Anomalies in the karyotypes of premature children]

A cytogenetic investigation of two groups of prematurely born babies was carried out on the basis of the specialized department for prematurely born children in Moscow and in the Moscow Region. The material for this investigation was the culture of lymphocytes. In the first group comprising 607 prematurely born babies without any perceptible developmental defects abnormalities of the karyotype were observed in 15 probands (2.5%) which is 3.5 times higher than the frequency of karyotypic abnormalities among newborn babies from the same population born in proper time. In the second group comprising 70 prematurely born babies with various congenital malformations various karyotypic abnormalities were observed in 13 probands (18,6%), which is 8 times the frequency among babies from the same population born in proper time. The main type of abnormalities observed were those affecting the system of sex chromosomes and the cases of trisomy of the 21st pair of autosomes and structural abnormalities. The high proportion of X- and 21-trisomies among the chromosome abnormalities observed suggests their important role in the etiology of premature births and postnatal death-rate of mutant organisms having D- and E-trisomies and structurally unbalanced chromosomal aberrations.     

Chromosome aberrations do not persist in the lymphocytes or bone marrow cells of mice irradiated in utero or soon after birth

Mice were exposed at various ages to 1 Gy or 2 Gy of X rays, and translocation frequencies in peripheral blood T cells, spleen cells, and bone marrow cells were determined with FISH painting of chromosomes 1 and 3 when the animals were 20 weeks old. It was found that the mean translocation frequencies were very low (< or =0.8%) in mice exposed in the fetal or early postnatal stages. However, with the increase in animal age at the time of irradiation, the frequency observed at 20 weeks old became progressively higher then reached a plateau (about 5%) when mice were irradiated when > or =6 weeks old. A major role of p53 (Trp53)-dependent apoptosis for elimination of aberrant cells was not suggested because irradiated fetuses, regardless of the p53 gene status, showed low translocation frequencies (1.8% in p53(-/-) mice and 1.4% in p53(+/-) mice) compared to the frequency in the p53(-/-) mother (7.4%). In contrast, various types of aberrations were seen in spleen and liver cells when neonates were examined shortly after irradiation, similar to what was observed in bone marrow cells after irradiation in adults. We interpreted the results as indicating that fetal cells are generally sensitive to induction of chromosome aberrations but that the aberrant cells do not persist because fetal stem cells tend to be free of aberrations and their progeny replace the pre-existing cell populations during the postnatal growth of the animals.     

Mycoplasma infection as a possible cause of hybridoma instability

Cytogenetic analysis of mouse hybridoma producing monoclonal antibodies to diphtheria toxin and of its derivative, that lost secretory activity at the third passage in vivo, has been carried out. 58% cells of antibody secreting cell lines belonged to a modal class (76-79 chromosomes per cll). The modal chromosomal number of the subline that has stopped producing antibodies decreased to 63-66 per cell and the stem line of this derivative consisted of 30% of cell population only. Chromosome aberrations were much more frequent in hybridoma cells, that ceased to secrete antibodies, than in cells of original hybridoma: 32.3% of aberrant metaphases (1.38 break per cell) and 6.3% of aberrant metaphases (0.1 break per cell), respectively. Mycoplasma infection was found in the hybridoma subline that stopped producing antibodies as defined by the microbiological and cytochemical techniques. Mice might be the possible source of infection. By means of cloning of hybridoma variant, that did not secrete immunoglobulins, several sublines with the recovered secretory function were obtained.     

In vivo effect of selenium on the mutagenic activity of aflatoxin B1

Experiments were carried out to verify the effect of selenium on the mutagenic activity of AFB1. After 14 days of selenium administration to experimental animals (Chinese hamsters, Cricetulus griseus) in the form of 2 ppm Na2SeO3 solution available ad libitum the incidence of chromosomal aberrations in bone marrow cells due to a single p.o. administration of 5 mg AFB1 per 1 kg body weight was significantly reduced. The incidence of chromosomal aberrations was monitored till day 32 after AFB1 administration. A significant decrease in the frequency of aberrant cells, breaks and gaps was observed at almost any time during the investigation. 2 ppm Na2SeO3 solution itself did not enhance the frequency of chromosomal aberrations. The mechanism of the protective effect of selenium vis-a-vis the mutagenic and carcinogenic action of AFB1 remains obscure.     

Chromosomal instability parameters in the population affected by nuclear explosions at the Semipalatinsk nuclear test site

A population genetic survey of 149 persons who were born and have permanently lived in the contaminated zones of the Semipalatinsk region has been performed. A cytogenetic study has demonstrated that the frequency of aberrant cells is 1.7-3 times higher than control parameters. The total frequencies of chromosome aberrations are 3.43 +/- 0.48, 3.1 +/- 0.3, 1.8 +/- 0.2, and 1.15 +/- 0.17 aberrations per 100 cells in the populations of the extreme radiation risk (ERR), maximum radiation risk (MaxRR), minimum radiation risk (MinRR), and control zones, respectively. The high chromosome aberration rate in all three zones of radiation risk has been detected mainly due to radiation-induced chromosome markers, including paired fragments (1.2 +/- 0.2, 0.94 +/- 0.13, and 0.43 +/- 0.06 per 100 cells, respectively), dicentric and ring chromosomes (0.44 +/- 0.04, 0.45 +/- 0.07, and 0.11 +/- 0.02 per 100 cells, respectively), and stable chromosome aberrations (0.74 +/- 0.16, 0.8 +/- 0.1, and 0.63 +/- 0.13 per 100 cells, respectively). The qualitative spectra of the cytogenetic lesions observed in these groups indicate a mutagenic effect of ionizing radiation on chromosomes in the populations studied.     

Results of dynamic cytogenetic study of children and teenagers living in areas, radioactive by contaminated after the Chernobyl accident

Results of multiyear cytogenetic study of children and teenagers living in areas, radioactive by contaminated after Chernobyl accident, were adduced. Mean density of 137Cs contamination in two compared living areas were 111 and 200 kBq/m2 and mean external doses accumulated for 1986-2001 were 6.7 and 11.4 mGy correspondingly. Averaged thyroid doses receives by subjects of all age groups in the second area were approximately 1.5 times higher than in the first area; in the youngest group (0-1 year) the doses were 114.3 and 174.3 mGy. During 17 years cytogenetic investigation approximately from 30% to 60% of examined persons were observed the increased level of chromosome aberrations in lymphocytes of peripheral blood. Average frequency of unstable aberrations (acentrics, dicentrics and centric rings) constituted about 0.4 per 100 cells (0.22 per 100 cells in controls) during all period of observation. Level of marker aberrations (dicentrics and centric rings) was increased almost all times of study and varied within 0.04-0.19 per 100 cell (0.03 in control group). The parallel investigation of frequency of stable aberrations by FISH method showed up their level about 3 times exceeding observed dicentrics level. Comparably higher indexes of cytogenetic disturbances were revealed in group exposed in utero during period of accident.     

Aberrant and multiaberrant (rogue) cells in peripheral lymphocytes of Hodgkin's lymphoma patients after chemotherapy

We analyzed spontaneous chromosome lesions in peripheral lymphocytes cultured from Hodgkin's lymphoma (HL) patients before and after cytostatic chemotherapy. The mean aberration frequency was significantly higher in HL patients after chemotherapy (7.20+/-0.58 per 100 metaphases) than in non-treated HL patients (4.80+/-0.54), and in non-treated patients than in healthy subjects (2.12+/-0.13). In lymphocytes of HL patients, who received chemotherapy, we found, in addition to ordinary aberrant cells, a large number of multiaberrant (or rogue) cells, i.e. metaphases carrying multiple (at least four) chromosome-type exchange aberrations. Rogue cells were found in 15 out of 18 chemotherapeutically treated HL patients (in total, 60 rogue cells per 5,568 scored cells), whereas in 30 non-treated patients only 1 rogue cell was found (per 4,988 scored cells). No correlation was found between the yield of rogue cells and the aberration frequency in ordinary aberrant cells. Aberration spectra (ratios of chromatid- to chromosome-type aberrations and of breaks to exchanges) were essentially different in ordinary aberrant and multiaberrant cells. These data, as well as analysis of cellular distributions of aberrations, implied independent induction of chromosome damage in ordinary aberrant and rogue cells. Analysis of aberration patterns in diploid and polyploid rogue metaphases belonging to the first, second, and third in vitro division indicated that rogue cells could be formed both in vivo and in vitro, and could survive at least two rounds of in vitro replication, given blocked chromosome segregation. These results suggested that formation of rogue cells, unlike ordinary aberrant cells, was triggered by events other than direct DNA and/or chromosome lesions. A hypothesis regarding disrupted apoptosis as a candidate mechanism for rogue cell formation seems to be most suitable for interpretation of our data. Cultured lymphocytes of chemotherapeutically treated HL patients may represent a model system for further examination of the multiaberrancy phenomenon.     

Chromosomal aberrations and sister-chromatid exchanges in swine

Frequencies of chromosomal aberrations and sister-chromatid exchanges (SCEs) in peripheral blood lymphocytes were investigated in 56 swine from 3 herds (I, breeding sows; II and III, fattening pigs). The mean frequencies of aberrant cells (AB.C.) were 3.58 +/- 1.59%, 2.10 +/- 1.52% and 6.20 +/- 3.21%, respectively. The mean numbers of SCEs per cell were 7.73 +/- 0.86, 6.51 +/- 0.89 and 7.06 +/- 1.47, respectively. A significant difference was found between the herds under study with regard to the number of aberrant cells but not the SCE frequency. In a parallel study, the presence of aflatoxin B1, polychlorinated biphenyls (PCB), dichlorodiphenyltrichloromethylmethane (DDT), lindane, mercury, lead and cadmium in the environment of fattening pigs was investigated. The total exposure to mutagens of pigs from herd III with a mean frequency of 6.2% AB.C., was markedly higher than that of herd II with the mean frequency of 2.1% AB.C.     

Clastogenic effects of cis-diamminedichloroplatinum. I. Induction of chromosomal aberrations in somatic and germinal cells of mice

The clastogenicity of cisplatin, cis-diamminedichloroplatinum(II), an extensively used antitumor drug, has been studied employing (101/E1 X C3H/E1)F1 mice, aged 12-14 weeks. Chromosomal aberrations were assessed in mitotic divisions of bone marrow cells and differentiating spermatogonia. The drug was tested at 3 doses, 0.5, 1.0 and 2.5 mg/kg and 1.0, 2.5 and 5.0 mg/kg, respectively, for bone marrow and spermatogonia. Cisplatin had a clastogenic effect which was dose-dependent in both cell types. The frequencies of aberrant cells increased non-linearly in bone marrow and the dose-response relationship could be best described by a linear-quadratic equation. At the highest dose the affected cells carried multiple aberrations. An average of 2.7 aberrations per aberrant cell was observed 12 h after treatment of the mice with 2.5 mg/kg of cisplatin. In differentiating spermatogonia the dose response for aberrant cells could be described by a linear equation. The damage to the individual affected cell was less dramatic than in bone marrow, averaging 1.4 aberrations per damaged cell at the highest dose tested. Gaps were excluded from these considerations but they generally also showed a dose-related increase. A quantitative comparison of the clastogenic response to cisplatin was based on the dose-response relationships using 2 criteria, the doubling dose and the dose of unit increase (DUI). For both comparisons the general conclusion was that bone marrow cells were twice as sensitive as differentiating spermatogonia to the clastogenic action of cisplatin.     

Chromosome aberrations in the lymphocytes of persons working with the use of polychloropinene in agriculture

A cytogenetic examination of persons exposed to the action of polychlorpinene under agriculture conditions was carried out. The frequency of aberrant cells in the group of persons under examination accounted for 5.8 %, which was much higher than that of aberrations in the control group (1.6%). The average frequency of aberrant cells and character of aberrations under repeated cytogenetic examination 11 months after were similar to those described above.     

The effect of 0-methylhydroxylamine on the chromosomes of Chinese hamster cells]

0-methylhydroxylamine increases the frequency of all kinds of aberrations in Chinese hamster cells, except chromatid exchange. The percentage of aberrant metaphases and the average number of breakages per cell increases by 5,5-6 times as compared with the control. OMHA proves to be very effective inducer of chromosome aberrations. Since OMHA induces, except gene mutations, also chromosome aberrations, there are reasons to suppose that its effect is connected not only with transitions, but also with some other molecular mechanisms.     

Cytogenetic studies on the effect of feeding mice with stored wheat grains treated with malathion.

The cytogenetic effect of malathion residues in wheat grains stored for different periods of time (4, 12, 24 weeks) was evaluated in Swiss mice. The studies included: (1) chromosomal aberrations analysis in bone-marrow and spermatocyte cells; (2) chromosomal aberrations and sister chromatid exchange (SCE) analysis in spleen cell culture from mice fed with stored wheat grains. The tested doses were 8.36 (applied dose), 25.08 and 41.80 mg malathion kg(-1) wheat grains. The results demonstrated that the cytogenetic effect induced in different mouse tissues by malathion residues was dose-dependent and increased with increasing of both feeding and storage periods.Feeding mice with wheat grains stored for 4 weeks had a non-significant effect with respect to the induction of chromosomal aberrations or SCEs. Significant chromosome damage and increase of SCEs were observed in mice fed with wheat grains stored for 12 weeks. The maximum effect was recorded in mice fed for 12 weeks with the grains treated with the highest tested dose and stored for 24 weeks. However, mitomycin C i.p.-injected in mice at 1 mg kg(-1) body weight (b.w.) (positive control) induced a higher effect. The percentage of chromosome aberrations reached 13.60+/-0.98, 13.60+/-0.77 and 11.73+/-0.98 (P<0.01) in bone-marrow, cultured spleen cells and spermatocytes, respectively. The significant increase of abnormalities in spermatocytes was seen for univalent formation only, predominantly of the sex chromosomes. The frequency of SCEs was 10.76+/-0.62 per cell (P<0.01) in cultured spleen cells compared with 5.46+/-0.45 per cell for control and 14.66+/-0.54 per cell for the positive control.The obtained results indicate that malathion residues in stored wheat grains have potential genotoxic effect in mice under the conditions tested.     

Early discharge of infants of low birth weight: a prospective study.

A total of 495 African infants of low birth weight were discharged from Harari Maternity Hospital, Salisbury, between October 1972 and September 1973. Criteria used for discharge were (a) no clinical evidence of disease, (b) satisfactory feeding by mouth (breast or bottle or both), and (c) stable temperature control under normal room conditions. Of the 495 babies 264 fulfilled these criteria when they weighed 1801-1900 g (group 1), 99 when they weighed 1901-2000 g (group 2), and 132 (group 3) when they weighed 2001-2500 g. The overall follow-up rate of those infants living in greater Salisbury was 85-5%, the health visitor playing an important contributory role in their progress, especially those in group 1. More than two clinic visits in the first four to five weeks after discharge were essential for continuing weight gain in groups 1 and 2 but not in group 3. The mean daily weight gain for all babies at the end of four to five weeks was 26 g. Readmission rates for babies in groups 1,2, and 3 were 9-5%, 1%, and 0-8%, respectively, the largest single cause for readmission being bronchopneumonia associated with hypothermia. Altogether 60% of the readmissions occurred during the two winter months (June and July). Hypothermia, associated with low environmental temperatures played a significant part in morbidity and mortality, and twins, particularly in group 1, had a mortality rate three times greater than singletons in the same group. In general, even in underdeveloped communities singleton babies born outside the winter months with reasonable clinic or home visiting facilities can be discharged at a weight of 1800 g or more.     

Increasing Live Birth Rate by Preimplantation Genetic Screening of Pooled Polar Bodies Using Array Comparative Genomic Hybridization

Meiotic errors during oocyte maturation are considered the major contributors to embryonic aneuploidy and failures in human IVF treatment. Various technologies have been developed to screen polar bodies, blastomeres and trophectoderm cells for chromosomal aberrations. Array-CGH analysis using bacterial artificial chromosome (BAC) arrays is widely applied for preimplantation genetic diagnosis (PGD) using single cells. Recently, an increase in the pregnancy rate has been demonstrated using array-CGH to evaluate trophectoderm cells. However, in some countries, the analysis of embryonic cells is restricted by law. Therefore, we used BAC array-CGH to assess the impact of polar body analysis on the live birth rate. A disadvantage of polar body aneuploidy screening is the necessity of the analysis of both the first and second polar bodies, resulting in increases in costs for the patient and complex data interpretation. Aneuploidy screening results may sometimes be ambiguous if the first and second polar bodies show reciprocal chromosomal aberrations. To overcome this disadvantage, we tested a strategy involving the pooling of DNA from both polar bodies before DNA amplification. We retrospectively studied 351 patients, of whom 111 underwent polar body array-CGH before embryo transfer. In the group receiving pooled polar body array-CGH (aCGH) analysis, 110 embryos were transferred, and 29 babies were born, corresponding to live birth rates of 26.4% per embryo and 35.7% per patient. In contrast, in the control group, the IVF treatment was performed without preimplantation genetic screening (PGS). For this group, 403 embryos were transferred, and 60 babies were born, resulting in live birth rates of 14.9% per embryo and 22.7% per patient. In conclusion, our data show that in the aCGH group, the use of aneuploidy screening resulted in a significantly higher live birth rate compared with the control group, supporting the benefit of PGS for IVF couples in addition to the suitability and effectiveness of our polar body pooling strategy.     

Correlation of human lymphocyte SCE frequency with smoking history

The relationship between the level of occupational exposure to epichlorohydrin (ECHH) and the clastogenic effect was studied on a group of 33 workers. The effect of ECHH was assessed by differences in the frequency of chromosome aberrations in peripheral blood lymphocytes in ECHH-exposed and control groups. In the group exposed to the average ECHH concentration, 0.384 mg X m-3, during the last 6 months, the cytogenetic analysis revealed 2.00 +/- 0.23% AC (aberrant cells) (0.0203 B/C, breaks per cell) as compared with 1.68 +/- 0.23% AC (0.0172 B/C) in the matching controls. These results indicate that an average concentration lower than 0.40 mg X m-3 ECHH in the working atmosphere has no significant clastogenic effect on human peripheral lymphocytes.     

The mechanisms of adaptive response. Estimation of capacity of human blood lymphocytes to radiation adaptive response using different criteria

Blood lymphocytes of 15 healthy donors have been investigated for the ability to decrease their radiosensitivity after treatment with low dose irradiation named radioinduced adaptive response (AR). The unstable chromosome aberrations were used to evaluate the radiosensitivity change after irradiation of cells with low adaptive dose (5 cGy) and subsequent high challenge dose (1.0 Gy) in comparison with the effect of challenge irradiation only. Three indexes were used: the frequency of cells with aberrations in all analyzed cells (A), the number of chromosome aberrations per cell (B) and the number of chromosome aberrations per one aberrant cell (C). It has been discovered that all donors examined can be divided into four groups: 1--individuals which cells did not show AR by all indexes used; 2--individuals which cells showed AR by indexes A and B, but not C; 3--AR was demonstrated by indexes B and C; 4--AR was confirmed by all three indexes. Generally accepted repair model for AR formation explains only the case of donor groups 3 and 4, but can not explain the mechanism leading to the case of group 2. For understanding this mechanism, the distribution of metaphases by the number of chromosome aberrations per cell was analyzes for each donor. It was shown that the part of cells without aberrations in group 2 donors increased significantly after treatment with the adaptive and challenge irradiation in comparison with that after irradiation with challenge dose only. The conclusion is that in this case AR is formed as a result of change in the frequency 0 cell class--population shift. The analogous shift was observed in the distributions of metaphases for all donors of the group 4, but was absent in the group 3 donors. The data obtained suggest that AR of blood lymphocytes might be a result of several processes: activation of submutational genome damage repair; population shifts manifested by the change in the part of undamaged cells; and, possibly, activation of apoptotic cell death. The complex nature of AR affects each of radiosensitivity evaluation criteria to a different extent.     

Chromosomal Instability Parameters in the Population Affected by Nuclear Explosions at the Semipalatinsk Nuclear Test Site

A population genetic survey of 149 persons who were born and have permanently lived in the contaminated zones of the Semipalatinsk region has been performed. A cytogenetic study has demonstrated that the frequency of aberrant cells is 1.7–3 times higher than control parameters. The total frequencies of chromosome aberrations are 3.43 ± 0.48, 3.1 ± 0.3, 1.8 ± 0.2, and 1.15 ± 0.17 aberrations per 100 cells in the populations of the extreme radiation risk (ERR), maximum radiation risk (MaxRR), minimum radiation risk (MinRR), and control zones, respectively. The high chromosome aberration rate in all three zones of radiation risk has been detected mainly due to radiation-induced chromosome markers, including paired fragments (1.3 ± 0.2, 0.94 ± 0.13, and 0.43 ± 0.06 per 100 cells, respectively), dicentric and ring chromosomes (0.44 ± 0.04, 0.45 ± 0.07, and 0.11 ± 0.02 per 100 cells, respectively), and stable chromosome aberrations (0.74 ± 0.16, 0.8 ± 0.1, and 0.63 ± 0.13 per 100 cells, respectively). The qualitative spectra of the cytogenetic lesions observed in these groups indicate a mutagenic effect of ionizing radiation on chromosomes in the populations studied.     

Regularities in forming chromosome aberrations in cattle lymphocytes in external and combined radiation exposure

Aberrations in lymphocytes of cattle blood exposed to gamma-radiation and combined radiation were found. It was shown that seven days after the exposure to doses from 64.5 to 103.3 mC/kg a number of aberration varied in the range from 16.1 to 37.7 per 100 cells, whereas a frequency of aberrated cells was from 13.5 to 29.8. After the exposure to 77.3 mC/h and the following inclusion of fused radioactive particles into the fodder (48.1-762.2 Mbq/kg of the live weight), the number of aberrations increased from 25.5 up to 55.0 per 100 cells and the number of aberrated cells increased from 21 up to 43%.     

Possible role of the T antigen in inducing chromosome aberrations in SV40 virus-transformed cells

A possible role of the simian virus 40 T antigen in chromosome damages in transformed cells was examined. Two lines of Golden hamster embryonal fibroblasts, transformed by SV40 tsA30 and ts239 mutants (He30 and He239, respectively), were incubated at nonpermissive (40.5-41 degrees C) or permissive (33 degrees C) temperatures. Chromosome aberrations were registered in either subline after 3, 6, 9 and 12 weeks of cultivation under the above conditions. In the both cell lines kept at 33 degrees the frequency of aberrant metaphases and the number of chromosome breaks per cell increased drastically by week 3 of cultivation, and such a state was preserved up to week 12. The frequency of aberrant metaphases in cells cultivated at 41 degrees was maintained at the constant level (He239) or at slightly higher than that in the original culture (He30). The sublines He239, originally incubated at 33 or 40.5 degrees, were then shifted to 40.5 and 33 degrees, respectively. As a result the number of chromosome aberrations either decreased (33----40.5 degrees) or increased (40.5----33 degrees) as early as on day 2, and these patterns were stabilized at the level corresponding to the new conditions. We assayed the induction of DNA breaks in cells, grown at the permissive or nonpermissive temperatures, by using DNA sedimentation in the alkaline sucrose gradient. The DNA sedimentation peaks of cells cultured at 37 and 41 degrees coincided, whereas the DNA of cells cultured at 33 degrees was represented by shorter fragments.     

Twin pregnancy with complete hydatidiform mole and coexisting fetus following ovulation induction with a non-prescribed clomiphene citrate regimen: a case report

Introduction

Until now, studies on paracetamol given intravenously have mainly been performed with the pro-drug propacetamol or with paracetamol in preterm babies above 32 weeks of gestation. Studies in these babies indicate that intravenous paracetamol is tolerated well, however studies on the efficacy of intravenous paracetamol are lacking. There are no pharmacokinetic data on the administration of multiple doses of paracetamol in preterm babies with a gestational age below 32 weeks.

Case presentation

We present a case series of nine Caucasian preterm babies, six boys and three girls, with a mean gestational age of 28.6 weeks (range 25.9 to 31.6 weeks). Case one, a girl with a gestational age of 25 weeks and six days, presented with necrotizing enterocolitis. In the second case, a female baby with a gestational age of 26 weeks and two days presented with hematoma. In case three, a female baby with a gestation of 26 weeks and one day developed intraventricular hemorrhage. In case four, a male baby with a gestational age of 31 weeks and four days presented with pain after vacuum delivery. Case five, a female baby born after a gestation of 29 weeks and six days presented with hematoma. In case six, a male baby with a gestation of 30 weeks and six days presented with hematoma. In case seven, a male baby, born with a gestational age of 30 weeks and six days, presented with caput succedaneum and hematoma. In case eight, a male baby, born after a gestation of 28 weeks and four days, developed abdominal distention. Case nine, a female baby, born with a gestational age of 27 weeks and three days presented with hematoma. These babies were treated with intravenous paracetamol 15 mg/kg every six hours. Serum concentrations and aspartate transaminase were determined after prolonged administration. Pain scores were assessed using the Premature Infant Pain Profile.

Conclusion

Paracetamol serum concentrations ranged from 8 to 64 mg/L after eight to 12 doses of intravenous paracetamol. Adequate analgesia was obtained in seven babies. During paracetamol therapy the median serum level of aspartate transaminase was 20 U/L (range 12 to 186 U/L). This case series indicates that prolonged intravenous administration of paracetamol in preterm babies with a gestational age of less than 32 weeks is tolerated well in the first days after birth. However, in the absence of proper pharmacokinetic data in this age group we cannot advocate the use of paracetamol intravenously.