母血、脐血INS、GLUC、COR RIA及其意义

目的：测定胎龄儿（AGA）母血、脐血胰岛素（INS）、胰高血糖素（GLUC）、皮质醇（COR）水平,探讨AGA体重与孕妇体重指数（BMI）及母血脐血INS、GLUC、COR相关性及意义。方法：随机选取无明显产科并发症的母亲及新生儿,共26对,新生儿分为体重偏低组（A组）及体重偏高组（B组）,采用放射免疫分析测定INS、GLUC、COR含量。结果：新生儿体重与孕妇BMI有明显关系,B组孕妇BMI显著高于A组（P〈0．05）;新生儿GLUC与COR水平与孕妇比较也具重要的统计学意义（P〈0．05,P〈0．01）;B组新生儿COR含量远高于A组水平（P〈0．01）,而GLUC则相反（P〈0．05）。结论：胎儿发育与孕妇BMI及母血、脐血INS、GLUC及COR水平有关,提示母亲营养状况与上述三种代谢激素的分泌水平直接影响胎儿发育。     

A study of serum bilirubin in neonates in relation to the maternal age

A comparative study of neonatal serum bilirubin levels was done in neonates of different age groups of mothers. A total 122 healthy, new borns were selected for the study, born at Queen Mary's Hospital, Lucknow. Mothers were divided into two groups i.e. < 30 years and > 30 years of age. Samples of blood were collected thrice, first on day 1 from cord blood, 2nd and 3rd on days three and five of life from neonates by heel prick method, using small bore capillaries for blood collection, serum bilirubin estimation were done by the method of Malloy & Evelyn and Mean +/- SD were calculated. P-Value was observed between different age groups. In both the groups of mothers i.e. < 30 years and > 30 years serum bilirubin levels in their neonates raised to highly significant levels on day 3 (P-Value < 0.001) as compared to their cord blood serum bilirubin levels. On comparing serum bilirubin levels in neonates of both the maternal groups, it was observed that there is no significant difference between two groups on day of birth and day day 5 but statistically significant difference was observed on day 3 (P < 0.05), serum bilirubin levels were higher in neonates of younger age group mothers.     

Relationship between maternal and infant iron stores: 1. Full term infants

Serum ferritin, serum iron and total iron binding capacity were determined in 218 pregnant women at term and in the cord blood of their normal term infants. Both the mean weight (3210 g) and serum ferritin level (geometric mean 81 micrograms/l) of the neonates of iron deficient mothers were significantly lower than those of mothers with "normal" iron stores (weight 3390 g; cord ferritin level 115 micrograms/l). A weakly significant correlation was found between the logarithm of the maternal and neonatal serum ferritin concentration (r = 0.15, p less than 0.05) and the maternal log serum ferritin and the newborn's weight (r = 0.15, p less than 0.05). The weak correlations were supported by the differences between the values of cord samples from babies of iron deficient mothers and those whose mothers had "normal" iron values. Adequate iron supplementation during the early period of pregnancy is suggested.     

Correlation of serum HDL-cholesterol and LCAT levels with the fraction of ionized magnesium in children.

Correlation of serum lipids and apolipoprotein levels with serum total magnesium concentration and whole blood ionized magnesium level was determined in 47 children (14 female and 33 male; mean age, 8.7 +/- 4.2 years). Mean serum concentration of magnesium was 2.19 +/- 0.19 mg/dl, whole blood concentration of ionized magnesium 1.23 +/- 0.08 mg/dl, and fraction of ionized magnesium (ratio of whole blood ionized magnesium to serum total magnesium) 0.56 +/- 0.04. Neither serum total magnesium level nor whole blood ionized magnesium level had any correlation with serum albumin, lipid, and apolipoprotein levels. However, the fraction of ionized magnesium was significantly correlated with HDL-cholesterol (n = 46, r = 0.31, p = 0.0345), apolipoprotein A-1 (n = 41, r = 0.39, p = 0.0124), and lecithin-cholesterol acyltransferase (LCAT) (n = 20, r = 52, p = 0.0184). These results suggest that fraction of ionized magnesium is more closely linked to serum HDL-cholesterol and LCAT level than with the serum total magnesium level or whole blood ionized magnesium.     

Cord blood resistin and adiponectin in term newborns of diabetic mothers

Introduction

Adipose tissue can release hormones into the blood stream in response to specific extracellular stimuli or changes in metabolic status. Resistin, an adipose-secreted factor, is primarily involved in the modulation of insulin sensitivity and adipocyte differentiation. Adiponectin, an adipocyte-specific hormone with insulin sensitizing, anti-inflammatory and anti-atherogenic effects, is reduced in obesity and type II diabetes. The aim of the study was to assess the influence of maternal pre-existing diabetes on cord blood resistin and adiponectin at birth in relation to neonatal anthropometric parameters and cord blood insulin levels.

Material and methods

A total of 60 term newborns were prospectively enrolled and categorized into three groups: 20 were macrosomic infants of pre-gestational diabetic mothers (group I), 20 were non-macrosomic infants of pre-gestational diabetic mothers (group II) and 20 were healthy non-macrosomic infants born to non-diabetic mothers serving as controls (group III). Infants’ anthropometric indices were recorded. Cord blood samples for glucose, insulin, resistin and adiponectin assay, together with maternal glycosylated haemoglobin were obtained.

Results

Serum insulin was increased while resistin and adiponectin were significantly decreased in infants of diabetic mothers (IDMs) compared to the control group. Serum glucose, insulin, resistin and adiponectin were comparable in group I and II. Cord serum resistin correlated positively with cord blood glucose in IDMs in both macrosomic and non-macrosomic groups. Cord serum insulin correlated positively with triceps skinfold thickness in all studied neonates. Cord serum resistin and adiponectin showed no correlation with neonatal anthropometric indices. Multiple regression analysis demonstrated that insulin, resistin and adiponectin together were highly correlated with birth weight, with adiponectin as the one responsible for this positive correlation.

Conclusions

Infants of diabetic mothers had elevated levels of cord serum insulin and suppressed levels of cord serum resistin and adiponectin, suggesting that the regulation of these metabolic pathways is probably operational before birth. Levels were comparable in both macrosomic and non-macrosomic neonates.     

Wound healing: time to look for intelligent, ‘natural’ immunological approaches?

Oxidative damage present in obese/overweight mothers may lead to further oxidative stress conditions or inflammation in maternal and cord blood samples. Thirty-four pregnant women/newborn pairs were included in this study to assess the presence of oxidative stress biomarkers and their relationship with serum cytokine concentrations. Oxidative stress biomarkers and antioxidant enzymes were compared between the mother/offspring pairs. The presence of 27 cytokines was measured in maternal and cord blood samples. Analyses were initially performed between all mothers and newborns and later between normal weight and mothers with overweight and obesity, and diabetic/non-diabetic women. Significant differences were found in biomarker concentrations between mothers and newborns. Additionally, superoxide-dismutase activity was higher in pre-pregnancy overweight mothers compared to those with normal weight. Activity for this enzyme was higher in neonates born from mothers with normal pregestational weight compared with their mothers. Nitrites in overweight/obese mothers were statistically lower than in their offspring. Maternal free fatty acids, nitrites, carbonylated proteins, malondialdehyde and superoxide dismutase predicted maternal serum concentrations of IL-4, IL-13, IP-10 and MIP-1β. Arginase activity in maternal plasma was related to decreased concentrations of IL-4 and IL-1β in cord arterial blood. Increased maternal malondialdehyde plasma was associated with higher levels of IL-6 and IL-7 in the offspring. Oxidative stress biomarkers differ between mothers and offspring and can predict maternal and newborn cytokine concentrations, indicating a potential role for oxidative stress in foetal metabolic and immunologic programming. Moreover, maternal obesity and diabetes may affect maternal microenvironments, and oxidative stress related to these can have an impact on the placenta and foetal growth.     

Prenatal immune priming with helminth infections: parasite-specific cellular reactivity and Th1 and Th2 cytokine responses in neonates

The present investigation aimed to determine to what extent maternal helminth infection primes parasite-specific cellular responsiveness in neonates. Umbilical cord mononuclear blood cells (UCBC) and peripheral blood mononuclear cells (PBMC) from mothers proliferated in response to mitogenic stimulation with concanavalin A, as well as to bacterial Streptococcus pyogenes-derived (streptolysin O) and helminth-specific antigens of Necator americanus and Onchocerca volvulus. Cellular responses to Echinococcus multilocularis (Em) and Oesophagostomum bifurcum (Oes), helminth parasites not endemic in the study area, were absent (for Em) or very low (for Oes due to antigenic cross-reactivity). Cellular responsiveness to mitogen and antigens was higher in mothers than in their neonates. Several Th1-type (IL-2, IL-12, and IFN-gamma) and Th2-type (IL-5 and IL-10) cytokines were produced by UCBC from neonates and PBMC from mothers. Low levels of IFN-gamma were elicited by UCBC in response to helminth and bacterial antigens, while secretion of IL-2 was pronounced and similarly high in neonates and their mothers. Amounts of IL-5 produced by UCBC in response to bacterial SL-O and mitogenic stimulation (PHA) were low, but equivalent levels of IL-5 were induced by intestinal helminth and filaria-derived antigens in neonates and mothers. A pronounced production of IL-10 and IL-12 by UCBC was observed--spontaneous IL-10 and IL-12 secretion by UCBC was higher in neonates than by PBMC from mothers. Net amounts of IL-10 elicited by helminth antigens were similar, while net IL-12 in response to mitogen, and bacterial and helminth antigens was significantly higher in mothers than their offspring. Our results indicate that human maternal helminth infection does sensitize in utero for parasite-specific cellular responsiveness in offspring, and also activates specific production of several cytokines, and such children do not present a dominant expression of immunity of either Th1 or Th2.     

Antithyroid drug therapy for Graves' disease during pregnancy. Optimal regimen for fetal thyroid status

We compared fetal and maternal serum indexes of thyroid status at delivery in 70 patients with Graves' disease who required therapy with thionamides (such as propylthiouracil) during pregnancy. Forty-three mothers required thionamides until delivery (Group 1), whereas the drugs were discontinued during pregnancy after remission in 27 mothers (Group 2). Maternal free thyroxine levels were closely correlated with cord levels in both groups, being essentially identical in Group 2 but slightly lower in fetuses than in mothers in Group 1. Normal maternal free thyroxine levels did not preclude fetal hypothyroidism. The mothers and fetuses in Group 1 had a significantly higher incidence of antibodies that inhibit thyrotropin binding than did those of Group 2. However, a significant correlation between maternal levels of these antibodies and cord levels of free thyroxine or triiodothyronine was found only in Group 2, in which some maternal and cord thyroxine levels were in the thyrotoxic range at delivery, presumably because therapy was discontinued. These findings indicate that high free thyroxine levels and the presence of antibodies that inhibit binding of thyrotropin are useful indexes of the fetal need for antithyroid treatment, and that the thionamide dosage that maintains maternal free thyroxine levels in a mildly thyrotoxic range seems appropriate for maintaining euthyroid status in the fetus.     

Maternal-fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis

The fact that neonates who subsequently have severe hypothyroidism have no evidence of the condition at birth suggests the possibility of the placental transfer of thyroid hormones. Recent studies have demonstrated the existence of such transfer in hypothyroid rats. To determine whether there is a transfer of thyroxine (T4) from mother to fetus, we studied 25 neonates born with a complete inability to iodinate thyroid proteins and therefore to synthesize T4. This total organification defect is an autosomal recessive disorder with an incidence of approximately 1 in 60,000 neonates in the Netherlands. In the cord serum of affected neonates, T4 levels ranged from 35 to 70 nmol per liter. Since these patients were unable to produce any T4, the T4 must have originated in their mothers. The estimated biologic half-life of serum T4 was 3.6 days (95 percent confidence interval, 2.7 to 5.3). In 15 neonates with thyroid agenesis, the serum levels and the disappearance kinetics of T4 were the same as those in the neonates with a total organification defect, suggesting that in these infants, the T4 also had a maternal origin. We conclude that in infants with severe congenital hypothyroidism, substantial amounts of T4 are transferred from mother to fetus during late gestation.     

Decreased opsonic activity forStaphylococcus aureus in neonatal and late gestation maternal sera

Heat-killedStaphylococcus aureus (ATCC strain 25923) andEscherichia coli K-12 were used as target microorganisms for opsonization by serum from neonates or mothers at various stages of pregnancy or postpartum. The level of opsonic activity was evaluated by titrating serum for the ability to coat bacteria for recognition by normal human PMN. Recognition of the organisms was quantitated by measuring the PMN Superoxide anion generation response to opsonized organisms. Studies show that opsonic activity forS. aureus was markedly decreased in serum from mothers in their second and third trimesters of pregnancy, in cord blood, and from infants at two weeks of age. Decreased activity was not observed in maternal serum in the first trimester of pregnancy and returned to control levels shortly after delivery. No significant difference was seen in opsonic activity forE. coli in these sera. The reduction in serum opsonic activity in mothers during the second and third trimesters of pregnancy suggests a systemic suppression of maternal immune responses during fetal development. This decreased activity is also observed in neonatal sera.Supported in part by DHHS grant CA20819 from the National Cancer Institute.     

Magnesium levels in critically ill patients. What should we measure?

We studied the relation between ionized magnesium, total magnesium, and albumin levels in serum of 115 critically ill patients and the role of extracellular and intracellular magnesium in outcome prediction. Levels of serum total and ionized magnesium, serum albumin, and magnesium in mononuclear blood cells and erythrocytes were measured and the APACHE II score and 1-month mortality recorded. Of all patients, 51.3% had a serum total magnesium concentration below the reference range. In 71% of these hypomagnesemic patients, a normal serum ionized magnesium concentration was measured. None of the patients had an intracellular magnesium concentration below the reference limit. Except for serum total and ionized magnesium, none of the magnesium parameters correlated significantly with each other. A significantly negative correlation was found between serum albumin and the fraction ionized magnesium. There was no association between low extracellular or intracellular magnesium and clinical outcome. The observation of hypomagnesemia in critically ill patients depends on which magnesium fraction is measured. The lack of correlation with clinical outcome suggests hypomagnesemia to be merely an epiphenomenon. Reliable concentrations of serum ionized magnesium can be obtained only by direct measurement and not by calculation from serum total magnesium and albumin.     

The infant of the diabetic mother: correlation of increased cord C-peptide levels with macrosomia and hypoglycemia.

C peptide is secreted by pancreatic beta cells in amounts equimolar with insulin, and its levels provide a direct indication of endogenous fetal levels of insulin despite the presence of maternal insulin antibodies. To determine the presence of hyperinsulinemia and its relation to the development of complications in infants of diabetic mothers, we measured cord serum levels of C peptide in 79 infants of diabetic mothers and 62 infants of nondiabetic mothers. Infants of diabetic mothers had higher cord levels of C peptide, which were significantly associated with neonatal hypoglycemia and macrosomia (P less than 0.001) but not with hyaline-membrane disease. Cord levels of C peptide in infants of diabetic mothers were elevated at the earliest gestational age studied (less than 34 weeks) and were directly related to the severity of maternal diabetes, as assessed by the White classification. We conclude that hyperinsulinemia is present in infants of diabetic mothers and that it is related to some major complications in such infants.     

Relationship between hypermagnesaemia in preterm labour and adverse health outcomes in babies.

The Magnesium and Neurologic Endpoints Trial (the so-called MagNET Trial) was a randomized clinical trial that was undertaken to establish whether the antenatal usage of magnesium sulphate could protect neonates from having adverse neurologic outcomes. Unfortunately, the trial was suspended after 15 months of enrolment because of excess total paediatric mortality among those exposed to magnesium sulphate. Following our original report and contrary to the original hypotheses, additional analyses of our data have actually shown a statistically significant increase in the risk of neonatal intraventricular hemorrhage, as well as total adverse paediatric outcomes, among those with higher levels of ionized magnesium at delivery. Nonetheless, it has been postulated, but not established, that anions of magnesium other than sulphate could have a more benign, or even beneficial, effect on health outcomes in the neonate.     

Divalent cations in essential hypertension. Relations between serum ionized calcium, magnesium, and plasma renin activity

We studied the relation of plasma renin activity to serum levels of ionized calcium and magnesium in 102 normotensive patients and in 98 patients with essential hypertension who were divided into low-renin, normal-renin, and high-renin groups. Serum magnesium levels were higher in patients with low-renin hypertension and lower in patients with high-renin hypertension than in those with normal-renin hypertension (P less than 0.025 for both comparisons) or in normotensive controls (P less than 0.005, P less than 0.05, respectively). In contrast, serum levels of ionized calcium were lower in patients with low-renin hypertension and higher in patients with high-renin hypertension than in those with normal-renin hypertension (P less than 0.001, P less than 0.05, respectively) or in normotensive controls (P less than 0.001, P less than 0.05, respectively). Altogether, the range of plasma renin activity in essential hypertension shows a continuous negative correlation with the serum magnesium level (r = -0.60, P less than 0.001) and a positive correlation with the serum ionized calcium level (r = 0.44, P less than 0.001). Accordingly, plasma renin activity in hypertension may reflect or contribute to changes in calcium and magnesium fluxes across cell membranes.     

Elevated concentrations of salivary secretory immunoglobulin A anti-cow's milk protein in newborns at risk of allergy

Secretory immunoglobulin A (SIgA) anti-casein and SIgA anti-beta-lactoglobulin (BLG) were determined in the saliva of 158 healthy mature infants at birth and in breast milk samples using a direct Elisa technique. IgG anti-casein and anti-BLG were measured in serum samples from mothers and newborns (cord blood). A high risk of allergy was defined in 66 infants who had cord blood (CB)-IgE levels greater than or equal to 0.9 IU/ml and/or parents with atopic diseases. Thirty infants had CB levels less than 0.9 IU/ml and parents without clinical symptoms of atopy but with elevated serum IgE concentrations or type I skin reactions to common allergens (low risk). Sixty-two infants had CB-IgE levels less than 0.9 IU/ml and healthy parents (no risk). The groups were matched for social status, smoking and dietary habits. SIgA anti-casein and anti-BLG were detected in all newborns. SIgA anti-casein was significantly higher (p less than 0.05) in high risk infants (medium 157; 50% confidence limits 45-270) than in no risk (48; 25-150) or low risk infants (43; 21-130). SIgA anti-casein values correlated with maternal allergy, maternal allergy plus CB-IgE, but not with paternal allergy. Breast milk SIgA anti-BLG was depressed (p less than 0.05) in mothers with manifest allergy compared to healthy mothers. Determination of salivary SIgA anti-casein may represent an additional screening method for early detection of infants with atopic disposition.     

Effect of immune status on dengue 2 virus replication in cultured leukocytes from infants and children.

Cord blood leukocytes from neonates with maternal dengue antibody supported dengue 2 virus replication in vitro; those from neonates without maternal antibody did not. Cord bloods of infants born to dengue-immune mothers contained a potent enhancing factor which gradually decayed with age and which was absent from neonates born to nonimmune mothers. Permissiveness of cultures of washed peripheral blood leukocytes from infants with maternal antibody declined steadily with increasing age in parallel with the decay of maternal antibody, and the leukocytes were no longer permissive after 10 to 12 months. The demonstration of a dengue maternal infection-enhancing factor in human cord blood from dengue-immune mothers supports the hypothesis that severe primary dengue hemorrhagic fever with shock seen in Bangkok infants is related to maternal immune status.     

正常新生儿出生时的生长抑素和神经紧张素水平

采用放射免疫技术，测定了14例正常足月新生儿及其母亲血中生长抑素和神经紧张素浓度，发现脐动脉生长抑素和神经紧张素浓度明显高于脐静脉浓度（P均＜0．01），二者均明显高于分娩后即刻母亲静脉血中相应的激素浓度（P均＜0．01）；脐动脉pH与脐动脉生长抑素和神经紧张素浓度存在一种负相关关系（P均＜0．01）。提示脐血中高浓度的生长抑素和神经紧张素极可能是胎儿源性的，且可能与分娩引起的胎儿应激有关。     

Effect of albumin on neonatal serum ionized magnesium in vitro.

BACKGROUND: Human serum albumin (HAS) is used to treat hypoproteinaemia in neonates and as a volume expander. The aim of this study was to quantify the decrease in serum concentration of ionized magnesium ([Mg2+]) when human serum albumin is added to neonatal serum in vitro. METHODS: Human serum albumin was added to 20 cord serum samples of term infants to reach incremental concentrations of 0 to 20.0 g/l and [Mg2+] were measured. RESULTS: Serum [Mg2+] decreased significantly with the addition of serum albumin. At incremental serum albumin concentration of 10 to 20 g/l, which is within the range of the desired aim in the treatment of hypoalbuminaemia, the magnitude of the decrease in serum [Mg2+] was approximately 0.041 to 0.052 mmol/l (10 to 13 per cent) from the average baseline value. CONCLUSION: The addition of albumin causes a decrease in [Mg2+]. From this in vitro study we speculate that fast infusion of albumin in human neonates may potentially cause a clinically significant decrease in serum [Mg2+].     

Evidence for allergen‐specific IgE of maternal origin in human placenta

Background: Immunoglobulin E (IgE) has been identified on macrophage‐like cells in the villi of human placenta, irrespective of the serum IgE levels or allergy status of the mother. The origin of placental IgE is debated and it is not known if it is spontaneously produced, so‐called ‘natural IgE’, or if it has any specificity for certain allergens. The aim of this study was to investigate if placental IgE originates from mother or child and to analyse its specificity. Methods: Immunoglobulin E was eluted from placenta by lowering the pH. Total and allergen‐specific IgEs were measured in placenta eluate, maternal and cord blood plasma by means of ImmunoCAP (Phadia AB). The levels of natural antibodies were determined with an anti‐phosphorylcholine (PC) enzyme‐linked immunosorbent assay, as natural IgE has been shown in one previous publication with this assay. Results: Detectable amounts of IgE were eluted from 11/12 full‐term placentas. Natural (anti‐PC) IgE antibodies were detected in low amounts in maternal plasma but not in the placental eluate or in cord blood plasma. There was a significant correlation between the amount of total IgE eluted from placenta and the levels of total IgE in maternal plasma; however, not between maternal and cord blood plasma. Allergen‐specific IgE was only found in placental eluates from mothers with specific IgE towards these allergens. Furthermore, there was a significant correlation between the amount of allergen‐specific IgE eluted from placenta and the levels of allergen‐specific IgE in maternal plasma. Allergen‐specific IgE could not be detected in cord blood. Conclusion: These results suggest a maternal origin of placental IgE, which can be allergen‐specific.