Maternal nutrient restriction at specific stages of gestation has differential effects on fetal development such that the offspring are programmed to be at increased risk of adult disease. We investigated the effect of gestational age and maternal nutrition on the maternal plasma concentration of leptin and cortisol together with effects on fetal adipose tissue deposition plus leptin, IGF-I, IGF-II ligand, and receptor mRNA abundance near to term. Singleton bearing ewes were either nutrient restricted (NR; consuming 3.2-3.8 MJ/d of metabolizable energy) or fed to appetite (consuming 8.7-9.9 MJ/d) over the period of maximal placental growth, i.e. between 28 and 80 d gestation. After 80 d gestation, ewes were either fed to calculated requirements, consuming 6.7-7.5 MJ/d, or were fed to appetite and consumed 8.0-10.9 MJ/d. Pregnancy resulted in a rise in plasma leptin concentration by 28 d gestation, which continued up to 80 d gestation when fed to appetite but not with nutrient restriction. Plasma cortisol was also lower in NR ewes up to 80 d gestation, a difference no longer apparent when food intake was increased. At term, irrespective of maternal nutrition in late gestation, fetuses sampled from ewes NR in early gestation possessed more adipose tissue, whereas when ewes were fed to appetite throughout gestation, fetal adipose tissue deposition and leptin mRNA abundance were both reduced. These changes may result in the offspring of NR mothers being at increased risk of obesity in later life.

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Objective: To examine the ability of three different proteinuria assessment methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24-hour urine collection) to predict adverse pregnancy outcomes Methods:We performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated Estimate of RiSk), in seven academic tertiary maternity centres practising expectant management of preeclampsia remote from term in Canada, New Zealand, and Australia Eligible women were those admitted with preeclampsia who had at least one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio, and/or 24-hour urine collection Proteinuria assessment was done either visually at the bedside (by dipstick) or by hospital clinical laboratories for spot urine Pr/Cr and 24-hour urine collection We calculated receiver operating characteristic area under the curve (95% CI) for each proteinuria method and each of the combined adverse maternal outcomes (within 48 hours) or adverse perinatal outcomes (at any time) Models with AUC ≥ 070 were considered of interest Analyses were run for all women who had each type of proteinuria assessment and for a cohort of women ("ALL measures") who had all three proteinuria assessmentsResults: More women were proteinuric by urinary dipstick (≥ 2+, 614%) than by spot urine Pr/Cr (≥ 30g/mol, 504%) or 24-hour urine collection (≥ 03g/d, 347%) Each proteinuria measure evaluated had some discriminative power, and dipstick proteinuria (categorical) performed as well as other methods No single method was predictive of adverse perinatal outcome Conclusion:The measured amount of proteinuria should not be used in isolation for decision-making in women with preeclampsia Dipstick proteinuria performs as well as other methods of assessing proteinuria for prediction of adverse events

1. Platelet angiotensin II binding was measured in 34 primigravid women (between 28 and 32 weeks gestation), in whom the pressor response to infused angiotensin II was also determined. 2. There was a significant correlation between the platelet angiotensin II binding and the slope of the curve relating the diastolic pressor response to infused angiotensin II (P less than 0.01), suggesting that co-linearity between the two techniques exists and supporting the use of platelet angiotensin II binding as a model of vascular smooth muscle pressor responsiveness. 3. Ten of the 34 women subsequently developed pregnancy-induced hypertension. Platelet angiotensin II binding in the patients who subsequently developed pregnancy-induced hypertension was sixfold higher than in the patients who remained normotensive (P less than 0.001). There were, however, no significant differences between the groups in any of the parameters derived from the angiotensin II infusion experiments. 4. The use of platelet angiotensin II binding alone in predicting the outcome of the pregnancies, as assessed using discriminant analysis, was more successful than when any of the infusion parameters were used, with 77% of patients being correctly classified.

Objective To compare the angiotensinogen genotypes in normotensive and pre-eclamptic pregnancies Design Prospective observational study.Setting University Hospital, Queen's Medical Centre, Nottingham.Population Forty-three women with pre-eclampsia and 84 normotensive pregnant women. Fetal samples were available for genotyping from 96% of the pregnancies.Methods Maternal and fetal DNA was genotyped at angiotensinogen codon 235 and at a dinucleotide repeat polymorphism in the 3' flanking region of the gene. Angiotensinogen and renin concentrations were measured in maternal plasma by radioimmunoassay. ResultsIn contrast to earlier studies, no association was demonstrated between the angiotensinogen 235 Thr variant and pre-eclampsia. Normotensive pregnant women homozygous for this variant had significantly lower plasma angiotensinogen concentrations (median 2.2 ng AUmL; IQR 1.8-3.0) than women homozygous for the 235 Met allele (3.6 ng AYmL; IQR 2 . 5 4 1 ; P = 0.04). In pre-eclamptic pregnancies, 79% (1 1/14) of mothers heterozygous for the dinucleotide repeat allele designated A9 transmitted this allele to the fetus, more frequently than would be expected by chance (P = 0.02). The A9 allele was associated with low plasma angiotensinogen concentrations (P = 0.001) and high renin concentrations (P = 0.02) in normotensive women. ConclusionsThere is no evidence that the angiotensinogen 235 Thr allele is associated with preeclampsia in the Nottingham population. The angiotensinogen 235 Thr allele is associated with low plasma angiotensinogen concentrations in normotensive pregnant women, in contrast to the high levels associated with this variant in non-pregnant women, suggesting that regulation of angiotensinogen expression in normal pregnancy may differ significantly from that in the non-pregnant state. There is preliminary evidence that maternal-fetal transmission of an angiotensinogen allele associated with low plasma angiotensinogen concentrations is associated with pre-eclampsia. Impaired generation of angiotensin I1 at the maternal-fetal interface may be a factor in the pathogenesis of pre-eclampsia.in maternal and fetal samples.