Evidence from human and animal studies suggests that maternal nutrition can induce developmental programming of adult hypertension in offspring. We have previously described a model of maternal dietary imbalance in Sprague‐Dawley rats whereby administration of a maternal diet rich in animal lard programmes the development of increased blood pressure, insulin resistance, dyslipidaemia, obesity and mesenteric artery endothelial dysfunction in adult offspring. To further characterize the mechanism of hypertension in this model we have examined vascular and renal structure in adult offspring of Sprague‐Dawley rats fed a control diet (OC) or lard‐rich diet (OHF) during pregnancy and suckling followed by a control diet post‐weaning. To gain further insight, we assessed aortic reactivity and elasticity in an organ bath preparation and renal renin and Na⁺,K⁺‐ATPase activity. Plasma aldosterone concentration was also measured. Stereological examination of the aorta in OHF demonstrated reduced endothelial cell volume and smooth muscle cell number compared with OC. Adult OHF animals showed increased aortic stiffness and reduced endothelium‐dependent relaxation. Renal stereology showed no differences in kidney weight, glomerular number or volume in OHF compared with OC, but renin and Na⁺,K⁺‐ATPase activity were significantly reduced in OHF compared with controls. Programmed alterations to aortic structure and function are consistent with previous observations that exposure to maternal high fat diets produces systemic vascular changes in the offspring. Despite normal renal stereology, altered renal Na⁺,K⁺‐ATPase and renin activity offers further insight into the mechanism underlying the increased blood pressure characteristic of this model.

Recent studies have proposed a link between impaired nephrogenesis, decreased activity of the renin–angiotensin system and the onset of hypertension in rats exposed in the uterus to a maternal low-protein diet. However, there is no detailed information about renal function in this model; hence the aim of the present study was to assess renal function in young (4-week-old) rats exposed in the uterus to a maternal low-protein diet. Pregnant Wistar rats were fed isocalorific diets containing either 18% (normal protein; offspring denoted NP rats) or 9% (low protein; offspring denoted LP rats) (w/w) protein from conception until birth. At 4 weeks of age, male offspring were anaesthetized and prepared for the study of renal function, during which animals received saline alone, a bolus of enalapril (5 mg·kg-1) or a bolus of enalapril followed by an infusion of angiotensin II (30 ng·min-1·kg-1). Under control conditions, renal haemodynamic and tubular function did not differ. However, when challenged with angiotensin II, LP rats responded with a greater decrease in glomerular filtration rate than did NP rats [NP, 2.0±0.2 ml·min-1·g-1 kidney weight (n=9); LP, 1.0±0.2 ml·min-1·g-1 kidney weight (n=5); P<0.05]. Renal electrolyte excretion did not differ. LP rats had significantly fewer glomeruli than NP rats (P<0.01). Renal angiotensin II AT1 receptor expression was increased (P<0.01) by 24% in LP rats. It is concluded that blood pressure may be elevated in LP rats in order to maintain glomerular filtration rate against a background of fewer nephrons. Increased AT1 receptor expression, which may arise as a result of the direct effect of protein restriction or in response to the reported decrease in renal tissue angiotensin II concentration, could also contribute to the elevated blood pressure of this model.

Although exempt, many pregnant Muslim women partake in the daily fast during daylight hours during the month of Ramadan. In other contexts an impoverished diet during pregnancy impacts on birth weight. The aim of this systematic review was to determine whether Ramadan fasting by pregnant women affects perinatal outcomes. Primary outcomes investigated were perinatal mortality, preterm birth and small for gestational age (SGA) infants. Secondary outcomes investigated were stillbirth, neonatal death, maternal death, hypertensive disorders of pregnancy, gestational diabetes, congenital abnormalities, serious neonatal morbidity, birth weight, preterm birth and placental weight. Systematic review and meta-analysis of observational studies and randomised controlled trials was conducted in EMBASE, MEDLINE, CINAHL, Web of Science, Google Scholar, the Health Management Information Consortium and Applied Social Sciences Index and Abstracts. Studies from any year were eligible. Studies reporting predefined perinatal outcomes in pregnancies exposed to Ramadan fasting were included. Cohort studies with no comparator group or that considered fasting outside pregnancy were excluded, as were studies assuming fasting practice based solely upon family name. Quality of included studies was assessed using the ROBINS-I tool for assessing risk of bias in non-randomised studies. Analyses were performed in STATA. From 375 records, 22 studies of 31,374 pregnancies were included, of which 18,920 pregnancies were exposed to Ramadan fasting. Birth weight was reported in 21 studies and was not affected by maternal fasting (standardised mean difference [SMD] 0.03, 95% CI 0.00 to 0.05). Placental weight was significantly lower in fasting mothers (SMD -0.94, 95% CI -0.97 to -0.90), although this observation was dominated by a single large study. No data were presented for perinatal mortality. Ramadan fasting had no effect on preterm delivery (odds ratio 0.99, 95% CI 0.72 to 1.37) based on 5600 pregnancies (1193 exposed to Ramadan fasting). Ramadan fasting does not adversely affect birth weight although there is insufficient evidence regarding potential effects on other perinatal outcomes. Further studies are needed to accurately determine whether Ramadan fasting is associated with adverse maternal or neonatal outcome.

In the rat, protein restriction during pregnancy increases offspring blood pressure by 20–30 mmHg. We have shown in an earlier study that this is associated with a reduction in nephron number and increased glomerular sensitivity to angiotensin II (Ang II) in vivo. Hence, we hypothesized that exposure to a maternal low‐protein diet increases glomerular Ang II AT₁ receptor expression and decreases AT₂ receptor expression. To test this hypothesis, pregnant Wistar rats were fed isocalorific diets containing either 18% (control) or 9% (LP) protein from conception until birth. At 4 weeks of age, the kidneys of male offspring were harvested to measure cortical AT₁ and AT₂ receptor expression, ¹²⁵I‐Ang II glomerular binding, tissue renin activity, tissue Ang II and plasma aldosterone concentrations. AT₁ receptor expression was increased (62%) and AT₂ expression was decreased (35%) in LP rats. Maximum ¹²⁵I‐Ang II (¹²⁵I‐Ang II) binding (B_max) was increased in LP rats (control n= 9, 291.6 ± 27.4 versus LP n= 7, 445.7 ± 27.4 fmol (mg glomerular protein)⁻¹, P < 0.01), but affinity (K_D) was not statistically different from controls (control 2.87 ± 0.85 versus LP 0.84 ± 0.20 pmol ¹²⁵I‐Ang II, P= 0.059). Renal renin activity, tissue Ang II and plasma aldosterone concentrations did not differ between control and LP rats. Increased AT₁ receptor expression in LP rat kidneys is consistent with greater haemodynamic sensitivity to Ang II in vivo. This may result in an inappropriate reduction in glomerular filtration rate, salt and water retention, and an increase in blood pressure.

Prenatally programmed hypertension induced by maternal protein restriction is associated with increased expression of the renal tubular Na⁺/K⁺/2Cl⁻ co-transporter (NKCC2) and the Na⁺/Cl⁻ co-transporter (NCC). This has led to the suggestion that renal Na⁺ retention contributes to the development of hypertension in the LP rat (offspring exposed to a maternal low-protein diet in utero). However, this hypothesis has not been tested in vivo. Renal clearance measurements in hypertensive 4-week-old male and female LP rats showed that, although the glomerular filtration rate remained unaltered, urine flow (P<0.01) and urinary Na⁺ excretion rates (1.6±0.3 and 3.0±0.4 μmol·min⁻¹·100 g⁻¹ of body weight in control male and LP male respectively; P<0.001) were increased. Na⁺ excretion was positively correlated with mean arterial pressure in both males (P<0.01) and females (P<0.05), but neither the slope nor the intercept differed between control and LP rats. Fractional excretion of Na⁺ was increased in male (1.5±0.2 and 3.0±0.5% in control and LP rats respectively; P<0.001) and female LP rats, implying reduced tubular reabsorption of Na⁺. Western blotting and quantitative PCR showed that NKCC2 expression was increased, whereas NCC mRNA was not up-regulated. Na⁺/K⁺ ATPase α₁ subunit expression did not differ from controls; however, there was a significant reduction in whole kidney pump activity (23.4±1.8 and 17.7±1.2 nmol of phosphate·μg⁻¹ of protein·h⁻¹ in control male and male LP rats respectively; P<0.001); immunohistochemistry showed that the α₁ subunit was virtually absent from the inner medulla. The greater Na⁺ excretion of LP rats can be explained, in part, by a pressure–natriuresis mechanism; however, the loss of the Na⁺/K⁺ ATPase α₁ subunit from the inner medulla and up-regulation of NKCC2 suggests that altered renal Na⁺ handling is also programmed prenatally.