Decreasing maternal nutrient intake during the final third of pregnancy in previously overnourished adolescent sheep: effects on maternal nutrient partitioning and feto-placental development

When pregnant adolescent sheep are overnourished during pregnancy normal nutrient partitioning priorities to the gravid uterus are altered, leading to impaired placental development and fetal growth restriction. We hypothesized that decreasing dietary intake in overnourished dams during the final third of gestation may reverse this inappropriate nutrient partitioning in favor of the fetus. Adolescent ewes were offered control (C; n?=?12) or high (H; n?=?20) dietary intakes to induce normal vs. compromised placental development. Ten ewes receiving the H intake were switched to a low intake at d90 of gestation (HL). Between d90 to 130, HL dams lost weight and adiposity, and metabolic hormones and glucose at d130 were less than H and similar to C. In spite of these maternal changes, at d130 fetal bodyweight was equivalent in HL and H groups and ～20% less than in C. A greater degree of brain sparing was evident in HL fetuses and glucose and insulin concentrations were more perturbed than in H fetuses. Relative to C, placentome weight was reduced by 46 and 32% in H and HL and the fetal:placentome weight ratio was H?>?HL?>?C. Placental vascular morphology was largely unaffected by maternal diet during late gestation but mRNA expression of five angiogenic genes was up-regulated in the fetal cotyledon of HL pregnancies, commensurate with blood vessel remodeling. Nevertheless, overfeeding to promote maternal anabolic growth during adolescent pregnancy impairs feto-placental development that cannot be rescued by reducing maternal intake during the final third of gestation.     

Effect of maternal overnutrition during pregnancy on pituitary gonadotrophin gene expression and gonadal morphology in female and male foetal sheep at day 103 of gestation

The aim was to determine whether nutritionally mediated restriction of placental growth alters foetal body growth, pituitary gonadotrophin gene expression and gonadal development at Day 103 of gestation. Embryos recovered from adult ewes inseminated by a single sire were transferred, singly, into the uteri of adolescent recipients. After transfer, adolescent ewes were offered a high (H, n=16) or moderate (M, n=12) level of a complete diet. Ewes were slaughtered at 103+/-0.2 days of gestation and foetal blood, brain, pituitary and gonads were collected. Mean placental weight was lower (P< 0.01) in H than in M groups but foetal weight and reproductive organ weights were similar. Maternal nutrition did not influence LHbeta or FSHbeta mRNA expression in either sex but FSHbeta mRNA expression was higher (P< 0.001) in female (n=11) than in male (n=17) foetal pituitaries. Mean foetal plasma gonadotrophin concentrations were not influenced by dietary intake in either sex. Plasma progesterone concentrations were lower (P=0.001) in foetuses derived from H compared with M intake dams. Compared with M foetuses (n=5), ovaries from H foetuses (n=6) had fewer primordial follicles (P< 0.05) and fewer follicles in total (P< 0.005). In contrast, maternal nutritional status did not influence either seminiferous cord or Sertoli cell numbers in male foetuses (H, n=10; M, n=7). It is concluded that high maternal nutrient intakes restricted placental growth and altered foetal ovarian follicular development prior to the end of the second third of gestation. The latter effect was independent of gonadotrophin secretion.Crown     

Serial measurement of uterine blood flow from mid to late gestation in growth restricted pregnancies induced by overnourishing adolescent sheep dams

Uterine blood flow (UtBF) is a major regulator of transplacental fetal nutrient supply. The aim was to serially measure uterine blood flow from mid to late pregnancy in a paradigm of relatively late onset placental and fetal growth restriction. Singleton bearing adolescent dams was fed high (H) or control (C) nutrient intakes to induce putatively compromised or normal pregnancies, respectively. A perivascular flow probe was attached to the uterine artery of the gravid horn on Day 83 of gestation and UtBF was then recorded continuously for 2h, three times weekly until approximately Day 135, when pregnancies were either terminated or ewes allowed to deliver at term ( approximately Day 145). Pregnancy outcome was determined at term in contemporaneous ewes without UtBF assessment. Placental and fetal weights were lower (P<0.001) in H compared with C intake groups and were independent of flow probe surgery and monitoring. Uterine blood flow was lower in H compared with C groups at the first assessment (Day 88, P<0.001) and was positively correlated with adjusted fetal weight at term, irrespective of treatment group (P<0.01). UtBF increased throughout the second half of gestation in both groups. Linear regression analysis of UtBF against day of gestation revealed that the slope was equivalent (5.5 vs. 5.3ml/min per day) and the mean intercept lower (212 vs. 370ml/min, P<0.001) in H compared with C groups, respectively. This study demonstrates the feasibility of serially measuring UtBF within the same individual sheep for a protracted period during the second half of gestation. UtBF was already lower at mid gestation in putatively growth restricted compared with control pregnancies, ahead of any reduction in placental and fetal weight, but increased similarly during the second half of gestation in both groups. These data are commensurate with the reported decrease in placental angiogenic growth factor expression at mid gestation, and, indicate that attenuated UtBF is an early defect in this adolescent paradigm.     

Effect of variable long-term maternal feed allowance on the development of the ovine placenta and fetus

Maternal feed allowance during pregnancy can affect the development of the ovine placenta and fetus. The impact of variations in feed allowance prior to as well as throughout pregnancy has received less attention. Ewes were offered 0.6 (R), 1.2 (C) or 1.8 (AL) maintenance requirements from 89 days before conception until day 133 of pregnancy. Ewes were euthanised on days 50, 92 and 133 of pregnancy. Ewe live weight and body condition score, maternal and fetal metabolic and hormonal profiles, fetal body dimensions and organ weights, and the number, weight and morphology of placentomes were measured. Maternal live weight and condition score were lower in R compared to AL ewes at all stages of pregnancy (P<0.05). Plasma glucose and albumin concentrations of R ewes were significantly reduced (P<0.05) at mid and late gestation, respectively. Placental components were generally unresponsive to long term variations in maternal feed allowance. However, placental weight was significantly (P<0.05) correlated with fetal weight at days 50 (r=0.59) and 133 (r=0.69) of gestation. By late gestation growth-retarded singleton fetuses from R ewes were 19% lighter (P<0.05), with reduced abdominal (9%) and thoracic (10%) girths (P<0.05) but of similar crown-rump length compared with fetuses from AL ewes. These differences were associated with significantly reduced IGF-I concentrations in fetal plasma (P<0.05). In conclusion, maternal, placental and fetal adaptations to long established planes of variable maternal feed allowance were able to maintain fetal growth during early and mid-pregnancy while fetal growth restriction, associated with reduced fetal IGF-I levels, became apparent in late pregnancy.     

The carotid bodies influence growth responses to moderate maternal undernutrition in late-gestation fetal sheep

Objective  To determine the role of carotid sinus innervation on differential fetal organ growth during maternal nutrient restriction in late pregnancy.
Design  Randomised controlled study.
Setting  University research facility.
Sample  Thirty-nine Merino ewes.
Methods  At 113 days gestational age (dGA), fetuses were bilaterally carotid sinus denervated or sham denervated. From 118 dGA, the surgery groups were subdivided into two dietary groups, and their ewes were fed 100% of nutrient requirements or 50% until tissue collection at 140 dGA. This provided four groups (sham/control diet, sham/restricted diet, denervated/control diet and denervated/restricted diet).
Main outcome measures  Fetal organ weights and hormone levels and maternal weight change during the dietary restriction.
Results  Adrenal glands were larger in sham/restricted diet fetuses than in sham/control diet or denervated/restricted diet fetuses ( P < 0.05). Fetal adrenal weight and brain-to-liver weight ratio were positively related to maternal weight change during the nutritional challenge in sham fetuses only ( P < 0.05). Fetal liver weight was negatively related to maternal weight change during nutritional challenge in sham fetuses only ( P < 0.05).
Conclusions  We have shown a reduction in liver growth but sparing of adrenal growth in response to moderate maternal undernutrition, which is dependent on intact carotid body innervation. This suggests a new role for the carotid bodies in the control of differential organ growth during such undernutrition.     

L-Arginine treatment for asymmetric fetal growth restriction.

OBJECTIVES: [corrected] To investigate the effects of L-Arginine in treating asymmetric fetal growth restriction (FGR). METHODS: A total of 66 pregnant women whose fetuses were diagnosed with asymmetric fetal growth restriction were divided into two groups. Group 1 consisted of 36 women who were given routine therapy alone; group 2 consisted of 30 women who were given L-Arginine and routine therapy; and the control group consisted of 30 more women with a normal pregnancy. RESULTS: Before treatment, mean maternal serum levels of NO2-/NO3- were significantly lower in groups 1 and 2 than in the control group (P<0.01). After treatment, maternal serum levels of NO2-/NO3- were considerably higher in group 2 than in group 1 (P<0.01). Mean birth weight was significantly higher in group 2 than in group 1 (P<0.05), but still lower in group 2 than in the control group (P<0.01). CONCLUSIONS: A deficiency in nitric oxide may play an important role in the development of asymmetric fetal growth restriction. L-Arginine can be used to increase maternal NO2-/NO3- levels and newborn birth weight.     

Intrauterine growth restriction and pregnancy outcome

AIM: This prospective study was performed to evaluate perinatal outcome and maternal risk factors in pregnancies complicated by fetal intrauterine growth restriction (IUGR). METHODS: A total of 3 537 women pregnant with a singleton gestation were enrolled in the study: 219 of these pregnancies were complicated by fetal growth restriction (6.2%). Statistical analysis was performed using Wilcoxon test, Kruskall-Wallis test, c2 analysis of variance and ANOVA test. Statistical significance was set at P-value <0.05. Correlations were calculated by Spearman's coefficient. RESULTS: Ethnic group, physical demanding work, maternal smoking, alcohol abuse do not seem to be associated with lower birth weight and worse Apgar score. Sonographic assessment of fetal weight obtained by Hadlock's formula underestimate real newborn's weight. The difference between estimate weight and real weight is statistically significant. Women with intrauterine growth restriction underwent caesarean sections more often than women with appropriate fetal growth selected as controls (P<0.05). CONCLUSION: In conclusion, the obstetrician must recognize and accurately diagnose inadequate fetal growth and attempt to determine its cause (especially placental factors) in order to reduce fetal and maternal risks and establish the appropriate clinical management, timing and mode of delivery. If the growth-restricted fetus is identified and appropriate management instituted, perinatal mortality can be reduced.     

Maternal serum and umbilical cord blood leptin concentrations with fetal growth restriction

OBJECTIVE: To ascertain whether fetal growth restriction is associated with alterations of leptin concentrations in umbilical cord blood and maternal serum. METHODS: Maternal serum and umbilical cord blood leptin concentrations were determined by immunoradiometric assay at term in 43 women with uncomplicated singleton pregnancies (group A) and in 27 women with singleton pregnancies complicated by fetal growth restriction (group B), all with normal pregravid body mass index (BMI). RESULTS: Maternal serum leptin concentrations were significantly higher in group B compared with group A (45.0 ng/mL [range 34.2-54.9] versus 29.0 ng/mL [range 24.7-33.3]; P<.01). Umbilical cord blood leptin levels were significantly lower in group B compared with group A (8.4 ng/mL [range 3.6-13.2] versus 13.1 ng/mL [9.7-16.5]; P<.01). Maternal serum leptin levels were not significantly correlated with maternal BMI or with neonatal birth weight in either group. Umbilical cord blood leptin concentrations were significantly correlated with neonatal birth weight in both groups. CONCLUSION: Growth restricted fetuses at term show umbilical cord blood leptin concentrations significantly lower than those in normal fetuses, suggesting that fetal adipose tissue is a major source of leptin. Maternal serum leptin concentrations are higher in the presence of a growth restricted fetus. This increase might be due to an intrinsic placental mechanism, by which small placentas produce more leptin as a compensatory mechanism, or to early hypoxia.     

Morphologic alterations in ovine placenta and fetal liver following induced severe placental insufficiency

OBJECTIVES: Umbilical-placental embolization with microspheres has been used as a model of placental insufficiency and intrauterine growth restriction (IUGR). However, the effects of embolization on placental structure and organ morphology of the resulting IUGR fetus are relatively unexplored. In this study using ovine fetuses, we determined the location and distribution of microspheres within the placenta and explored the extent of placental and fetal organ morphologic changes induced by placental embolization. We hypothesized that microspheres administered into the umbilical circulation over 4 days would cause placental damage without significant morphologic alterations in fetal kidney or liver. METHODS: Eleven pregnant sheep at 118 +/- 1 (SE) days' gestation were studied. In six fetuses, embolization was induced by injections of 15-microm diameter microspheres on 4 successive days into the fetal descending aorta proximal to the umbilical arteries. Five fetuses served as time controls. RESULTS: In embolized fetuses, microspheres were detected in the placenta embedded in the fetal cytotrophoblastic layer or maternal parenchyma adjacent to villous cytotrophoblasts. Fetal cytotrophoblasts appeared normal except for loss of distinct separation between fetal and maternal cell layers. Microspheres were also detected in the fetal membranes within capillaries. The body weights of embolized fetuses were lower than controls, as were the body weight-normalized liver but not kidney weights. In the liver of the embolized fetuses, the number of hematopoietic cell clusters was markedly reduced, whereas the fetal kidneys appeared normal. CONCLUSIONS: We conclude that after 4 days of umbilical-placental embolization, microspheres were concentrated at the fetal villi proximal to the apical maternal-fetal interface and in the fetal membranes. There were noticeable morphologic changes in the embolized placentas, with no apparent gross damage to the placenta. The reduction in fetal liver weight and liver extramedullary hematopoietic cell abundance associated with embolization may predispose the fetus to alterations in liver function that could persist after birth.     

Maternal serum copeptin as a marker for fetal growth restriction

ObjectivesCopeptin is a hormone of endogenous stress. The aim was to evaluate whether the measurement of maternal serum copeptin is useful for differentiation between fetal growth retardation and constitutionally small fetuses among small for gestational age fetuses.Study Designprospective case control clinical study.Patients and MethodsMaternal serum copeptin levels were measured by ELISA technique in 53 pregnant females subdivided into a control group (group 1) of 20 women with normal gestation & a group of 33 pregnant women with small for gestational age fetuses. The small for gestational age fetuses were subclassified into constitutionally small fetuses (17 cases) with normal umbilical artery Doppler studies (group 2), and fetal growth restriction with abnormal umbilical artery Doppler studies (16 idiopathic cases) as group 3.ResultsThe fetal growth restricted group had a significantly higher maternal serum copeptin levels as compared with the control group (P < 0.01). The maternal serum copeptin levels in fetal growth restriction were significantly higher than in constitutionally small fetus (P < 0.05).ConclusionMaternal serum copeptin level can differentiate between the normal sized and small for gestational age fetuses. Also, it can differentiate between constitutionally small and growth restricted fetuses.     

Differential effects of maternal and fetal betamethasone injections in late-gestation fetal sheep

OBJECTIVE: To determine the effects of single or repeated intramuscular injections of betamethasone, given maternally or directly to the fetus, on chronically catheterized, late-gestation fetal sheep. METHODS: Fetal or maternal sheep received either repeated intramuscular injections of betamethasone (0.5 mg/kg body weight at 104, 111, and 118 days' gestation), single betamethasone injection (at 104 days' gestation, followed by saline at 111 and 118 days' gestation), or repeated saline injections; n = 6 or 7 per group. At approximately 130 days' gestation fetuses were catheterized for serial measurements of heart rate, arterial pressure, blood gases, metabolites, and electrolytes. RESULTS: Repeated maternal betamethasone injections reduced birth weight (P =.03) without fetal hypoxemia or hypoglycemia. Circulating fetal calcium and lactate concentrations were reduced (P =.002 and P =.014, respectively) by repeated maternal betamethasone only. Fetal hematocrit tended to be lower after fetal (P =.3) and maternal (P =.07) betamethasone. CONCLUSION: Growth restriction caused by repeated maternal betamethasone treatments is not due to overt chronic placental insufficiency but may be caused by alterations in hormonal mediators of fetal growth or impairment of placental transport of specific nutrients.     

A Modification of the Uterine Artery Restriction Technique in the Guinea Pig Fetus Produces Asymmetrical Ultrasound Growth

AimsTo evaluate the use of diathermy ablation of branches of the uterine artery to produce growth restriction in the fetal guinea pig, and to compare this new approach with the more conventional use of uterine artery ligation. The development of growth restriction was documented by measuring fetal biparietal diameter (BPD) and the resistance index (RI) of the umbilical artery blood flow velocity waveform.MethodsAt 30–35 days of gestation (term = 70 days), one uterine artery was ligated in 29 sows. In another 16 sows, branches of one uterine artery were ablated using diathermy. Fetuses in contralateral horns were used as controls. Ultrasound measurements were made weekly, and at 59–69 days of gestation animals were euthanased to determine fetal position in utero as well as fetal and placental weights. In some fetuses, brain and liver weights were also recorded.ResultsBoth surgical techniques resulted in similar reductions in fetal body and placental weights. The number of fetuses surviving to term was greater in the diathermy group (53%) compared to the ligation group (22%) (P < 0.05). Results from these two groups were combined and referred to as “treated” fetuses. The brain/liver weight ratio was increased by 245% in the treated fetuses compared to control fetuses. Ultrasound measures of BPD in the treated fetuses were within the normal range. The mean RI of the treated group showed a slight but significant increase near term compared to the mean RI of the normal range.ConclusionWe have shown that the diathermy technique produces asymmetrical fetal growth restriction (with normal head size) in the guinea pig to the same extent as the conventional ligation technique. It is associated with a lower fetal mortality rate and therefore should be the preferred method. The minimal increase in umbilical artery resistance index only at the end of gestation amongst the intrauterine growth restriction (IUGR) fetuses suggests that an obliterative vasculopathy in the umbilical circulation is not the cause of growth failure when there is maternal uteroplacental restriction.     

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

OBJECTIVE: The aim of this study was to determine the effects of intrauterine growth restriction on fetal lung liquid and lung development. STUDY DESIGN: Intrauterine growth restriction was induced in 7 fetal sheep from 120 to 140 days' gestation (term, approximately 147 days' gestation) by umbilicoplacental embolization. We used 6 control fetuses. Volumes and production rates of fetal lung liquid were measured, and lungs were removed post mortem (140 days' gestation) for analysis of concentrations of deoxyribonucleic acid, protein, and messenger ribonucleic acid for surfactant proteins A, B, and C. RESULTS: Umbilicoplacental embolization induced fetal hypoxemia, hypoglycemia, and intrauterine growth restriction. At 140 days' gestation lung weight was reduced by 34%, and the fetal lung liquid production rate (15.9 +/- 1.8 mL/h for intrauterine growth restriction vs 24.8 +/- 3.9 mL/h for control) and volume (110.9 +/- 16.3 mL for intrauterine growth restriction vs 178.1 +/- 11.9 mL for control) were reduced in the intrauterine growth restriction group. After adjustment for body weight, however, values were not different from those in the control group. Pulmonary deoxyribonucleic acid and plasma cortisol concentrations were elevated by intrauterine growth restriction, but levels of messenger ribonucleic acid for surfactant proteins were unchanged. CONCLUSION: In intrauterine growth restriction, lung liquid and lung growth were proportionate to body weight, and surfactant protein expression was unaffected. Alterations in lung deoxyribonucleic acid concentrations suggest that the lungs may be structurally immature.     

Cardiac output and uteroplacental blood flow in diet-restricted and diet-repleted pregnant rats

Cardiac output and uteroplacental blood flow were measured with 15 mu radioactive microspheres in anesthetized pregnant rats which were fed: (1) ad libitum throughout gestation; (2) a 50% restricted diet from day 5 of gestation; and (3) a 50% restricted diet from days 5 to 13 of gestation and ad libitum from day 14 of gestation. An additional group of nonpregnant rats fed ad libitum was also used. Dietary restriction caused a net maternal weight loss and a 20% reduction in mean fetal weight and mean placental weight by day 21 of gestation. Restricted dams fed ad libitum during the last week of gestation showed a net maternal weight gain, while mean fetal weight, but not placental weight, was near that of the ad libitum--fed controls. In the diet-restricted rats, total cardiac output was reduced 30% relative to controls by days 20 and 21 of gestation, but cardiac output per unit maternal body weight was not significantly different. Dietary restriction decreased both total uterine and placental blood flow by about 65%. Diet repletion late in gestation did not significantly increase total cardiac output or cardiac output per unit body weight. Total uterine and placental blood flows were near those of controls, primarily because of an increased fraction of cardiac output distributed to the uterus.     

Impact of maternal cigarette smoking on fetal growth and body composition

OBJECTIVE: The aim of this study was to determine the impact of maternal cigarette smoking on the fetal accretion of fat and lean body mass. We hypothesized that maternal smoking would result in a reduction in the deposition of lean body mass. STUDY DESIGN: Longitudinal ultrasonographic examinations on 65 singleton fetuses without anomalies of smoking mothers were compared with 36 singleton fetuses without anomalies of nonsmoking mothers. A total of 214 ultrasonographic examinations were performed between 27 and 37 weeks' gestation. All subjects underwent at least 2 ultrasonographic examinations separated by 4 weeks. We compared the slopes of the growth curves for individual morphometric parameters including head circumference, femur length, abdominal circumference, thigh muscle area, thigh fat area, estimated fetal weight and percentage of thigh fat between groups. Analysis was performed with a repeated measures analysis of covariance. Potential covariates included prepregnancy body mass index (in kilograms per square meter), weight gain during pregnancy, maternal age, parity, and fetal sex recorded at birth. Demographic variables are expressed as mean +/- SD; fetal measurements are expressed as mean +/- SE. Both t tests and chi(2) analyses were used to compare groups with respect to demographic variables. P <.05 was accepted for significance. RESULTS: There were no significant differences between groups in maternal prepregnancy weight, maternal height, maternal prepregnancy body mass index, weight gain in pregnancy, parity, or fetal sex. Smokers were younger than nonsmokers (smokers, 23.7 +/- 6.0 years; nonsmokers, 31.8 +/- 6. 0 years; P <.0001), and neonatal weight was reduced among smokers (smokers, 3269 +/- 507 g; nonsmokers, 3519 +/- 411 g; P <.01). There were no differences in the growth rates of head circumference (P =. 79) and femur length (P =.67). Growth rates of abdominal circumference (smokers, 9.0 +/- 0.3 mm/wk; nonsmokers, 10.3 +/- 0.5 mm/wk; P =.01), estimated fetal weight (smokers, 171 +/- 5.4 g/wk; nonsmokers, 193 +/- 8.0 g/wk; P =.008), and muscle area (smokers, 64. 1 +/- 3.8 mm(2)/wk; nonsmokers, 76.4 +/- 5.6 mm(2)/wk; P =.03) were significantly reduced among smokers. There was a reduction in the rate of fat deposition in the thighs of fetuses of smoking mothers (smokers, 38.7 +/- 3.7 mm(2)/wk; nonsmokers, 54.6 +/- 5.4 mm(2)/wk; P =.004); however there was no absolute difference in the amount of fat measured in the thigh between 33 and 37 weeks' gestation. CONCLUSION: We detected reduced fetal growth that selectively affected abdominal circumference and peripheral muscle mass while not affecting head circumference and femur length in fetuses of smoking mothers. The effect of cigarette smoking on fetal fat deposition was less clear. Cigarette smoking appears to have a selective effect within lean body mass compartments, with affected compartments including peripheral fetal muscle. The findings of a reduction in abdominal circumference growth compared with control subjects in combination with no difference in subcutaneous fat content beyond 33 weeks' gestation are potentially explained by a reduction in fetal liver size that may result from maternal smoking.     

Maternal citrulline supplementation enhances placental function and fetal growth in a rat model of IUGR: involvement of insulin-like growth factor 2 and angiogenic factors

Objective: To determine the effects of maternal citrulline supplementation on fetal growth and placental efficiency in a rat model of intrauterine growth restriction (IUGR) induced by maternal protein restriction.

Methods: Pregnant Sprague–Dawley rats were randomly assigned to three groups: NP (receiving a control 20% protein diet), LP (a 4% protein diet), or LP-CIT (an LP diet along with L-citrulline, 2?g/kg/d in drinking water). On the 15th and 21st day of gestation (GD15 and GD21, respectively), dams underwent a C-section, by which fetuses and placentas were extracted. The expression of genes involved in placental growth and angiogenesis was studied by quantitative RT-PCR.

Results: Maternal citrulline supplementation increased fetal weight at GD21, and fetal weight/placental weight ratio, an index of placental efficiency, from mid gestation (p?Igf2-P0, a placenta-specific variant of insulin-like growth factor 2 (Igf2) gene, and Vegf and Flt-1, involved in angiogenic pathways, was enhanced in the LP-CIT group (versus NP, p?p?p?Igf2-P0, Vegf, and Flt-1, respectively).

Conclusions: In a model of IUGR induced by protein deprivation, citrulline enhances fetal growth, placental efficiency, and the expression of genes involved in angiogenesis. The relevance of such effect in human pregnancies complicated by IUGR warrants further study.     

Long-term testosterone treatment during pregnancy does not alter insulin or glucose profile in a sheep model of polycystic ovary syndrome

The administration of testosterone to pregnant sheep to resemble fetal programming of the polycystic ovary syndrome could alter other hormones/factors of maternal origin with known effects on fetal growth. Hence, we studied the weekly profile of insulin, progesterone and glucose during a treatment with testosterone propionate given biweekly from weeks 5 to 17 of pregnancy (term at 21 weeks) and checked the outcome of their fetuses at 17 weeks of gestation after C-section. Control dams were only exposed to the vehicle of the hormone. The testosterone administration did not cause any significant change in the maternal weekly profile of insulin, progesterone or glucose concentration, although the plasma levels of testosterone in the treated dams were inversely correlated to the levels of progesterone. Testosterone treatment also induced an inverse correlation between mean maternal insulin levels and fetal insulin levels; however, the fetal zoometric parameters, body weight, or insulin levels did not differ between exposed and not exposed fetuses. Therefore, treatment with testosterone during pregnancy does not cause significant impact on insulin levels in the mother, leading to less effect on the programming of fetal growth.     

Histologic chorioamnionitis is associated with fetal growth restriction in term and preterm infants

OBJECTIVE: Our aim was to evaluate associations between chorioamnionitis and fetal growth restriction in infants enrolled in the Collaborative Perinatal Project. STUDY DESIGN: A total of 2579 nonanomalous, singleton infants delivered at 28 to 44 weeks' gestation with chorioamnionitis were matched 1:3 for ethnicity, gestational age, parity, and maternal cigarette use (all of which were correlated with both chorioamnionitis and markers of fetal growth restriction) with 7732 control infants. Moderate or marked leukocytic infiltrates of the placenta defined chorioamnionitis. Birth weight, length, head circumference, weight/length ratio, ponderal index, and birth weight/head circumference ratio in the lowest 5th percentile were markers of fetal growth restriction. Placental weight and the birth weight/placental weight ratio were also evaluated. RESULTS: Compared with data on matched control infants, histologic chorioamnionitis was associated with all markers of fetal growth restriction and with low birth weight/placental weight ratios (odds ratios, 1.3-1.7). The strongest associations were found at 28 to 32 weeks' gestation (odds ratios, 2.2-11). Attributable risks for several markers of fetal growth restriction exceeded 50% in infants born at <33 weeks' gestation. CONCLUSION: Histologic chorioamnionitis is associated with multiple markers of fetal growth restriction, with stronger associations noted in prematurity.     

Intrauterine growth restriction

Pathophysiological processes underlying intrauterine growth restriction are very complex and poorly understood. Growth restricted fetuses are at risk of hypoxia and, therefore, an early diagnosis of intrauterine growth restriction is important for initiation of fetal surveillance. Application of a three-dimensional ultrasound method for estimation of fetal weight promises better precision. Use of conditional standard deviation scores of fetal biometric variables has been suggested for improved individualized evaluation of intrauterine growth. Application of umbilical artery Doppler velocimetry in the clinical management of growth-restricted fetuses after 32 weeks of gestation leads to decreased perinatal mortality and lower rates of obstetric interventions. Evaluation of fetal state before 32 weeks is difficult and should include Doppler examination of placental circulation and several fetal arterial and venous vessel beds. In addition, recordings of short-term variability of fetal heart rate and biophysical profile have been suggested for fetal surveillance. Important new data on the time sequence of Doppler changes in various vessels of compromised very preterm growth restricted fetuses have been presented, which will enable the establishment of clinical management protocols for evaluation in prospective randomized studies.     

脂联素和胰岛素与胎儿生长的关系

目的:探讨脂联素,胰岛素与胎儿生长发育的关系。方法:选取21例分娩生长受限胎儿(FGR组)、21例分娩巨大儿(巨大儿组)及21例分娩正常儿(对照组)的产妇,抽取3组产妇分娩后肘静脉血及其新生儿脐静脉血.分离血清。采用双抗体夹心酶联免疫吸附法和放射免疫法测定3组产妇血清及新生儿脐静脉血清中脂联素和胰岛素的水平。结果:FGR组产妇血清脂联素水平明显低于对照组及巨大儿组(P<0.01);FGR组新生儿脐血清脂联素水平明显低于对照组及巨大儿组(P<0.05);3组产妇血清中脂联素水平均明显低于新生儿脐血清中脂联素水平(P<0.01)。FGR组胎盘重量明显低于对照组及巨大儿组(P<0.01);3组产妇血清及新生儿脐血血清中胰岛素水平差异无显著性(P>0.05)。3组产妇血清脂联素水平与胰岛素水平无相关(P>0.05);3组新生儿脐血清脂联素水平与胰岛素水平呈明显负相关性(P<0.05);3组产妇血清脂联素水平与新生儿脂联素水平无相关(P>0.05);3组产妇血清胰岛素水平和新生儿脐血胰岛素水平无相关性(P>0.05)。3组新生儿脐血清脂联素水平与新生儿出生体重、胎盘重量、新生儿头围、身长、体重/身长比呈明显正相关关系(P<0.05);3组新生儿脐血清胰岛素水平、产妇血清脂联素水平、产妇血清胰岛素水平与新生儿出生体重、胎盘重量、头围、身长、体重/身长比均无相关性。结论:脐血中的脂联素、胰岛素在胎儿宫内生长和发育过程中可能起重要的调节作用,可作为评价胎儿生长发育及体内脂肪储备状态的临床指标之一。胎儿自身分泌的脂联素与胎儿生长关系密切。