Fetal Body Growth Research Articles

Experimental hypo/hyperthyroidism in rats and the perinatal development of the hypothalamo-neurohypophysial system in comparison with the thyroid gland state and external features.

Neurophysin was detected immunohistochemically in the hypothalamo-neurohypophysial system of Wistar rats not before fetal day 18. Formerly, neurophysin was identified on day 16 of intrauterine life using another breeding stock of Wistar rats, but the same immunohistochemical reagents. In pregnant rats, experimentally induced hypo/hyperthyroidism beginning with day 13 of gestation failed to show any evident influence on the first appearance of immunohistochemically detectable neurophysin during the fetal development. Otherwise, significant effects on fetal body growth and other external features as well as the fetal thyroid state and histochemically demonstrable thyroid peroxidase activity were shown. The influence of thiamazol on the fetal thyroid peroxidase points out a primary effect and indicates the permeability of the placenta to this antithyroid drug.

Developmental Changes in Ovine Myocardial Glucose Transporters and Insulin Signaling Following Hyperthermia-Induced Intrauterine Fetal Growth Restriction

Developmental changes in ovine myocardial glucose transporters and insulin signaling following hyperthermia-induced intrauterine fetal growth restriction (IUGR) were the focus of our study. Our objective was to test the hypothesis that the fetal ovine myocardium adapts during an IUGR gestation by increasing glucose transporter protein expression, plasma membrane-bound glucose transporter protein concentrations, and insulin signal transduction protein concentrations. Growth measurements and whole heart tissue were obtained at 55 days gestational age (dGA), 90 dGA, and 135 dGA (term = 145 dGA) in fetuses from control (C) and hyperthermic (HT) pregnant sheep. Additionally, in 135 dGA animals, arterial blood was obtained and Doppler ultrasound was used to determine umbilical artery systolic (S) and diastolic (D) flow velocity waveform profiles to calculate pulsatility (S - D/mean) and resistance (S - D/S) indices. Myocardial Glut-1, Glut-4, insulin signal transduction proteins involved in Glut-4 translocation, and glycogen content were measured. Compared to age-matched controls, HT 90-dGA fetal body weights and HT 135-dGA fetal weights and gross heart weights were lower. Heart weights as a percent of body weights were similar between C and HT sheep at 135 dGA. HT 135-dGA animals had (i) lower fetal arterial plasma glucose and insulin concentrations, (ii) lower arterial blood oxygen content and higher plasma lactate concentrations, (iii) higher myocardial Glut-4 plasma membrane (PM) protein and insulin receptor beta protein (IRbeta ) concentrations, (iv) higher myocardial glycogen content, and (v) higher umbilical artery Doppler pulsatility and resistance indices. The HT ovine fetal myocardium adapts to reduced circulating glucose and insulin concentrations by increasing plasma membrane Glut-4 and IRbeta protein concentrations. The increased myocardial Glut-4 PM and IRbeta protein concentrations likely contribute to or increase the intracellular delivery of glucose and, together with the increased lactate concentrations, enhance glycogen synthesis, which allows for maintained myocardial growth commensurate with fetal body growth.

Restriction of placental growth results in greater hypotensive response to α‐adrenergic blockade in fetal sheep during late gestation

Placental insufficiency resulting in restriction of fetal substrate supply and fetal hypoxaemia is a major cause of restricted fetal growth and increased neonatal morbidity. Fetal adaptations to placental restriction (PR) include increases in circulating catecholamines and cortisol and decreased fetal body growth, with relative sparing of brain growth. The mechanisms underlying the redistribution of fetal cardiac output in PR fetuses are not known and the aim of this study was to determine whether maintenance of fetal blood pressure (BP) in the PR fetus is dependent on alpha-adrenergic stimulation. PR was induced by removing the majority of uterine caruncles in the ewe before conception. Sterile vascular surgery was performed on seven PR and six control fetuses at 113-120 days' gestation (term = 150 +/- 3 days). Fetuses with a mean arterial PO2 < 17 mmHg between 123 and 127 days' gestation were defined as hypoxic. There was a greater fall (P < 0.05) in fetal BP during phentolamine infusion (i.v: 5 mg bolus, 0.2 mg kg(-1) min(-1) for 2 h) in the hypoxic PR group (-15 +/- 2 mmHg) compared with normoxic controls (-5 +/- 1 mmHg). The fall in fetal BP during phentolamine infusion was directly related to the level of fetal PO2. Fetal BP and HR responses to phenylephrine (i.v.: 40 microg kg(-1)) were not different between PR and control fetuses. The maintenance of BP in the chronically hypoxic fetus is therefore dependent on alpha-adrenergic activation, and this fetal adaptation to a suboptimal intrauterine environment pre-dates the development of significant growth restriction. While this adaptation may play a critical role in the redistribution of fetal cardiac output to ensure the sparing of brain growth, it may have adverse consequences for peripheral vascular function in the neonatal period and in adult life.

Prenatal smoke exposure alters growth in limb proportions and head shape in the midgestation human fetus.

The objective of this study was to examine the effects of smoke exposure on the growth patterns of the head, limbs, and torso of the midgestation human fetus. Four hundred maternal/fetal pairs contributed to this analysis: 366 individuals were assessed cross-sectionally (87 smokers and 279 nonsmokers) at approximately 20 and 32 weeks, and 34 individuals were followed longitudinally at 23, 27, and 32 weeks (10 smokers, 24 nonsmokers). Ten body parameters were measured by fetal ultrasound. In both samples, controlling for day of measurement, smoke exposure was significantly associated with early growth acceleration in head and abdominal diameters at 20-27 weeks (P < 0.05). This was followed by altered head shape (a significantly smaller biparietal to occipital frontal diameter ratio at 32 weeks, P < 0.01), and a proximal/distal growth gradient as proportionately long arms (P < 0.05 at 27 and 32 weeks) and short legs were apparent by 32 weeks, with a significant reduction in the tibia/femur ratio (P = 0.04). These fetal body growth patterns, expressed in terms of size and proportionality, are consistent with the presence of chronic hypoxia associated with maternal smoking. The growth pattern differences identify that prenatal smoking is not merely an insult resulting in consistent size and growth rate reduction across developmental ages. Instead, smoke exposure alters the growth rate of individual body segments at variable developmental stages as the fetus experiences selective growth restriction and augmentation. We hypothesize that the growth patterns observed here reflect the unique pattern of fetal blood flow favoring upper body oxygen distribution and extraction, together with genetically based adaptive strategies that permit the fetus to adjust the timing and magnitude of its growth to local environmental resources. It is possible that dolichocephaly is a previously unappreciated marker of fetal hypoxia. Reduced tibial growth may be a good marker for shortfall and a useful proxy for the adequacy of circulating resources more generally.

Studies on the maturation of the small intestine of the fetal sheep. I. The effects of bilateral adrenalectomy.

The effect of bilateral adrenalectomy at 120 d gestation on subsequent maturation of proximal and distal small intestine was investigated in chronically catheterized fetal sheep. Ten adrenalectomized and fourteen controls were examined at 136 d; some following infusion of [3H]thymidine at 3-6 d or 4 h before termination of pregnancy. Mean plasma cortisol levels were 5.3 +/- 0.7 ng/ml in the adrenalectomized group; control values ranged from 14 to 39 ng/ml level during the 2-week experimental period. Fetal body growth was significantly increased following adrenalectomy. In the small intestine, growth of mucosal structures was reduced, especially in distal regions. Villus height was significantly reduced in both regions. External muscle thickness was significantly increased in both regions. Despite these changes there was no alteration in villus enterocyte morphology, nor were there any significant changes in villus or crypt densities. The proportion of crypt cells labelled with [3H]thymidine was unaffected by adrenalectomy. In proximal regions, migration rate of labelled enterocytes declined from 12.0 to 5.83% villus height/d (P less than 0.025) after adrenalectomy; there was no change in migration rate in distal regions. The estimated renewal time was greater in both proximal and distal regions in adrenalectomized compared with control fetuses.

Diabetes in pregnancy: decreased placental blood flow and disturbed fetal development in the rat.

Placental blood flow was measured with the aid of radioactive microspheres, in normal (N) and manifest diabetic (MD) rats, and related to fetal body growth and incidence of congenital malformations. The total blood flow in the placentae of the MD rats was decreased to about one-half of the normal flow on gestational days 20 and 22. The placentae of the MD offspring were enlarged, whereas the fetuses in this group were smaller than normal. Thus, the placental blood flow per placental weight was drastically decreased in the MD fetuses on both days 20 and 22. In contrast, the placental blood flow per fetal weight was not different in the N and MD groups on gestational day 20 whereas it was decreased in the MD offspring on gestational day 22. Placental blood flow in the malformed fetuses of the MD group did not differ significantly from that in the nonmalformed MD fetuses.

Increased thymidine incorporation into fetal rat cartilage in vitro in the presence of human somatomedin, epidermal growth factor and other growth factors.

The incorporation of [3H]thymidine by rat costal cartilage in vitro was studied at different fetal and postnatal ages and the effect of partially purified human somatomedin, mouse epidermal growth factor, platelet secretion products, insulin and growth hormone on thymidine uptake by fetal cartilage was examined. Thymidine uptake in plasma-free medium was many times greater in late fetal life than after birth. The incorporation of [3H]thymidine into costal cartilage from 21-day fetuses was significantly (P less than 0.05) increased above control values in the presence of 10 micrograms somatomedin/1, and when cartilage was incubated in medium containing somatomedin and diluted human plasma there was a synergistic action. Epidermal growth factor at a concentration of 1 ng/l was a potent stimulator of thymidine uptake. Secretion products from human platelets after their aggregation by thrombin stimulated [3H]thymidine uptake at a concentration of 2% (v/v), but were inhibitory at high concentrations. High concentrations of platelet secretion products stimulated the incorporation of [35S]sulphate by cartilage. A pharmacological concentration of 10 mu. insulin/ml stimulated [3H]thymidine uptake, but not concentrations of 1 or 100 mu./ml. Growth hormone had no effect. The results showed that fetal cartilage had a greater endogenous mitogenic activity than postnatal cartilage. While somatomedins may be important in the regulation of fetal body growth, other protein growth factors also stimulate fetal skeletal tissues.

The Influence of Maternal Somatostatin Administration on Fetal Brain Cell Proliferation and its Relationship to Serum Growth Hormone and Brain Trophin Activity

The effect of maternal somatostatin administration from days 14 to 20 of gestation was examined. Fetal body growth was unchanged but brain cell DNA synthesis per gram of tissue decreased. Maternal serum levels of growth hormone and brain trophin were elevated following treatment conclusion. It was suggested that this was a rebound phenomenon and that short term blockade of pituitary growth hormone release during somatostatin treatment had impaired fetal brain cell DNA synthesis.

Chronic low level maternal carbon monoxide exposure and fetal growth and development.

We investigated the effects on fetal growth and development of continuous exposure of pregnant rats to low level carbon monoxide (30 or 90 ppM CO) and a low oxygen atmosphere (13% O/sub 2/). While neither CO concentration induced a hematologic response in the pregnant animals, 13% O/sub 2/ exposure elicited an increase in hematocrit, the number of erythrocytes and hemoglobin concentration. Fetal body growth was unaffected by either CO concentration; however, it was reduced significantly in fetuses exposed to 13% O/sub 2/. The individual organ weights were differentially affected by 90 ppM CO. The fetal brain wet weight increased 14%, whereas the lung weight decreased 24%. We attribute the brain enlargement in the 90 ppM CO fetuses to an increased water content as evidenced by decreased concentrations of brain protein, DNA, norepinephrine and serotonin and a reduced dry-wet weight ratio. The results indicate that the fetus in utero is affected by relatively low CO concentrations in the maternal environment.

55 HEAD CIRCUMFERENCE AT BIRTH AS A PREDICTOR OF NEUO-BEHAVIORAL OUTCOME

Neurobehavioral (NB) outcome of low birth weight infants was studied in relation to head circumference (HC) at birth. Infants weighed ≤2250 gms. and/or were <than 37 weeks gestation (Dubowitz examination). Follow-up NB evaluation performed on 127 infants at the corrected chronologic age of 7 months consisted of a neurologic examination and administration of the Bayley Mental Scale (MDI). Ninety-one infants (71.7%) had appropriate HC for gestational age (AHA, <10th percentile, Lubchenko) and 35 (28.3%) had a small HC (SHA). MDI was <80 in 34.3% of SHA infants compared to only 16.3% of AHA infants (p<0.05). Severe neurologic deficit was found in 20% of SHA infants compared to only 5.5% of AHA infants (p<0.05). The incidences of MDI<80 and severe neurologic deficit in subgroups of AHA and SHA were not significantly affected by whether total body weight was appropriate or small for gestational age (AGA or SGA). Thus: Previously reported associations of fetal body growth retardation with poor NB outcome probably apply primarily in those infants with fetal head growth retardation (SHA). Evaluation of HC at birth in relation to gestational age adds an important dimension to the prediction of neurologic outcome.