Respiratory quotient evolution during normal pregnancy: what nutritional or clinical information can we get out of it?

Food intake increases to a varying extent during pregnancy to provide extra energy for the growing fetus. Measuring the respiratory quotient (RQ) during the course of pregnancy (by quantifying O2 consumption and CO2 production with indirect calorimetry) could be potentially useful since it gives an insight into the evolution of the proportion of carbohydrate vs. fat oxidized during pregnancy and thus allows recommendations on macronutrients for achieving a balanced (or slightly positive) substrate intake. A systematic search of the literature for papers reporting RQ changes during normal pregnancy identified 10 papers reporting original research. The existing evidence supports an increased RQ of varying magnitude in the third trimester of pregnancy, while the discrepant results reported for the first and second trimesters (i.e. no increase in RQ), explained by limited statistical power (small sample size) or fragmentary data, preclude safe conclusions about the evolution of RQ during early pregnancy. From a clinical point of view, measuring RQ during pregnancy requires not only sophisticated and costly indirect calorimeters but appears of limited value outside pure research projects, because of several confounding variables: (1) spontaneous changes in food intake and food composition during the course of pregnancy (which influence RQ); (2) inter-individual differences in weight gain and composition of tissue growth; (3) technical factors, notwithstanding the relatively small contribution of fetal metabolism per se (RQ close to 1.0) to overall metabolism of the pregnant mother.

Changes in fat, fat-free mass and body water in human normal pregnancy

Measurements of body weight, total body water and total body potassium (40K) were made serially on three occasions during pregnancy and once post partum in 27 normal pregnant women. Skinfold thickness and fat cell diameter were also measured. A model of body composition was formulated to permit the estimation of changes in fat, lean tissue and water content of the maternal body. Total maternal body fat increased during pregnancy, reaching a peak towards the end of the second trimester before diminishing. Serial measurements of fat cell diameter showed poor correlation, whilst total body fat calculated from skinfold thickness correlated well with our estimated values for total body fat in pregnancy.

Lifestyle and health status in a sample of Swedish women four years after pregnancy : a comparison of women with a history of normal pregnancy and women with a history of gestational diabetes mellitus

Background: Despite the recommendations to continue the regime of healthy food and physical activity (PA) postpartum for women with previous gestational diabetes mellitus (GDM), the scientific evidence reveals that these recommendations may not be complied to. This study compared lifestyle and health status in women whose pregnancy was complicated by GDM with women who had a normal pregnancy and delivery. Methods: The inclusion criteria were women with GDM (ICD-10: O24.4 A and O24.4B) and women with uncomplicated pregnancy and delivery in 2005 (ICD-10: O80.0). A random sample of women fulfilling the criteria (n = 882) were identified from the Swedish Medical Birth Register. A questionnaire was sent by mail to eligible women approximately four years after the pregnancy. A total of 444 women (50.8%) agreed to participate, 111 diagnosed with GDM in their pregnancy and 333 with normal pregnancy/ delivery. Results: Women with previous GDM were significantly older, reported higher body weight and less PA before the index pregnancy. No major differences between the groups were noticed regarding lifestyle at the follow-up. Overall, few participants fulfilled the national recommendations of PA and diet. At the follow-up, 19 participants had developed diabetes, all with previous GDM. Women with previous GDM reported significantly poorer self-rated health (SRH), higher level of sick-leave and more often using medication on regular basis. However, a history of GDM or having overt diabetes mellitus showed no association with poorer SRH in the multivariate analysis. Irregular eating habits, no regular PA, overweight/obesity, and regular use of medication were associated with poorer SRH in all participants. Conclusions: Suboptimal levels of PA, and fruit and vegetable consumption were found in a sample of women with a history of GDM as well as for women with normal pregnancy approximately four years after index pregnancy. Women with previous GDM seem to increase their PA after childbirth, but still they perform their PA at lower intensity than women with a history of normal pregnancy. Having GDM at index pregnancy or being diagnosed with overt diabetes mellitus at follow-up did not demonstrate associations with poorer SRH four years after delivery.

Vascular endothelial growth factor-A and aldosterone: relevance to normal pregnancy and preeclampsia

Aldosterone levels are markedly elevated during normal pregnancy but fall even though volume contracts when preeclampsia occurs. The level of aldosterone in either condition cannot be explained solely by the activity of the renin-angiotensin II system. In normal gestation, vascular endothelial growth factor (VEGF) is thought to maintain vascular health, but its role in adrenal hormone production is unknown. We hypothesized that the role of VEGF in the adrenal gland is to maintain vascular health and regulate aldosterone production. Here, we demonstrate that supernatant of endothelial cells grown in the presence of VEGF enhanced aldosterone synthase activity in human adrenocortical cells. VEGF either alone or combined with angiotensin II increased aldosterone production in adrenal cells. These data suggest that endothelial cell-dependent and independent activation of aldosterone is regulated by VEGF. In contrast to angiotensin II, VEGF did not upregulate the steroidogenic acute regulatory protein. Consistent with this observation, angiotensin II stimulated both aldosterone and cortisol synthesis from progesterone, whereas VEGF stimulated selectively aldosterone production. In rats, overexpression of soluble fms-like tyrosine kinase-1, an endogenous VEGF inhibitor, led to adrenocortical capillary rarefaction and fall in aldosterone concentrations that correlated inversely with soluble fms-like tyrosine kinase-1 levels. These findings may explain why aldosterone increases so markedly during normal gestation and why preeclampsia, a condition characterized by high soluble fms-like tyrosine kinase-1, is associated with inappropriately low aldosterone levels in spite of relatively lower plasma volumes.

The influence of ApoE genotype on the lipid profile and lipoproteins during normal pregnancy in a Southern African population.

Background: Pregnancy is associated with increases in fasting triglycerides and total cholesterol.1 ApoE isoforms are known to influence the concentration of cholesterol, with apoE2 homozygosity lowering and apoE4 homozygosity raising the cholesterol concentration compared with E3 homozygosity.2 The lipid profiles ApoE status and prevalence of small dense LDL species were evaluated for subjects attending an antenatal clinic. Results: Samples from 690 women aged between 16 and 42 years of age were analyzed during and after pregnancy. The fasting plasma triglyceride concentration (in mmol/L) was significantly higher in pregnancy (median = 1.5, IQR 1.0-2.0 vs median = 0.6, IQR 0.5-0.8 respectively, p < 0.0001). Similarly, the total cholesterol (in mmol/L) was increased during pregnancy (median=4.1, IQR 3.6-4.7 vs median 3.5, IQR 3.1-3.5, respectively p=0.0167). The median LDL cholesterol and HDL cholesterol did not change. Higher proportions of small density LDL species were seen during pregnancy compared to after pregnancy. The distribution of the LDL species during pregnancy and 6 weeks post-partum were significantly different p<0.0001 with the smaller species being much higher during pregnancy. Conclusion: ApoE4 genotype was associated with increased total cholesterol and LDL cholesterol concentrations during pregnancy. Pregnancy results in a reversible remodeling of LDL to smaller species, the significance of which is unknown but may indicate a predisposition to atherosclerosis

Gestation-specific reference intervals for comprehensive spot urinary steroid hormone metabolite analysis in normal singleton pregnancy and 6 weeks postpartum

BACKGROUND: Normal pregnancy depends on pronounced adaptations in steroid hormone concentrations. Although in recent years, the understanding of these hormones in pregnancy has improved, the interpretation is hampered by insufficient reference values. Our aim was to establish gestation-specific reference intervals for spot urinary steroid hormone levels in normal singleton pregnancies and 6 weeks postpartum. METHODS: Cross-sectional multicentre observational study. Women recruited between 2008 and 2013 at 3 University Hospitals in Switzerland (Bern), Scotland (Glasgow) and Austria (Graz). Spot urine was collected from healthy women undergoing a normal pregnancy (age, 16-45 years; mean, 31 years) attending routine antenatal clinics at gestation weeks 11, 20, and 28 and approximately 6 weeks postpartum. Urine steroid hormone levels were analysed using gas-chromatography mass spectrometry. Creatinine was also measured by routine analysis and used for normalisation. RESULTS: From the results, a reference interval was calculated for each hormone metabolite at each trimester and 6 weeks postpartum. Changes in these concentrations between trimesters and postpartum were also observed for several steroid hormones and followed changes proposed for index steroid hormones. CONCLUSIONS: Normal gestation-specific reference values for spot urinary steroid hormones throughout pregnancy and early postpartum are now available to facilitate clinical management and research approaches to steroid hormone metabolism in pregnancy and the early postpartum period.

Effects of eNOS polymorphisms on nitric oxide formation in healthy pregnancy and in pre-eclampsia

Pre-eclampsia (PE) is associated with decreased nitric oxide (NO) formation. However, no previous study has examined whether genetic variations in the endothelial NO synthase (eNOS) affect this alteration. We hypothesized that PE decreases NO formation depending on eNOS polymorphisms. We examined how three eNOS polymorphisms [T-786C, rs2070744; Glu298Asp, rs1799983; 27 bp variable number of tandem repeats (VNTR) in intron 4] affect plasma nitrite concentrations in 205 pregnant women [107 healthy pregnant (HP) and 98 PE]. Genotypes were determined and eNOS haplotypes were inferred using the PHASE 2.1 program. The plasma nitrite concentrations were determined using an ozone-based chemiluminescence assay. The Glu298Asp polymorphism had no effects on the plasma nitrite concentrations. Higher nitrite levels were found in HP women with the CC versus TT genotype for the T-786C polymorphism (277.9 +/- 19.5 versus 140.6 +/- 8.2 nM; P < 0.05). Lower nitrite levels were found in healthy women with the 4a4a versus 4b4b genotype for the VNTR polymorphism (95.1 +/- 3.3 versus 216.1 +/- 16.8 nM; P < 0.05). No effects of genotypes were found in PE women (all P > 0.05). The `C Glu b` haplotype was more frequent in the HP group than in the PE group (20 versus 5; P = 0.0044). This haplotype was associated with higher nitrite concentrations than the other haplotypes in healthy pregnancies (P < 0.05). No differences in nitrite concentrations were found among PE women with different eNOS haplotypes (P > 0.05). These findings indicate that eNOS polymorphisms affect endogenous NO formation in normal pregnancy, but not in PE, and that the `C Glu b` haplotype may protect against the development of PE by increasing endogenous NO formation.

Incretin receptor null mice reveal key role of GLP-1 but not GIP in pancreatic beta cell adaptation to pregnancy.

Islet adaptations to pregnancy were explored in C57BL6/J mice lacking functional receptors for glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). Pregnant wild type mice and GIPRKO mice exhibited marked increases in islet and beta cell area, numbers of medium/large sized islets, with positive effects on Ki67/Tunel ratio favouring beta cell growth and enhanced pancreatic insulin content. Alpha cell area and glucagon content were unchanged but prohormone convertases PC2 and PC1/3 together with significant amounts of GLP-1 and GIP were detected in alpha cells. Knockout of GLP-1R abolished these islet adaptations and paradoxically decreased pancreatic insulin, GLP-1 and GIP. This was associated with abolition of normal pregnancy-induced increases in plasma GIP, L-cell numbers, and intestinal GIP and GLP-1 stores. These data indicate that GLP-1 but not GIP is a key mediator of beta cell mass expansion and related adaptations in pregnancy, triggered in part by generation of intra-islet GLP-1.

Assessment of embryo/fetus during pregnancy by threedimensional ultrasonography using the HD live software: iconographic essay

Fetal development is studied since the advent of two-dimensional ultrasonography. However, a detailed assessment of structures and surfaces improved with three-dimensional ultrasonography. Currently, it is possible to identify embryonic components and fetal parts with greater detail, at all pregnancy trimesters, using the HD live software, where the images gain realistic features by means of appropriate control of lighting and shadowing effects. In the present study, the authors utilized this resource to follow-up, by means of images, the development of a normal pregnancy along all trimesters.

Enhanced expression of Ang-(1-7) during pregnancy

Pregnancy is a physiological condition characterized by a progressive increase of the different components of the renin-angiotensin system (RAS). The physiological consequences of the stimulated RAS in normal pregnancy are incompletely understood, and even less understood is the question of how this system may be altered and contribute to the hypertensive disorders of pregnancy. Findings from our group have provided novel insights into how the RAS may contribute to the physiological condition of pregnancy by showing that pregnancy increases the expression of both the vasodilator heptapeptide of the RAS, angiotensin-(1-7) [Ang-(1-7)], and of a newly cloned angiotensin converting enzyme (ACE) homolog, ACE2, that shows high catalytic efficiency for Ang II metabolism to Ang-(1-7). The discovery of ACE2 adds a new dimension to the complexity of the RAS by providing a new arm that may counter-regulate the activity of the vasoconstrictor component, while amplifying the vasodilator component. The studies reviewed in this article demonstrate that Ang-(1-7) increases in plasma and urine of normal pregnant women. In preeclamptic subjects we showed that plasma Ang-(1-7) was suppressed as compared to the levels found in normal pregnancy. In addition, kidney and urinary levels of Ang-(1-7) were increased in pregnant rats coinciding with the enhanced detection and expression of ACE2. These findings support the concept that in normal pregnancy enhanced ACE2 may counteract the elevation in tissue and circulating Ang II by increasing the rate of conversion to Ang-(1-7). These findings provide a basis for the physiological role of Ang-(1-7) and ACE2 during pregnancy.

Síndrome metabólica e fatores associados: estudo comparativo com mulheres que apresentaram pré-eclâmpsia e gravidez normal, acompanhadas cinco anos após o parto

Preeclampsia is defined as an extremely serious complication of the pregnancy-puerperium cycle with delayed emergence of cardiovascular risk factors, including metabolic syndrome. The research aimed estimate the prevalences of metabolic syndrome and associated factors in women with preeclampsia and normal pregnancy followed five years after childbirth. This is a cross-sectional observational study using a quantitative approach, conducted at a maternity school in the city of Natal in Rio Grande do Norte state. The sample was composed of 70 women with previous preeclampsia and 75 normal selected by simple random probability sampling. Subjects were analyzed for sociodemographic, obstetric, clinical, anthropometric and biochemical parameters. International Diabetes Federation criteria were adopted to diagnose metabol ic syndrome. The Kolmogorov-Smirnov, Mann-Whitney, Student s t, Pearson s chi-squared, and Fisher s exact tests, in addition to simple logistic regression, were used for data analysis, at a 5% significance level (p ≤ 0.05). Statistical tests demonstrated elevated body mass index (p = 0.001), predominance of family history of diabetes mellitus (p = 0.022) and significantly higher prevalence of metabolic syndrome in the preeclampsia group (37.1%) when compared to normal (22.7%) (p = 0.042). Intergroup comparison showed a high number of metabolic syndrome components in women with previous preeclampsia. Altered systolic and diastolic blood pressure (p < 0.001) was the most prevalent, followed by low concentrations of high-density lipoproteins (p = 0.049), and hyperglycemia (p=0.030). There was a predominance of the metabolic syndrome in women with schooling 0-9 years (42.4%) (p = 0.005), body mass index above 30Kg.m 2 (52.3%) (p < 0.001), uric acid high (62.5%) (p = 0.050 and family history of hypertension (38.5%) (p< 0.001). Multivariate analysis of the data showed that the body mass index above 30 kg.m2, education level less than 10 years of study (p < 0.001) and family history of hypertension (p = 0.002) remained associated with the metabolic syndrome after multivariate analysis of the data. It is considered Women with previous preeclampsia exhibited high prevalence of metabolic syndrome and their individual components in relation to normal, especially, altered systolic and diastolic blood pressure, low concentrations of high-density lipoproteins and hyperglycemia. The factors associated to this ou tcome were obesity, less than 10 years of schooling, and family history of hypertension. Overall, this study identified young women with a history of PE exposed to a higher cardiovascular risk than normal

Developmental aspects of early pregnancy in mares

In mares, the embryo migrates to the uterus between days 5 and 6 postovulation beginning its mobility through all uterine segments, which is essential for the maternal recognition of pregnancy. During the mobility phase, the embryonic vesicle shows a linear growth rate until its fixation between days 15 and 17, when the orientation phenomenon occurs. From fixation to day 28 of pregnancy, the embryonic growth is less evident (plateau) by cross-section ultrasound examination. After this period the linear growth rate is reestablished until day 46. This plateau is attributed to the increased uterine tone that compresses the vesicle and to volume expansion, making it difficult to detect the conceptus growth only by the cross-section diameter. Around day 20, the embryo proper is visualized as an echogenic spot in the ventral aspect of the vesicle. Additionally, development of allantoic sac, embryonic heartbeat, yolk sac regression and posterior umbilical cord formation also can be visualized from days 20 to 40. An intimate interaction between uterus and conceptus is essential for the normal pregnancy development. Color-and spectral-Doppler ultrasonography can be useful for the evaluation of this interface. A gradual increase on uterine vascularity during the early pregnancy and transient changes in endometrial vascularity accompanying the vesicle location during the mobility phase have been described. Around day 38 of gestation, the formation of the endometrial cups begins and, consequently, the synthesis of the equine chorionic gonadotropin (eCG) induces the formation and development of supplementary corpora lutea, which are important to secrete progesterone and to maintain pregnancy until around day 120.

Prospective study of fetal DNA in serum and disease activity during pregnancy in women with inflammatory arthritis

OBJECTIVE: Rheumatoid arthritis (RA) usually improves during pregnancy and recurs postpartum. Fetal cells and cell-free DNA reach the maternal circulation during normal pregnancy. The present study investigated dynamic changes in levels of fetal DNA in serum from women with RA and inflammatory arthritis during and after pregnancy to test the hypothesis that the levels of circulating fetal DNA correlate with arthritis improvement. METHODS: Twenty-five pregnant patients were prospectively studied. A real-time quantitative polymerase chain reaction panel targeting unshared, paternally transmitted HLA sequences, a Y chromosome-specific sequence, or an insertion sequence within the glutathione S-transferase M1 gene was used to measure cell-free fetal DNA. Results were expressed as fetal genomic equivalents per milliliter (gE/ml) of maternal serum. Physical examinations were conducted during and after pregnancy. RESULTS: Levels of fetal DNA in women with improvement in or remission of arthritis were higher than those in women with active disease, especially in the third trimester. Overall, an inverse relationship between serum fetal DNA levels and disease activity was observed (P < 0.001). Serum fetal DNA increased with advancing gestation, reaching median levels of 24 gE/ml (range 0-334), 61 gE/ml (range 0-689), and 199 gE/ml (range 0-2,576) in the first, second, and third trimesters, respectively, with fetal DNA clearance observed postpartum. Arthritis improvement was initially noted in the first trimester for most patients, increased further or was sustained with advancing gestation, and was active postpartum. CONCLUSION: Changes in serum fetal DNA levels correlated with arthritis improvement during pregnancy and recurrence postpartum. Immunologic mechanisms by which pregnancy might modulate RA activity are described.

High aldosterone-to-renin variants of CYP11B2 and pregnancy outcome

BACKGROUND: Increased aldosterone concentrations and volume expansion of normal pregnancies are hallmarks of normal pregnancies and blunted in pre-eclampsia. Accordingly, we hypothesized an active mineralocorticoid system to protect from pre-eclampsia. METHODS: In pregnant women (normotensive n = 44; pre-eclamptic n = 48), blood pressure, urinary tetrahydro-aldosterone excretion and activating polymorphisms (SF-1 site and intron 2) of the aldosterone synthase gene (CYP11B2) were determined; 185 non-pregnant normotensive individuals served as control. Amino acid-changing polymorphisms of the DNA- and agonist-binding regions of the mineralocorticoid receptor were evaluated by RT-PCR, SSCP and sequencing. RESULTS: Urinary tetrahydro-aldosterone excretion was reduced in pre-eclampsia as compared to normal pregnancy (P < 0.05). It inversely correlated with blood pressure (r = 0.99, P < 0.04). Homozygosity for activating CYP11B2 polymorphisms was preferably present in normotensive as compared to pre-eclamptic pregnancies, identified (intron 2, P = 0.005; SF-1 site, P = 0.016). Two mutant haplotypes decreased the risk of developing pre-eclampsia (RR 0.16; CI 0.05-0.54; P < 0.001). In contrast, intron 2 wild type predisposed to pre-eclampsia (P < 0.0015). No functional mineralocorticoid receptor mutant has been observed. CONCLUSIONS: High aldosterone availability is associated with lower maternal blood pressure. In line with this observation, gain-of-function variants of the CYP11B2 reduce the risk of developing pre-eclampsia. Mutants of the mineralocorticoid receptor cannot explain the frequent syndrome of pre-eclampsia.