Glial contributions to visceral pain: implications for disease etiology and the female predominance of persistent pain.

In the central nervous system, bidirectional signaling between glial cells and neurons ('neuroimmune communication') facilitates the development of persistent pain. Spinal glia can contribute to heightened pain states by a prolonged release of neurokine signals that sensitize adjacent centrally projecting neurons. Although many persistent pain conditions are disproportionately common in females, whether specific neuroimmune mechanisms lead to this increased susceptibility remains unclear. This review summarizes the major known contributions of glia and neuroimmune interactions in pain, which has been determined principally in male rodents and in the context of somatic pain conditions. It is then postulated that studying neuroimmune interactions involved in pain attributed to visceral diseases common to females may offer a more suitable avenue for investigating unique mechanisms involved in female pain. Further, we discuss the potential for primed spinal glia and subsequent neurogenic inflammation as a contributing factor in the development of peripheral inflammation, therefore, representing a predisposing factor for females in developing a high percentage of such persistent pain conditions.

Muscle mass deficits are associated with bone mineral density in men with idiopathic vertebral fracture.

INTRODUCTION AND HYPOTHESIS: The causes of idiopathic vertebral fractures (IVF) in men are poorly understood. We hypothesised that in IVF, areal bone mineral density (aBMD) deficits would be associated with reduced muscle mass. METHODS: In this case-control study, 48 men (61.5 +/- 12.1 years old) presenting with symptomatic IVF were compared with 48 healthy controls matched for age (+/-5 years) and stature (+/-5 cm). The aBMD and soft-tissue body composition were determined by dual energy X-ray absorptiometry (DXA). Muscle mass was defined as the ratio of appendicular lean mass to the square of height (ALMI). Sex hormones, IGF-I and its binding protein IGFBP-3 were measured by immunoassay. RESULTS: ALMI was significantly lower in IVF patients (8.27 +/- 0.90 vs 8.65 +/- 0.88 kg/m(2), t = 2.193, df = 47, P = 0.033 by paired sample t-test). Hierarchical regression analysis revealed that for IVF patients, ALMI explained the greatest proportion of variance in BMD at the lumbar spine, femoral neck and total hip (R (2) (change) = 16.4-22.7%, P = 0.012-0.002) and only IGFBP-3 explained variance in ALMI (R (2) (change) = 19.9%, P = 0.006). CONCLUSIONS: In men with IVF, ALMI was reduced and associated with IGFBP-3. ALMI was identified as a novel factor that explained a greater proportion of variance in BMD than either fat mass or serum biochemistry.

Impact of domestic violence and drug abuse in pregnancy on maternal attachment and infant temperament in teenage mothers in the setting of best clinical practice.

We examined whether the prenatal detection of family violence and initiation of a comprehensive prenatal individualised care program could ameliorate the impact of family violence on maternal attachment to her infant at 6-months of age. An assessment of domestic violence was established for each subject at the 1(st) antenatal visit and women were classified as being exposed to domestic violence in pregnancy (EDV) or as being not exposed to domestic violence. Outcomes were determined 6 months postpartum. Of 173 consecutive women who met the eligibility criteria, consent was obtained from 150 (87% response). Women who had been subjected to domestic violence showed reduced overall attachment scores to their infants. Following multivariate analysis, drug use in pregnancy and domestic violence showed a significant independent effect on maternal attachment. Drug abuse and domestic violence were also associated with an increase in the easy-difficult scale of infant temperament. Thus, despite excellence in prenatal care, drug abuse and domestic violence were associated with poorer maternal attachment and assessment of infant temperament, suggesting that additional interventions are still required.

A bio-assay for effectors of osteoclast differentiation in serum from patients with bone disease.

UNLABELLED: Osteoclast differentiation and activity, and hence bone loss, depend on two opposing cytokines. Receptor activator of NF-(kappa)B ligand (RANKL) produced by osteoblasts and T-cells stimulates, while osteoprotegerin inhibits. Both of these cytokines are found in serum. Our aim was to develop a functional assay for any factors present in human serum that can affect osteoclast differentiation and to assess whether any such factors vary in diseases in which bone loss occurs. METHODS: Using a culture model of osteoclast differentiation in the presence of macrophage colony stimulating factor and soluble RANKL, we have measured the effects of different human sera on osteoclast differentiation. The production of a marker enzyme for the osteoclast, tartrate-resistant acid phosphatase (TRAP), was used to follow osteoclast differentiation. RESULTS: In general, human serum stimulates osteoclast differentiation as indicated by TRAP activity, but in patients with low bone density this stimulation was attenuated. Sera from 40 female subjects with low bone mineral density showed significantly lower TRAP cell differentiation activity than sera from the healthy female controls. CONCLUSION: We describe a functional bio-assay for factors in human serum which can affect osteoclast differentiation. This assay may have application in monitoring the effects of therapy in bone disease.

The progression of disease stage in twin-twin transfusion syndrome.

OBJECTIVE: To estimate the frequency of progression or regression of disease stage in pregnancies complicated by twin-twin transfusion syndrome (TTTS) managed with non-placental laser techniques. METHODS: A cohort of TTTS pregnancies within the sole perinatal center for the state of Western Australia was examined. All cases of prenatally identified TTTS from 1992 to 2002 were staged at diagnosis (retrospectively prior to 2000, prospectively since). Amnioreduction and septostomy were the principal therapies used. Features associated with progression, regression or stability were identified. RESULTS: During the study period, 71 cases of TTTS were managed. Amnioreduction was performed in 73.2%, with no difference in the median number of procedures by stage (p = 0.178). In 21.1% of cases, TTTS resolved completely with persistent normalization of amniotic fluid volumes after amnioreduction (median number of procedures: 2). Disease resolution was associated with pregnancy prolongation, greater gestational age at delivery (36 weeks vs. 28.4 weeks, p < 0.001) and increased perinatal survival (100% vs. 42.6%, p < 0.001) compared with stage progression. Logistic regression analysis predicted that the probability of both infants surviving was 80% if the pregnancy remained at Stage I or II throughout, compared with a probability of 50% if it reached Stage III or more at 26 weeks, and only 25% if the disease reached Stage III or more at 16 weeks' gestation. CONCLUSION: Pregnancy outcome for TTTS managed with amnioreduction techniques is correlated with stage at diagnosis and the subsequent disease evolution. However, the progression of stage in TTTS is unpredictable and the likelihood of spontaneous fetal demise was not different between stages.

Intrathecal fentanyl-induced pruritus during labour: the effect of prophylactic ondansetron.

Fentanyl is commonly used for spinal analgesia during labour but it is associated with a high incidence of pruritus. This randomised, double-blind, placebo-controlled study was performed to evaluate the effect of prophylactic ondansetron on the incidence and severity of pruritus among parturients receiving intrathecal fentanyl as part of combined spinal-epidural analgesia. Seventy-three women were randomised to receive either saline placebo (group P, n = 25), ondansetron 4 mg (group O4, n = 23) or ondansetron 8 mg (group O8, n = 25) intravenously before intrathecal fentanyl 25 micrograms and bupivacaine 2 mg. The incidence and severity of pruritus were measured using a verbal rating and a visual analogue scale, and by the requirement for rescue anti-pruritic medication (naloxone). The overall incidence of pruritus was 95% (group P 100%, group O4 95%, group O8 90%). There were no significant differences between groups for severity of pruritus or requirement for treatment (naloxone given to 45%, 28% and 35% of groups P, O4 and O8 respectively). Secondary outcomes such as the incidence of headache, pain and nausea were not significantly different between groups. We conclude that prophylactic ondansetron 4 or 8 mg intravenously was ineffective in reducing the incidence or severity of intrathecal fentanyl-induced pruritus during labour.

Effectiveness and safety of a structured swimming program in previously sedentary women during pregnancy.

OBJECTIVE: To determine whether undertaking a swimming program in sedentary women during pregnancy would improve maternal fitness without adverse fetal consequences. METHODS: Prospective observational investigation of healthy sedentary pregnant women participating in a monitored swimming program. RESULTS: Twenty-three women attended swimming sessions from 16 to 28 weeks of gestation resulting in increasing distances swum and improved aerobic fitness as measured by physical work capacity (PWC170) (p = 0.003). Resting maternal heart rate decreased (p = 0.041) and resting systolic (p = 0.092) and diastolic (p = 0.971) blood pressures remained unchanged over gestation. The mean fetal heart rates decreased with advancing gestational age (p = 0.001), consistent with normal physiology. Non-stress tests and umbilical artery systolic/diastolic ratios were similar before and after swimming sessions, providing evidence that fetal well-being was unchanged. CONCLUSIONS: A structured swimming program in sedentary pregnant women increases maternal fitness without any alteration in maternal and fetal well-being.

Effect of postural supports on neuromotor function in very preterm infants to term equivalent age.

OBJECTIVE: To determine the effect of a postural support nappy and/or a postural support roll on neuromotor function in very preterm infants when nursed prone to term equivalent age. METHODS: A randomized observer blind controlled trial of 123 very preterm infants was conducted in the neonatal intensive care unit of the sole tertiary referral centre in Western Australia. Infants were stratified by gestational age (< 29 weeks or 29-30 weeks), then randomized into one of three intervention groups: postural support nappy, postural support nappy and postural support roll, or disposable nappy and postural support roll. Interventions started when infants were stable and ceased when routine side-lying commenced. Measurements of shoulder and hip posture were performed pre-intervention, 5 weeks post-intervention and term postmenstrual age. RESULTS: Infants nursed with a postural support roll and a postural support nappy demonstrated improved hip posture to term equivalent age compared with infants nursed with either a postural support roll only, or a postural support nappy only. Infants nursed with a postural support roll either with or without a postural support nappy demonstrated improved shoulder posture to term equivalent age. CONCLUSIONS: Combined use of a postural support roll and a postural support nappy while very preterm infants are nursed prone improves hip posture up to term postmenstrual age. Use of a postural support roll improves shoulder posture up to term equivalent age.

Oral corticosteroid prescribing in women over 50, use of fracture prevention therapy, and bone densitometry service.

OBJECTIVE: To identify the most common diseases and age of corticosteroid use in women over 50, dosage in last year, duration of oral corticosteroid use, prescription for fracture prevention (drug used), and referrals for bone densitometry. METHODS: General practice records from 41 practices in Shropshire identified 62,230 women aged >50 from a population of 80,082. Data on fractures, duration of corticosteroid use, dose in the study year (1 April 1997-31 March 1998), use of fracture prevention therapy and bone densitometry were sampled from one out of three records. RESULTS: 3.2% were prescribed corticosteroids; 633 patients investigated in detail aged 70.1 (SD 10.5) years, had been prescribed 1526 (SD 1727) mg prednisolone (median 1040 mg) for 3.31 (SD 3.20) years (median 2.0 years). Patients with asthma/lung disease, most common in the younger group, had the lowest annual corticosteroid use; patients with rheumatoid arthritis (RA), polymyalgia rheumatica/temporal arteritis (PMR/TA), who were more likely to be elderly, had the highest annual use. Between the age of 70 and 79 years patients with RA had significantly more hip fractures than the other groups, and corticosteroid prescribing was most common. Bisphosphonates or hormone replacement therapy were prescribed for 48% aged 50-59 years but only 32% at 70-79 years (p<0.01); patients with asthma and RA being less likely recipients (p<0.01). Referrals for bone densitometry had occurred in 20.2%,with 60.2% having osteoporosis. Referrals were more common in those taking corticosteroids for longer periods (p<0.01). CONCLUSIONS: The elderly had the most prescriptions for corticosteroid treatment but the fewest for effective fracture prevention therapy. Patients with RA, PMR/TA had the greatest corticosteroid dosage, for the longest time. Patients with RA sustained more hip fractures than other groups but were least likely to have effective fracture prevention therapy prescribed.

The effect of anaesthetic technique on postoperative nausea and vomiting after day-case gynaecological laparoscopy.

Gynaecological surgery is of high emetogenic potential and both total intravenous anaesthesia (TIVA) and prophylactic antiemetic therapy may reduce the incidence of postoperative nausea and vomiting (PONV). We studied 144 patients scheduled for day-case gynaecological laparoscopy in a randomized trial comparing balanced inhalational anaesthesia and prophylactic dolasetron (group I+D) with propofol TIVA and dolasetron (group T+D) or TIVA alone (group T). The primary outcome of "complete response" (no vomiting, no treatment for PONV) was not significantly different among groups (34%, 51%, 32%; groups I+D vs T+D vs T, P=0.12). During the first hour after surgery, group I+D had nausea of greater severity (P<0.03). During hospital admission, group T had more vomiting (P<0.03). From discharge until 24 hours postoperatively, 55% of group I+D experience nausea and 38% vomited. The incidence and severity of nausea were significantly lower in the TIVA groups (P<0.04 and <0.05 respectively). There were no significant differences between groups T+D and T, although comparing all groups the complete response rate was highest and the post-discharge incidence and severity of nausea lowest in group T+D. In conclusion, propofol TIVA, with or without dolasetron, reduced postoperative nausea, but not perioperative vomiting or antiemetic requirement, when compared with inhalational anaesthesia plus dolasetron.

Low body size and elevated sex-hormone binding globulin distinguish men with idiopathic vertebral fracture.

Factors predisposing to vertebral fracture in men are less well defined compared with women. Most studies of osteoporosis in men have included patients with low bone mineral density (BMD), with or without vertebral fracture, or have included other fractures. To clarify these associations we investigated sex hormone levels, bone markers, and (indirectly) lean body mass (LBM) in 81 men with idiopathic vertebral fracture. Serum testosterone, estradiol, sex-hormone binding globulin (SHBG), 24-hr urinary creatinine (24-hr UCr), urinary free deoxypyridinoline (UfDPD) and serum type I procollagen carboxy-terminal propeptide, type I procollagen amino-terminal propeptide, type I collagen carboxy-terminal telopeptide, and osteocalcin were measured. SHBG was higher and 24-hr UCr lower in osteoporotic subjects. UfDPD was higher when corrected for 24-hr UCr. Serum bone turnover markers were not significantly increased, nor were serum sex hormones (and free hormone indices) significantly decreased in patients. SHBG levels were inversely related with lumbar spine and femoral neck BMD in both patients and control subjects. Free estradiol index was only correlated with BMD in men with osteoporosis. Body size is lower in men with established osteoporosis. The normal free hormone indices suggest that SHBG does not affect free hormone levels whereas the relationship between SHBG (but not sex hormones) and 24-hr UCr points to a relationship between SHBG and LBM. The association of high levels of SHBG with low levels of LBM may indicate an action via the known inverse relationship of SHBG with IGF-I, though any action through IGF-I probably occurred at an earlier age than that at which the patients presented. Estrogen has no relationship with BMD in normal men but may play a role in men with osteoporosis.

Statistical measures of foetal growth using linear mixed models applied to the foetal origins hypothesis.

Statistical models of the relationship between the distribution of each of five foetal dimensions and gestational age are developed based on serial ultrasound biometric data from a prospective longitudinal study in Perth, Western Australia. Both the response variable and the gestational age timescale are transformed to establish an approximately linear relationship within subjects. This relationship is modelled using a linear mixed effects model that accounts for between-subject heterogeneity by incorporating subject specific random effects for both intercept and gradient. These models are used to motivate three measures of foetal growth: the conditional centile or z-score of a current measurement given an earlier value for the same measurement; the best linear unbiased predictor (BLUP) of the subject specific random effect gradient (which is shown to be invariant to transformations of location and scale), and the standardized residual at a given gestational age, which characterizes departures from the modelled growth trajectory. We illustrate how these three measures of growth might be applied to subsequent health outcomes in later life by relating growth in foetal abdominal circumference to blood pressure in children from the same cohort at six years of age. Foetuses whose summary measures indicate poor growth in abdominal circumference have higher blood pressure in early childhood, supporting the 'foetal origins' hypothesis that many chronic diseases of adulthood have their origins before birth.

Repeated prenatal corticosteroid administration delays astrocyte and capillary tight junction maturation in fetal sheep.

Glucocorticoids are powerful regulators of cell differentiation and maturation. Their synthetic counterparts, the corticosteroids, are used widely in obstetric practice to enhance fetal lung maturation in cases of threatened preterm birth. Here we examined the effects of repeated corticosteroid administration on astrocyte and capillary tight junction development in the fetal sheep brain, selecting the corpus callosum for analysis. Pregnant ewes were given saline or betamethasone (0.5 mg/kg) at 104, 111, 118 and 124 days gestation. Lambs were delivered at term, terminally anaesthetized and transcardially perfused. Transverse semi-thin sections of the corpus callosum were cut and immuno-stained with antibody against glial fibrillary acidic protein (GFAP). Ultra-thin sections were examined in the electron microscope. The percentage area of GFAP staining was reduced in the corticosteroid-treated group compared to control (5.2 vs. 8.7%, P<0.05). The expression of GFAP in peri-capillary and parenchymal astrocytes was also reduced compared to control (peri-capillary: 3.0 vs. 9.5 microm2; parenchymal: 14.6 vs. 29.4 microm2, P<0.05). Furthermore, capillary tight junction maturation was delayed compared to control. Immature 'type II' junctions were more common in the corticosteroid-treated group (63 vs. 22%, P<0.05), whereas more mature 'type III' junctions were less common (27 vs. 65%, P<0.05). Our data suggest that repeated corticosteroids delay both astrocyte and capillary tight junction maturation. The implications for clinical practice are as yet unknown.

Repeated ultrasound guided fetal injections of corticosteroid alter nervous system maturation in the ovine fetus.

INTRODUCTION: Recent studies in sheep have shown that repeated maternal injections of betamethasone are associated with adverse effects within the nervous system. Repeated fetal injections of betamethasone achieve serial improvements in preterm lung function in sheep and are a possible alternative to repeated maternal therapy. We have evaluated the effect of repeated fetal administration of betamethasone on nervous system maturation in an ovine model. METHODS: Date-mated ewes (n = 48) were randomized to receive ultrasound-guided fetal injections of betamethasone or saline between days 104 to 124 of gestation and were delivered by cesarean section on day 125 or 145 (term = 150). Optic and sciatic nerves were prepared for light and electronmicroscopy. Eye diameters were measured and transverse sections of retinae were evaluated. Data were analyzed using a mixed model analysis of variance. RESULTS: Repeated fetal administration of corticosteroid did not significantly affect optic nerve myelination but resulted in significant delays in sciatic axonal growth (p < 0.02) and retinal maturation (p < 0.04). The process of performing repeated fetal injections also significantly affected some retinal parameters. CONCLUSION: Repeated fetal administration of betamethasone alters some aspects of nervous system maturation in sheep. It is premature to plan trials of repeated fetal corticosteroid therapy in humans.

A prospective cohort study of the impact of domestic violence on young teenage pregnancy outcomes.

INTRODUCTION: The incidence of domestic violence among pregnant Australian teenagers is higher than rates reported for the general community. However, there are limited data that address the impact of this abuse upon pregnancy outcome. We have examined the significant antenatal associations of domestic violence in young teenage pregnancy, and the impact of this abuse upon pregnancy outcome. DESIGN, SETTING, PARTICIPANTS: A multicenter prospective cohort study was performed between January 1, 1997 and June 30, 1999. Patients were interviewed and completed questionnaires in the antenatal period to establish whether they were victims of domestic violence. Labor and delivery details were independently collated after discharge for mother and infant. Data were analyzed using an analysis of variance, with a P-value of 0.05 considered significant. RESULTS: Of 537 patients enrolled in the study, 157 (29.2%) were victims of domestic violence; 380 (70.8%) were not and acted as pregnant teenage controls. Key findings were that teenage victims of domestic violence (VDV) were more likely to smoke, drink alcohol, or use illegal drugs than controls (P < 0.0001). VDV had a higher incidence of infectious morbidity and Pap smear abnormalities (P < 0.007) and psychosocial pathology (P < 0.0001) than controls. A higher incidence of puerperal and neonatal morbidity was observed in VDV and their newborns compared to controls (P < 0.007). The estimated cost of hospital care for teenage VDV was double that of the Australian average. CONCLUSION: We need to identify all teenage mothers exposed to domestic violence and provide them with expert intervention services. Early intervention programs are likely to be cost effective.

Repeated prenatal corticosteroid administration delays myelination of the corpus callosum in fetal sheep.

Glucocorticoids regulate oligodendrocyte maturation and the myelin biosynthetic pathways. Synthetic glucocorticoids, the corticosteroids have been successfully used in clinical practice as a single course to enhance lung maturation and reduce mortality and morbidity in preterm infants with no long-term neurologic or cognitive side effects. However, a trend has arisen to use repeated courses despite an absence of safety data from clinical trials. We examined the effects of clinically appropriate, maternally administrated, repeated courses of corticosteroids on myelination of the corpus callosum using sheep as a large animal model. The corpus callosum is a major white matter tract that undergoes protracted myelination, underpins higher order cognitive processing and developmental damage to which is associated with, for example, cerebral palsy, mental retardation and attention deficit hyperactivity disorder. Pregnant ewes were given saline or betamethasone (0.5 mg/kg) at 104,111,118 and 124 days gestation, stages equivalent to the third trimester in humans. Lambs were delivered at 145 days (term), perfused and the corpus callosum examined light and electron microscopically. Total axon numbers were unaffected (P>0.05). However, myelination was significantly delayed. Myelinated axons were 5.7% in the experimental group and 9.2% in controls (P<0.05); conversely, unmyelinated axons were 88.3 and 83.7% (P<0.05). Myelinated axon diameter and myelin sheath thickness were also reduced (0.68 vs. 0.94 and 0.11 vs. 0.14 microm, P<0.05). Our data suggest that repeated prenatal corticosteroid administration delays myelination of the corpus callosum and that further safety data are needed to evaluate clinical practice.

The effect of intravenous ketorolac on opioid requirement and pain after cesarean delivery.

Nonsteroidal antiinflammatory drugs, including ketorolac, are widely used for postoperative analgesia. This randomized, double-blinded trial compared IV ketorolac or saline combined with meperidine patient-controlled epidural analgesia (PCEA) after cesarean delivery. Fifty healthy parturients scheduled for elective cesarean delivery under combined spinal-epidural anesthesia received PCEA plus either IV ketorolac (Group K) or saline (Group C) for 24 h. The ketorolac dose was modified, after six patients had been studied, based on new product information recommending a maximum of 120 mg ketorolac over 24 h. Group K (n = 24) and Group C (n = 20) were demographically similar. During the first 24 h, Group K used significantly less meperidine (P < 0.05). Postoperative pain at rest and with movement, and patient satisfaction, did not differ significantly between groups, except that worst pain at 12 h was less in Group K (P < 0.005). The two groups were similar with respect to patient recovery and side effects. IV ketorolac, as an adjunct to PCEA after cesarean delivery, produced a meperidine dose-sparing effect of approximately 30%, but did not significantly improve pain relief, reduce opioid-related side effects, or change patient outcome.

Adjustment for current weight and the relationship between birth weight and blood pressure in childhood.

OBJECTIVE: To determine the role of current weight in mediating the relationship between birth weight and blood pressure within the context of the 'fetal origins' hypothesis. DESIGN: Prospective cohort study of 2507 pregnant women and their singleton offspring, delivered live at term, in Perth, Western Australia between 1989 and 1992. The study commenced at 16 weeks gestation with serial weight and blood pressure measurements recorded through early childhood. RESULTS: Inverse associations were found between birth weight and systolic blood pressure at ages 1, 3 and 6. The effect of birth weight on systolic blood pressure at age 6 reached statistical significance and was increased fourfold in magnitude to -2.3 mmHg [95% confidence interval = (-3.3 to -1.3), P < 0.01] after adjustment for current weight. The interaction term for birth weight and current weight was not statistically significant. Including intermediate weights did not produce a statistically significantly better model but did increase the magnitude of the estimated regression coefficient of birth weight on blood pressure, and only the birth weight and current weight terms were significant CONCLUSIONS: Adjustment for current weight serves to highlight the relationship between birth weight and blood pressure in childhood. Nevertheless, birth weight, rather than birth weight adjusted for current weight, is still the relevant predictor of later blood pressure within the context of the 'fetal origins' hypothesis.

Fetal sciatic nerve growth is delayed following repeated maternal injections of corticosteroid in sheep.

AIMS: A single course of prenatal corticosteroid reduces the mortality and morbidity of preterm birth. Repeated courses of prenatal corticosteroids are widely prescribed despite a lack of safety data. Repeated corticosteroids delay myelination in the ovine central nervous system at the time of preterm delivery but with catch-up at term. We aimed to evaluate their effect in the peripheral nervous system. METHODS: Thirty date-mated ewes were administered either saline, a single injection of betamethasone, or four injections of betamethasone between 104 and 124 days' gestation, with delivery on day 125 or 145 (term = 150 days). Sciatic nerves were dissected and fixed in modified Karnovsky's fixative and prepared for light and electron microscopy to determine the proportion of myelinated axons and mean axon diameter. RESULTS: Repeated, but not single, corticosteroid administration resulted in significant decreases in the total cross-sectional and fascicle-containing areas of the sciatic nerve, and in the mean diameter of myelinated and unmyelinated axons. Deficits persisted at term. The proportion of myelinated axons was unaffected. CONCLUSION: Repeated prenatal corticosteroids have the capacity to affect the growth of peripheral nerve axons in sheep. Documentation of their effects in human pregnancy await randomized trials.

Maternal cigarette smoking during pregnancy, low birth weight and subsequent blood pressure in early childhood.

Given the widely acknowledged inverse relationship between birth weight and blood pressure, a raised blood pressure in the offspring of smoking mothers as compared to those whose mothers did not smoke, would be anticipated by virtue of the reduction in birth weight associated with smoking during pregnancy. The objective of the present study was to test the hypothesis that maternal cigarette smoking during pregnancy has an effect on blood pressure in childhood independent of its effect on birth weight. Data was obtained from a prospective cohort study of 1708 pregnant women and their singleton offspring, delivered live at term, in Perth, Western Australia, commenced at 16 weeks gestation with serial blood pressure measurements through early childhood. Statistically significant associations were found between maternal smoking during pregnancy and systolic blood pressure at age six, between birth weight and systolic blood pressure at ages three and six, and between maternal smoking during pregnancy and birth weight. The relationship between birth weight and blood pressure in early childhood differed significantly on the basis of maternal cigarette smoking or not during pregnancy. This differential relationship persisted after adjustment for the child's current weight and socio-economic status. We concluded that intra-uterine exposure to maternal cigarette smoking increased children's blood pressure at age one through to age six. This was not wholly attributable to an effect on birth weight or confounding of the association between birth weight and subsequent blood pressure by the child's current weight or socio-economic factors. Furthermore, maternal smoking during pregnancy does not account for the acknowledged elevation in blood pressure associated with low birth weight. The present study is an exploration of a possible causal pathway underlying the birth weight/blood pressure association rather than simply a confirmation of such an association which has been detailed in many other papers.