Non-infectious risk factors for different types of cerebral palsy in term-born babies: a population-based, case-control study.

OBJECTIVE: To identify non-infectious antenatal and perinatal risk factors for cerebral palsy (CP) and its subtypes in children born at term. DESIGN: A population-based, case-control study. SETTING: The western healthcare region of Sweden. POPULATION: A population-based series of children with CP born at term during 1983-94 (n=309) was matched with a control group (n=618). METHODS: A total of 62 variables, maternal characteristics, and prepartal, intrapartal and postpartal variables were retrieved from obstetric records. Both univariate and multivariate analyses were performed for spastic and dyskinetic CP, and for the total CP group. MAIN OUTCOME MEASURES: Cerebral palsy (CP) and subtypes. RESULTS: Univariate analysis resulted in 26 significant risk factors for CP. Birthweight (OR 0.54, 95% CI 0.39-0.74), not living with the baby's father (OR 2.58, 95% CI 1.11-5.97), admittance to a neonatal intensive care unit (NICU) (OR 4.43, 95% CI 3.03-6.47), maternal weight at 34 weeks of gestation (OR 1.02, 95% CI 1.00-1.03) and neonatal encephalopathy (OR 69.2, 95% CI 9.36-511.89) were found to be risk factors for CP in the total CP group in our multivariate analysis. Factors during the periods before, during and after delivery were all shown to increase the risk of spastic diplegia and tetraplegia, whereas mostly factors during the period before delivery increased the risk of spastic hemiplegia, and only factors during delivery increased the risk of dyskinetic CP. Admittance to an NICU was a risk factor for all CP subtypes. CONCLUSIONS: The risk factor pattern differed by CP subtype. The presented risk factors may be useful indicators for identifying children at risk of developing CP, and helpful for targeting individuals for early intervention programmes.

Cerebral palsy and restricted growth status at birth: population-based case-control study.

OBJECTIVE: To evaluate the association between growth status at birth and subsequent development of cerebral palsy in preterm and term infants. DESIGN: Population-based case-controlled study. SETTING: Cerebral palsy register in Western Sweden. Subjects Cohort of 334 singletons born between 1983 and 1990, with cerebral palsy diagnosed from age 4, and 668 singletons matched for gestation, gender and delivery unit. METHOD: Growth status at birth was determined using small for gestational age (SGA) categories, with customised birthweight percentiles (SGAcust) based on the Swedish population. MAIN OUTCOME MEASURES: Proportion of babies that were SGAcust, comparing cases and controls in three gestational age categories: early preterm (24-33 weeks), late preterm (34-36 weeks) and term (37+ weeks). RESULTS: Of the 334 children with cerebral palsy, 87 (26.6%) were born early preterm, 27 (8.1%) late preterm and 218 (66%) at term. Children who had been born at term were more likely to have been SGA <1st customised percentile (SGAcust1) than their matched controls (OR 6.6, 95% CI 2.3-18.6). In contrast, children with cerebral palsy born preterm were not more likely to have been SGAcust1 (OR 0.9, 95% CI 0.4-1.9), and this applied to early preterm as well as late preterm births. For less severely small babies (SGA between 1st and 5th customised percentiles), the association with cerebral palsy remained significant for term births (OR 5.2, 95% CI 2.7-10.1) but was again not significant for preterm births. CONCLUSIONS: Term singletons with severely SGA birthweights had a five- to seven-fold risk of developing cerebral palsy compared with gestational age-matched infants with birthweights within normal limits. For children born preterm, SGA was not more likely to be present in cases than in controls. These findings support the concept of cerebral palsy as a multifactorial condition and highlight the importance of antenatal surveillance of fetal growth.

Blockade of nitric oxide synthesis reduces myocardial oxygen consumption in vivo.

BACKGROUND: Although cardiac myocytes and coronary vascular endothelium are known to express a constitutive form of NO synthase, the in vivo effects of tonic endogenous production of NO on myocardial O2 consumption and contractile performance remain unclear. METHODS AND RESULTS: The effects of blockade of NO synthase were determined in intact dogs. Myocardial O2 consumption decreased systematically over a wide range of hemodynamic demand after the systemic administration of N omega-nitro-L-arginine methyl ester (L-NAME) or N omega-nitro-L-arginine. Decreases after doses of 1 and 10 mg/kg L-NAME averaged 23 +/- 3.8% and 34 +/- 7.2% at a heart rate of 90 bpm in open-chest animals. Similar reductions occurred after the administration of L-NAME and N omega-nitro-L-arginine in chronically instrumented animals and were unaffected by beta-adrenergic blockade. Intracoronary infusion of L-NAME in chronically instrumented animals reduced both myocardial O2 consumption and regional segment shortening, even at a dose that did not increase systemic arterial pressure. CONCLUSIONS: The blockade of NO synthesis reduces myocardial O2 consumption in vivo. The decrease in O2 consumption is accompanied by a decrease in segment shortening. It involves a direct myocardial action of NO, is unaffected by beta-blockade, and is consistent with in vitro studies indicating that low levels of NO augment contractile performance by inhibition of a cGMP-dependent phosphodiesterase.

Endothelium-derived relaxing factor (nitric oxide) has a tonic vasodilating action on coronary collateral vessels.

OBJECTIVES: We sought to determine whether endothelium-derived relaxing factor (nitric oxide) exerts a tonic vasodilating effect on coronary collateral channels developed in response to myocardial ischemia. BACKGROUND: Although the coronary collateral circulation is known to react to several vasoactive agents, the role of endogenously produced nitric oxide is unclear. METHODS: Coronary collateral channels were induced in the left circumflex artery bed of 12 chronically instrumented dogs by either ameroid implantation or repeated occlusion of the left circumflex coronary artery. With the native circumflex artery occluded, aortic and circumflex pressures and microsphere flows were measured before and after systemic administration of NG-nitro-L-arginine methyl ester, an arginine analogue known to block the synthesis of nitric oxide. RESULTS: NG-nitro-L-arginine methyl ester increased mean aortic pressure from a mean +/- SEM of 92 +/- 4 to 114 +/- 4 mm Hg, whereas pressure in the occluded circumflex artery decreased from 61 +/- 4 to 55 +/- 4 mm Hg. The increase in aortic-circumflex pressure gradient (from 31 +/- 4 to 59 +/- 5 mm Hg) was accompanied by a decrease in flow in the circumflex bed (from 1.31 to +/- 0.14 to 1.09 +/- 0.15 ml/min per g), resulting in an increase in coronary collateral resistance averaging 173 +/- 37% (from 26 +/- 4 to 64 +/- 9 mm Hg/ml per min per g, p < 0.01). The increase in collateral resistance could be partially reversed by administration of L-arginine. CONCLUSIONS: We conclude that nitric oxide normally exerts a substantial tonic dilating effect in coronary collateral vessels. Disease-induced alterations in endothelial function may limit collateral perfusion importantly.

Rapeseed products from double-low cultivars as feed for dairy cows: effects of long-term feeding on thyroid function, fertility and animal health.

Eighty-five dairy cows of the Swedish Red and White Breed (SRB) were included in a long-term experiment during 3 consecutive lactations. The cows were divided into 3 different dietary groups that received no rapeseed (NR), up to 1.2 kg dry matter (DM) 00-rapeseed meal plus 0.2 kg DM full-fat 00-rapeseed (MR), and up to 2.5 kg DM 00-rapeseed meal plus 0.9 kg DM full-fat 00-rapeseed (HR) per day. No significant differences in culling rates or disease rates were found between the feeding groups at any time during the experiment. The interval from calving to conception among the primiparous cows was longer for the HR-group (125 days) than for the NR-group (100 days). The response to a thyrotroph releasing hormone around 90 days postpartum during the first lactation was significantly higher for the HR-group (86.7 mu/L/h) than for the NR-group (55.2 micrograms/L/h). This indicates that at the highest level of rapeseed feeding, glucosinolates had a very mild, suppressive influence on thyroid hormone release, apparently compensated for by an increased activity along the hypothalamic-pituitary-thyroid axis. No significant differences in fertility or thyroid function were found among the pluriparous cows. During 2nd lactation the concentration of serum urea was higher in the NR-group (7.31 mmol/L) than in the HR-group (6.83 mol/L). The effects of independent environmental factors influenced fertility and thyroid function to a much greater extent than the rapeseed feeding. It was concluded that the feeding of rapeseed products from certified double low varieties of B. napus to adult dairy cows in amounts up to 3 kg rapeseed meal per cow and day would not have any negative effects on animal health or fertility.

Profiles of progesterone in milk and clinical ovarian findings in postpartum cows with ovarian dysfunctions.

Milk progesterone profiles, based on twice or once weekly sampling, were constructed for postpartum dairy cows. The cows were simultaneously examined by rectal palpation and clinical ovarian findings were related to the progesterone profiles. The combination of progesterone analysis and clinical examination may be used to optimize diagnostic accuracy and a number of practical recommendations are given on the basis of the results from this study.

The effect of mastitis on milk progesterone concentration in dairy cows.

A within cow comparison was made between milk progesterone levels in healthy and mastitic quarters. Material was collected from cows with mastitis induced by bacterial inoculation, or by inoculation with bacterial endotoxin. Furthermore material from cows with spontaneous subclinical mastitis was used. Milk progesterone levels were lowered due to mastitis. However, the decrease was not large enough to cause misinterpretation of where in the oestrous cycle (luteal phase or non-luteal phase) the samples were taken.

The male genital tract and the nipples of male and female offspring of rats given the non-steroidal antiandrogens DIMP and Sch 13521, during pregnancy.

Male and female offspring of rats given antiandrogens, the steroidal BOMT or the non steroids DIMP or Sch 13521, daily during the last third of pregnancy were studied. Detailed examinations were made of the genital tract of male, and of the nipples of male and female offspring. A) Male offspring. 1) Genital tract of newborn and 31-91 day old males : Modifications of the development of accessory sexual tissues were found in all treatment groups. As indicated by the severity of deviations from normal (morphology and weight of sex accessories), the antiandrogenic effect of the preparations, in the doses given to the mother rats, increased from BOMT (50 or 75 mg/day) via Sch 13521 (30 mg/day) and DIMP (50 or 60 mg/day) to Sch 13521 (60 mg/day). 2) Nipples of 10-60 day old males : Whole mount preparations were made unilaterally of the row of 6 mammary glands with nipples. The number of intact and abnormal nipples, respectively, was recorded. The relation between intact and abnormal nipples served as indicator of the efficiency of the antiandrogenic substances studied. The result showed that the antiandrogenic effect increased from BOMT to Sch 13521, 60 mg, in the same order as that arrived at from studies of the genital tract. The combined results obtained from the male offspring indicated that the tissues of the genital region, the growth and differentiation of which was most readily impaired by antiandrogens, were the same as those known from other work to be stimulated most easily in female rat fetuses by testosterone. B) Female offspring. Nipples of 31-60 day old females were judged from whole mount preparations and recorded as in the males. The nipples of adult virginal females were examined macroscopically. The same procedure was applied to lactating females, but the results were controlled in consecutive lactational periods and at autopsy. The 3 groups of females showed uniformly that 1) offspring of rats given BOMT during pregnancy had many (about 50 per cent) malformed nipples and 2) the treatment of mother rats with DIMP or Sch 13521 did not influence the development of nipples in female offspring. The result was assumed to be due to an androgenic effect of the steroidal antiandrogen, BOMT, on the nipple anlage.