Jean F. Kenny

797 NEONATAL STABILIZATION AT COMMUNITY HOSPITALS IS IMPROVED BY OUTREACH EDUCATION: A PROSPECTIVE STUDY

We describe the first prospective evaluation of the effects of an outreach education program on pre-transport stabilization of sick neonates born in community hospitals. The relationship between the adequacy of stabilization and the timing of participation in a perinatal outreach program was studied.Information regarding stabilization procedures done by referring hospital personnel prior to the arrival of our transport team was recorded and expressed as the percentage of appropriate actions. Highly significant improvement was seen in these percentage scores in the six-month period following outreach education compared to the 12 months immediately preceding the educational program (mean post-outreach score 81%, n=58 transports versus pre-outreach score 68%, n=40, p < .001). In contrast, no spontaneous improvement with time (i.e. without outreach education) was seen during the two years prior to the program (mean pre-outreach score A 64%, n=3t, pre-outreach score B 68%, n=10, non-significant).This study shows that neonatal outreach education improves the stabilization of neonates in community hospitals and implies a beneficial effect on neonatal outcome.

NEONATAL ANDROGEN LEVELS AND ANTIBODY PRODUCTION

While data suggest that the effects of sex hormones mainly estrogen(E), may be the basis for sex differences in immunity in later life, the reason for the differences in infancy are obscure. Though serum levels of E in male and female babies are low and not significant, recent data show marked sex differences in serum concentrations(C)of testosterone(T)with levels in males of 0-3months ranging from 350pg/ml to 2000pg/ml and those in females from 50-100pg/ml. To determine what effects these C of T might have on numbers of anti-bacterial antibody producing cells (APC)spleen cells from outbred male Swiss mice injected with 3×106heat-killed E.coli 3 days before were incubated in vitro with C of T of 5-5000pg/ml. After 24hours, numbers of anti-E.coli APC as determined in an agar-gel were compared in T-treated and untreated(U)portions of the same suspension. At 50pg/ml 21 of 27(77%)of T-treated suspensions had increased numbers of APC over U(p=.003). The mean number of APC/spleen of 1280 for T-treated was 45% greater than that of U. By contrast, at 500pg/ml and above, APC were reduced;at 500pg/ml 27 of 36 suspensions had fewer APC than U(p=.002). T-treated averaged 42% fewer. Similar studies show that at C of estradiol(E2)of 500-5000pg/ml and of progesterone(P) of 500pg-50ng/ml increases in APC occur but at C of 50ng/ml and 500ng/ml respectively AFC are reduced. T, E2 and P enhance at lower and suppress numbers of APC at higher C. T is the most potent with its effects at the lowest C. Findings suggest that serum levels of T in male infants may suppress whereas those in female infants may enhance the proliferation and/or differentiation of APC.

EFFECT OF ESTRADIOL(E) ON IMMUNE COMPETENCE

Human females have higher serum levels of IGM antibody than males; this sex difference is greatest in late childhood and adulthood. In Swiss mice which also demonstrate sex differences in immunity, females have more splenic antibody producing cells (SAPC)than males, a phenomenon dependent on estrogen secretion. The purpose of this study was to determine when in the antibody producing process E exerts its effect. A single physiologic dose of E(2.5μg) was given to male mice at times from 2 days prior to 4 days after the injection of 5×105heat-killed E.coli (HKE). Mice were sacrificed 4 days after the antigen and counts of anti-E.coli SAPC compared to those of littermate controls. Greatest increases in SAPC were observed in groups of 65 mice receiving E 1-3 days after the antigen(p<.01). Significant increases (p<.05)were observed in 42 mice receiving E as late as 12 hrs before sacrifice, but not in those given E 1-2 days before the antigen or 2 hrs before killing. Spleen cells from mice injected with HKE 3 days before were grown for 18 hrs in vitro. SAPC or uptakes of H3 thymidine were compared in the same suspensions incubated with and without E(500pg/ml). In 33/44 suspensions treated with E, SAPC were increased a mean of 61%;cpm of H3 were an average of 40% greater in 10/10 such suspensions. Findings suggest that small amounts of E increase the rates of replication and DNA synthesis of antigen-stimulated spleen cells. These effects which may be observed late in the proliferative phase of antibody production appear to be independent of the enhancing effect of E on phagocytosis.

IMMUNOLOGIC RESPONSIVENESS DURING PREGNANCY

Female sex hormones significantly increase immunologic responsiveness by stimulating the proliferation of immunocompetent cells. To determine whether the immune response is altered during pregnancy and lactation, Swiss mice(gestation 19-21d) were studied during early, mid and late pregnancy and in the early postpartum (PP) period. Groups of pregnant (PR) and nursing mice along with equal numbers of nonpregnant female littermate controls(C) were injected with 2×106 heat-killed E.coli 0127 and sacrificed 4 days later for enumeration of splenic anti-E.coli plaque-forming cells(PFC). Total PFC/108 spleen cells were analyzed by rank and comparison of results from test and control littermate pairs.Results indicate that primary immunologic responsiveness is increased during early and mid pregnancy, depressed immediately prior to delivery and normal during lactation. The marked variations observed may be secondary to changes in the balance of female sex hormones and adrenocorticosteroids which occur as pregnancy progresses.

Hormonal basis for sex differences in immunity

To investigate the greater susceptibility of the male to severe infections we have studied antibody production by individual spleen cells in immature and adult Swiss mice. Previous studies using the Jerne agar-plaque technique have shown: 1) following enteric colonization with E. coli or injection of small numbers of heat-killed E. coli (HKE) significantly more cells produce specific antibody in weanling and adult females than males; 2) after injection of small numbers of HKE (3 × 105) sexually mature females respond with significantly greater numbers of antibody producing cells (APC) than weanling females, but responses of adult males are only slightly better than those of male weanlings; 3) mean amounts of antibody produced by male and female cells are the same.Responses of prepubertal ovariectomized females (OF) were compared to those of equal numbers of their sham-operated male (SM) and female (SF) littermates. Three weeks postoperatively, 4 days after intraperitoneal injection of 3 × 105 HKE, total APC/spleen ranged from 0–600. When individual totals of APC were ranked, responses of OF and SM were alike and those of SF were significantly better (p < .001). 10/28 SF vs. 6/28 OF and 7/30 SM were in the top third of the rank order. In a similar study total APC for castrated males and SM were the same. Estradiol-17β (500 ng) was given to 50 weanling males the week of challenge (5 × 105 HKE). In responses ranging from 0–1550 APC/spleen, the estradiol-treated males ranked higher than 53 saline-injected littermate controls (p < .05).Findings show that the significantly better immunologic responsiveness of the female is dependent on ovarian function; small amounts of estradiol appear to enhance the proliferation of immunocompetent cells.