Biomedical subjects

John P Newnham

Publications and source records attributed to John P Newnham.

At least 19 recordsLinked to original sources

PubMed2006

Prenatal betamethasone exposure results in pituitary-adrenal hyporesponsiveness in adult sheep.

Fetal exposure to synthetic glucocorticoids in sheep results in increased fetal hypothalamic-pituitary-adrenal (HPA) activity persisting to one year of age. We aimed to determine the effects of single or repeated maternal or fetal betamethasone injections on offspring HPA activity at 2 and 3 yr of age and whether changes in adrenal mediators of steroidogenesis contribute to changes in pituitary-adrenal function. Pregnant ewes or their fetuses received either repeated intramuscular saline or betamethasone injections (0.5 mg/kg) at 104, 111, 118, and 124 days of gestation (dG) or a single betamethasone injection at 104 dG followed by saline at 111, 118, and 124 dG. Offspring were catheterized at 2 and 3 yr of age and given corticotrophin-releasing hormone + arginine vasopressin challenges. Adrenal tissue was collected for quantitative RT-PCR mRNA determination at 3.5 yr of age. In 2-yr-old offspring, maternal betamethasone injections did not alter basal ACTH or cortisol levels, but repeated injections elevated ACTH responses. At 3 yr of age, basal ACTH was elevated, and both basal and stimulated cortisol levels were suppressed by repeated maternal injections. Basal and stimulated cortisol-to-ACTH ratios and basal cortisol-to-cytochrome P-450 17alpha-hydroxylase (P450c17) mRNA ratios were suppressed by repeated injections. Repeated fetal betamethasone injections attenuated basal ACTH and cortisol levels in offspring at 2 but not 3 yr of age. Plasma changes were not associated with altered adrenal P450c17, ACTH receptor, beta-hydroxysteroid dehydrogenase, or glucocorticoid receptor mRNA levels. These data suggest that maternal, but not fetal, betamethasone administration results in adrenal suppression in adulthood.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

PubMed2006

IL-1 alpha causes lung inflammation and maturation by direct effects on preterm fetal lamb lungs.

Intra-amniotic endotoxin induces IL-1, causes chorioamnionitis, lung inflammation, lung injury and lung maturation in preterm lambs. Intra-amniotic IL-1alpha also causes chorioamnionitis, lung inflammation and lung maturation. We asked if IL-1alpha effects on the preterm lung are mediated by direct signaling to the lung rather than by indirect effects from the chorioamnionitis. To study IL-1 effects independently of chorioamnionitis, the lungs and the amniotic fluid were surgically separated in fetal sheep by diverting fetal lung fluid via a tracheostomy tube to a sialastic bag. A mini-osmotic pump delivered an intratracheal infusion of recombinant sheep IL-1alpha (10 microg) or saline (control) over 24 h. Preterm lambs were delivered 1d or 7d after the start of the infusion at 124d gestational age (Term = 150d). IL-1alpha recruited inflammatory cells and increased pro-inflammatory cytokine mRNA expression in the fetal lungs. Compared with controls, IL-1alpha did not alter lung antioxidant enzyme activity or alveolar numbers. IL-1alpha had minimal effects on the mRNA or protein expression of proteins essential for vascular development. IL-1alpha induced large increases in alveolar surfactant saturated phosphatidylcholine and increased lung gas volumes. Lung inflammation and maturation result from direct exposure of the fetal lung to a single cytokine - IL-1alpha.

Animals↗

PubMed2006

Does magnesium sulfate reduce the short- and long-term requirements for pain relief after caesarean delivery? A double-blind placebo-controlled trial.

OBJECTIVE: The purpose of this study was to determine whether magnesium sulfate decreases postoperative pain and analgesic consumption. STUDY DESIGN: Women who underwent elective cesarean delivery were randomized into groups according to high-dose magnesium sulfate (50 mg/kg load and 2 g/h), low-dose magnesium sulfate (25 mg/kg load and 1 g/h), or placebo. Before the delivery, the dose of patient-controlled opioid that was used and the visual analogs of pain during the first 48 hours after delivery and at 6 weeks were assessed. RESULTS: Forty-two women were assigned randomly to the high-dose arm; 38 women were assigned to the low-dose magnesium arms, and 40 women were assigned to the control arm. The cumulative opioid use (P = .636); pain scores at 6, 12, 24, and 48 hours at rest (P = .786) and with movement (P = .179); the use of analgesics after hospital discharge (P = .711); and wound pain with movement (P = .429) or pressure (P = .144) after 6 weeks were similar. CONCLUSION: Magnesium sulfate does not reduce the severity of short-term or long-term (6 weeks) pain after cesarean delivery.

Adult↗

PubMed2006

Chronic exposure to intra-amniotic lipopolysaccharide affects the ovine fetal brain.

OBJECTIVE: Fetal brain injury is associated with chorioamnionitis, which is often present without signs of overt infection or fetal compromise. We aimed to determine if prolonged exposure to intrauterine inflammation caused by intra-amniotic infusion of lipopolysaccharide (LPS) would affect the fetal brain. METHODS: At 80 days of pregnancy ewes bearing singletons had osmotic pumps implanted intra-amniotically to infuse Escherichia coli LPS (055:B5; n = 8) or saline (n = 7) for 28 days. At delivery (110 days), umbilical arterial blood and chorioamnion were assessed for inflammation; cytokine concentrations (interleukin [IL]-6 and IL-8) in amniotic fluid and fetal and maternal plasma were measured. The fetal cerebral hemispheres were examined for gross anatomical changes and the number of activated microglia/macrophages, astrocytes, and oligodendrocytes estimated after immunohistochemical staining. RESULTS: Intra-amniotic administration of LPS caused chorioamnionitis, fetal leucocytosis, and a moderate to extensive infiltration of activated microglia/macrophages in the subcortical white matter in six of eight fetuses; the remaining two fetuses were less affected. Within these focal regions of damage there was an attenuation of astrocytic processes, axonal injury, and a reduction in the number of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) immunoreactive oligodendrocytes in areas of extensive focal damage. In control fetuses there was mild (3/7) or no infiltration of activated microglia/macrophages in the subcortical white matter. Overall the infiltration of activated microglia/macrophages in the white matter was significantly greater in LPS-exposed fetuses compared to controls. In regions devoid of injury, the number of oligodendrocytes and astrocytes was not different between groups, nor was there a difference in the volume of cerebral white matter or density of blood vessels within the white matter. Amniotic fluid IL-6 and IL-8, and maternal plasma IL-8 concentrations were significantly increased by LPS infusion. CONCLUSIONS: An increase in inflammatory cells and axonal disruption in the subcortical white matter of the fetal brain can accompany chorioamnionitis induced by intra-amniotic administration of LPS, but cystic lesions do not occur. Thus, the effect on the fetal brain is milder than that reported from animal models of acute fetal/intrauterine infection.

Amniotic Fluid↗

PubMed2006

Periodontal disease and adverse pregnancy outcomes.

Periodontal disease is a common infectious disease in women of reproductive age. The disease is often not diagnosed and in studies of over 10 000 women has been associated with preterm birth, small for gestational age newborns, and preeclampsia. It has been shown in a smaller number of women that treatment of periodontal disease may reduce the rate of preterm birth. The pregnancy complications of periodontal disease may be due to lipopolysaccharide from the periodontal pockets inciting prostaglandin pathways controlling parturition. Three large randomized controlled trials of treatment of periodontal disease are underway and may provide confirmation of the importance of periodontal disease in causing complications of pregnancy.

Abortion, Spontaneous↗

PubMed2005

Recruited inflammatory cells mediate endotoxin-induced lung maturation in preterm fetal lambs.

RATIONALE: Chorioamnionitis is paradoxically associated with a decreased incidence of respiratory distress syndrome in preterm infants. In preterm lambs, intraamniotic endotoxin and interleukin 1 (IL-1) induce lung inflammation followed by lung maturation. OBJECTIVE: To test if inflammatory cells are required to mediate induced lung maturation. METHODS: Lung inflammation was induced by intraamniotic injection of endotoxin or IL-1. Inflammatory cell recruitment to the lung was inhibited by an anti-CD18 blocking antibody given intramuscularly to the fetus. Preterm lambs were delivered at 124-d gestation (term = 150 d) 2 or 7 d after exposure to endotoxin/IL-1 or endotoxin/IL-1 + anti-CD18 antibody. MEASUREMENTS: Lung inflammation was measured by bronchoalveolar lavage fluid cell count, inflammatory scoring of lung parenchyma, and expression of proinflammatory cytokines and inducible nitric oxide synthase. Lung maturation was quantitated by surfactant protein mRNA expression, saturated phosphatidylcholine pool size, and pressure-volume curves. MAIN RESULTS: Inhibition of CD18 significantly reduced endotoxin-induced but not IL-1-induced fetal lung inflammatory cell recruitment and activation as well as expression of proinflammatory cytokines. Compared with control lungs, both endotoxin and IL-1 induced lung maturation. Anti-CD18 antibody administration inhibited only endotoxin-induced but not IL-1-induced increases in surfactant protein mRNA and surfactant saturated phosphatidylcholine. Exposure to anti-CD18 antibody moderated endotoxin-induced increases in lung volumes but had no effect on IL-1-induced increases in lung volumes. CONCLUSIONS: (1) Endotoxin- but not IL-1-induced inflammatory cell recruitment in the preterm fetal lamb lung is CD18 dependent; (2) recruited inflammatory cells mediate some aspects of fetal lung maturation.

Animals↗

PubMed2005

Hepatic glucose regulation and metabolism in adult sheep: effects of prenatal betamethasone.

Fetal exposure to synthetic glucocorticoids in sheep results in increased fetal hepatic 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) and corticosteroid-binding globulin (CBG) protein levels and insulin resistance in postnatal life. The aim was to determine whether these changes persisted to adulthood and whether alterations in mediators of hepatic glucocorticoid and glucose regulation contributed to changes in metabolism. Pregnant ewes or their fetuses received either repeated intramuscular saline (MS, FS) or betamethasone injections (0.5 mg/kg; M4, F4) at 104, 111, 118, and 124 days of gestation (dG), or a single betamethasone injection at 104 dG followed by saline at 111, 118, and 124 dG (M1, F1). Offspring were catheterized at 2 and 3 yr of age and given an intravenous glucose challenge (0.5 mg/kg). Hepatic tissue was collected at 3.5 yr. At 2 yr of age, basal plasma insulin was elevated in M4 offspring and at 3 yr of age was elevated in F4 offspring. Basal insulin-to-glucose ratio was significantly elevated in M4 offspring at 2 yr of age and elevated in M1, M4, and F4 offspring at 3 yr of age. All betamethasone treatments resulted in significant increases in hepatic glucose-6-phosphatase (G-6-Pase) activity. Hepatic glucocorticoid receptor protein levels were not altered in M1 and M4 offspring but were increased in F1 and F4 offspring. Hepatic CBG protein levels were lower in F4 but not F1 offspring and were unchanged from control in M1 and M4 offspring. Prenatal betamethasone exposure results in elevated hepatic G-6-Pase activity in adulthood and may contribute to long-term changes in metabolism.

Animals↗

PubMed2005

Chronic endotoxin exposure does not cause sustained structural abnormalities in the fetal sheep lungs.

Chronic early gestational chorioamnionitis is associated with development of bronchopulmonary dysplasia in preterm infants. A single intra-amniotic exposure to endotoxin decreased alveolarization and reduced expression of endothelial proteins in 125-day gestational age preterm lambs. We hypothesized that prolonged exposure to intra-amniotic endotoxin would cause progressive lung inflammation and inhibit alveolar and pulmonary vascular development. Endotoxin (1 mg/day) or saline was administered via an intra-amniotic osmotic pump from 80 to 108 days of gestational age (continuous pump) or by four weekly 10-mg intra-amniotic endotoxin injections starting at 100 days of gestational age (multiple dose). Lung morphometry, lung inflammation, vascular effects, and lung maturation were measured at delivery. The continuous pump lambs delivered at 100 days (approximately 70% of total endotoxin exposure) had lung inflammation, fewer saccules, and decreased endothelial proteins endothelial nitric oxide synthase and VEGF receptor 2 expression compared with controls. The continuous pump (delivered at 138 days) and multiple dose lambs (delivered at 130 and 145 days) had mild persistent lung inflammation and no significant differences in lung morphometry or expression of endothelial proteins compared with controls. Surfactant saturated phosphatidylcholine pool sizes were increased in all endotoxin-exposed groups, but lung function was not changed relative to controls. Contrary to our hypothesis, a prolonged fetal exposure to intra-amniotic endotoxin caused mild persistent inflammation but did not lead to progressive structural abnormalities in lungs of near-term gestation lambs.

Amniotic Fluid↗

PubMed2005

Effects into adulthood of single or repeated antenatal corticosteroids in sheep.

OBJECTIVE: To determine effects of maternal or fetal injections of betamethasone on postnatal growth and arterial pressure. STUDY DESIGN: We measured body weight, arterial pressure, and heart rate serially in sheep born after single or repeated maternal or fetal betamethasone injections. At approximately 3.5 years, organ weights were measured. RESULTS: Repeated maternal betamethasone injections caused intrauterine growth restriction, and low body weight and blood pressure at 3 months. From 6 months to 3 years, body weight, blood pressure, and heart rate were not affected by treatment. At approximately 3.5 years, brain weight was reduced after single or repeated maternal betamethasone by 13% and 18%, respectively (P = .001). Fetal betamethasone reduced brain weight by 7% to 8% (P = .018). Weights of other organs were not affected by treatment. Brain weight was unrelated to body weight at approximately 3.5 years (P = .649) but was related to birth weight (P = .029). CONCLUSION: Prenatal betamethasone does not have long-term effects on blood pressure but causes a persistent deficit in brain weight.

Animals↗

PubMed2005

Experimental intrauterine Ureaplasma infection in sheep.

OBJECTIVE: Prenatal Ureaplasma spp exposure is associated with preterm birth and modulates the neonates' susceptibility to respiratory distress syndrome and bronchopulmonary dysplasia. We hypothesized that intra-amniotic ureaplasmas would cause lung inflammation and alter fetal lung development. STUDY DESIGN: Pregnant ewes bearing singleton fetuses were given an intra-amniotic injection of 20 x 10 6 CFUs of U parvum (serovar 3) or vehicle, either 1, 3, 6, or 10 weeks before the delivery of preterm lambs at 124 days of gestation (n = 4-10 per group) for evaluation of inflammation and fetal lung maturation. RESULTS: Ureaplasmas were recovered from amniotic and fetal lung fluids after intra-amniotic injection. Body weight and umbilical arterial pH were reduced by Ureaplasma exposure for 10 weeks ( P < .05). Ureaplasmas caused progressive lung inflammation and improvements in lung function that were associated with increased surfactant lipids (control, 0.13 +/- 0.02 micromol/kg; 10 weeks of Ureaplasma exposure, 7.43 +/- 3.0 micromol/kg; P < .001) and surfactant protein messenger RNA expression. CONCLUSION: Long-term exposure to ureaplasmas in amniotic fluid alters ovine fetal development.

Analysis of Variance↗

PubMed2005

The effects of intra-amniotic injection of periodontopathic lipopolysaccharides in sheep.

OBJECTIVE: Periodontal disease may cause several complications of pregnancy, including fetal death. The purpose of this study was to investigate in sheep the effects of the intra-amniotic injection of lipopolysaccharide from 3 periodontopathic organisms and to compare these effects with those resulting from similar injection of Escherichia coli lipopolysaccharide. The outcomes that were studied included the rates of fetal death and the features of inflammation and lung maturation in survivors. STUDY DESIGN: At 118 days of pregnancy, ewes that were bearing single fetuses were allocated at random to receive intra-amniotic injections of saline solution (n = 13 fetuses), or lipopolysaccharide from Porphyromonas gingivalis (in doses from 0.1 to 10 mg [n = 22 fetuses]), Actinobacillus actinomycetemcomitans (10 mg [n = 6 fetuses]; 1 mg [n = 6 fetuses]), Fusobacterium nucleatum (10 mg [n = 6 fetuses]) or Escherichia coli (10 mg [n = 14 fetuses]; 1 mg [n = 7 fetuses]). Surviving fetuses were delivered abdominally at 125 days of gestation (term, 150 days). RESULTS: When compared with Escherichia coli lipopolysaccharide at similar dosages, periodontopathic lipopolysaccharides had high rates of fetal lethality. Only 6 of 22 fetuses that were exposed to intra-amniotic Porphyromonas gingivalis lipopolysaccharide survived doses of 0.1 to 10 mg, and only 3 of 6 fetuses survived 10-mg Actinobacillus actinomycetemcomitans lipopolysaccharide. Escherichia coli lipopolysaccharide did not cause fetal loss when given at doses of 10 mg (n = 14 fetuses) or 1 mg (n = 7 fetuses). Fetuses that survived exposure to these lipopolysaccharides showed features of inflammation in amniotic fluid and cord blood at birth and enhanced lung maturation. CONCLUSION: Lipopolysaccharides from these 3 periodontopathic organisms have much higher rates of fetal lethality than Escherichia coli lipopolysaccharide but can cause similar intrauterine inflammatory responses and improvements in lung volumes in survivors. Sources of inflammation that are distant from the uterus may underlie a proportion of unexplained stillbirth and other complications of pregnancy.

Acid-Base Equilibrium↗

PubMed2005

Breastfeeding and overweight: longitudinal analysis in an Australian birth cohort.

OBJECTIVE: To examine adiposity in relation to breastfeeding using longitudinal analysis in an Australian birth cohort. STUDY DESIGN: Repeated surveys from 16 weeks gestation to 8 years in a cohort (N = 2087) recruited through antenatal clinics. Overweight was defined by National Center for Health Statistics 95th percentiles for weight-for-length at 1 year and body mass index (BMI) at 3, 6, and 8 years. Overweight was examined using Generalized Estimating Equations with results summarized as OR. BMI Z scores were analyzed in mixed models. RESULTS: At 1 year, infants breastfed >12 months were the leanest group (mean Z score -0.16, 95% CL -0.28, -0.04; not breastfed 0.16, 95% CL 0.02, 0.29; breastfed < or = 4 months 0.31, 95% CL 0.22, 0.40; 5-8 months 0.17, 95% CL 0.06, 0.27; 9-12 months 0.11, 95% CL 0.01, 0.22). From 1 to 8 years, children breastfed < or = 4 months had the greatest risk of overweight (OR 1.29, 95% CL 0.89, 1.97) and the highest prevalence of maternal obesity, smoking, and lower education. CONCLUSIONS: Infants breastfed >12 months were leaner at 1 year but not at 8 years. Breastfeeding < or = 4 months was associated with greatest risk of overweight and adverse maternal lifestyle. Familial factors may modify associations between breastfeeding and adiposity beyond infancy.

Body Mass Index↗

PubMed2005

The effects of standing, lifting and noise exposure on preterm birth, growth restriction, and perinatal death in healthy low-risk working military women.

OBJECTIVE: The effects of standing, lifting and noise in low-risk, healthy pregnant women are uncertain. In the past, the heterogeneity of the populations studied, the limitations of the designs of the retrospective and case control studies, and a failure of some of the larger investigations to evaluate all the potential confounding variables has hampered many studies. The purpose of this investigation was to evaluate, throughout pregnancy, the effects of standing, repetitive lifting, and noise in the workplace compared with no standing, lifting or noise exposure, on maternal and perinatal outcomes in a large prospective study of a low-risk healthy population of working women cared for by a single group of health providers. METHODS: This prospective observational study used an extensive questionnaire to collect antepartum, intrapartum, and postpartum information. Information was collected on the initial visit, each subsequent visit, and immediately after delivery. The participating women were divided into groups based on the amount of time spent standing, the amount and extent of repetitive lifting, and noise exposure in the workplace. RESULTS: Eight hundred and fourteen low-risk active duty women participated in this investigation over a 4-year period. Multivariate analysis with non-exposure compared with exposure reinforced the effect of standing on preterm labor (OR 1.80, 95% CI 1.05, 3.16) and preterm birth (OR 1.69, 95% CI 1.03, 2.80) and showed a trend toward an effect of noise exposure on preterm labor (OR 1.76, 95% CI 0.78, 3.39) after controlling for other exposures. CONCLUSIONS: This investigation suggests an association of occupational standing with preterm labor and preterm birth.

Adult↗

PubMed2004

Endotoxin-induced chorioamnionitis modulates innate immunity of monocytes in preterm sheep.

The preterm fetus is immune naive and has immature innate immune function. Although the preterm fetus is frequently exposed to chorioamnionitis, the effects of exposure of the fetal lung to inflammation on innate immune responses are unknown. Using the fetal sheep model of chorioamnionitis, cord blood monocytes were isolated from preterm lambs 1 to 14 days after intra-amniotic endotoxin injection, cultured for approximately 16 hours, and challenged with endotoxin in vitro. Compared with monocytes from adult sheep, the preterm monocytes produced less H(2)O(2) and interleukin-6, and toll-like receptor 4 expression was decreased. Three days after intra-amniotic endotoxin exposure, preterm monocyte responses to in vitro endotoxin challenge demonstrated decreased H(2)O(2) and interleukin-6 production and decreased CD14 and major histocompatibility complex class II expression. Preterm monocyte responses 7 to 14 days after endotoxin tended to exceed those of adults and preterm control animals indicating augmented function. In contrast, a second intra-amniotic endotoxin injection 7 days after the initial endotoxin exposure suppressed monocyte function at 14 days. The fetal monocytes demonstrated patterns of responses consistent with endotoxin tolerance (immune paralysis) as well as maturation of function. Modulation of fetal innate immune responses by exposure to inflammation may alter subsequent immune adaptation after birth.

Amnion↗

PubMed2004

Variability in preterm lamb lung mechanics after intra-amniotic endotoxin is associated with changes in surfactant pool size and morphometry.

Antenatal exposure to intra-amniotic (i.a.) endotoxin initiates a complex series of events, including an inflammatory cascade, increased surfactant production, and alterations to lung structure. Using the low frequency forced oscillation technique as a sensitive tool for measurement of respiratory impedance, we aimed to determine which factors contributed most to measured changes in lung mechanics. Respiratory impedance data obtained from sedated preterm lambs exposed to either i.a. injection with saline or 20 mg of endotoxin 1, 2, 4, and 15 days before delivery at 125 days gestation were studied, and association with indexes of standard lung morphometry, inflammatory response, and alveolar surfactant-saturated phosphatidylcholine (Sat PC) pool size was demonstrated. Reduction in tissue impedance with increasing interval between exposure and delivery was evident as early as 4 days after i.a. endotoxin injection, coinciding with resolution of inflammatory reaction, increased alveolar surfactant pools, and contribution of alveolar ducts to the parenchymal fraction, and a later decrease in the tissue component of the parenchymal fraction. Decreases in tissue damping (resistance) were more marked than decreases in tissue elastance. Log alveolar Sat PC accounted for most variability in tissue damping (88.9%) and tissue elastance (73.4%), whereas tissue fraction contributed 2 and 6.4%, respectively. The alveolar Sat PC pool size was the sole factor contributing to change in tissue hysteresivity. No changes were observed in airway resistance. Despite the complex cascade of events initiated by antenatal endotoxin exposure, variability in lung tissue mechanics is associated primarily with changes in alveolar Sat PC pool and lung morphology.

Animals↗

PubMed2004

Antenatal betamethasone changes cord blood monocyte responses to endotoxin in preterm lambs.

Corticosteroids are routinely administered to women at risk for preterm delivery to induce fetal lung maturation. Antenatal corticosteroids have immunomodulatory effects on fetal immune cells that are poorly understood. We hypothesized that maternal betamethasone would alter in fetal monocytes both the initiation of inflammation in response to pro-inflammatory stimuli and the resolution of inflammation by phagocytosis of apoptotic neutrophils. Preterm lambs at 124 d gestation were delivered 15 h, 1 d, 2 d, or 7 d after 0.5 mg/kg maternal intramuscular betamethasone. Monocytes from cord blood were isolated and cultured and results were compared with monocytes from preterm lambs exposed to maternal saline or monocytes from adult sheep. Phagocytosis of Escherichia coli was not changed, however, phagocytosis of apoptotic neutrophils was low in fetal monocytes but increased after 7 d exposure to maternal betamethasone to the level found in adult monocytes. Hydrogen peroxide production after endotoxin stimulus was significantly reduced to 7.1 +/- 2.2 micromol at 5 h, 8.7 +/- 2.9 micromol at 24 h, and 4.1 +/- 1.9 micromol at 48 h versus 16.4 +/- 3.6 micromol in control animals; at 7 d, the hydrogen peroxide production increased to 74.3 +/- 19.7 micromol (p < 0.05, per 10(6) monocytes). IL-6 production was reduced at 15 h after maternal betamethasone but at no other time point. Maternal betamethasone initially suppressed several fetal monocyte functions, however, at 7 d, measurements of initiation and resolution of inflammation were increased to levels similar to monocytes from adult sheep. The time-dependent changes in maternal betamethasone modulation of the responses of fetal monocytes may influence immune function of the preterm lamb after delivery.

Adrenal Cortex Hormones↗

PubMed2004

Indicators of fetal growth do not independently predict blood pressure in 8-year-old Australians: a prospective cohort study.

Inverse associations between size at birth and blood pressure (BP) in later life are commonly statistically significant only after adjustment for current size, consistent with change in size as the determinant. Few studies have been prospective or have included a range of potential confounders. Using regression models, including maternal and demographic variables, we examined associations between size at birth and BP in Australian children followed from week 16 of gestation to the age of 8 years. BP measurements were available from 1417 children born after 37 weeks gestation without congenital abnormalities. In models adjusted only for sex, the birthweight (BW), birth length, ponderal index, head circumference, chest circumference, abdominal girth, mid-arm circumference, triceps skinfold, placental weight, or BW/placental weight ratio did not significantly predict SBP in 8-year-olds. With adjustment for current size, associations were inverse but not statistically significant (regression coefficients: BW, -1.11; 95% confidence limits [CL], -2.22, 0.01; birth length, -0.25; 95% CL, -0.52, 0.24) and remained nonsignificant after adjustment for confounders. Current weight, height, or body mass index significantly predicted SBP and DBP (P<0.001) with differences of 8/4 mm Hg between upper and lower quartiles; effects were similar in infants with lower and higher BW. These findings are consistent with postnatal change in size as the major determinant of BP in 8-year-olds and are important in the context of the worldwide "epidemic" of obesity in childhood as a likely precursor of increasing rates of hypertension in adults.

Australia↗

PubMed2004

Repeated antenatal corticosteroids: effects on cerebral palsy and childhood behavior.

OBJECTIVE: This study was undertaken to determine the effects of repeated courses of antenatal corticosteroids on childhood behavior and disabilities, including cognitive delay and cerebral palsy. STUDY DESIGN: Nonrandomized regional cohort of 541 very preterm infants born in Western Australia from singleton pregnancies and alive at 3 years were included in the study. MAIN OUTCOME MEASURES: Physical, cognitive, and psychological assessments up to 6 years. RESULTS: Increasing numbers of antenatal corticosteroid courses were associated with a reduction in the rate of cerebral palsy. Three or more courses were also associated with increased rates of aggressive/destructive, distractible, and hyperkinetic behavior and these effects were present at both ages 3 and 6 years. Measures of internalizing behavior and intelligence quotient were unaffected by antenatal corticosteroid use. CONCLUSION: Repeated antenatal courses of corticosteroids may protect against cerebral palsy but are associated with hyperactivity later in childhood.

Adrenal Cortex Hormones↗