Sister chromatid exchanges in peripheral lymphocytes in newborns treated with phototherapy and vitamin E

A study was undertaken to determine whether blue fluorescent light might affect the sister chromatid exchange (SCE) frequency of peripheral lymphocytes in icteric newborns undergoing continuous phototherapy treatment (72 h). Also, the potential preventive effect of vitamin E on SCE frequency was studied in a subgroup of 11 preterm and 9 fullterm newborns after daily administration of vitamin E (46.44 mumol/kg/d, im). The results revealed that only the preterm icteric newborns showed an increase in mean SCE frequency of peripheral lymphocytes after phototherapy (9%, p = 0.02), but in no case did the highest SCEs/cell ratio exceed the normal values. No correlation was found between the average SCE rate and birth weight, gestational age or bilirubin levels. Also, no difference in SCEs was observed between newborns treated or untreated with vitamin E.     

Hemorrhagic disease of the newborn despite vitamin K prophylaxis at birth

Late hemorrhagic disease of the newborn (HDN) presents 0.5-6 months after birth with mucocutaneous and intracranial bleeding. We describe here two cases of late HDN in infants who received vitamin K. The first case is a previously healthy breastfed male who received one dose of oral vitamin K at birth and developed an intracranial hemorrhage 5 weeks later. He was treated with intravenous vitamin K and recombinant factor VIIa prior to emergent craniectomy. An unrelated infant presented at 5 months of age with diarrhea and easy bruising despite IM vitamin K at birth. These cases illustrate the morbidity associated with late HDN.     

Sister chromatid exchanges in peripheral lymphocytes of children vaccinated against rubella and measles-mumps-rubella

This study was undertaken in order to evaluate the cytogenetic and immunological responses to the effective, harmless and world-wide used vaccines of I. rubella and II. measles-mumps-rubella (M-M-RII). In one group (A) of five girls vaccinated against rubella and in another group (B) of four boys and two girls vaccinated against measles-mumps-rubella, the following parameters were studied before and repeatedly after vaccination: (a) SCE frequency, in peripheral lymphocytes, (b) DNA-synthesis, in peripheral mononuclear cells, and (c) antibody titres. The mononuclear cell proliferation rate was elevated between the 3rd and 7th day, preceeding the humoral immunological reactions, which began after the 25th day (group A) and the 28th day (group B). The latter findings coincided with a significant increase of SCE frequency in group A (one child) and in group B (all six children); in no case did the highest SCE/cell ratio exceed the normal value.     

Plasma concentrations of vitamin K1 and PIVKA-II in bottle-fed and breast-fed infants with and without vitamin K prophylaxis at birth

Plasma vitamin K₁ and proteins induced by vitamin K absence (PIVKA) were assayed simultaneously 1–4 days and 29–35 days after delivery in three groups of infants: breast-fed not receiving vitamin K at birth (n=12), bottle-fed without vitamin K administration at birth (n=7) and breast-fed receiving 1 mg vitamin K₁ administered by intramuscular injection at birth (n=13). The bottle-fed infants had a significantly higher vitamin K₁ plasma level than breast-fed infants who did not receive vitamin K₁ at birth. Extremely high levels of vitamin K were obtained 1–4 days after intramuscular administration. At the age of 1 month, breast-fed infants had the same plasma vitamin K₁ concentration whether or not they had received vitamin K₁ supplements. Decarboxy prothrombin (PIVKA-II) a reliable indicator of biochemical vitamin K deficiency, was found in 5 out of 12 breast-fed and in 2 out of 6 bottle-fed infants who had not received supplemental vitamin K₁ after birth. In a separate study, we followed up to 90 days after birth a larger group if infants. PIVKA-II was found with significantly greater frequency in breast-fed infants receiving no vitamin K than in breast-fed infants receiving 1 mg vitamin K intramuscularly at birth, or in bottle-fed infants without extra vitamin K₁. These data form a strong argument for routine vitamin K prophylaxis after birth for all breast-fed infants. The optimum dose and manner of administration require further study.Abbreviations PIVKA proteins induced by vitamin K absence - PIVKA-II decarboxy prothrombin - AU arbitrary units     

Relationship of milk intake and vitamin K supplementation to vitamin K status in newborns

Vitamin K status was evaluated by measuring blood acarboxyprothrombin (PIVKA-II) levels on the fifth day of life. The incidence of PIVKA-II-positive infants was higher in breast-fed babies than in those given supplementary (mixed) feeding. The median of total amount of milk intake during the first 3 days was significantly lower in PIVKA-II-positive infants than in PIVKA-II-negative infants among infants given both types of feedings. In addition, there was a significant negative correlation between a positive PIVKA-II proportion and the amount of milk intake in the breast-fed babies. The minimum dose of vitamin K2 necessary to prevent a positive PIVKA-II reading was 15 micrograms among babies with a normal absorption potential.     

Increased number of chromosome aberrations in the peripheral blood culture of a retinoblastoma patient

Chromosome studies were performed on blood lymphocytes from an eight-year-old patient whose left eye had been enucleated earlier because of retinoblastoma. GTG-banded karyotypes showed both numerical and structural chromosome aberrations, and the number of the patient's lymphocytes with chromosome aberration increased. It was concluded that retinoblastoma survivors need continuous control because of the increased risk of second primary tumors.     

新生儿出生后24小时内凝血功能检测的临床意义分析

目的探讨不同胎龄以及不同体重新生儿凝血功能指标的差异,为判断凝血功能指标的临床意义提供参考。方法2015年1月至2018年12月期间,在解放军总医院第五医学中心新生儿科住院治疗的新生儿中,纳入170例胎龄28~42周、出生8 h内入院的新生儿,其中男性87例,女性83例。按胎龄分为早期早产儿组、晚期早产儿组和足月儿组。按新生儿出生体重分为正常出生体重组、低出生体重组和极低出生体重组。按是否小于胎龄分为早产适于胎龄儿组、早产小于胎龄儿组、足月适于胎龄儿组、足月小于胎龄儿组。于生后24 h内抽取静脉血,检测活化部分凝血活酶时间(activatedpartial thromboplastin time,APTT)、凝血酶原时间(prothrombin time,PT)、纤维蛋白原(fibrinogen,FIB)、凝血酶时间(thrombin,TT)及D-二聚体(D-dimer)。结果早期早产儿组的APTT、PT、D-二聚体水平均高于晚期早产儿组及足月儿组(P值均<0.05),FIB水平低于晚期早产儿组及足月儿组(P值均<0.05);晚期早产儿组的APTT、PT水平均高于足月儿组(P值均<0.05),但两组间D-二聚体、FIB水平比较,差异无统计学意义(P值均>0.05)。极低出生体重组的APTT、PT、D-二聚体水平均高于低出生体重组及正常出生体重组(P值均<0.05),FIB水平低于低出生体重组及正常出生体重组(P值均<0.05);低出生体重组的APTT、PT水平均高于正常出生体重组(P值均<0.05),但两组间D-二聚体、FIB水平比较,差异无统计学意义(P值均>0.05)。早产小于胎龄儿组D-二聚体水平高于早产适于胎龄儿组(P<0.05),其余指标比较差异无统计学意义(P值均>0.05);足月适于胎龄儿与足月小于胎龄儿组的凝血指标比较,差异均无统计学意义(P值均>0.05)。早产儿出血发生率高于足月儿[26.6%(29/109)与8.2%(5/61),χ^2=9.019,P=0.003]。结论新生儿凝血指标有胎龄和体重差异,胎龄越小、体重越低的新生儿凝血功能越不完善。     

Elevated blood levels of endogenous ouabain-like factor in preterm versus mature newborns at birth

Compared to healthy adults, elevated levels of endogenous ouabain-like factor (OLF) have already been shown in the cord blood, and a role of OLF in the maintenance of high Na(+) excretion by reducing tubular sodium reabsorption during intrauterine life was suggested. In this study, we aimed to measure OLF cord blood levels of premature and mature newborns to provide further data on the possible physiological significance of this compound in neonates. OLF was assessed in the cord blood of newborns (28-41 weeks) and in the blood of healthy adults using ouabain radioimmunoassay. HPLC was employed to isolate endogenous OLF. Newborns had about twelve times higher OLF levels than healthy adults (41.96 +/- 4.64 vs. 3.1 +/- 1.1 pg/ml, p < 0.001). Further, there was a highly significant correlation (p < 0.004) between maturity and OLF concentration; OLF level increased with gestational age, however there was a rapid drop in its concentration at week 39 (43.26 +/- 7 vs. 35.47 +/- 1.84 pg/ml, p = NS). Further studies are needed to evaluate the physiological relevance of higher OLF in preterm versus mature newborns.     

Nucleated red blood cell count in term and preterm newborns: reference values at birth

The prognostic value of nucleated red blood cell count at birth in relation to neonatal outcome has been established. However, reference values were needed to usefully interpret this variable. The normal range of reference values for absolute nucleated red blood cell count in 695 preterm and term newborns is reported.     

Oral vitamin K1 prophylaxis for newborns with a new mixed-micellar preparation of phylloquinone: 3 years experience in Switzerland

In 1995, a new water-soluble mixed-micellar analogue of vitamin K₁ (Konakion MM paediatric) was introduced in Switzerland to replace the formerly used fat-soluble Konakion drops for the prevention of vitamin K₁-deficiency-bleeding (VKDB) in infants. According to the new guidelines, an oral dose of 2 mg is given after birth and again on the 4th day of life. We examined the compliance with these guidelines and the impact on the incidence of VKDB. To assess compliance, questionnaires were sent to all hospitals with delivery services 6 months after the introduction of the new guidelines. Using the database of the Swiss Paediatric Surveillance Unit (SPSU) which records rare paediatric diseases, we assessed the incidence of VKDB in Switzerland between July 1995 and June 1998. In addition, we determined the precise circumstances under which the episodes of VKDB occurred. More than 99% of infants received vitamin K₁ prophylaxis. Since July 1995, 93% of newborns have received prophylaxis according to the new guidelines; the remaining infants were given fat-soluble Konakion drops or parenteral vitamin K₁. Within 3 years, one case of classical and 12 cases of late-onset VKDB (11 confirmed, 1 probable) were reported to the SPSU. Of the 11 confirmed late-onset cases, 7 received the recommended prophylaxis, whereas 3 had not and 1 had been given fat-soluble Konakion drops. All confirmed cases of late-onset VKDB occurred in fully breast-fed infants and 8 of 11 had hepatobiliary disease. Conclusion With the introduction of two oral doses of a mixed-micellar vitamin K₁ preparation administered in the 1st week of life, the incidence of late vitamin K₁-deficiency-bleeding has decreased from 7.2:100 000 between 1986–1987 to 2.8:100 000 between 1995 and 1998. This regimen may be suitable for prophylaxis of vitamin K₁-deficiency-bleeding, however, it does not fully protect infants with cholestatic disease from late-onset bleeding. If oral prophylaxis is considered for these infants, vitamin K₁ has to be administered repeatedly to all infants during the breast feeding period. Received: 13 October 1998 / Accepted in revised form: 5 January 1999     

New aspects of vitamin K prophylaxis in newborn infants and infants

Discussion about vitamin K prophylaxis has again become a matter of major concern since cases of life threatening bleeding due to late onset vitamin K deficiency have been observed in Germany. This review tries to summarize present knowledge about the clinical presentation, pathogenesis and the potential prevention of vitamin K deficiency caused bleeding in the neonatal period and infancy.     

Effects of oral and intramuscular vitamin K prophylaxis on vitamin K1, PIVKA-II, and clotting factors in breast fed infants.

A randomised clinical trial was conducted to establish the effects of oral and intramuscular administration of vitamin K at birth on plasma concentrations of vitamin K1, proteins induced by vitamin K absence (PIVKA-II), and clotting factors. Two groups of about 165 healthy breast fed infants who received at random 1 mg vitamin K1 orally or intramuscularly after birth were studied at 2 weeks and 1 and 3 months of age. Although vitamin K1 concentrations were statistically significantly higher in the intramuscular group, blood coagulability, activities of factors VII and X and PIVKA-II concentrations did not reveal any difference between the two groups. At 2 weeks of age vitamin K1 concentrations were raised compared with reported unsupplemented concentrations and no PIVKA-II was detectable. At 3 months vitamin K1 concentrations were back at unsupplemented values and PIVKA-II was detectable in 11.5% of infants. Therefore, a repeated oral prophylaxis will be necessary to completely prevent (biochemical) vitamin K deficiency beyond the age of 1 month.     

Vitamin K1 increases sister chromatid exchange in vitro in human leukocytes and in vivo in fetal sheep cells: a possible role for "vitamin K deficiency" in the fetus

The levels of the vitamin K-dependent clotting factors are markedly lower in the human fetus and newborn than in older infants and adults. Direct measurement of vitamin K1 in cord plasma records low or undetectable levels. This phenomenon, although the norm, is referred to as vitamin K deficiency and is a significant risk factor for hemorrhage in the fetus and newborn. Sister chromatid exchange (SCE), which may be used as an index of mutagenic activity, was assayed in cultured leukocytes of placental and adult blood following phytohemagglutinin stimulation. The mean number of SCEs per metaphase in human placental blood was 3.32 +/- SE 0.219 as compared with levels of 5.13 +/- SE 0.273 in young adults (p less than 0.01), and in the presence of added vitamin K1 at a concentration of 1 X 10(-6) M the SCE increased significantly in both adult and placental cells. In vitro SCE dose response curves to K1 in the blood of fetal and maternal sheep were obtained. When five fetal sheep were given 1 mg of K1 by catheter into the femoral vein the SCE increased from 3.94 +/- SE 0.15 preinjection to 5.38 +/- SE 0.23 at 24 h postinjection (p less than 0.01). In the pretreatment fetal sheep, serum vitamin K1 was below detectable levels in all seven animals in which it was assayed and reached levels as high as 0.3 X 10(-6) M 1 h post-K1 injection. The low level of K1 in the fetus may in fact confer some biological advantage by reducing the risk of mutagenic events during a period of rapid cell proliferation.     

Neonatal vitamin K prophylaxis in Denmark: three years' experience with oral administration during the first three months of life compared with one oral administration at birth

A Danish surveillance group established after the introduction of oral vitamin K prophylaxis monitored Danish cases with late onset vitamin K deficiency bleeding by regular questionnaires to all paediatric departments. Six cases were reported, one of whom died and three are severely handicapped. All cases occurred among an estimated 134,500 infants given a single oral 1 mg vitamin K' dose at birth. No cases have been reported so far during the existent regimen: 2 mg at birth and 1 mg weekly orally administered vitamin K during the first 3 months of life, given to at least 163,000 infants. The present study is concordant with the only other study on weekly peroral prophylaxis published. We consider the mentioned weekly regimen safe and appropriate.     

The effect of formula versus breast feeding and exogenous vitamin K1 supplementation on circulating levels of vitamin K1 and vitamin K-dependent clotting factors in newborns

The influence of breast or formula feeding together with that of a single supplementation of vitamin K₁ at birth, on the vitamin K₁ level and vitamin K-dependent clotting factors were studied in 65 breast and 15 formula fed infants. All breast fed newborns without supplementation (n=25) had very low serum vitamin K₁ at weeks 1 and 6. Oral vitamin K supplementation (n=22) or i.m. (n=18) at birth resulted in high serum levels at week 1, while at week 6 the effect had disappeared. Formula fed infants had vitamin K₁ values within the normal adult range at all study points. The low serum levels of vitamin K₁ were not associated with haemorrhagic disorders or coagulation abnormalities. The mean values of vitamin K₁ in maternal sera at weeks 1 and 6 were 2.3 nmol/l and 1.8 nmol/l and in breast milk 2.7 nmol/l and 2.0 nmol/l respectively. No correlation existed between the values in breast milk and maternal serum. To maintain serum levels of vitamin K₁ within the adult physiological range, repeated administration of low doses is needed in breast fed newborns beyond 1 week of age.