Intrauterine infection and cord immunoglobulin M: I. Analysis of methods of assay and levels of immunoglobulin M in normal newborns

An analysis of methods of assay and levels of immunoglobulin M in the cord serum of 100 normal newborn infants is reported. The geometric mean level of cord IgM was found to be 9.8 mg.%. The 95th percentile value was 19.6 mg.%. IgM levels on day one were not significantly different from cord levels, while by day five a significant increase had occurred (geometric mean 13.6 mg.%). IgA was present in only 3/100 cord sera (in levels above 6.0 mg.%). Any increment of day five IgM over cord levels greater than threefold is thought to be abnormal and this parameter will be further evaluated as an index of neonatal sepsis. Use of locally produced reagents in the IgM assay was found to be more accurate and inexpensive than the commercially available reagents.     

Intrauterine infection and cord immunoglobulin M III. Serological analysis of infants with elevated cord serum immunoglobulin M

The presence of antibodies to rubella, cytomegalovirus and Toxoplasma gondii was determined at birth and at 6 months of age in a group of 147 infants with cord serum IgM levels ≥ 19.0 mg/dl and in 92 control infants. Maternal syphilis serology was determined in both groups as well. No significant differences in the prevalence or levels of antibodies to these pathogens were found between the two groups which might have led to the diagnosis of unsuspected intrauterine infection. Persistence of antibodies to 6 months of age was similar in the two groups, indicating that this is not a useful index of intrauterine infection.Analysis of the results yielded the following data on the prevalence of antibodies to the pathogens studied: rubella virus, 90 and 75% seropositivity at birth and 6 months respectively; cytomegalovirus, 65 and 35%; and Toxoplasma gondii, 33% seropositivity at birth.     

Enhancement of antitoxic immunity in newborn infants by peroral administration of donor antistaphylococcal immunoglobulin

The possibility of enhancing specific immunity by the oral administration of homologous antistaphylococcal immunoglobulin in a dose of 50 I. U./kg b. w. before the first feeding was shown in 75 newborn infants with a high risk of staphylococcal infection. 24 hours after the first administration of Ig the titer of staphylococcal anti-alpha toxin in the blood rose from 0.68 +/- 0.05 I. U./ml to 2.9 +/- 0.14 I. U/ml, on day 7 this titer persisted at the level of 2.86 +/- 0.12 I. U./ml, and 3 months later the titer was 1.5 +/- 0.05 I. U./ml. No side effects were observed. In the reference group (50 infants) antitoxic titers remained low. No suppurative-septic diseases were observed in the test group within 3 months, while in the controls, focal forms of staphylococcal infection (12 cases) and sepsis (1 case) were registered.     

The creation of specific immunity to staphylococcal infection in newborn infants by the intranasal administration of adsorbed staphylococcal anatoxin

The possibility of enhancing specific immunity in newborn infants by the intranasal administration of adsorbed staphylococcal toxoid to infants with a high risk of staphylococcal infection in doses of 1 drop (0.05 ml) into each nostril during the first 7-9 years of their life. On days 7-9 the level of anti-alpha-toxin in the blood rose to 3.8 +/- 0.14 I. U./ml and remained sufficiently high 3-6 months later. When this method was used for the simultaneous immunization of mothers, their antitoxic titers were not as high as in newborn infants. No side effects were observed. In the control group, the titers of anti-alpha-toxin were low during the whole period of observation. Infants immunized by the proposed method had no staphylococcal infections both during the newborn period and within the first year of their life. In the control group, 8 cases of minor forms of purulent septic infection were registered during the newborn period, and in 2 infants umbilical staphylococcal sepsis was diagnosed.     

Immunoglobulin Levels in Newborn Infants with Hepatosplenomegaly

Serum IgM and IgA levels were measured in 97 newborn infants with and 141 without hepatosplenomegaly. All were considered normal at birth and had no apparent disease on clinical examination. Thirty per cent. of the infants with hepatosplenomegaly were found to have IgM levels of 20 mg/100 ml or greater, a level established as abnormal when compared with the control group. The number of infants with raised IgM level and the geometric mean level were significantly different (P < 0·001) from those in the control group. No difference, however, was found in serum IgA levels between the two groups of infants. The results suggest that intrauterine infections may sometimes be the cause of hepatosplenomegaly in newborn infants without apparent disease.     

Leptin concentrations in cord blood in normal newborn infants and offspring of diabetic mothers.

Leptin has been implicated in the regulation of body weight and energy balance; Leptin is produced by adipocytes and placental tissue. Chronic fetal hyperinsulinemia and accelerated fetal growth with increased amounts of body fat are frequent findings in the offspring of diabetic mothers. In this study, we examined whether leptin levels in cord blood of infants of type 1 diabetic mothers (n = 29), gestational diabetic mothers (n = 6 and controls (n = 96) correlated with level of maternal glucose control, maternal leptin level at delivery, gender, fetal and placental size, and C-peptide in cord blood at birth. Leptin was significantly elevated in infants of type 1 diabetic (24.7 ng/ml) and gestational diabetic mothers (29.3 ng/ml) as compared to controls (7.9 ng/ml). C-peptide was also significantly higher in infants of type 1 diabetic (0.91 nmol/l) and gestational diabetic mothers (0.99 nmol/l) vs controls (0.34 nmol/l). Infants of type 1 diabetic mothers with a leptin level in cord blood above the upper normal range, i.e. > 30 ng/ml (n = 13), had an average maternal HbA1c level of 5.4% (normal < 5.5%) that was not different from 5.2% in infants with a leptin level < 30 ng/ml (n = 15). In both neonatal groups of diabetic mothers, leptin in cord blood did not correlate with maternal leptin concentrations, placental weight, birthweight, gender and cord blood C-peptide. In controls, leptin in cord blood was higher in girls than in boys (p = 0.044) and correlated significantly with birthweight (p = 0.41, p < 0.001) and cord blood C-peptide (p = 0.44, p < 0.001) but not with maternal leptin level or placental weight. The 3-4 times higher leptin levels in the offspring of diabetic mothers than normal could reflect increased adipose tissue mass and/or increased contribution from other sources such as placental tissue.     

Thyroxine-binding globulin, triiodothyronine, thyroxine and thyrotropin in newborn infants and children.

Thyroxine-binding globulin (TBG), triiodothyronine (T3), thyroxine (T4) and thyrotropin (TSH) have been determined by radioimmunoassay in plasma of newborn infants and throughout childhood until puberty. Mean maternal TBG concentration was 1.65 +/- 0.09 mg/100 ml (SEM) and significantly higher (p less than 0.01) than cord blood levels of TBG (1.16 +/- 0.08 mg/100 ml (SEM). Throughout infancy and childhood TBG remained significantly elevated (p less than 0.01) compared to a middle age control group of healthy blood donors. T3, T4 and TSH concentrations behaved postnatally as known from previous studies. The T3 and T4 increase observed immediately after birth was not a secondary phenomenon due to changes in TBG concentration since this globulin did not change significantly during this period.     

Prospective Study of Serum Cholesterol Levels during First Year of Life

A longitudinal prospective study of serum cholesterol concentrations during the first year of life has been carried out in 302 healthy babies. The results show that serum cholesterol estimations in cord blood cannot be used as a screening test for the diagnosis of familial hypercholesterolaemia. The only child subsequently found to have the condition had a cord serum cholesterol of 85 mg/100 ml compared with the mean value for the group of 78 mg/100 ml. The babies who had cord values greater than 100 mg/100 ml had values distributed throughout the normal range when re-examined at 1 year of age. Serum cholesterol concentrations during the early months of life were markedly influenced by the type of milk fed; it is suggested that investigations to establish the diagnosis of familial hypercholesterolaemia are deferred until the child is about 1 year old and feeding with cows'' milk and mixed diet is established.Values obtained for serum cholesterol concentrations (mg/100 ml, mean ± 1 S.D.) in healthy infants in this study were: at birth 78 ± 23, at 1 week 155 ± 31, at 6 weeks 155 ± 31, at 4 months 184 ± 36, at 8 months 195 ± 37, and at 1 year 191 ± 36.     

Failure of Glucagon Release in Infants of Diabetic Mothers

Two hours after birth 30 normal infants had a fall in blood glucose of 20·6 mg/100 ml and a rise of plasma pancreatic glucagon of 50·7 pg/ml. Fifteen infants of diabetic mothers treated with insulin had a much greater fall in blood glucose of 77·5 mg/100 ml and a smaller rise of glucagon of 20·9 pg/ml. By comparison 14 small-for-dates infants, who are also prone to hypoglycaemia, had a blood glucose fall of 32·8 mg/100 ml and a larger rise of pancreatic glucagon of 96·0 pg/ml. It is suggested that the impaired pancreatic glucagon rise in the infants of diabetic mothers may be a significant factor in their hypoglycaemia.     

Fatty acid values in the plasma of neonates, umbilical cord and maternal blood

The proportion of a wide range of fatty acids was studied in the plasma of 15 healthy newborn infants following a physiological pregnancy and delivery. The same measurements were done in seven healthy mothers (immediately after parturition) and the proportion of fatty acids was analysed in mixed umbilical cord blood (n = 7). The fatty acids were identified by gas chromatography as their methyl esters (FAME). In newborn infants the proportion of saturated fatty acids was found to be 42.3%, of monoene fatty acids 31.3% and of polyene fatty acids 25.4%; type n-6 fatty acids formed 13.9% and n-3 11.1%. The proportion of the various fatty acids in healthy maternal plasma was 37.9% (saturated), 34.4% (monoene) and 25.0% (polyene) respectively; type n-6 fatty acids formed 21.6% and type n-3 only 3.6%. The values in mixed cord blood were 44% (saturated FA), 34.8% (monoene FA) and 20% (polyene FA); group n-6 FA accounted for 17.4% and n-3 for only 2.1%. In the above three series we also described the sequence of the fatty acids present in the largest amounts. This is part of an extensive study, in a large series, of the commonest perinatal risks. We particularly draw attention to the high proportion of long-chain fatty acids (C 22 - C 26) in the plasma of healthy newborn infants.     

The Neurological and Developmental Effects of Neonatal Hypoglycemia: A Follow-up of 22 Cases

Twenty-two infants in whom hypoglycemia (blood sugar less than 20 mg./100 ml.) was noted during the first few days of life were followed up when eight to 30 months of age. In eight such symptoms as muscular tremors, cyanosis, apneic spells and convulsions were associated with the hypoglycemia; five of these had abnormal central nervous system signs and retarded development. One other had possible impairment of development and another had a recurrence of hypoglycemia after having been well for four years. Fourteen of the 22 infants had no symptoms associated with the hypoglycemia, and on follow-up only two of these showed possible impairment. The rest were normal.This preliminary study suggests that hypoglycemia associated with neurological symptoms in the newborn period carries a poor prognosis with respect to permanent neurological damage. Asymptomatic hypoglycemia may have a relatively good prognosis.     

PCT, IL-6及CRP 对新生儿宫内细菌感染的诊断价值

目的:探讨降钙素原(PCT)、白细胞介素-6(IL-6)及C反应蛋白(CRP)对新生儿宫内细菌感染的诊断价值。方法:根据感染结局将2013年3月-2014年9月在我院分娩且有宫内感染高危因素的179例新生儿分为感染组(34例)和无感染组(145例),检测两组新生儿的PCT、IL-6及CRP水平,并比较其对宫内细菌感染的诊断价值。结果:感染组新生儿脐带血PCT、IL-6、CRP水平均高于无感染组,差异有统计学意义(P0.05)。感染组新生儿各单个指标阳性率、两指标联合检测阳性率高于无感染组,差异均有统计学意义(P0.05),感染组新生儿PCT、IL-6阳性率高于CRP,PCT+IL-6的阳性率高于PCT+CRP、IL-6+CRP,差异均有统计学意义(P0.05)。PCT+IL-6的灵敏度、准确率高于单个指标及其他两个指标联合检测,差异均有统计学意义(P0.05),各项指标检测的特异性比较,差异无统计学意义(P0.05)。结论:新生儿宫内感染采用脐带血PCT检测具有灵敏度高、特异性好的特点,联合IL-6检测是临床诊断新生儿宫内感染的有效方式。     

Evaluation of cord blood immunoglobulin E and its association with maternal factors in a group of Iranian newborns

Allergic disorders are among the most common diseases around the world especially in children. Many factors contribute to the pathogenesis of atopic disorders, but early events during the pregnancy are very important. The aim of this study was to evaluate the level of cord blood immunoglobulin E (CB-IgE) and its association with maternal in a group of Iranian newborns. In a cross-sectional study, 163 pregnant women randomly selected and information about pregnancy and atopy were taken by questionnaire. Blood samples of mothers and matched cord blood were collected and total serum IgE levels were measured by enzyme-linked immunosorbent assay (ELISA) method. To rolling out the possibility of contamination with maternal blood, total IgA was checked for all the cord blood samples. Sixteen percent of mothers had the history of atopic diseases and the mean IgE level was significantly higher in an atopic than nonatopic mothers (241 vs 102, P < 0.001). About 73.9% of cord blood samples, had high IgE level (>0.9 IU/mL). The level of cord blood IgE (CB-IgE) was not significantly different in male and female newborns (2.14 vs 2.15 IU/mL). There was no significant correlation between maternal factors such as age, pregnancy variables, allergens exposure, smoking, and maternal IgE with cord blood IgE. The results of this study showed that CB-IgE is high in a remarkable number of samples; independent of maternal or fetal factors. Further studies need to evaluate the reasons for the high level of IgE in cord blood in our area.     

乙型肝炎病毒胎内及围产期传播的研究

对78名HBsAg携带者母亲的新生儿系列血清,用ELISA检测抗-HBc·IgM,有5名出生后48小时血清阳性滴度在1:1,000以上,占6％。有3名母血HBeAg阳性的新生儿,其脐血、出生后48小时足跟血及以后的连续血清标本HBsAg均阳性,且滴度趋于升高。母血抗-HBc·IgM均阴性。认为前者可能为HBV眙内感染,后者为母血通过胎盘溃面直接进入胎儿血循环所致。     

Cord transferrin and ferritin values for erythropoiesis in newborn infants of diabetic mothers

Neonatal polycythemia is a perinatal complication in infants of diabetic mothers. The cord CBC (complete blood counts), serum iron, transferrin and ferritin concentrations were studied in newborn infants of 9 GDM (gestational diabetes), 21 NIDDM (noninsulin-dependent diabetes mellitus), and 8 IDDM (insulin-dependent diabetes mellitus) mothers. The RBC (red blood cell) count, Hb (hemoglobin) and Hct (hematocrit) of these infants were higher than control infants. There was no difference between the serum iron concentration of the infants of each group diabetic mothers and the infants in the control group, but the transferrin concentration was significantly higher and the ferritin was significantly lower in the infants of diabetic mothers than in those of control mothers. There was a significant negative correlation between transferrin and ferritin (r = -0.491 p less than 0.001). Erythropoiesis is considered to be enhanced in the fetuses of diabetic mothers, and the iron needed for erythropoiesis is reportedly transported from the mother to the fetus according to the demands of the fetus, but the iron storage was shown to be reduced in the fetuses of diabetic mothers.     

Hypoglycemia Associated with Symptoms in the Newborn Period

Hypoglycemia in the neonatal period is a well-recognized phenomenon, but many authors have commented upon the infrequent association of symptoms attributable to it. Six infants were seen who appeared normal at birth but who, between 24 and 72, hours of age, developed apnea, irritability, lethargy, muscular twitchings and convulsions. Blood sugar concentrations of 10 mg./100 ml. or less were found in each case. The mothers of four of the babies had toxemia of pregnancy. Three babies were premature. The hypoglycemia was self-limiting in all cases, and four of the babies recovered completely without sequelae. The other two showed evidence of permanent brain damage, but it is not known whether this was the cause of their symptoms or the result of the hypoglycemia. It is concluded that hypoglycemia may cause neurological symptoms in the newborn period and that treatment by glucose administration is necessary. Whether symptomless hypoglycemia requires treatment remains an open question.     

A prostaglandin-mediated suppressive activity of cord as compared to maternal or other adult adherent cells in OKT3 antibody-induced proliferation

In a previous study we reported that cord blood lymphocytes show lower OKT3 responses as compared to their mothers and to other, unrelated adults. In the study reported here, we investigated the interactions between lymphocytes and adherent accessory cells in OKT3-stimulated cultures of newborn (cord), maternal, and other adult peripheral blood mononuclear leukocytes (PBML) and determined the following. (1) Removal of adherent cells (AC), by two cycles of plastic adherence or by nylon wool columns, impaired the OKT3-induced proliferation of maternal/adult cells, but significantly enhanced the OKT3 responsiveness of cord cells. (2) Addition of indomethacin, and other prostaglandin (PG) synthesis inhibitors, caused a more than twofold augmentation of cord PBML OKT3 responses, but had only a small, if any, enhancing effect on maternal/adult PBML. Cord PBML cultures deprived of AC were no longer enhanced by indomethacin. (3) Exogenous PGE2 (1.4 X 10(-6) through 1.4 X 10(-9) M) strongly inhibited OKT3-induced proliferation of maternal, cord, and adult PBML, at a wide range of antibody concentrations (5-100 ng/ml). However, an obvious difference in the extent of PG-mediated inhibition was observed among these three populations, and the order of PG sensitivity, from most to least sensitive, was cord greater than maternal greater than adult. (4) Purified interleukin-1 (IL-1) could not replace the accessory function of AC in the OKT3-induced proliferation of maternal/adult lymphocytes. In contrast, IL-1 increased by greater than 50% the OKT3 responsiveness of cord PBML in the absence, but not in the presence, of cord monocytes. Our observations strongly argue for a distinct, predominantly suppressive function of cord monocytes as compared to maternal/adult monocytes in OKT3-induced mitogenesis, and indicate prostaglandins as major mediators of this suppression.     

Cell-mediated immune responses to Chlamydia trachomatis in mothers and infants

Cell-mediated immunity to Chlamydia trachomatis was studied in pregnant women with chlamydial infection of the cervix, in infants born vaginally to these women, and in infants presenting with chlamydial conjunctivitis. Uninfected pregnant women and their infants were studied as controls. McCoy cell cultures were used to isolate C. trachomatis from clinical specimens. Cell-mediated immunity was measured by lymphocyte proliferative responses in vitro to stimulation by chlamydial antigens. Chlamydial IgG antibody in serum specimens was detected by a microenzyme-linked immunosorbent assay technique. The mean lymphocyte proliferative responses to chlamydial antigens were greater in infected women than in uninfected women both during pregnancy and in the postpartum period. Lymphocyte responsiveness in infected pregnant women, however, was less than in postpartum women. Despite failure to detect chlamydial infection in exposed infants, lymphocyte proliferative responses were greater in umbilical cord blood and later in peripheral blood samples from neonates born to infected mothers than in infants born to uninfected mothers. These responses were also greater in infants with chlamydial conjunctivitis than in infants of uninfected mothers. These data suggest that cellular immune responses to chlamydial antigens are increased in infected mothers and infants and that infants may acquire chlamydial cell-mediated immunity transplacentally.     

Modification of cord blood IL-6 production with IgM enriched human immunoglobulin in term and preterm infants

Pro-inflammatory cytokines contribute significantly to the morbidity of premature infants. IL-6 and IL-8 are involved in the pathogenesis of pulmonary and cerebral tissue injury. The effect of human immunoglobulin preparations on cytokine production in preterm infants has not been studied. We investigated the influence of immunoglobulin on LPS stimulated IL-6 and IL-8 production in cord blood of healthy preterm neonates. Ten non-infected preterm infants delivered by cesarean section and 5 healthy term neonates were included. In the preterm infants, significant IL-6 production was observed in the absence of immunoglobulin after 4 h [median 113 (39-725) pg/ml], 8 h [375 (234-1795) pg/ml] and 12 h [360 (248-2765) pg/ml] of LPS incubation. IL-6 concentrations were significantly lower after incubation with LPS+immunoglobulin after 4 h [median 38 (5-568) pg/ml; p=0.005], 8 h [178 (10-1830) pg/ml; p=0.001] and 12 h [182 (29-2530) pg/ml; p=0.002]. Cultures from term infants produced IL-6 levels approx. 4 times of those from premature infants unaffected by immunoglobulin. IL-8 production also correlated to gestational age and was not affected by immunoglobulin in both groups. Human immunoglobulin preparation may modify IL-6 production in cord blood cultures from premature infants.     

Cord blood and breast-milk antibodies in neonatal rotavirus infection.

Studies were carried out during an outbreak of rotavirus type 2 infection in a neonatal nursery to determine the protective role of antibodies in cord blood and breast milk. The range, distribution, and geometric mean titres of rotavirus-specific antibody in the cord blood were similar among rotavirus-positive and rotavirus-negative neonates, and the amount of virus excreted did not correlate with antibody levels. Despite the protective effect of breast feeding, the pattern of rotavirus-specific IgA and IgG antibodies in the expressed breast milk of mothers of babies who were rotavirus excreters and non-excreters was similar. Nevertheless, a higher proportion of expressed breast milk samples contained rotavirus-specific IgA group 2 (92%) and type 2 (97%) specific antibodies than type I (67%) antibodies, and the geometric mean titres of group 2 and type 2 specific antibodies were tenfold higher than type I antibodies. Among breast-fed babies who excreted rotavirus there was no correlation between type 2 rotavirus-specific IgA antibodies in expressed breast milk and the amount of neonatal virus excretion. These studies suggest that factors other than the rotavirus antibodies in expressed breast milk are of importance in preventing rotavirus infection in newborn infants.