During Ramadan, many pregnant Muslim women fast between dawn and sunset. Although the impacts of prolonged maternal intermittent fasting (IF) on fetal growth and placental function are under-researched, reported effects include reduced placental weight and birth weight. In the present study, pregnant Wistar rats were used to model repeated cycles of IF on fetal development and placental function and to examine sex-specific effects. In the IF group, food was withdrawn daily from 17:00 to 09:00 over 21 days of gestation, while the control group received food ad libitum . Both groups had free water access. IF dams consumed less food, had significantly reduced weight compared with controls, with reduced plasma glucose and amino acids. Both fetal sexes were significantly lighter in the IF group with reduced fetal plasma amino acids. Placental weights and morphology were unchanged. The profile of placental metabolites was altered in the IF group with sex-specific responses evident. Transplacental flux of 14 C-methylaminoisobutyric acid ( 14 C-MeAIB), a system A amino acid transporter substrate, was significantly reduced in both fetal sexes in the IF group. Sodium-dependent 14 C-MeAIB uptake into isolated placental plasma membrane vesicles was unchanged. The gene expression of system A transporter Slc38a1, Slc38a2 and Slc38a4 was up-regulated in IF male placentas only. No changes were observed in placental SNAT1 and SNAT2 protein expression. Maternal IF results in detrimental impacts on maternal physiology and fetal development with changes in the placental and fetal metabolite profiles. Reduced placental system A transporter activity may be responsible for fetal growth restriction in both sexes.

When rat dams consume a diet low in protein during pregnancy, their offspring develop high blood pressure. On a low-protein diet, the endogenous formation of the amino acid glycine is thought to become constrained. Glycine may become conditionally essential, as its rate of endogenous formation is inadequate to meet metabolic needs, and may be limiting for the normal development of the fetus. In the present study, five groups of Wistar rats were provided during pregnancy with one of five diets: a control diet containing 18% (w/w) casein (CON), a low-protein diet containing 9% casein (MLP), or the low-protein diet supplemented with 3% glycine (MLPG), alanine (MLPA) or urea (MLPU). The offspring were weaned on to standard laboratory chow, and blood pressure was measured at 4 weeks of age. Blood pressure was significantly increased in the MLP, MLPA and MLPU groups compared with the CON group, but for the MLPG group blood pressure was not significantly different from CON. Compared with the CON group, body weight was significantly reduced for the MLP, MLPA and MLPG groups, but for the MLPU group body weight was not different from CON. These data show that different forms of non-essential dietary nitrogen, when consumed during pregnancy, exert different effects upon the growth and function of the offspring. The availability of glycine appears to be of critical importance for normal cardiovascular development.

1. Many human fetuses have to adapt to a limited supply of nutrients. In doing so they permanently change their structure and metabolism. 2. These ‘programmed' changes may be the origins of a number of diseases in later life, including coronary heart disease and the related disorders stroke, diabetes and hypertension. 3. This review examines the evidence linking these diseases to fetal undernutrition and provides an overview of previous studies in this area.

1. Animal and human work has indicated that maternal oxytocin secretion is under the control of endogenous opiates. Previous workers have described the fetal production of oxytocin in addition to maternal production. The study of the interaction between exogenously administered opiates and oxytocin secretion may give insight into the activity of any opiate-mediated regulatory mechanism of oxytocin secretion in the fetus. This study was designed to investigate the effect of an opiate (5 mg of morphine) given to the mother on the fetal production of oxytocin in labour. 2. Morphine was given by the attending clinicians for analgesic purposes to women in the first stage of labour. After delivery umbilical artery vein and maternal vein specimens were taken. 3. Four groups of patients were studied: women after normal vaginal delivery without analgesia in labour ( n = 10); women after normal vaginal delivery who had morphine administration in the first stage of labour ( n = 12); women who had an emergency Caesarean section in the first stage of labour ( n = 11); women who had an elective Caesarean section at term who were not in labour ( n = 11). 4. Oxytocin levels were measured by radioimmunoassay in the maternal vein, umbilical artery and umbilical vein specimens. Morphine was measured by radioimmunoassay in the umbilical vein specimens. 5. The umbilical artery minus vein concentration of oxytocin was calculated for each patient ( A - V ). There was no change in the umbilical ( A - V ) concentration of oxytocin if morphine had been given to the mother in labour; this applied to fetuses delivered vaginally or by Caesarean section. When the fetuses who were exposed to morphine were analysed separately, there was no correlation between the umbilical vein morphine concentration and the umbilical ( A - V ) oxytocin concentration either in Caesarean or vaginal deliveries. 6. Fetal oxytocin production was not affected by the maternal administration of morphine in the first stage of labour. This applies to the oxytocin production in the first and second stage of labour.

1. Two distinct notions of variability have been defined to assess heart rate: deviation from a constant output (SD) and irregularity. One statistical measure of irregularity is approximate entropy, with greater irregularity corresponding to larger approximate entropy values. The specific aims of this investigation were to determine the manner in which SD and irregularity evolve during fetal development and whether this evolution is coincident or distinct. 2. Fetal heart rate was computed in 14 males and 17 females for 15 min of undisturbed recording using a fetal actocardiograph at 4 week intervals from 20 to 36 weeks gestation. 3. Mean heart rate decreased significantly with gestational ages ( P < 0.05). SD increased significantly from 4.4+0.3 ms (SEM) at 20 weeks to 7.7±0.4 ms at 36 weeks ( P < 0.05) and was similar between male and female fetuses ( P = 0.57). Fixed approximate entropy increased significantly from 0.47 ±0.04 to 0.78 ±0.03, paralleling the change in SD ( P < 0.01). Notably, normalized approximate entropy, which decorrelates SD from regularity, increased significantly with gestational age ( P < 0.01) for males, while it remained relatively constant for females ( P = 0.68). Approximate entropy was significantly lower at 20 weeks in males than females ( P < 0.05); however, the values were similar by 28 weeks gestation. 4. Our results demonstrate that variability increases, and that irregularity increases, independently in male fetuses but not female fetuses, consistent with an increase in the coupling of emerging networks with gestational age. The present study demonstrates the complementary information obtained by analyses of both measures of variability and regularity. This reinforces a difference in gender-based development as noted in the separate context of fetal lung maturation.

1. Lipid, apolipoprotein concentration and composition were determined in maternal venous and umbilical arterial and venous blood at delivery by elective Caesarean section in 13 full-term pregnancies and in 25 healthy non-pregnant females. The indications of Caesarean section were a previous Caesarean section or breech presentation. None of the women was in labour and there were no other complications of pregnancy or fetal distress. 2. The objectives of the study were to establish whether the placenta has a role in feto-maternal cholesterol metabolism through either synthesis or transplacental cholesterol flux. The potential for free cholesterol diffusion between mother and fetus and rates of cholesterol esterification and transfer between lipoproteins were determined and related to the differences in composition between fetal and maternal lipoproteins. 3. Pregnant women had raised levels of all lipid and lipoprotein fractions compared with control subjects. The greatest increases were in free cholesterol and triacylglycerol ( P < 0.0001). Lipoprotein (a) levels were significantly greater in the pregnant women [112(12.2) mg/l] than in the control women [50 (10.0) mg/l]. 4. The only significant correlation between maternal and fetal lipoprotein concentrations was in lipoprotein (a) levels ( r = 0.791, P = 0.002). In both umbilical venous and arterial blood, concentrations of very-low- and low-density lipoproteins, particularly apolipoprotein B, cholesteryl ester and triacylglycerol, were lower than in maternal blood ( P < 0.0001), but high-density lipoprotein levels were similar. 5. There was no umbilical arteriovenous differences in lipoprotein concentration or composition. This suggests that cholesterol synthesis or free cholesterol diffusion does not occur in the placenta. The relative concentrations of free cholesterol to phospholipid in maternal and fetal lipoproteins do not indicate the existence of a concentration gradient favouring free cholesterol diffusion across the placenta. 6. The esterification of free cholesterol was significantly reduced in maternal [17.7 (2.4) μmol h −1 l −1 , P < 0.001] and fetal [6.7 (3.5) μmol h −1 l −1 , P < 0.0001] compared with control [40.9 (13.2) μmol h −1 l −1 ] blood. 7. In fetal compared with maternal high-density lipoproteins the ratios cholesteryl ester/apoliproprotein A-I [0.84 (0.35) versus 0.40 (0.05), P < 0.01] and phospholipid/apolipoprotein A-I [1.66 (0.14) versus 0.58 (0.10), P < 0.0001] indicated lipid enrichment of these particles in the fetus. 8. Lipid enrichment of high-density lipoprotein is due in part to a marked reduction in transfer of cholesteryl ester in the fetus [1.0 (0.6) μmol h −1 l −1 ] compared with maternal [6.15 (1.3) μmol h −1 l −1 , P = 0.004] and control [17.3 (7.2) μmol h −1 l −1 , P < 0.0001] blood. 9. In conclusion, there was no evidence for involvement of the placenta in cholesterol metabolism during pregnancy. In fetal life high-density lipoproteins are lipid rich, partly because of a reduction in transfer of esterified cholesterol to other particles. Maternal and fetal lipoprotein levels are not correlated, although the results suggested that lipoprotein (a) levels may be related.

1. Possible associations between maternal nutrition in pregnancy and non-communicable diseases of adulthood were assessed using a rat model. Rats were habituated to diets containing a range of protein levels (18, 12, 9 and 6% by weight), over a 14 day period, before mating. The low protein diets were maintained throughout pregnancy. Lactating mothers and their offspring were transferred to a standard chow diet (20% protein). 2. Pregnant rats demonstrated a graded response to the diets, with those fed 9 and 6% protein tending to consume less energy and gain less weight than 18% protein fed controls. Litter size and newborn death rates were not significantly altered by the low protein diets. 3. Offspring of 12 and 9% protein fed dams were grossly normal, gaining weight at a similar rate to those born to 18% protein fed control rats. Offspring of the 6% protein fed dams were smaller than pups from all other groups, over a 21 week period. 4. At 9 weeks of age, systolic blood pressure was determined in the offspring. All offspring from the three low protein groups were found to have significantly elevated blood pressure (15–22 mmHg) relative to the control group. An inverse relationship between maternal protein intake and the systolic blood pressure of the offspring was observed. Blood pressure remained elevated in the offspring of the 9 and 6% protein fed dams until 21 weeks of age. The observed hypertension was associated with increased pulmonary angiotensin-converting enzyme activity in the low protein groups. 5. The data are consistent with the hypothesis that poor maternal nutrition in pregnancy may irreversibly impair aspects of physiological and biochemical function in the fetus. This has potential adverse consequences for the later health of the offspring.