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Biomedical subjects

J E Harding

Publications and source records attributed to J E Harding.

At least 37 records · Page 2Linked to original sources
PubMed1999

The vulnerable stomach in babies born with pure oesophageal atresia.

Nine babies with pure oesophageal atresia were treated in our institution in the years 1979-1996. All received a feeding gastrostomy as their initial operation. After initiation of gastrostomy feeds seven (78%) developed gastric complications, including two posterior gastric perforations (one fatal). We propose that the high complication rate is due to a small, abnormal stomach that is vulnerable to damage by operative trauma and the effects of handling large volumes of feed. We hypothesise that the stomach is abnormal because it has not been exposed to the maturing effects of amniotic fluid in utero. Feeds should be introduced very cautiously to these babies and built up very slowly.

Esophageal Atresia↗
PubMed1999

The maternal, fetal and postnatal somatotrophic axes in intrauterine growth retardation.

Both the maternal and fetal somatotrophic axes are closely linked to fetal substrate supply. Nutritional insults at critical stages of fetal development may lead to permanent reprogramming of the relationships between these factors. The consequences of reprogramming during fetal life may be harmful to metabolic, endocrine and cardiovascular homoeostatic mechanisms in postnatal life. The exact mechanisms that lead to reprogramming during fetal life need thorough investigation before effective strategies to deal with this problem can be devised.

Amniotic Fluid↗
PubMed1999

Metabolic effects of IGF-I in the growth retarded fetal sheep.

It has been shown that IGF-I has an anabolic effect in the normal fetus. However, there is evidence to suggest that there may be IGF-I resistance in the growth retarded fetus. Therefore, we investigated the effects of acute IGF-I infusion to chronically catheterised fetal sheep. At 128 days gestation, fetuses underwent a 4 h infusion of IGF-I (50 microg/kg/h). Three groups of animals were studied. Nine normally grown fetuses were studied as controls. Embolised animals (n=8) received microspheres into the uterine vasculature, and animals with spontaneous intra-uterine growth retardation (IUGR animals) (n=6) were fetuses found at post mortem to be spontaneously growth restricted. The effects of IGF-I infusion on feto-placental carbohydrate and protein metabolism were similar in our control group to previous similar experiments. IGF-I infusion decreased fetal blood glucose, oxygen, urea and amino-nitrogen concentrations, and inhibited placental lactate production. The same fetal blood metabolite concentrations also fell during IGF-I infusion in the embolised fetuses, but the effect on placental lactate production was not seen. The only effect of IGF-I infusion in the spontaneous IUGR animals was a fall in fetal blood amino-nitrogen concentrations. We conclude that fetal IGF-I infusion does not have the same anabolic effects in the growth retarded fetus as the normal fetus. In addition, the effects of IGF-I were different in the two growth retarded groups. Our data support previous evidence that the growth retarded fetus has altered IGF-I sensitivity, and this may vary depending on the cause, severity and duration of growth retardation.

Animals↗
PubMed1999

Enteral IGF-I enhances fetal growth and gastrointestinal development in oesophageal ligated fetal sheep.

Infants with upper gut atresia often have impaired intrauterine growth and gut function. IGF-I is important in fetal growth and is contained in amniotic fluid. We therefore wanted to test the hypothesis that IGF-I infused into fetal gut would reverse the effects of an upper gut obstruction on gut structure and growth in fetal sheep. At 90 days gestation fetuses (n=6 per group) underwent oesophageal ligation, followed by continuous infusion of IGF-I (1-8 microgram/day) or saline into the gut beyond the ligation until 137 days. Controls underwent sham ligation only. Oesophageal ligation tended to reduce fetal body and organ weights. IGF-I treatment prevented this reduction and increased body length and spleen weight above those of controls. The decrease in bowel wall thickness induced by oesophageal ligation was also prevented by IGF-I treatment. Amniotic fluid IGF-I concentrations did not change over gestation and were higher in the IGF-I treated group. No change in fetal plasma IGF-I concentrations were detectable. We conclude that enterally administered IGF-I may enhance fetal growth and gut development in utero and that IGF-I in amniotic fluid may play a physiological role in gut development in the fetus.

Animals↗
PubMed1998

Fetal growth and placental function.

Fetal growth is largely determined by the availability of nutrients to the fetus. The fetus is at the end of a supply line that ensures delivery of nutrients from the maternal/uterine circulation to the fetus via the placenta. However, this supply line can not be regarded as a linear relationship. Maternal undernutrition will not only reduce global nutrient availability but will also influence the maternal and fetal somatotrophic axis. Both endocrine systems react in a very similar way to limited substrate supply. The hormones of the fetal somatotrophic axis, and in particular insulin-like growth factor (IGF)-1, are important regulators of fetal growth. Placental function is pivotal to materno-fetal nutrient and metabolite transfer. Placental function in turn, is heavily influenced by the maternal and fetal growth hormone (GH)-IGF-1 system. The placenta itself is also an active endocrine organ and it produces a large number of hormones including GH and IGF-1 as well their corresponding receptors. Thus the placenta can no longer be considered merely a passive conduit for fetal nutrition. Rather, it is actively involved in the integration of nutritional and endocrine signals from the maternal and fetal somatotrophic axes.

Animal Nutritional Physiological Phenomena↗
PubMed1998

Does gut atresia cause polyhydramnios?

Fetal gut atresia is variably associated with polyhydramnios. In order to determine which pregnancies will develop polyhydramnios, the case notes of 80 babies with gut atresia and stenosis were reviewed. Maternal polyhydramnios developed in all cases of pure oesophageal atresia (n = 8), all cases of Type III duodenal atresia (DA) with a non-bifid bile duct (n = 8), 80% of cases with type I DA (n = 10), and 24% of atresias of the small intestine (n = 34). Polyhydramnios did not develop in any case where there was not total obstruction except in 1 baby with DA and a bifid bile duct (BBD). These included stenosis of the oesophagus and duodenum (n = 17) and DA type III with a BBD (n = 3). These results support the role of fetal swallowing and fluid absorption by the fetal gastro-intestinal tract in the regulation of amniotic fluid volume.

Duodenal Obstruction↗
PubMed1998

Chest physiotherapy may be associated with brain damage in extremely premature infants.

OBJECTIVES: To determine whether a characteristic form of brain damage (encephaloclastic porencephaly) was associated with chest physiotherapy treatment in preterm babies. METHODS: A retrospective case-control study was undertaken among 454 infants of birth weight less than 1500 gm cared for during the 3-year period of 1992 to 1994. Thirteen babies of 24 to 27 weeks of gestation who weighed 680 to 1090 gm at birth had encephaloclastic porencephaly. Twenty-six control subjects were matched for birth weight and gestation. RESULTS: The patients received two to three times as many treatments with chest physiotherapy in the second, third, and fourth weeks of life as did control infants (median 79 vs 19 treatments in the first 4 weeks, p < 0.001). Patients also had more prolonged and severe hypotension in the first week than did control subjects (median duration of hypotension 4 vs 0.5 days, p < 0.01), and were less likely to have a cephalic presentation (31% vs 81%, p < 0.01). Since December 1994 no very low birth weight baby has received chest physiotherapy treatment in the first month of life in our nursery, and no further cases have occurred. CONCLUSIONS: Encephaloclastic porencephaly may be a previously unrecognized complication of chest physiotherapy in vulnerable extremely preterm infants.

Birth Weight↗
PubMed1998

The role of neonatal chest physiotherapy in preventing postextubation atelectasis.

We retrospectively assessed atelectasis in 297 postextubation radiographs from 220 babies who underwent ventilation over a 2-year period. All 95 babies in the first year received peri-extubation chest physiotherapy; none of the 125 babies in the second year received chest physiotherapy. There was no difference in the incidence of postextubation atelectasis between the two groups.

Female↗
PubMed1998

Side effects of 2 different dexamethasone courses for preterm infants at risk of chronic lung disease: a randomized trial.

OBJECTIVE: We hypothesized that a pulsed course of dexamethasone would result in better linear growth than a 42-day reducing course in preterm infants at risk for chronic lung disease of prematurity. STUDY DESIGN: Forty infants with a birth weight of < or =1,250 g who required mechanical ventilation at 7 days of age were randomly assigned to a repeatable 3-day pulse course of dexamethasone commencing immediately or a 42-day (long) course commencing at 14 days of age if they still required mechanical ventilation and supplemental oxygen. The primary outcome measure was linear growth at 36 weeks' postmenstrual age measured by knemometry. RESULTS: There was no difference in lower leg length at 36 weeks' postmenstrual age. Infants receiving the pulse course had lower rises in blood pressure, less myocardial hypertrophy, and less adrenal suppression. However, more infants required supplemental oxygen at 28 days' postnatal age (14/18 vs 8/21, P < .05) and 36 weeks' PMA (8/16 vs 5/20, P = .12). CONCLUSION: In preterm infants at risk for chronic lung disease, a pulsed course of dexamethasone has fewer side effects than a long course but may be less effective at preventing chronic lung disease.

Administration, Inhalation↗
PubMed1998

Fetal programming of insulin-like growth factor (IGF)-I and IGF-binding protein-3: evidence for an altered response to undernutrition in late gestation following exposure to periconceptual undernutrition in the sheep.

It has been demonstrated in several animal models that undernutrition in utero has significant long lasting effects on subsequent fetal and postnatal development. To address the hypothesis that the insulin-like growth factors (IGFs) may mediate such effects, our study examined whether a period of periconceptual maternal undernutrition could have a lasting influence on the IGF axis in the fetal sheep. Ewes were either allowed to feed ad libitum or kept undernourished from day 60 prior to mating until day 30 after conception, and then both groups were allowed to feed ad libitum. These groups were further divided at day 105 of gestation, either being fed ad libitum or undernourished until day 115 of gestation. Fetal and maternal blood samples were obtained at both day 105 and 115 of gestation. We describe the development of a specific homologous RIA to measure ovine IGF-binding protein-3 (IGFBP-3) in fetal and maternal sheep plasma. Fetal plasma IGFBP-3 and IGF-I concentrations were significantly (P<0.05) reduced at day 115 of gestation after maternal undernutrition. The fetal plasma IGFBP-2 levels were unchanged. The degree of reduction in fetal plasma IGFBP-3 and IGF-I between day 105 and 115 of gestation as a response to acute maternal undernutrition was significantly greater (P<0.05) in fetuses of mothers receiving low periconceptual nutrition. The response of maternal plasma IGFBP-3 and IGF-I to undernutrition did not depend on the level of periconceptual nutrition. Western blot data indicate that changes in either maternal or fetal plasma IGFBP-3 concentrations were not the result of increased proteolytic activity. These results suggest that exposure to maternal periconceptual undernutrition reprograms IGFBP-3 and IGF-I regulation in the developing sheep fetus, altering its response to undernutrition in late gestation.

Analysis of Variance↗
PubMed1997

How many neonates in New Zealand would qualify for extracorporeal membrane oxygenation?

AIM: To estimate how many neonates in New Zealand would qualify for extracorporeal membrane oxygenation (ECMO), using both standard published criteria and locally derived criteria. METHODS: Retrospective chart review of all babies with a birth weight over 2000 g admitted to neonatal intensive care in Auckland from June 1990 to June 1993. Ventilation and blood gas indices were calculated for all babies who were ventilated in 100% O2 for more than 4 hours and who met the basic criteria for ECMO (less than 1 week old with no neurological or chromosomal problems). These indices were compared with published ECMO criteria. Using a threshold of an 80% mortality, Auckland criteria for ECMO were derived. RESULTS: Of the published criteria for ECMO, only an oxygenation index of greater than 40 for 4 hours predicted a mortality of more than 80% in our population. From our own findings a PaO2 < 6.5 kPa for 4 hours predicted a mortality of 79%. CONCLUSION: Approximately 19 neonates might qualify for ECMO in New Zealand each year.

Extracorporeal Membrane Oxygenation↗
PubMed1997

Are babies with gastroschisis small for gestational age?

A large proportion of babies with gastroschisis (GS) have low birth weights. It is not clear, however, whether only certain subgroups or the whole population of babies with GS have low birth weights. The aim of this study was to ascertain if the birth weights of babies with GS are significantly lower than those of the general population and to determine if the birth weights of babies with GS from two different populations were significantly different. From 1969 to 1995, 44 babies with GS were treated at Auckland Children's Hospital, New Zealand. From 1980 to 1993, 69 babies were treated at Birmingham Children's Hospital, England. For each group, the mean birth weight relative to the mean birth weight for gestation (WtStdev) was significantly different from zero (Auckland = -0.806, Birmingham = -0.762, P < 0.001, one-sample analysis). The mean WtStdev scores from each centre were not significantly different from each other. Our data demonstrate that the birth weights of babies with GS are significantly lower than those of the general population and are similar in different populations. These findings support the notion that a normally functioning intestinal tract is essential for normal fetal growth.

Abdominal Muscles↗
PubMed1997

Gastroschisis: can the morbidity be avoided?

Although the mortality associated with gastroschisis (GS) has fallen markedly over recent years, postoperative morbidity and the incidence of complications remain high. Many different factors may contribute to this morbidity; the aim of this study was to determine which factors contributed most. Measures of morbidity used were time to full oral feeding (FOF), time on parenteral nutrition (PN), age at discharge, and incidence of complications. Between 1969 and 1995, 44 neonates with GS were treated; there were 6 deaths. The average initial temperature of the patients who died was 34.6 degrees C compared with 36.0 degrees C for the rest of the group (P = 0.02). Staged repair and prematurity were associated with increased time to FOF, time on PN, and age at discharge (P < 0.001). When the corrected post-term age was used, the difference between preterm and term babies was no longer significant. Mode of delivery did not influence any measure of morbidity. Seventeen patients (46%) had complications related to PN administration and 18 (43%) developed complications related to their surgery. There were no significant differences in these measures of morbidity when comparing patients born in the first half of the study period with those born in the last half. Multivariate analysis revealed that time to FOF, time on PN, and age at discharge were all strongly independently associated with staged repair and with the presence of complications of PN (all F > 7.2 and P < 0.01). Mode of delivery, gestational age, admission temperature, the need for postoperative ventilation, and complications of surgery were not independently associated with any of the measures of morbidity examined. Our data suggest that term delivery and primary closure of the defect are likely to minimise the morbidity experienced by infants with GS.

Abdominal Muscles↗
PubMed1997

Fetal growth retardation: underlying endocrine mechanisms and postnatal consequences.

Considerable advance has been made in our understanding of the regulation of fetal growth and of the pathophysiology of intrauterine growth retardation. The dominant determinant of fetal growth is nutrient delivery to the conceptus, and the insulin-like growth factors (IGFs) appear to play a central role in modulating the fetal growth response to the nutritional environment. It has also become clear that events early in gestation, or prior to conception, can be reflected in altered fetal growth and metabolism later in gestation. Intrauterine growth retardation (IUGR) may be due to identifiable genetic or toxic factors or to disordered nutrient delivery. The latter category of IUGR provides the greatest clinical concern with a high incidence of perinatal morbidity and mortality. More recently, epidemiological evidence supported by limited, but growing, experimental data suggest that the postnatal consequences of disturbed fetal growth may include metabolic disease (diabetes mellitus) and cardiovascular disease. This brief review discusses these advances with reference to data from our laboratory.

Cardiovascular Diseases↗
PubMed1997

Antenatal therapy for intrauterine growth retardation.

Currently, there is no effective antenatal therapy for intrauterine growth retardation (IUGR). Although the IUGR fetus is undernourished in utero and there have been many attempts to treat IUGR with nutritional supplements, most studies have been poorly controlled, and there is no evidence to date that nutrient supplements can reverse the process of IUGR once it is established. Nutrient supplementation is also potentially risky and a combination of nutrients is likely to be needed. Alternative approaches to antenatal therapy for IUGR that show promise include fetal growth hormone and insulin-like growth factor I treatment to improve fetal growth. Fetal and maternal hormone supplements may also prove useful in IUGR by improving placental function and thus fetal substrate supply. Fetal enteral supplementation by the administration of growth factors and/or nutrients into the amniotic fluid may also prove effective and clinically feasible. It seems likely that combinations of these approaches will be required before effective therapy can be devised for the IUGR fetus in utero.

Animals↗
PubMed1997

The physiology and pathophysiology of intrauterine growth retardation.

Insulin-like growth factor I (IGF-I) is the primary hormone influencing fetal growth in later gestation. The regulation of fetal IGF-I in utero is primarily influenced by placental glucose transfer, which regulates fetal insulin release. Furthermore, insulin has direct adipogenic effects on the fetus; fetal growth hormone (GH) may also have additional modes of action on fetal growth. Swallowed amniotic fluid contains IGF-I and may influence gastrointestinal maturation and fetal growth. Furthermore, both fetal and maternal IGF-I can influence placental metabolism. Experimentally, the maternal administration of GH and IGF-I can affect placental function and thus influence fetal growth; this may suggest therapeutic approaches to the treatment of intrauterine growth retardation (IUGR) in utero. Both experimental and clinical evidence support our hypothesis that IUGR is a multihormone relative resistance syndrome; relative resistance to insulin, IGF-I and GH can be demonstrated. Such resistance may be the basis of altered programming by which fetal growth retardation is associated with postnatal growth failure and a greater propensity to develop cardiovascular and metabolic disease in later life.

Animals↗