lower levels of IgA and IgM at et al., 1969), in the amount of placental transfusion, 1 year than controls. in methods, and in sample size, will account for Overwhelming staphylococcal sepsis was not infrequently seen in the past in mature infants who discrepancies in reported concentrations from http://adc.bmj.com/ various laboratories. presumably had the normal adult IgG levels at antibodies concerned with local birth, and thus antistaphylococcal antibody. The Secreted of more are and serum ability to synthesize antibody is probably immunity mainly of the IgA class, mechanism secretory are not identical (Tomasi et al., immediate importance as a defence and IgA of passively 1965), the latter containing a peptide known as against infection than the possession 'transport piece' which is synthesized in epithelial acquired antibody, and Smith and Eitzman (1964) cells (South et al., 1966). Transport piece without have urged that, far from making unfavourable IgA has been demonstrated in the parotid saliva comparison with the adult in this respect, we should on September 26, 2021 by guest. Protected of newborn infants (South et al., 1968), and in their regard the fetus and newborn as immunologically and Schafer, 1968), and the competent, and capable of developing mechanisms urine (Remington for latter authors suggest that its presence at an early at each stage of existence, which are appropriate gestation could be of phylogenetic importance, its the challenges likely to be met at these times. availability enabling any IgA produced by the fetus in response to intrauterine infection to be Complement. Complement (C') is the term transported to its secretions. IgA starts appearing used for a complex of 11 serum proteins in the in secretions shortly after birth (Haworth and globulin fraction. Bacterial cells are lysed by it Dilling, 1966), and may in fact be found some time after their exposure to specific antibody. Its before serum IgA is present in detectable amounts, various components are designated ntimerically as McKay and Thom (1969) have demonstrated in (Miiller-Eberhard, 1969). Total levels of C' in the tears of the newbom. They could not find any cord blood are less than those of maternal blood relation between bacterial colonization of the (Fishel and Pearlman, 1961), but adult levels are conjunctiva and the time of appearance of IgA in reached by 3 to 6 months of age (Fireman, Arch Dis Child: first published as 10.1136/adc.46.245.1 on 1 February 1971. Downloaded from Bacterial Infection in the Fetus and Newborn 3 Zuchowski, and Taylor, 1969). It appears that for it has been found in a small percentage of cord synthesis of complement by the fetus starts before bloods (Rozansky and Bercovici, 1956; Nemir, that of the immunoglobulins, and Adinolfi and Roberts, and Barry-LeDeaux, 1957).
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