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J E Harding

Publications and source records attributed to J E Harding.

At least 19 recordsLinked to original sources
PubMed2006

Long term effects of antenatal betamethasone on lung function: 30 year follow up of a randomised controlled trial.

BACKGROUND: Antenatal betamethasone is routinely used for the prevention of neonatal respiratory distress syndrome in preterm infants. However, little is known of the long term effects of exposure to antenatal betamethasone on lung function in adulthood. METHODS: Five hundred and thirty four 30 year olds whose mothers had participated in the first and largest randomised controlled trial of antenatal betamethasone were followed. Lung function was assessed by portable spirometric testing. The prevalence of asthma symptoms was assessed using the European Community Respiratory Health Survey questionnaire. RESULTS: Fifty (20%) betamethasone exposed and 53 (19%) placebo exposed participants met the criteria for current asthma (relative risk 0.98 (95% CI 0.74 to 1.30), p = 0.89). 181 betamethasone exposed and 202 placebo exposed participants had acceptable spirometric data. There were no differences in lung function between betamethasone and placebo exposed groups (mean (SD) forced vital capacity in the betamethasone and placebo groups 105.9 (12.0) v 106.6 (12.6)% predicted, difference = -0.7 (95% CI -3.2 to 1.8), p = 0.59; mean (SD) forced expiratory volume in 1 second in the betamethasone and placebo groups 98.9 (13.4) v 98.5 (13.6)% predicted, difference = 0.3 (95% CI -2.4 to 3.1, p = 0.80)). CONCLUSIONS: Antenatal exposure to a single course of betamethasone does not alter lung function or the prevalence of wheeze and asthma at age 30.

Asthma↗
PubMed2006

Effect of pulsatile growth hormone administration to the growth-restricted fetal sheep on somatotrophic axis gene expression in fetal and placental tissues.

We have previously reported (Bauer MK, Breier BH, Bloomfield FH, Jensen EC, Gluckman PD, and Harding JE. J Endocrinol 177: 83-92, 2003) that a chronic pulsatile infusion of growth hormone (GH) to intrauterine growth-restricted (IUGR) ovine fetuses increased fetal circulating IGF-I levels without increasing fetal growth. We hypothesized a cortisol-induced upregulation of fetal hepatic GH receptor (GH-R) mRNA levels, secondary increases in IGF-I mRNA levels, and circulating IGF-I levels, but a downregulation of the type I IGF receptor (IGF-IR) as an explanation. We, therefore, measured mRNA levels of genes of the somatotrophic axis by real-time RT-PCR in fetal and placental tissues of fetuses with IUGR (induced by uteroplacental embolization from 110- to 116-days gestation) that received either a pulsatile infusion of GH (total dose 3.5 mg/day) or vehicle from 117-126 days and in control fetuses (n = 5 per group). Tissues were collected at 127 days (term, 145 days). Fetal cortisol concentrations were significantly increased in IUGR fetuses. However, in liver, GH-R, but not IGF-I or IGF-IR, mRNA levels were decreased in both IUGR groups. In contrast, in placenta, GH-R, IGF-I, and IGF-IR expression were increased in IUGR vehicle-infused fetuses. GH infusion further increased placental GH-R and IGF-IR, but abolished the increase in IGF-I mRNA levels. GH infusion reduced IGF-I expression in muscle and increased GH-R but decreased IGF-IR expression in kidney. IUGR increased hepatic IGF-binding protein (IGFBP)-1 and placental IGFBP-2 and -3 mRNA levels with no further effect of GH infusion. In conclusion, the modest increases in circulating cortisol concentrations in IUGR fetuses did not increase hepatic GH-R mRNA expression and, therefore, do not explain the increased circulating IGF-I levels that we found with GH infusion, which are likely due to reduced clearance rather than increased production. We demonstrate tissue-specific regulation of the somatotrophic axis in IUGR fetuses and a discontinuity between GH-R and IGF-I gene expression in GH-infused fetuses that is not explained by alterations in phosphorylated STAT5b.

Animals↗
PubMed2006

Fetal exposure to excess glucocorticoid is unlikely to explain the effects of periconceptional undernutrition in sheep.

Periconceptional undernutrition alters fetal growth, metabolism and endocrinology in late gestation. The underlying mechanisms remain uncertain, but fetal exposure to excess maternal glucocorticoids has been hypothesized. We investigated the effects of periconceptional undernutrition on maternal hypothalamic-pituitary-adrenal axis function and placental 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) activity. Ewes received maintenance feed (N, n= 20) or decreased feed from -60 to +30 days from mating to achieve 15% weight loss after an initial 2-day fast (UN, n= 21). Baseline plasma samples and arginine vasopressin (AVP)-corticotrophin-releasing hormone (CRH) challenges were performed on days -61, -57, -29, -1, +29, 33, and 49 from mating (day 0). Maternal adrenal and placental tissue was collected at 50 days. Baseline plasma levels of adrenocorticotrophic hormone (ACTH) and cortisol decreased in the UN group (P < 0.0001). ACTH response to AVP-CRH was greater in UN ewes during undernutrition (P= 0.03) returning to normal levels after refeeding. Cortisol response to AVP-CRH was greater in UN ewes after the initial 2-day fast, but thereafter decreased and was lower in UN ewes from mating until the end of the experiment (P= 0.007). ACTH receptor, StAR and p450c17 mRNA levels were down-regulated in adrenal tissue from UN ewes. Placental 11betaHSD2 activity was lower in UN than N ewes at 50 days (P= 0.014). Moderate periconceptional undernutrition results in decreased maternal plasma cortisol concentrations during undernutrition and after refeeding, and adrenal resistance to ACTH for at least 20 days after refeeding. Fetal exposure to excess maternal cortisol is unlikely during the period of undernutrition, but could occur later in gestation if maternal plasma cortisol levels return to normal while placental 11betaHSD2 activity remains low.

Animals↗
PubMed2006

The late effects of fetal growth patterns.

The immediate prenatal and postnatal consequences of reduced fetal growth have long been known. The longer term associations between reduced birth weight and adult disease risk are also now well established. Reduced fetal growth is usually detected late in gestation, and the assumption has been that this is the time when factors regulating fetal growth have their greatest effect. However, recent evidence suggests that both the growth trajectory of the fetus and its adaptive responses to the prenatal and postnatal environment may be determined in the period around the time of conception.

Animals↗
PubMed2005

Exposure to repeat doses of antenatal glucocorticoids is associated with altered cardiovascular status after birth.

OBJECTIVE: To determine if exposure to more than one course of antenatal glucocorticoids is associated with changes in infant blood pressure and myocardial wall thickness in the first month after birth. DESIGN: Prospective cohort study. SETTING: Tertiary neonatal intensive care unit. PARTICIPANTS: Mothers who were eligible for but declined to enter a randomised trial of repeated doses of antenatal glucocorticoids (ACTORDS)-that is, who had a singleton, twin, or triplet pregnancy at <32 weeks gestation, had received an initial course of glucocorticoids seven or more days previously, and were considered to be at continued risk of preterm birth. MAIN OUTCOME MEASURES: Blood pressure daily for the first week then weekly until 4 weeks of age. End diastolic interventricular septal and left ventricular posterior wall (EDIVS and EDLVPW) thickness at 48-72 hours after birth. RESULTS: Thirty seven women were enrolled and delivered 50 infants. Thirty mothers (39 infants) were exposed to one course of glucocorticoids, and seven mothers (11 infants) to more than one course. Blood pressures were higher in the first week after birth in infants exposed to multiple courses of glucocorticoids, and in infants with a latency between last exposure and delivery of less than seven days. Systolic blood pressure on day 1 was >2SD above published normal ranges in 67% of babies exposed to multiple courses and 24% of babies exposed to a single course of glucocorticoids (p = 0.04). There was no difference between groups in thickness of the EDIVS or EDLVPW. However, 44/50 (88%) babies had EDIVS and 49/50 (98%) babies had EDLVPW thickness >2 SD above the expected mean for birth weight and gestation. EDIVS but not EDLVPW thickness increased with increasing latency (mean 0.02 mm/day, p = 0.03). CONCLUSION: Future randomised trials should assess the long term effects of exposure to antenatal glucocorticoids, particularly multiple courses, on the cardiovascular status of the infant.

Adult↗
PubMed2005

Variable interpretation of ultrasonograms may contribute to variation in the reported incidence of white matter damage between newborn intensive care units in New Zealand.

BACKGROUND: The incidence of cerebral white matter damage reported to the Australian and New Zealand Neonatal Network (ANZNN) varies between neonatal intensive care units (NICUs). HYPOTHESIS: Differences in the capture, storage, and interpretation of the cerebral ultrasound scans could account for some of this variation. METHODS: A total of 255 infants of birth weight <1500 g and gestation <32 weeks born between 1997 and 2002 and drawn equally from each of the six NICUs in New Zealand were randomly selected from the ANZNN database. Half had early cerebral ultrasound scans previously reported to ANZNN as normal, and half had scans reported as abnormal. The original scans were copied, anonymised, and independently read by a panel of three experts using a standardised method of reviewing and reporting. RESULTS: There was considerable variation between NICUs in methods of image capture, quality, and completeness of the scans. There was only moderate agreement between the reviewers' reports and the original reports to the ANZNN (kappa 0.45-0.51) and between the reviewers (kappa 0.54-0.64). The reviewers reported three to six times more white matter damage than had been reported to the ANZNN. CONCLUSION: Some of the reported variation in white matter damage between NICUs may be due to differences in capture and interpretation of cerebral ultrasound scans.

Brain Diseases↗
PubMed2005

Does variation in interpretation of ultrasonograms account for the variation in incidence of germinal matrix/intraventricular haemorrhage between newborn intensive care units in New Zealand?

BACKGROUND: The incidence of germinal matrix/intraventricular haemorrhage (GM/IVH) reported to the Australian and New Zealand Neonatal Network (ANZNN) varies between neonatal intensive care units (NICUs). HYPOTHESIS: Differences in the capture, storage, and interpretation of the cerebral ultrasound scans may account for some of this variation. METHODS: A total of 255 infants with birth weight <1500 g and gestation <32 weeks born between 1997 and 2002 were randomly selected from the ANZNN database, 44 from each of the six NICUs in New Zealand. Twenty two infants from each NICU had cerebral ultrasound scans previously reported to ANZNN as normal; another 22 had scans reported as abnormal. The original scans were copied using digital photography and anonymised and independently read by a panel of three experts using a standardised method of reviewing and reporting. RESULTS: There was considerable variation between NICUs in methods of image capture and quality and completeness of the scans. However, there was little variation in the reporting of scans between the reviewers and the reports to ANZNN (weighted kappa 0.75-0.91). Grade 1 GM/IVH was generally over-reported and grade 4 under-reported to the ANZNN. CONCLUSION: For all NICUs, a high level of agreement was found between the reviewers' reports and the reports to the ANZNN. Thus the variation between NICUs in the incidence of GM/IVH reported to the ANZNN is unlikely to be due to differences in capture, storage, and interpretation of the cerebral ultrasound scans. Further investigation is warranted into the reasons for the variation in incidence of GM/IVH between NICUs.

Cerebral Hemorrhage↗
PubMed2005

Amniotic IGF-I supplementation of growth-restricted fetal sheep alters IGF-I and IGF receptor type 1 mRNA and protein levels in placental and fetal tissues.

We have previously reported that chronic intra-amniotic supplementation of the late gestation growth-restricted (IUGR) ovine fetus with IGF-I (20 microg/day) increased gut growth but reduced liver weight and circulating IGF-I concentrations. Here we report mRNA and protein levels of IGF-I, the type 1 IGF receptor (IGF-1R) and IGF-binding proteins (IGFBP)-1, -2 and -3 in fetal gut, liver, muscle and placenta from fetuses in that earlier study in an attempt to explain these contrasting results. mRNA and protein were extracted from tissues obtained at post mortem at 131 days of gestation (term, 145 days) from three groups of fetuses (control, IUGR+saline and IUGR+IGF-I, n=9 per group). Control fetuses were unembolised and untreated. In the IUGR groups, growth restriction was induced from 113 to 120 days by placental embolisation; from 120 to 130 days fetuses were treated with daily intra-amniotic injections of either saline or 20 microg IGF-I. mRNA was measured by RT-PCR or real-time RT-PCR, and protein by Western blot. In liver, muscle and placenta, IGF-I mRNA and protein levels were reduced by between 8 and 30% in IGF-I-treated fetuses compared with saline-treated fetuses and controls with no change in IGF-1R mRNA or protein levels. In contrast, in the gut, IGF-I mRNA and protein levels were not significantly altered with IGF-I treatment, but IGF-1R levels were increased, especially in the jejunum. Immunolocalisation demonstrated that IGF-1R expression was confined to the luminal aspect of the gut. mRNA levels of all three IGFBPs were reduced in the gut of IGF-I-treated fetuses, but hepatic expression was significantly increased. These data demonstrated tissue-specific regulation of IGF-I, IGF-1R and IGFBPs-1, -2 and -3 in response to intra-amniotic IGF-I supplementation, though the underlying mechanisms remain obscure.

Amniotic Fluid↗
PubMed2004

Multicomponent fortified human milk for promoting growth in preterm infants.

BACKGROUND: For term infants, human milk provides adequate nutrition to facilitate growth, as well as potential beneficial effects on immunity and the maternal-infant emotional state. However, the role of human milk in premature infants is less well defined as it contains insufficient quantities of some nutrients to meet the estimated needs of the infant. Observational studies have suggested that infants fed formula have a higher rate of growth than infants who are breast fed. However, there are potential short term and long term benefits from human milk. Commercially-produced multicomponent fortifiers provide additional nutrients to supplement human milk (in the form of protein, calcium, phosphate, and carbohydrate, as well as vitamins and trace minerals). OBJECTIVES: The main objective was to determine if addition of multicomponent nutritional supplements to human milk leads to improved growth, bone metabolism and neurodevelopmental outcomes without significant adverse effects in premature infants. SEARCH STRATEGY: Searches were made of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 3003), MEDLINE (searched August 29, 2003), previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language. SELECTION CRITERIA: All trials utilising random or quasi-random allocation to supplementation of human milk with multiple nutrients or no supplementation in premature infants within a nursery setting were eligible. DATA COLLECTION AND ANALYSIS: Data were extracted using the standard methods of the Cochrane Collaboration and its Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author and synthesis of data using relative risk and weighted mean difference. MAIN RESULTS: Supplementation of human milk with multicomponent fortifiers is associated with short term increases in weight gain, linear and head growth. There is no effect on serum alkaline phosphatase levels; it is not clear if there is an effect on bone mineral content. Nitrogen retention and blood urea levels appear to be increased. There are insufficient data to evaluate long term neurodevelopmental and growth outcomes, although there appears to be no effect on growth beyond one year of life. Use of multicomponent fortifiers does not appear to be associated with adverse effects, although the total number of infants studied and the large amount of missing data reduces confidence in this conclusion. Blood urea levels are increased and blood pH levels minimally decreased, but the clinical significance of this is uncertain. REVIEWER'S CONCLUSIONS: Multicomponent fortification of human milk is associated with short-term improvements in weight gain, linear and head growth. Despite the absence of evidence of long-term benefit and insufficient evidence to be reassured that there are no deleterious effects, it is unlikely that further studies evaluating fortification of human milk versus no supplementation will be performed. Further research should be directed toward comparisons between different proprietary preparations and evaluating both short-term and long-term outcomes in search of the "optimal" composition of fortifiers.

Food, Fortified↗
PubMed2004

Maternal water intoxication as a cause of neonatal seizures.

A term infant was admitted at 6 h of age with seizures related to hyponatraemia. During the last hours of labour the infant's mother had drunk 3 L of water. After delivery the serum sodium was 121 mmol/L in the mother and 126 mmol/L in the infant. Both resolved spontaneously. We discuss this case and the impact of maternal fluid intake during labour on the fetus and neonate. Women should be advised that excessive oral fluid intake during labour could adversely affect both mother and infant.

Female↗
PubMed2004

Does radio-opaque contrast improve radiographic localisation of percutaneous central venous lines?

BACKGROUND: Percutaneous central venous lines (long lines) are commonly used in neonatal practice. The position of these lines is important, because incorrect placement may be associated with complications. AIMS: To determine whether the addition of radio-opaque contrast material improves the localisation of long line tips over plain radiography. METHODS: Radiographs taken to identify long line position were identified in two periods; 106 radiographs without contrast taken between October 1999 and August 2000, and 96 radiographs with contrast between September 2001 and July 2002. Two observers independently reviewed each radiograph to identify the position of the line tip. The formal radiology report was recorded as a third observer. RESULTS: The use of contrast increased the proportion of radiographs in which all observers reported they could see the long line tip (53 (55%) v 41 (39%)). It also increased the proportion where they agreed on anatomical position (57 (59%) v 39 (37%)) and there was a higher kappa coefficient for agreement (0.56 v 0.33). CONCLUSIONS: The use of contrast while taking radiographs for the localisation of long line position improves the likelihood that an observer can see a long line tip and reduces inter-observer variability. Even using contrast, precise localisation of a long line tip can be difficult.

Catheterization, Central Venous↗
PubMed2003

Perinatal predictors of growth patterns to 18 months in children born small for gestational age.

AIM: To determine factors before or at birth that are predictive of growth patterns to 18 months in children born small for gestational age (SGA). METHODS: Prospective cohort study of 186 SGA babies. Catch-up growth patterns were defined as early (>10th centile at 6 and 18 months), late (<10th centile at 6 months but >10th centile at 18 months), transient (>10th centile at 6 months but <10th centile at 18 months) or none (<10th centile at 6 and 18 months). RESULTS: Most children (75%) showed catch-up growth by 6 months. Of antenatal variables studied, only early gestation at diagnosis of SGA predicted late or failed catch-up. Late or failed catch-up was also associated with short gestation, small absolute and relative size at birth, increased placental weight/birthweight ratio (Pl/BW) and prolonged neonatal hospital stay. On logistic regression, both late and failed catch-up were associated with short birth length. Late catch-up growth was also associated with prolonged hospital stay and male sex. Failed catch-up was associated with increased Pl/BW. No antenatal or perinatal variables distinguished early from transient catch-up groups. CONCLUSION: SGA babies with late onset and less severe growth restriction have a good chance of catch-up growth by 6 months of age. Catch-up growth is likely to be delayed in SGA babies who are short at birth, are boys, and have prolonged hospital stays. However, poor growth over the first 6 months does not predict later growth patterns. Failure of catch-up growth in babies with increased Pl/BW may reflect an intrinsic growth defect. Transient catch-up growth may reflect environmental factors operating after birth.

Birth Weight↗
PubMed2003

Chronic pulsatile infusion of growth hormone to growth-restricted fetal sheep increases circulating fetal insulin-like growth factor-I levels but not fetal growth.

Intra-uterine growth restriction (IUGR) is a major cause of perinatal mortality and morbidity. Postnatally, growth hormone (GH) increases growth, increases circulating insulin-like growth factor (IGF)-I levels, and alters metabolism. Our aim was to determine if GH infusion to IUGR fetal sheep would alter fetal growth and metabolism, and thus provide a potential intra-uterine treatment for the IUGR fetus. We studied three groups of fetuses: control, IUGR+ vehicle and IUGR+GH (n=5 all groups). IUGR was induced by repeated embolisation of the placental vascular bed between 110 and 116 days of gestation (term=145 days). GH (3.5 mg/kg/day) or vehicle was infused in a pulsatile manner from 117 to 127 days of gestation. Embolisation reduced fetal growth rate by 25% (P<0.01) and reduced the weight of the fetal liver (20%), kidney (23%) and thymus (31%; all P<0.05). GH treatment further reduced the weight of the fetal kidneys (32%) and small intestine (35%; both P<0.04), but restored the relative weight of the fetal thymus and liver (P<0.05). Embolisation decreased fetal plasma IGF-I concentrations (48%, P<0.001) and increased IGF binding protein 1 (IGFBP-1) concentrations (737%, P<0.002). GH treatment restored fetal plasma IGF-I concentrations to control levels, while levels in IUGR+vehicle fetuses stayed low (P<0.05 vs control). IGFBP-1 and IGFBP-2 concentrations were about sevenfold lower in amniotic fluid than in fetal plasma, but amniotic and plasma concentrations were closely correlated (r=0.75, P<0.0001 and r=0.55 P<0.0001 respectively). Embolisation transiently decreased fetal blood oxygen content (40%, P<0.002), and increased blood lactate concentrations (213%, P<0.04). Both returned to pre-embolisation levels after embolisation stopped, but blood glucose concentrations declined steadily in IUGR+vehicle fetuses. GH treatment maintained fetal blood glucose concentrations at control levels. Our study shows that GH infusion to the IUGR fetal sheep restores fetal IGF-I levels but does not improve fetal growth, and further reduces the fetal kidney and intestine weights. Thus, fetal GH therapy does not seem a promising treatment stratagem for the IUGR fetus.

Animals↗
PubMed2002

Cost-effectiveness of palivizumab in New Zealand.

OBJECTIVE: To establish the preterm infant hospitalization risks from respiratory syncytial virus (RSV) in New Zealand and the net cost per hospitalization averted by palivizumab. METHODS: The 437 infants born < 32 weeks' gestation in 1997 and treated at five major neonatal units were identified. Subsequent admissions during the next 2 years for bronchiolitis, pneumonia and croup were tracked, and information collected on RSV tests performed. Data on the length of stay and hospital costs were used to calculate the potential net cost per hospitalization averted associated with the use of palivizumab and the number needed to treat (NNT) to prevent one hospitalization. RESULTS: Estimated RSV readmission risk before 1 year corrected age in infants < 32 weeks' gestation discharged home on oxygen, and those " 28 weeks' gestation, or between 29 and 31 weeks' gestation with or without chronic lung disease was 42%, 23%, 19%, 10% and 8%, respectively. The NNT with palivizumab to prevent one hospitalization ranged from six to 26 across subgroups. Mean (range) net cost per hospitalization averted was 60,000 New Zealand dollars ($28,000-$166,700). In no subgroup would prophylaxis result in net cost saving. Prophylaxis for all NZ infants " 28 weeks' gestation would cost approximately $1,090,000 net and prevent 29 hospitalizations annually, being equivalent to $37,000 net per hospitalization averted, with eight infants treated to prevent one hospitalization. Alternative assumptions about cost and efficacy failed to alter these findings. CONCLUSION: If value is placed on preventing morbidity, the priority groups for palivizumab prophylaxis are preterm infants discharged home on oxygen, followed by preterm infants of 28 weeks' gestation or less.

Antibodies, Monoclonal↗
PubMed2002

Follow up of a randomised trial of two different courses of dexamethasone for preterm babies at risk of chronic lung disease.

OBJECTIVES: To report 18 month outcome of a randomised trial of two courses of dexamethasone to prevent chronic lung disease of prematurity. STUDY DESIGN: Babies of birth weight 1250 g or less ventilated at 7 days of age were randomised to a 42 day reducing course (long) or a 3 day pulsed (pulse) course of dexamethasone. Growth, cardiovascular status, and respiratory and neurodevelopmental outcomes were assessed at 18 months. RESULTS: Seventy six babies were enrolled. Nine died and three were lost to follow up. Babies receiving the long course were weaned off oxygen more quickly than those receiving the pulse course (47% v 69% on oxygen at 28 days; p = 0.01), but there were no differences in 18 month outcomes. However, children averaged -1 SD for growth parameters, half had moderate or severe disability, and 35% and 19% respectively required oxygen at 36 weeks and discharge. CONCLUSIONS: The dexamethasone course used did not influence long term outcome. However, entry criteria for this study selected a group of babies at high risk of poor long term outcome.

Anti-Inflammatory Agents↗
PubMed2002

Measurement of the subarachnoid space by ultrasound in preterm infants.

BACKGROUND: Measurements of the subarachnoid space during routine cranial sonography may provide an indirect method of monitoring brain growth in preterm infants. METHODS: The width of the subarachnoid space was measured on coronal views during head sonography. Initial scans (within five days of birth) were compared with follow up scans. RESULTS: A total of 361 scans were performed on 201 preterm infants. The mean width of the subarachnoid space was < 3.5 mm for 95% of initial scans. It was slightly larger in neonates born closer to term, the equivalent of an increase of 0.02 mm/gestational week (95% confidence interval 0 to 0.10 mm) for initial scans. When the scans of all infants, born at 24-36 gestational weeks who were 36 weeks corrected gestational age were compared, the mean (SD) subarachnoid space was 60% larger for follow up scans than for initial scans: 3.2 (1.38) v 1.95 (1.35) mm (p = 0.002) or the equivalent of a mean increase of 0.20 mm/week (95% confidence interval 0.15 to 0.30 mm) for follow up scans. At 36 weeks corrected gestational age, mean head circumference was not different between those having initial or follow up scans (33.0 (2.0) v 32.2 (1.9) cm; p = 0.31). CONCLUSION: The mean subarachnoid space is normally < 3.5 mm in preterm infants. The difference between initial and follow up scans suggests reduced brain growth in extrauterine preterm babies.

Cephalometry↗
PubMed2002

The effect of a chronic maternal cortisol infusion on the late-gestation fetal sheep.

Exposure of the fetus to excess maternal glucocorticoids has been postulated to alter fetal growth and development, and thus provide a possible mechanism for the link between impaired fetal growth and altered postnatal physiology. However, the effects of exposure to excess maternal glucocorticoids on fetal physiology and metabolism in utero have not been described. We therefore studied the effects of chronic maternal cortisol infusion on fetal growth, blood pressure, metabolism and endocrine status in chronically catheterised fetal sheep. We infused hydrocortisone (80 mg/day, n=6) or saline (n=8) for 10 days into the pregnant ewes beginning at 119 days of gestation. Maternal cortisol infusion reduced fetal growth rate by 30% (girth increment 2.9+/-0.3 vs 1.8+/-0.4 mm/day, P=0.03). Maternal cortisol infusion increased fetal heart weight by 15% relative to body weight and increased ventricular wall thickness by 30% in the left and 50% in the right ventricle. The weight of the spleen was reduced by 30% and placental weight reduced by 25%. Fetal blood pressure increased by approximately 10 mmHg (20%) during maternal cortisol infusion. Maternal cortisol infusion did not alter amino-nitrogen concentrations. However, maternal lactate concentrations increased by 80% and fetal lactate concentrations increased by 74% with maternal cortisol infusion, and both maternal and fetal urea concentrations increased by 40%. Circulating maternal IGF-binding protein (IGFBP)-3 levels had increased by 20% by the end of the maternal cortisol infusion. Fetal IGF-I concentrations decreased during cortisol infusion and fetal IGFBP-1 concentrations were negatively correlated with fetal weight (r=-0.76, P=0.02). We conclude that even a modest elevation of maternal cortisol levels affects fetal growth, cardiovascular function, metabolism and endocrine status which may have long-term consequences.

Animals↗