Chronic oxygen dependency in infants born at 24-32 weeks' gestation: the role of antenatal and neonatal factors

OBJECTIVES: To study the incidence of chronic oxygen dependency (COD) among ventilated survivors born at 24-32 weeks gestation from 1986 to 1994 and to identify antenatal and neonatal factors that may have changed with time; and to identify antenatal and neonatal factors that could contribute to the development of COD in infants born at 24-32 weeks gestation using a case control model. METHODOLOGY: Infants born at 24-32 weeks gestation in one tertiary referral centre between 1986 and 1994 and admitted to the neonatal intensive care unit for respiratory support were studied. Data accumulated prospectively since 1986 in survivors of ventilation were analyzed to identify antenatal and neonatal factors that could have changed with time. The cohort of infants who developed COD were matched for gestation and time of birth with a control group of infants who did not have COD. Significant factors that could have contributed to the development of COD were identified using forward logistic regression analysis. RESULTS: The number of mothers admitted for threatened premature labour (TPL), and pregnancy induced hypertension decreased with time while the use of antenatal steroids and maternal antibiotics increased. More infants were delivered by Caesarean section during the later years. There was an increase in neonatal septicaemia with time while there were decreases in hyaline membrane disease, pneumothorax, pulmonary interstitial emphysema, use of high peak inspiratory pressure (PIP) and high inspired oxygen. The incidence of COD decreased. The case controlled study revealed a significant positive association between COD and male gender, birthweight less than the 10th percentile for gestation, PIP over 30 cm H2O, septicaemia and significant patent ductus arteriosus (PDA) requiring indomethacin. There was a negative association with TPL. CONCLUSIONS: Further decrease in COD can be achieved only if septicaemia, PDA and the use of high PIP can be avoided. The most effective way of reducing the incidence of COD is by reducing the incidence of prematurity.     

The effect of combined antenatal vitamin K and phenobarbital therapy on umbilical blood coagulation studies in infants less than 34 weeks' gestation

OBJECTIVE: To determine if antenatal vitamin K and phenobarbital therapy affect coagulation studies in umbilical blood at birth, and to provide 95% reference ranges for umbilical blood coagulation parameters in premature gestations. METHODS: Patients at imminent risk for spontaneous or indicated premature delivery less than 34 weeks' gestation were randomized to receive either placebo or vitamin K and phenobarbital. Prothrombin time (PT), activated partial thromboplastin time (PTT), functional coagulation factors, and decarboxylated prothrombin assays were performed on umbilical blood specimens. Decarboxylated prothrombin, also known as "protein induced by vitamin K absence-factor II" or precursor prothrombin, is a sensitive marker for vitamin K deficiency. Standardized values of PT and PTT are reported in seconds and standardized values of factor assays in percentage of normal adult functional activity (mean +/- one standard deviation). RESULTS: Newborns in the placebo and treatment groups had similar umbilical blood PT (12.6 +/- 1.2 versus 12.7 +/- 1.4 seconds), PTT (48.8 +/- 13.4 versus 49.6 +/- 13.8 seconds), and functional activity of factor II (40.3 +/- 12.5 versus 42.0 +/- 12.1%), factor VII (67.0 +/- 20.9 versus 66.8 +/- 18.9%), factor IX (27.4 +/- 12.8 versus 25.8 +/- 8.9%), and factor X (47.0 +/- 12.8 versus 49.2 +/- 11.6%). Newborns in the treatment group were about half as likely as those in the placebo group to have detectable decarboxylated prothrombin levels in umbilical blood at birth (gestational age-adjusted odds ratio 0.47, 95% confidence interval 0.22-1.01; P = .05). CONCLUSIONS: Combined maternal therapy with vitamin K and phenobarbital before premature delivery does not affect umbilical blood PT, PTT, or functional activity of vitamin K-dependent coagulation factors II, VII, IX, and X. However, it is associated with the reduced presence of decarboxylated prothrombin in umbilical blood at birth. There is significant improvement in umbilical blood coagulation tests as gestational age advances from 24 to 34 weeks.     

The structure and analysis of neonatal mortality in twins in 1991-1995 at the State University Hospital Maternity Home, Sofia

Until recently, the families of patients who have given the gift of life have been the invisible group in the transplant circle. They donated the organs and tissues of their loved ones to unknown transplant recipients and then were to grieve alone. As transplantation has matured and become the treatment of choice for end stage organ failure and for other life-enhancing procedures, the importance of the donor and the donor family is being recognised and their needs and expectations identified.     

Transepidermal water loss in infants born at 24 and 25 weeks of gestation

Bone tissue undergoes continual renewal in order to keep the mechanical competence of the bone matrix. This is performed by two cells: osteoclasts which resorb the calcified matrix and osteoblast which synthetize a new bone matrix. Biochemical markers of bone remodelling allow the evaluation of the activity of each type of bone cells. An unbalance in this process induces modifications of the amount of calcified tissue and of the bone microarchitecture. Several technics based on X-ray and ultrasound allow a non invasive evaluation of these modifications.     

The effect of dexamethasone administration at different stages of gestation on maternal plasma steroid concentrations in the baboon (Papio cynocephalus)

Dexamethasone administration at different stages of gestation in the baboon was studied for its effect on maternal steroid hormone concentrations. Dexamethasone (2 mg i.m. at 12 h intervals for three doses) was administered at early (days 37-39), mid (days 76-85) or late (days 112-123) gestation and morning blood samples were collected before, during and after dexamethasone suppression for 6 consecutive days. Dexamethasone treatment, at all stages of pregnancy, resulted in a significant decline in maternal serum cortisol concentrations, which rapidly return to normal concentrations after treatment. Progesterone concentrations were not affected by dexamethasone at any stage of gestation. Serum concentrations of oestradiol, testosterone and androstenedione were unchanged following dexamethasone administration in early pregnancy. A trend toward lower serum oestradiol was observed following dexamethasone administration in both mid and late gestation, but this was not significant. Both testosterone and androstenedione were significantly decreased following dexamethasone in both mid and late pregnancy and recovered to pretreatment concentrations within a few days after cessation of treatment. These results confirm other studies which demonstrate that adrenal precursors (maternal or fetal) are a major contributor to maternal serum concentrations of oestradiol. They also demonstrate that these adrenal precursors increase serum concentrations of testosterone and androstenedione in the pregnant baboon. Since these changes are only evident after that time (>40 days) when the fetal adrenal is steroidogenically competent, a role for fetal adrenal involvement in maternal serum androgen concentrations is suggested.     

Termination of pregnancy at 9-13 weeks' amenorrhoea with mifepristone and misoprostol

The effectiveness of a combined regimen of mifepristone and vaginal misoprostol for termination of pregnancies of 9-13 weeks of gestation was investigated in 120 UK abortion patients (median age, 22.1 years; median duration of amenorrhea, 10.3 weeks). Each woman received a single oral dose of 200 mg of mifepristone 36-48 hours before admission, at which time 800 mcg of misoprostol was administered vaginally. Where indicated, a further two doses of 400 mcg of misoprostol (vaginal or oral) were provided every 3 hours. All 120 women aborted on the day of prostaglandin administration; however, 6 women (5%) required exploratory curettage after the procedure for retained placenta. The median prostaglandin dose was 1200 mcg (range, 800-1600 mcg). The median time from misoprostol administration to abortion was 4.33 hours (range, 1.3-16.0 hours). 60 women (50%) required oral analgesics and 26 (22%) received parenteral analgesia. Diarrhea occurred in 38 women (32%). The median duration of bleeding after abortion was 12.5 days (range, 3-43 days). In questionnaires administered to 73 women, only 3 (4%) expressed dissatisfaction with medical abortion, because of pain or prolonged bleeding. The relatively high dose of misoprostol used in this study and the vaginal route of administration are presumed to account for the 95% success rate. Extension of medical abortion to later gestation times would decrease the need for surgery and expand women's choice of methods of pregnancy termination.     

Bilateral adrenalectomy of lambs in utero: effects on maternal hormone levels at induced parturition

Progesterone, 17 alpha, 20 alpha-dihydroxypregn-4-en-3-one, androstenedione, total unconjugated oestrogen and oestrone sulphate have been measured by radioimmunoassays in maternal utero-ovarian venous, maternal peripheral venous and/or foetal posterior vena caval plasma from six sheep bearing bilaterally adrenalectomized lambs, in which premature parturition was induced by administration of glucocorticoid. Three of the ewes were overiectomized, and in one of these three animals the foetal testes were also excised, at the time of foetal adrenalectomy. Adrenalectomy was judged to be complete on the basis of plasma cortisol levels in the neonatal lambs, and by examination of the site of ablation at necropsy. In all cases foetal administration of glucocorticoid led to the onset of labour, and lambing, and in all animals the hormonal changes preceding parturition were indistinguishable (either qualitatively or quantitatively) from the changes observed in animals carrying intact lambs. Since therapy with glucocorticoid alone successfully compensates for ablation of the foetal adrenal cortex, it is suggested that glucocorticoid is the only adrenal product required to cause parturition, and that foetal adrenal secretion of androgens may be unnecessary.     

Effects of PTH-rP(107-111) and PTH-rP(7-34) on adult cardiomyocytes

We investigated whether parathyroid hormone-related peptide (PTH-rP), recently found expressed in the heart, exerts growth and contractile effects on adult cardiomyocytes from rat hearts. Synthetic PTH-rP peptides were used covering either a protein kinase C (PKC)-activating domain [PTH-rP(107-111)], or an adenylate cyclase activating domain [PTH-rP(1-34) and PTH-rP(7-34)]. PTH-rP(107-111) (1 micro M) increased creatine kinase BB activity (CK-BB), a CK isoform re-expressed during cardiac hypertrophy, within 24 h by 62+/-12%. This induction was abolished in the presence of the mitogen-activated-protein (MAP)-kinase-kinase inhibitor PD 98059. PTH-rP(107-111) activated p42-MAP-kinase within 15 min, increased protein synthesis (19+/- 4%), total protein mass (19+/-5%), cell volume (45+/-7%), and cross-sectional area (38+/-9%) of cardiomyocytes. Activation of p42-MAP-kinase and increase in protein synthesis were abolished in presence of bisindolylmaleimide, a PKC inhibitor. PTH- rP(107-111) did not directly influence contractile activity but reduced the contractile response to isoprenaline. In contrast, PTH-rP(1-34) and PTH-rP(7-34) induced spontaneous contractile activity in 3-day-old cultures. This induction was abolished in presence of Rp-cAMPS, a protein kinase A inhibitor, indicating an involvement of cAMP in this response. PTH-rP(1-34) also increased the cellular accumulation of cAMP. It is concluded that PTH-rP exert direct effects on adult cardiomyocytes by activating either PKC via a functional domain covered by amino acids 107-111 or by activation of cAMP-dependent protein kinase via a functional domain covered by amino acids 7-34. Since these parts of PTH-rP have either no homology [PTH-rP(107-111)] or only a limited structural similarity [PTH-rP(7-34)] to parathyroid hormone, these activities of PTH-rP have to be clearly distinguished from those described for parathyroid hormone.     

Estimation of AIDS morbidity and mortality in Spain

BACKGROUND: To obtain corrected estimates of the cumulative incidence and mortality, as well as prevalence of AIDS in Spain on June 1992. METHODS: The number of cases in the National Register of AIDS by December 1992 was adjusted for reporting delays to estimate the cumulative incidence by June 1992. The prevalence and mortality in this date were obtained using this figure and the probabilities of survival after diagnosis from the AIDS Register of Madrid. This methodology was used for Spain as all, and for each Autonomous Community. RESULTS: The estimated cumulative incidence of AIDS in Spain by June 1992 was 16,486 cases, 13.4% greater than that reported by the same date. The prevalent cases were 6,351 (95% CI, 5,996-6,708) and the remaining 10,135 (61.5%) would have died. This number of deaths is 69.6% greater than the reported figure. There were considerable differences among Autonomous Communities. Some of them exhibited rates more than six times greater than others. CONCLUSIONS: The adjusted estimations provide a view of the actual situation more accurate than the raw figures from the register. These great differences should be taken into account for appropriate allocation of health care resources.     

Economic and occupational activities at an increased risk of mortality for lung tumors in Turin (1981-89) and in Italy (1981-82)

In the framework of occupational disease surveillance program, based on integration of current information systems, the first Italian occupational mortality study was carried out. This paper reports on excess lung cancer risk by industry and occupation. The study population consists of subjects included in the Italian Cross-Sectional Study (STI) and in the Turin Longitudinal Study (SLT), both of which are surveys based on record-linkage procedures between census records and death certificates. The STI is a six-month follow-up of Italian residents at the 1981 census. The SLT is a prospective study of Turin residents at the 1981 census, followed for mortality up to 1989. Only persons aged 18-64 years at entry, and economically active, were eligible for the occupational mortality analysis (i.e. 15,734 deceased individuals out of 13 million subjects in the STI, and 435,608 individuals, among whom 10,789 deaths occurred, in the SLT). Information about job and economic activity recorded at census consisted of the Italian standard 1981 industry and occupation codes. Lung cancer relative risks by category of industry and job were estimated as mortality odds ratios (MOR) in the STI, and as observed to expected death ratios (SMR) in the SLT. Only excess risks based on > or = 3 observed cases and with p < 0.1, were included in the present report. Lung cancer mortality was increased in different industries and jobs. The excess risks found in the mechanic and transport industries are of particular interest in a public health perspective, due to the high number of Italian workers employed in these sectors. From an etiologic point of view, however, careful attention should be paid to the excess lung cancer risks among workers in the wood manufacturing industry, in meat preparation, and in nursing occupations, where detailed analytical studies of exposure profile and cancer risk are warranted.     

Myocardial infarct and geomagnetic disturbances: analysis of data on morbidity and mortality

BACKGROUND: There is increasing evidence that the most effective way to improve delivery of preventive services in primary care is to establish organized preventive service systems. This study tests the hypothesis that a managed care organization (MCO) can help its contracted private primary care clinics to develop such systems. METHODS: Forty-four primary care clinics contracting with two large MCOs were randomized to a comparison (C) or an intervention (I) group. Group (I) clinic team leaders received training plus ongoing consultation and networking. Personnel at all 44 clinics completed surveys prior to and at the end of the intervention to measure adoption of the improvement process and the prevention system. RESULTS: All 22 (I) clinics identified teams that appeared to follow the seven-step improvement process. The mean numbers of system processes were identical at baseline, 11.2 (I) vs 12.1 (C), while after the intervention this had changed to 25.8 in (I) clinics vs 11.3 in (C) (P = 0.022). CONCLUSIONS: With training and assistance, interested primary care clinic teams will establish functioning CQI teams that will produce a substantial increase in the presence of functional prevention system processes. Whether this change is sufficient to increase the rates of preventive services remains to be documented.     

Speech and language development of children born at < or = 32 weeks' gestation: a 5-year prospective follow-up study

Speech and language comprehension and production were assessed at the age of 5 years in a cohort of children born preterm at < or = 32 weeks' gestational age (N=55) in comparison with children born at term and of similar age, sex, and social backgrounds. Data both including and excluding major neurological disabilities are presented. Mean performance for the entire group of preterm children was significantly lower than for the controls on most of the measures including the composite IQ scores. When the nine children who had major neurological disabilities were excluded from the preterm group, statistically significant differences were found on four of the total 12 speech and language measures. Intellectually normal preterm children without major neurological disability were slower than the controls on rapid word retrieval. In addition, difficulties in comprehending relative concepts were typical for the preterm children. The results suggest 'subtle dysnomia', which is indicative of later reading problems. On global verbal measures and on the basic speech and language aspects the study groups did not differ. Specific language impairment, defined as a discrepancy of > 1SD between Performance IQ and Verbal IQ scores, showed a tendency to be more common in the control group. Within both the study groups, the boys showed a tendency for a greater discrepancy between their Performance and Verbal IQ scores.     

Antenatal steroids, condition at birth and respiratory morbidity and mortality in very preterm infants

The study purpose was to compare the effect of exercise training on serum lipid and apolipoprotein concentrations and the activities of intravascular enzymes related to lipid transport in previously untrained eumenorrheic, premenopausal (PRM) women (n = 21; mean age, 36 +/- 3 years) and estrogen-free postmenopausal (POM) women (n = 16; mean age, 68 +/- 8 years). Subjects trained at a progressive intensity and duration (50% to 75% maximal O2 consumption [VO2max], 200 to 300 kcal/session) 4 d/wk for 12 weeks. Before and after training, VO2max, body weight, relative body fat, and fasting blood samples were obtained following 2 weeks on a standardized diet designed to maintain body weight and during the early follicular stage for the PRM group. Blood samples were analyzed for serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), the cholesterol content of the HDL3 subfraction, apolipoprotein (apo)A-I and apoB, lipoprotein(a), and the activity of lecithin:cholesterol acyltransferase (LCAT). Total and hepatic triglyceride lipase activity (HTGLA) were determined from plasma samples obtained after heparin administration. The cholesterol content of the low-density lipoprotein (LDL) and HDL2 subfractions and endothelial-bound lipoprotein lipase activity (LPLA) were calculated. A two (group) x two (time) multivariate ANOVA (MANOVA), with repeated measures for time indicated that the exercise-induced changes in physiological measurements, serum lipid or apolipoprotein concentrations, or enzyme activities did not differ between groups. Serum concentrations of TC, LDL-C, and HDL3 cholesterol, TG, and apo A-I and apoB were higher in POM women compared with the PRM group (P < .05 for all). For the combined groups, body weight and relative body fat did not change with training, but VO2max increased an average of 18.5% (P < .05). LPLA, HTGLA, and LCAT activity were unaltered with exercise training. Except for a small but significant decrease in HDL-C (-5.5%) and an elevation in apoB (4.3%; P < .05 for both), the concentrations of serum lipids and apolipoproteins did not change over the training period. We conclude that in previously untrained women, menopausal status does not influence the exercise training response of serum lipids or apolipoproteins or activities of intravascular enzymes related to lipid transport.     

Abnormal left ventricular filling after neonatal repair of congenital heart disease: association with increased mortality and morbidity

BACKGROUND: The presence of mid-diastolic flow reversal on the mitral valve Doppler inflow indicates abnormal left ventricular filling. To determine whether mid-diastolic flow reversal predicts outcome in patients undergoing repair or palliation of neonatal congenital heart disease, we reviewed the echocardiograms and medical records of 40 patients with either left ventricular outflow obstruction or transposition of the great arteries. METHODS: All patients underwent surgical repair; transposition of the great arteries (TGA) = 17, coarctation of the aorta (CoA) = 14, interrupted aortic arch (IAA) = 8, and aortic stenosis (AS) = 1. The presence of mid-diastolic flow reversal was determined by pulsed Doppler interrogation of the mitral valve on preoperative and postoperative echocardiograms. RESULTS: Preoperative echocardiograms showed diastolic flow reversal in only 5 patients; 1 of 1 with AS and 4 of 14 with CoA. Twenty-one of 40 patients showed postoperative diastolic flow reversal; 1 of 1 with AS, 8 of 8 with IAA, 1 of 14 with CoA, and 11 of 17 with TGA. Postoperative mid-diastolic flow reversal 1 to 3 days after surgery was associated with higher mortality rate: 7 of 21 patients with diastolic flow reversal and 0 of 19 without diastolic flow reversal died. Patients with diastolic flow reversal who survived had longer intensive care unit (26.2 +/- 13.5 days vs 7.1 +/- 4.1 days, P <.001) and hospital (57.4 +/- 38.8 days vs 14.8 +/- 5.2 days, P <.05) stays. CONCLUSION: Mid-diastolic flow reversal is an indicator of prolonged hospital stay and mortality in patients with left ventricular outflow tract obstruction or TGA.     

Epidemiology of liver cirrhosis morbidity and mortality in Iceland

Nine VA Medical Centers are participating in a 2-year double-blind placebo controlled study of antioxidant treatment for tardive dyskinesia (TD) conducted by the Department of Veteran Affairs Cooperative Studies Program. One of the principal outcome measures of this study is the score derived from the instrumental assessment of upper extremity dyskinesia. Dyskinetic hand movements are quantified by assessing the variability associated with steady-state isometric force generated by the patient. In the present report, we describe the training procedures and results of a multi-center reliability assessment of this procedure. Data from nine study centers comprising 45 individual patients with six trials each (three from left hand and three from right hand) were reanalyzed by an independent investigator and the results were subjected to reliability assessment. For the statistic of interest (average coefficient of variation over trials 2 and 3 for each hand, then take the larger of these two values), we found very high intraclass correlation coefficients for reliability over all patients across sites (ICC = 0.995). We also calculated the reliability of the measures across trials within patient for each combination of hand (right, left, dominant), rater group (site, control), and trials set (all three, trials 2 and 3). For a given hand and trial set, the reliability of the site raters was similar to that of the control. This study demonstrates that instrumental measures for the assessment of dyskinesia are reliable and can be implemented in multi-center studies with minimal training.