Effects of intrauterine growth restriction on lung liquid dynamics and lung development in fetal sheep

Cock, Megan L.; Albuquerque, Cheryl A.; Joyce, Belinda Jane; Hooper, Stuart B.; Harding, Richard

doi:10.1067/mob.2001.108858

Cited by 77 publications

(64 citation statements)

References 19 publications

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“…This concurs with our earlier observation that there was no evidence of altered fetal lung liquid volume or lung hypoplasia (i.e. reduced cell number or weight of lungs per kg of body weight) in near-term fetal sheep following 20 d of placental embolization (35).…”

Section: Discussionsupporting

confidence: 81%

Compromised Respiratory Function in Postnatal Lambs after Placental Insufficiency and Intrauterine Growth Restriction

et al. 2001

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Epidemiologic studies have shown persistent effects of low birth weight on respiratory function and lung health, but underlying mechanisms are not understood. Our aim was to determine the effects of intrauterine growth restriction (IUGR), a major cause of low birth weight, on postnatal respiratory function. IUGR was induced by umbilico-placental embolization during late gestation in chronically catheterized sheep. Umbilicoplacental embolization was performed between 120 d of gestation and term (~146 d) during which fetuses were hypoxemic and hypoglycemic relative to controls. Umbilico-placental embolization led to a 48% reduction in birth weight compared with controls, and throughout the postnatal study period IUGR lambs (n ϭ 8) remained lighter than controls (n ϭ 8). Respiratory function was repeatedly studied in lambs for 8 wk after birth; during this period, IUGR lambs were mildly hypoxemic and tended to be hypercapnic compared with controls. In IUGR lambs, relative to controls, O 2 consumption (mL/min/kg) and minute ventilation (mL/kg) were increased and pulmonary diffusing capacity (adjusted for functional residual capacity) was decreased. Functional residual capacity, measured by helium dilution, and total lung capacity (measured at 30 cm H 2 O) were smaller in IUGR lambs than in controls. When adjusted for functional residual capacity, static lung compliance was reduced and chest wall compliance was increased in IUGR lambs. Restricted fetal growth, resulting in low birth weight, has been associated with altered lung development and impaired respiratory function after birth. Recent studies of neonates and infants who have been growth restricted in utero indicate that they have an increased risk of mortality and morbidity (1), including respiratory distress (2, 3). Respiratory compromise may persist during postnatal development as it has been shown that children with evidence of growth restriction in utero have reduced forced expiratory flow rates (4, 5) indicative of impaired airway function. In addition, adults who were of low birth weight and, therefore, likely to have been growth restricted in utero, have reduced expiratory flow rates and an increased risk of respiratory morbidity and mortality (6, 7). Thus, a number of epidemiologic studies suggest that pulmonary gas exchange and airway function after birth may be affected by IUGR.Placental insufficiency and IUGR are common causes of low birth weight, and are associated with pregnancy-induced hypertension, maternal tobacco smoking, and placental pathology (8, 9). Fetuses identified as being growth restricted have been found to be hypoxemic, hypoglycemic, and to have elevated

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Section: Discussionsupporting

confidence: 81%

Compromised Respiratory Function in Postnatal Lambs after Placental Insufficiency and Intrauterine Growth Restriction

et al. 2001

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“…This finding confirms a previous study in sheep that used 20 d of umbilicoplacental embolization to induce IUGR (18). However, this has not been a consistent finding.…”

Section: Discussionsupporting

confidence: 68%

“…The differences between these experimental models of IUGR most likely reflect the timing of IUGR, rather than the method of inducing IUGR. Because glucocorticoids induce the production of SPs (21,22), the hypercortisolemia induced by IUGR in this and other studies (18)(19)(20) would be expected to increase SP mRNA expression. Another known regulator of SPs is fetal oxygenation (23).…”

Section: Iugr Glucocorticoids and Lung Developmentmentioning

confidence: 99%

The effects of intrauterine growth restriction and antenatal glucocorticoids on ovine fetal lung development

et al. 2012

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IntroductIon: Intrauterine growth restriction (IUGR) is associated with high rates of neonatal morbidity. IUGR babies are often born preterm and are, therefore, exposed to antenatal glucocorticoids. antenatal glucocorticoids significantly improve overall survival rates of preterm infants, but there is a paucity of information about their effects on IUGR Infants. Methods: We induced IUGR in sheep by single umbilical artery ligation (sUaL), or sham in control fetuses. To half the ewes, we administered betamethasone (BM) on d 5 (BM1) and 6 (BM2) following surgery, and collected fetal lung tissue on d 7. results: sUaL alone was associated with higher circulating fetal cortisol levels (2.8 ± 0.4 vs. 1.0 ± 0.4, P = 0.001) as compared with controls but not with changes in lung morphology or surfactant protein (SP) gene expression. BM was associated with a significant reduction in lung tissue density (P = 0.048). There were no significant differences between groups in lung DNa concentration or septal crest density. SP-A, SP-B, and SP-C gene expressions were significantly increased in control and sUaL fetuses that were administered BM. dIscussIon: These results show that in sUaL fetuses, maternal BM is associated with acceleration of fetal lung structure, as occurs in normally grown fetuses, and that BM induces sP production, an effect not observed in sUaL-induced IUGR fetuses alone.

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“…Our finding that the brain/body weight ratio in adult sheep was smaller in LBW animals than in controls, in spite of similar body weights at autopsy, implies that the postnatal brain weight of LBW animals did not increase at the same rate as in the controls. Fetal growth restriction has a "brain-sparing" effect, such that near-term, relative brain weights (g/kg BWt) of LBW fetal sheep that had undergone a similar degree of placental insufficiency as sheep in this study, were 30-50% greater than those of control fetuses (Table 2) [17,37]. Although we have previously shown that the increased relative brain weight of LBW animals was still evident at 8 postnatal weeks [14] [38] (Table 2), the present study indicates that this does not persist to maturity; at 2.3 years relative brain weights were 16% lower in the LBW animals compared to controls.…”

Section: Brain Growthmentioning

confidence: 99%

“…In this context, we considered it valid to study animals with different forms of LBW. Within the LBW animals, there [37] 53.0 ± 1.4 54.5 ± 1.8 12.4 ± 0.6 16.3 ± 0.3* 8 weeks after birth [14] 72.7 ± 1.4 70.3 ± 3. were no apparent differences between singles and twins; for example, correlations between postnatal weight gain and birth weight were not different, as shown in Fig. 4B.…”

Section: Brain Growthmentioning

confidence: 99%

Long Term Consequences of Low Birthweight on Postnatal Growth, Adiposity and Brain Weight at Maturity in Sheep

Louey

Cock

Harding

2005

Journal of Reproduction and Development

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Abstract. Low birth weight (LBW) as a result of restricted fetal growth increases the risk for later metabolic diseases and adiposity. However the relationship between LBW and postnatal growth and adult body composition has not been fully investigated. We have used sheep to determine the effects of LBW on postnatal growth and body composition at maturity. LBW was induced by twinning and placental embolization. At birth, LBW lambs were 38% lighter than controls (2.8 ± 0.2 vs 4.4 ± 0.3 kg, P<0.05), but had caught up in bodyweight by 8 weeks after birth. At ~2.3 years, bodyweights were not different between groups, but there were reductions in absolute (-8%) and relative (-17%) brain weights of LBW sheep (P<0.05) compared to controls. X-ray absorptiometry showed that the mature LBW sheep, compared to controls, had greater amounts of lean muscle (38.1 ± 1.3 vs 35.3 ± 0.5 kg, P<0.05) and tended to have more body fat (12.2 ± 1.2 vs 9.6 ± 0.9 kg; P=0.1); at autopsy abdominal fat mass was greater in LBW sheep (3.06 ± 0.26 vs 2.20 ± 0.25 kg, P<0.05). Plasma leptin concentrations were not different between groups. We conclude that, in sheep, LBW is associated with early postnatal catch-up in body weight, but body composition is permanently altered such that, relative to controls, adiposity is increased and brain weight is decreased. Key words: Adiposity, Fetal growth restriction, Body composition, Birth weight, Leptin (J. Reprod. Dev. 51: [59][60][61][62][63][64][65][66][67][68] 2005) he postnatal effects of low birth weight (LBW) are of considerable interest because in recent years LBW has been associated with an increased risk of several adult-onset diseases [1][2][3]. LBW, especially that caused by restricted fetal growth, is often followed by accelerated postnatal growth [4], and recent studies indicate that this catch-up growth can amplify the risk for cardiovascular and metabolic dysfunction. Individuals who had low birth weights but exhibited increased growth rates in terms of weight, height or body mass index (BMI) have been shown to be at a greater risk for abdominal adiposity [5], hypertension [2, 3] and non-insulin dependent diabetes mellitus [6] than those who failed to catch up [7].As well as differing postnatal growth rates, body c o m p o si t i o n c a n d i f f e r b e t w e e n L B W a n d appropriately grown individuals. At birth, LBW infants have reduced body fat, lean mass and bone m i n e r a l c o n t e n t ( B M C ) c o m p a r e d w i t h appropriately grown newborns [8]. However, these reductions are related to lower body weights, and body composition is not different between LBW and normally grown infants of similar weights [8]. After birth, age-related changes in body composition differ between LBW and appropriately grown infants. For example, the postnatal increase in BMC in LBW infants is less than that of appropriately grown infants [9], and adults of low birth weight have reduced total BMC and reduced bone mineral density (BMD) [10]. Adiposity is also affected, such that body fat content...

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Effects of intrauterine growth restriction on lung liquid dynamics and lung development in fetal sheep

Cited by 77 publications

References 19 publications

Compromised Respiratory Function in Postnatal Lambs after Placental Insufficiency and Intrauterine Growth Restriction

Compromised Respiratory Function in Postnatal Lambs after Placental Insufficiency and Intrauterine Growth Restriction

The effects of intrauterine growth restriction and antenatal glucocorticoids on ovine fetal lung development

Long Term Consequences of Low Birthweight on Postnatal Growth, Adiposity and Brain Weight at Maturity in Sheep

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