Developmental pattern of fetal growth hormone, insulin-like growth factor I, growth hormone binding protein and insulin-like growth factor binding protein-3.

AIMS: To evaluate the developmental pattern of fetal growth hormone (GH), insulin-like growth factor I (IGF-I), GH binding protein (GHBP) and IGF binding protein-3 (IGF-3); to determine the implications for fetal growth. METHODS: Serum GH, IGF-I, GHBP and IGFBP-3 were measured in 53 fetuses, 41 aged 20-26 weeks (group A) and 12 aged 31-38 weeks (group B). Fetal blood samples were obtained by direct puncture of the umbilical vein in utero. Fetal blood samples were taken to rule out beta thalassaemia, chromosome alterations, mother to fetus transmissible infections, and for maternal rhesus factor. GHBP was determined by gel filtration chromatography of serum incubated overnight with 125I-GH. GH, IGF-I and IGFBP-3 were determined by radioimmunoassay. RESULTS: Fetal serum GH concentrations in group A (median 29 micrograms/l, range 11-92) were significantly higher (P < 0.01) than those of group B (median 16.7 micrograms/l, range 4.5-29). IGF-I in group A (median 20 micrograms/l, range 4.1-53.3) was significantly lower (P < 0.01) than in group B (median 75.2 micrograms/l, range 27.8-122.3). Similarly, IGFBP-3 concentrations in group A (median 950 micrograms/l, range 580-1260) were significantly lower than those of group B (median 1920 micrograms/l, range 1070-1770). There was no significant difference between GHBP values in group A (median 8.6%, range 6.6-12.6) and group B (median 8.3%, range 6-14.3). Gestational age correlated positively with IGF-I concentrations (P < 0.0001) and IGFBP-3 (P < 0.0001) and negatively with GH (P < 0.0001). GHBP values did not correlate with gestational age. Multiple regression analysis showed a negative correlation between GH:IGF-I ratio and fetal growth indices CONCLUSIONS: The simultaneous evaluation of fetal GH, IGF-I, IGFBP-3 and GHBP suggests that the GH-IGF-I axis might already be functional in utero. The progressive improvement in the efficiency of this axis in the last part of gestation does not seem to be due to an increase in GH receptors.

[Neonatal necrotizing enterocolitis (NEC). Observations of 21 cases studied from 1977 to 1980]. / Enterocolite necrotizzante del neonato (NEC). Rilievi su 21 casi osservati negli anni 1977-1980.

We have carried out a study together with neonatologists, paediatricians, paediatric surgeons and paediatric radiologist on the etiopathogenic, clinical-statistical, therapeutical and evolutionary aspects of NEC during the period from 1977 to 1980 in the Neonatology Clinic and in the Paediatric Surgery Department University of Bologna. The most important data were as follows: a high percentage of full-term newborns, the apparently unfavourable action of artificial feeding, a little amount of infectious etiology, an absence of predisposing factors in more than half the cases, an uniform symptomatology in a lot of patients with adverse evolution in the cases of secondary colic stenosis. The mortality was 33 percent, specially among the small for gestational age infants. The surgical therapy during four years period was modified technically, i.e. there was an orientation towards conservative surgery. The final surgical operation has recently been made right after the fourth month from the acute crisis as it has recently been demonstrated that secondary stenosis always occurs during this period of time. Long - term follow - ups showed: completely satisfactory progress in patients treated only with medical therapy, particularly unfavourable evolution in patients after a more demolishing - type of operation (resectioning of the last ansa of ileum and ileum - caecum valve), considerable improvement in auxological and nutritional parameters also in the latter cases after the final surgical operation.

Sonography of unilateral megalencephaly in the fetus and newborn infant.

A 27-year-old primigravida women was referred for ultrasound studies at 32 weeks' gestation because of the suspicion of fetal ventriculomegaly. Sonographic examination of the fetal brain found a marked shift of the midline, with enlarged left hemisphere and ipsilateral occipital horn, and abnormal convolutions. A 3500 gm male infant was delivered by cesarean section at 39 weeks' gestation because of worsening macrocrania after which the diagnosis of unilateral megalencephaly was confirmed by computed tomography.

Cerebrospinal fluid shunt infections in infants.

Infection remains a major cause of morbidity and mortality following CSF shunt procedures. In this study 191 shunt procedures carried out from January 1981 to December 1992 in a series of 81 infants (less than 6 months old) were retrospectively analyzed for possible risk factors. The overall surgical infection rate was 7.8%, with 15 infections occurring in 14 patients (17.2%). No significant difference in the rate of infections was found in relation to sex, birth weight, gestational age, and type of shunt procedure (primary insertion/revision). The occurrence of other infections during the period of shunt surgery did not influence the infection risk either. Intraventricular hemorrhage and central nervous system infections as causes of the hydrocephalus were found to correlate with septic risk. Young age (less than 6 months) seems to represent the main risk factor, and this is related both to the immunologic deficiency and to the particular features of residential bacterial flora in this age group.

Erythropoietin course in newborns with Rh hemolytic disease transfused and not transfused in utero.

This study reports the Hb, erythropoietin (Epo), and reticulocyte course at different postnatal ages (range, 8-83 d) of 56 blood samples from 30 newborns (range, one or two blood samples from each newborn) with erythroblastosis fetalis (18 intrauterine transfused (IUTd) and 12 non-IUTd). Hb, Epo, and reticulocyte values were not statistically different in IUTd and non-IUTd cases. As age increased, decreasing Hb values and increasing Epo levels were observed. The reticulocyte count was relatively low in all but six cases. There was an inverse correlation between Epo and Hb (r = -55, p < 0.001), but no correlation was found between Hb and reticulocytes or between Epo and reticulocytes. When groups were formed on the basis of Hb levels, anemic newborns showed higher serum Epo than did nonanemic patients (p < 0.02). In the present study we found a significant increase in Epo levels in anemic newborns without a rise in the reticulocyte count. These results suggest that other mechanisms, rather than low Epo production, could be involved in the pathogenesis of this anemia. Persisting anti-D antibodies, probably at a medullary level, may destroy erythrocyte precusors, leading to anemia with a low reticulocyte count.

Increased risk of maternal-infant hepatitis C virus transmission for women coinfected with human immunodeficiency virus type 1. Italian Study Group for HCV Infection in Children.

To estimate the risk of mother-to-child transmission of hepatitis C virus (HCV) and identify correlates of transmission, 245 perinatally exposed singleton children followed prospectively beyond 18 months of age were studied. Overall, 28 (11.4%) of the 245 children acquired HCV infection. Transmission occurred in 3 of 80 children (3.7%) whose mothers had HCV infection alone and in 25 of 165 (15.1%; P < .01) whose mothers had concurrent infection with human immunodeficiency virus type 1 (HIV-1). The percentage of HIV-1-infected children was similar (22 of 165, 13.3%), but each virus was transmitted independently; only six infants (3.6%) were coinfected with HCV and HIV-1. The risk of HCV transmission was not associated with maternal HIV-1-related symptoms, intravenous drug use, prematurity, low birth weight, or breast-feeding, whereas it was lower with cesarean section than with vaginal delivery (5.6% vs. 13.9%, P = .06). This suggests that transmission occurs mainly around the time of delivery.

Immunoblotting analysis of IgA and IgM antibody to human immunodeficiency virus type 1 (HIV-1) polypeptides in seropositive infants.

Seventy infants born to human immunodeficiency virus type 1 (HIV-1) seropositive mothers were studied for specific antibody (IgA, IgM and IgG) production and the presence of active infection (detectable level of virus in peripheral blood lymphocytes). Among these children, followed for up to 15-40 months after birth, 11 presented unequivocal signs of HIV-1 infection (persistent p24 antigenemia and/or positive virus isolation). Analysis of sera by immunoblotting showed that IgA antibody to HIV-1 p24 core protein, alone or associated with envelope glycoproteins (gp120, gp41), was present in the majority of infected babies (7 of 11), while IgM was found in a lower percentage of cases (4 of 11). No IgA and or IgM antibody to HIV-1 was ever found in babies, born to seropositive mothers, who seroreverted after birth or in the control group enrolled in this study. Our results indicate that immunoblotting analysis of IgA antibody to HIV-1 polypeptides may represent a useful complementary prognostic marker in children born to HIV-1 seropositive mothers.

Prognostic factors and survival in children with perinatal HIV-1 infection. The Italian Register for HIV Infections in Children.

The signs that may arise after perinatal infection with human immunodeficiency virus type 1 (HIV-1) have been classified by the Centers for Disease Control, but the clinical usefulness of the classification system and the prognostic importance of each disease pattern have not been established. We sought to address these issues by analysing data from the Italian Register for HIV infection in children. We studied 1887 children born to HIV-1-seropositive mothers. 1045 were identified at birth and the others were registered later (median age 4.8 [range 0.4-72] months). HIV-1-associated signs developed in 433 (81.8%) of 529 seropositive infected children at a median age of 5 (0.03-84) months. These signs appeared significantly earlier in the 102 children who died of HIV-1-related illness than in those who are still alive (median 3 [0.03-55] vs 6 [0.03-84] months; p less than 0.001). The cumulative proportion surviving at age 9 years was 49.5% (95% confidence interval 27-65%) and the median survival time was 96.2 months. Separate analysis of the 112 seropositive infected children followed from birth and older than 15 months gave similar results. Hepatomegaly, splenomegaly, lymphadenopathy, parotitis, skin diseases, and recurrent respiratory tract infections formed the mildest disease pattern. Lymphoid interstitial pneumonitis and thrombocytopenia were signs of intermediate disease. By contrast, in multivariate analysis specific secondary infectious diseases, severe bacterial infections, progressive neurological disease, anaemia, and fever were significant and independent negative predictors of survival. Growth failure, persistent oral candidosis, hepatitis, and cardiopathy were associated in univariate analysis with significantly shorter survival. Our findings suggest that the outlook for children with perinatal HIV-1 infection is better than previously thought and that a new clinical staging system of single disease patterns is needed.

Immunohematological study in newborn infants with erythroblastosis fetalis transfused in utero.

The present study reports immunohematological data (anti-erythrocyte titer, anti-erythrocyte functional activity, percentage of sensitized erythrocytes) in 11 patients with erythroblastosis fetalis transfused in utero (IUTd). At birth it was possible to define two groups of newborns: one with low (group 1) and one with high (group 2) percentage of circulating sensitized erythrocytes, respectively. The presence of a low rate of sensitized red cells at birth in IUTd infants did not reduce the number of exchange transfusions required postnatally. On the contrary, babies of this group were affected by a more severe disease as shown by higher anti-erythrocyte maternal titer, higher anti-erythrocyte functional activity and a higher degree of fetal hemolysis. The persistence of hemolysis after birth, in spite of the absence of sensitized circulating erythrocytes, may be due to intramedullary hemolysis.

GH, ACTH, LH and FSH behaviour in the first seven days of life.

--43 neonates, born vaginally after spontaneous labor between the 38th and the 42nd week of pregnancy, were examined. GH and ACTH levels were assayed in 14 newborn infants. LH and FSH were determined in the remaining 29 patients (16 boys and 13 girls). Samples were collected from all infants for the assay of the above mentioned hormones at the 2nd, 6th, 12th and 24th hour of life, then every day for 7 consecutive days. During the whole first week of life plasma GH gave values that were significantly higher than those found in subjects over four years of age. The highest mean value of plasma ACTH was found at the 2nd hour of life (162.2 +/- 34.1 pg/ml). Then, there is a significant fall in the hormone level beginning with the 12th hour (p less than 0.01). Minimum level was reached on the 7th day. Plasma hCG-LH presents its maximum mean value at the 2nd hour, both in boys and girls (48.5 +/- 16.2 and 33.0 +/- 24.9 mU/ML, respectively). after this, plasma hCG-LH decreases progressively. No significant differences between the two sexes were found. Even though the mean values of plasma FSH do not change significantly during the whole test period, they do demonstrate a sex difference (significantly higher values in the females) from the fifth day afterwards.