According to metabolic programming theory, small-for-gestational age patients are at high risk of cardiovascular diseases also because of the possible malfunction of the autonomic nervous system. Autonomic disorders can be assessed by heart rate variability. The aims of this study were to compare time domain parameters of heart rate variability in children born as small-for-gestational age and appropriate-for-gestational age and to assess the correlation of the postnatal and current somatic parameters with the time domain parameters. The small-for-gestational age group consisted of 68 children aged 5–10 years who were born with birth weight below the 10th percentile. The appropriate-for-gestational age group consisted of 30 healthy peers, matched in terms of gender and age. On the basis of Holter monitoring, slightly higher average heart rate was observed in the small-for-gestational age group than in the appropriate-for-gestational age group. It was found that all the time domain parameters (SDNN, SDNNi, SDANNi, rMSSD, pNN50) were lower in the small-for-gestational age group than in the appropriate-for-gestational age group. In the small-for-gestational age group, girls had lower heart rate and some of the heart rate variability parameters (SDNN, SDNNi, SDANNi) in comparison with boys.

Children born as small-for-gestational age have impaired function of the autonomic nervous system. Moreover, in the small-for-gestational age group, autonomic balance moved towards the sympathetic component, which was evidenced by higher heart rate. Children with faster heart rate and lower heart rate variability parameters may be at risk of cardiovascular disease.

Intrauterine variations in nutrient allowance can alter body composition and tissue features of the porcine offspring around birth. This study aimed to determine the effects of fetal weight variations between littermates and of maternal dietary regimen during gestation on fetal muscle traits just before birth. Fourteen pregnant gilts were reared under a conventional (control, CTL; n=7) or an experimental (treatment, TRT; n=7) dietary regimen during gestation. The dietary treatment provided 70% of the protein and digestible energy contents of the CTL diet during the first 70 days of gestation and then, 115% of the protein and digestible energy contents up to farrowing. At 110 days of gestation, sows were sacrificed and one fetus having a low (824±140 g) and one having a normal (1218±192 g) BW per litter were sampled. Irrespective of maternal dietary regimen, the longissimus muscle of the small fetuses exhibited higher expression levels of DLK1/Pref1 and NCAM1/CD56, two genes known to be downregulated during normal skeletal muscle development. Expression levels of the embryonic isoform of the myosin heavy chain (MyHC), both at the mRNA and at the protein levels, were also higher in small fetuses. In addition, the ratios of perinatal to embryonic and of adult fast to developmental MyHC isoforms were generally lower in light fetuses compared with their medium-weight littermates. These modifications suggest a delayed myofiber development in spontaneous growth-retarded fetuses. Finally, GLUT1 was expressed to a lesser extent in the muscle of small v. normal fetuses, suggesting decreased ability for glucose uptake in muscle. Initial feed restriction and subsequent overfeeding of sows during gestation led to a lower expression of the myogenic factor MYOD1, a prerequisite for myogenic initiation in skeletal muscle. This maternal strategy was also associated with a lower expression level of insulin-like growth factor 1 receptor (IGFR) but an upregulation of IGF2. This suggests an altered susceptibility of muscle cells to IGFs’ signal in fetuses from treated sows. Altogether, intrauterine growth restriction impaired fetal muscle development, and restricted feeding followed by overfeeding of gestating sows did not allow small fetuses to recover normal contractile and metabolic characteristics.

Poor fetal growth is associated with later-life changes in adult body composition and decrements in muscle strength and morphology. Few studies have investigated the association of poor fetal growth with whole-body exercise. The purpose of this study was to investigate the association of poor fetal growth with the maximal oxygen consumption (VO2max), lactate levels during exercise and the response to aerobic training. Thirty-six college-aged men and women (aged 20.8 ± 0.3 years), born to term (37–42 weeks gestation), were recruited to participate in an 8-week training program. Participants comprised two groups, high ponderal index (HIGHPI) and low ponderal index (LOWPI) (n = 18/group), identified as falling above and below the 10th percentile of the ponderal index (g/cm3)-for-gestational age distribution, respectively. The HIGHPI and LOWPI were matched pair-wise on age, sex, body mass index and pre-study physical activity patterns. The LOWPI and HIGHPI did not differ significantly before training, after training or with a change (Δ) in training VO2max (l/min or ml/min kg/fat-free mass (FFM)). However, LOWPI had significantly lower pre-training lactate levels at similar levels of relative work output (P = 0.016), and significantly smaller decreases in lactate at a fixed level of absolute work after training (P = 0.044). These differences were independent of pre-training aerobic fitness, the change in fitness with training, diet and fuel substrate choice. The lower lactate of untrained LOWPI subjects during exercise could reflect metabolic reprograming due to intrauterine growth restriction, or could be secondary to muscle morphological and/or fiber-type distribution changes that also associate with poor fetal growth.

The predictive relation between neonatal reactivity and 12-, 18-, and 24-month temperament was assessed for 22 appropriate-for-gestational-age (AGA)/small-for-gestational-age (SGA) twin pairs. Neonatal reactivity included ratings of visual and auditory orienting responses to a bull's-eye, rattle, bell, voice, and face plus voice combined, as well as alertness. Infant temperament ratings were made of emotional tone, activity, attentiveness, and social orientation to staff during ageappropriate activities in the laboratory. There were no group differences in the neonatal or infant ratings. For AGA twins, a pattern of predictive correlations was obtained between neonatal reactivity and temperament at each age. A similar predictive pattern was not observed for the SGA twins. Group differences in rates of maturation related to stresses associated with intrauterine growth retardation influenced the significance of the neonatal variables for later temperament development.

In this study we examined the association between intrauterine growth, indexed either as a categorical variable or continuous dimension, and neuropsychological outcome, in a very low birth weight (VLBW) sample of 143 preschoolers. When the commonly used split at the 10th percentile rank was applied to classify intrauterine growth restriction (IUGR), we found that the growth restricted group (n = 25) exhibited significantly poorer performance in the global motor domain, but not on any other neuropsychological measure. In contrast, when adequacy of intrauterine growth was indexed by standardized birth weight, a continuous dimension, this early risk factor explained a unique portion of the variance in global cognitive abilities and visuospatial skills, as well as in global, fine, and gross motor skills. These findings are consistent with recent magnetic resonance imaging data disclosing global neurodevelopmental changes in the brains of preterm infants with IUGR. When cases classified with IUGR (<10th percentile) were excluded, the relationship between adequacy of intrauterine growth and global cognitive abilities remained significant despite range restriction. Hence, an association between appropriateness of intrauterine growth and global intellectual outcome may be observed even within the population of VLBW preschoolers with adequate standardized birth weight. (JINS, 2012, 18, 200–211)

The ‘fetal origins’ hypothesis (Barker, 1995) would predict that the rising epidemic of diabetes and CHD in India would be due to poor intrauterine growth of the Indian babies. While this explanation may be valid to an extent, the higher prevalence of these disorders in urban compared with rural India (where birth weights are lower) would suggest a significant role for postnatal factors. In a cohort of 477 children born in the King Edward Memorial Hospital, Pune, we found that at 8 years of age current obesity strongly predicted insulin resistance. When this effect was allowed for, low birth weight was significantly associated with insulin-resistance variables and other cardiovascular risk factors. Children who were born small but had grown heavy (or tall) were the most insulin resistant and had the highest levels of cardiovascular risk factors. Accelerated growth in relation to mid parental height was similarly predictive. Poor intrauterine growth also predicted higher central adiposity at 8 years of age. We have also studied maternal nutrition and fetal growth in six villages near Pune. A newborn Indian baby is small (2650 g, SD score (SDS) –1.6 compared with an average white Caucasian baby born in the UK) and ‘thin’ (ponderal index 2.45 kg/m3, SDS –1.2), but has preserved its subcutaneous fat (subscapular skinfold thickness SDS –0.6). The thinness of the Indian babies is due to poor muscle and small abdominal viscera. We have proposed this composition as the ‘thrifty phenotype’ (Hales & Barker, 1992) of Indian babies. Maternal size and intake of certain food groups during pregnancy were important determinants of the baby’s phenotype. Thus, the small Indian babies are programmed to deposit fat from their intrauterine life. Exaggeration of this tendency in later life is associated with insulin-resistance syndrome. Control of the insulin-resistance epidemic in India might depend on improved intrauterine development and prevention of childhood obesity.

Food restriction during pregnancy in rats induces intrauterine growth retardation with consequences persisting into adulthood. In the present study we have investigated the hypothesis that malnutrition in pregnant rats may lead to altered cardiovascular function in adult female offspring. Perinatal growth retardation was induced by a 50 % reduction of normal dietary intake in rats during the second half of pregnancy. Systolic and diastolic blood pressure values and heart rate were recorded in conscious female offspring (100 d old) using a femoral artery probe. No significant differences in heart rate, or in systolic and diastolic blood pressures were recorded between control offspring and offspring of nutritionally deprived rats. In order to ascertain whether cardiovascular variables in the offspring were influenced by lactation, subgroups of offspring from food-restricted dams were fostered with lactating dams fed on a normal diet. Blood pressure and heart rate were also found to be normal in these offspring. The rise in blood pressure associated with NO inhibition was similar in all groups. Isolated resistance artery function was assessed in vitro in offspring (100–120 d old) of a second group of semi-starved dams. Small mesenteric arteries from these animals showed reduced endothelium-dependent relaxation (to acetylcholine and bradykinin), but enhanced sensitivity to exogenous NO (sodium nitroprusside). We conclude that food restriction during the second half of pregnancy and/or lactation does not induce hypertension in adult offspring, but may effect subtle changes in vascular function.

Reference intervals for human placental lactogen (hPL) and dU-estrogens (dU-E) in uncomplicated twin pregnancies are found to be higher than singleton pregnancies and considerably wider. Significantly more monozygotic than dizygotic pregnancies, and significantly more monoplacental than diplacental pregnancies showed hPL values below the median on the normal range curve. The same was not found for dU-E. Significantly more growth-retarded fetuses were found in monoplacental than diplacental pregnancies. The benefit of measuring the two parameters in order to identify the intrauterine growth retarded fetuses were evaluated in terms of sensitivity and specificity. Both parameters were found less suitable for the purpose.

Factors presumed to influence intrauterine growth were analyzed among 192 twin pairs. Mean birthweight was considerably reduced compared to single pregnancies, and a high proportion of twins were growth retarded (12.4%). One fifth of the twin pairs presented an intrapair birthweight difference exceeding 20%. DZ twins were sligthly heavier than the MZ, while dichorionic twins had a somewhat higher birthweight than the monochorionic. The intrapair weight differences were greater in twins with fused dichorionic placentae than in those with separate ones. The umbilical cord insertion seemed to influence intrauterine growth. Fetuses with velamentously or marginally inserted cords presented more frequently retarded growth than twins with centrally inserted umbilical cords. Though a total of 13 cases of twin transfusion syndromes were observed, these were not characterized by great intrapair weight differences.

Four hundred and thirty four twins occurring in 220 women were studied during a period of 11 years (1969–1979) at Notre-Dame Hospital.

Perinatal mortality (< 28 days) was compared before and after 1974, and the impact of ultrasound technique upon perinatal outcome was assessed during the second period (1974–1979). The main factor associated with perinatal mortality was low birth weight caused by either prematurity or intrauterine growth retardation.

While fetal mortality remained unchanged within the two study periods, neonatal mortality decreased from 68.2/1,000 to 28.9/1,000 mainly due to increased survival rate of twins below 1,500 g at birth.

With identical perinatal care during the same period, perinatal mortality and incidence of intrauterine growth-retarded twins remained unchanged despite early diagnosis by ultrasound.

Serial ultrasonic measurement of the biparietal diameter is an unsatisfactory means of detecting the small-for-gestational age (SGA) fetus in twin pregnancies. A new two-stage ultrasound examination schedule, highly effective in detecting the SGA singleton fetus, has been evaluated prospectively in 31 twin pregnancies. The schedule comprises ultrasonic assessment of gestational age in early pregnancy, followed by measurement of the product of the crown–rump length and trunk area of both fetuses at 34–36 weeks. All Nineteen SGA twin fetuses were detected using this schedule; the technique offers several other advantages over serial biparietal cephalometry.

Four hundred and thirty-four twins delivered from 220 women at Notre-Dame Hospital were studied during a period of 11 years (1969–1979). The maternal, fetal, and neonatal outcome was compared before and after 1974, the year ultrasonography and other changes in perinatal care were introduced in our institution. Early diagnosis occurred more frequently after 1974, together with increased antenatal hospitalization. Preeclampsia and hepatic cholestasis occurred in 19.5% and 9.5% of women, respectively. Preterm delivery occurred in 42.2% of the cases. The corrected fetal mortality rate was 30.2/1,000 and corrected perinatal mortality rate was 74.9/1,000. About 90% of the neonatal deaths occurred in infants born before 36 weeks. Internal version and complete extraction of the second twin increased the neonatal mortality sixfold compared to spontaneous delivery. Availability of ultrasound examination significantly reduced preterm delivery.