scholarly journals The Gestational Effects of Maternal Appetite Axis Molecules on Fetal Growth, Metabolism and Long-Term Metabolic Health: A Systematic Review

2022 ◽  
Vol 23 (2) ◽  
pp. 695
Author(s):  
Angelos Dimas ◽  
Anastasia Politi ◽  
George Papaioannou ◽  
Thomas M. Barber ◽  
Martin O. Weickert ◽  
...  

Increased maternal food intake is considered a normal pregnancy adjustment. However, the overavailability of nutrients may lead to dysregulated fetal development and increased adiposity, with long-lasting effects on offspring in later life. Several gut-hormone molecules regulate maternal appetite, with both their orexigenic and anorectic effects being in a state of sensitive equilibrium. The aim of this manuscript is to systematically review literature on the effects of maternal gut-hormone molecules on fetal growth and metabolism, birth weight and the later metabolic health of offspring. Maternal serum ghrelin, leptin, IGF-1 and GLP-1 appear to influence fetal growth; however, a lack of consistent and strong correlations of maternal appetite axis hormones with birth weight and the concomitant correlation with fetal and birth waist circumference may suggest that these molecules primarily mediate fetal energy deposition mechanisms, preparing the fetus for survival after birth. Dysregulated intrauterine environments seem to have detrimental, sex-dependent effects on fetal energy stores, affecting not only fetal growth, fat mass deposition and birth weight, but also future metabolic and endocrine wellbeing of offspring.

2020 ◽  
Vol 29 (R1) ◽  
pp. R66-R72
Author(s):  
Diana L Cousminer ◽  
Rachel M Freathy

Abstract In recent years, genome-wide association studies have shed light on the genetics of early growth and its links with later-life health outcomes. Large-scale datasets and meta-analyses, combined with recently developed analytical methods, have enabled dissection of the maternal and fetal genetic contributions to variation in birth weight. Additionally, longitudinal approaches have shown differences between the genetic contributions to infant, childhood and adult adiposity. In contrast, studies of adult height loci have shown strong associations with early body length and childhood height. Early growth-associated loci provide useful tools for causal analyses: Mendelian randomization (MR) studies have provided evidence that early BMI and height are causally related to a number of adult health outcomes. We advise caution in the design and interpretation of MR studies of birth weight investigating effects of fetal growth on later-life cardiometabolic disease because birth weight is only a crude indicator of fetal growth, and the choice of genetic instrument (maternal or fetal) will greatly influence the interpretation of the results. Most genetic studies of early growth have to date centered on European-ancestry participants and outcomes measured at a single time-point, so key priorities for future studies of early growth genetics are aggregation of large samples of diverse ancestries and longitudinal studies of growth trajectories.


2012 ◽  
Vol 72 (12) ◽  
pp. 1995-2001 ◽  
Author(s):  
Florentien D O de Steenwinkel ◽  
Anita C S Hokken-Koelega ◽  
Yaël A de Man ◽  
Y B de Rijke ◽  
Maria A J de Ridder ◽  
...  

BackgroundHigh rheumatoid arthritis (RA) disease activity during pregnancy is associated with a lower birth weight. Active RA is characterised by high circulating levels of cytokines, which can mediate placental growth and remodelling.ObjectivesTo assess the influence of maternal serum cytokine levels on birth weight in RA pregnancy.MethodsThis study is embedded in the PARA Study, a prospective study on RA and pregnancy. In the present study, 161 pregnant women with RA and 32 healthy pregnant women were studied. The main outcome measures were birth weight SD score (birth weight SDS) in relation to maternal serum levels of interleukin-10 (IL-10), interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα) at three different time points: preconception and during the first and third trimester. Single-nucleotide polymorphisms (SNPs) in the corresponding cytokine genes were also studied.ResultsDuring the first trimester, IL-10 was detectable in 16% of patients with RA, IL-6 in 71%, and TNFα in all patients with RA. Mean birth weight SDS of children born to mothers with RA was higher when IL-10 level was high compared with low (difference=0.75; p=0.04), and lower when IL-6 was high compared with low (difference=0.50; p<0.01) in the first trimester. No correlation was seen at the other time points studied or with TNFα. Cytokine levels were not related to their corresponding SNPs.ConclusionsMaternal IL-10 and IL-6 levels are associated with fetal growth in RA. In the first trimester, high IL-10 levels are associated with higher birth weight SDS, and high IL-6 levels are associated with lower birth weight SDS, even after correction for disease activity.


2019 ◽  
Vol 20 (10) ◽  
pp. 2398 ◽  
Author(s):  
Jolanta Patro-Małysza ◽  
Marcin Trojnar ◽  
Katarzyna E. Skórzyńska-Dziduszko ◽  
Żaneta Kimber-Trojnar ◽  
Dorota Darmochwał-Kolarz ◽  
...  

Two-thirds of pregnant women exceed gestational weight gain recommendations. Excessive gestational weight gain (EGWG) appears to be associated with offspring’s complications induced by mechanisms that are still unclear. The aim of this study was to investigate whether umbilical cord leptin (UCL) and ghrelin (UCG) concentrations are altered in full-term neonates born to EGWG mothers and whether neonatal anthropometric measurements correlate with UCL and UCG levels and maternal serum ghrelin and leptin as well as urine ghrelin concentrations. The study subjects were divided into two groups, 28 healthy controls and 38 patients with EGWG. Lower UCL and UCG levels were observed in neonates born to healthy mothers but only in male newborns. In the control group UCG concentrations correlated positively with neonatal birth weight, body length and head circumference. In the control group maternal serum ghrelin levels correlated negatively with neonatal birth weight, body length and head circumference as well as positively with chest circumference. In the EGWG group UCG concentrations correlated negatively with neonatal birth weight and birth body length. UCL correlated positively with birth body length in EGWG group and negatively with head circumference in the control group. In conclusion, EGWG is associated with disturbances in UCL and UCG concentrations.


Obesity Facts ◽  
2021 ◽  
pp. 1-8
Author(s):  
Małgorzata Stefaniak ◽  
Ewa Dmoch-Gajzlerska

<b><i>Introduction:</i></b> Leptin is a polypeptide hormone, and in pregnancy, it is secreted by the placenta and maternal and fetal adipose tissues. Normal leptin production is a factor responsible for uncomplicated gestation, embryo development, and fetal growth. The study compared maternal serum and cord blood leptin concentrations at delivery in normal pregnancies and in pregnancies complicated by intrauterine growth restriction (IUGR). <b><i>Methods:</i></b> The study was performed in 25 pregnant women with isolated IUGR and in 194 pregnant women without any complications. Leptin concentrations in maternal serum and in cord blood samples collected at delivery were measured by ELISA and subsequently analyzed by maternal body mass index (BMI), mode of delivery, and infant gender and birth weight. For comparative analyses of normally distributed variables, parametric tests were used, that is, the Student <i>t</i> test and a one-way ANOVA. The nonparametric Mann-Whitney test was used when the distribution was not normal. The Pearson correlation coefficient was calculated to assess the correlation between normally distributed variables (<i>p</i> &#x3c; 0.05). <b><i>Results:</i></b> In pregnancies complicated by IUGR, the mean maternal serum leptin concentration at delivery was significantly higher (52.73 ± 30.49 ng/mL) than in normal pregnancies (37.17 ± 28.07 ng/mL) (<i>p</i> = 0.01). The mean cord blood leptin concentration in pregnancies complicated by IUGR was 7.97 ± 4.46 ng/mL and significantly lower than in normal pregnancies (14.78 ± 15.97 ng/mL) (<i>p</i> = 0.04). In normal pregnancies, but not in pregnancies complicated by IUGR, a statistically significant correlation was established between maternal serum leptin concentrations and maternal BMI at delivery (<i>r</i> = 0.22; <i>p</i> = 0.00). No statistically significant correlation was found between cord blood leptin concentrations and maternal BMI in either study subjects or controls. In normal pregnancies, but not in pregnancies complicated by IUGR, a strong correlation was observed between cord blood leptin concentrations and birth weight (<i>r</i> = 0.23; <i>p</i> = 0.00). <b><i>Conclusions:</i></b> Elevated maternal blood leptin concentrations in pregnancies complicated by IUGR may indicate a significant adverse effect of elevated leptin on fetal growth. The differences in leptin concentrations, measured in maternal serum and in cord blood, between the study subjects and controls suggest that deregulated leptin levels may increase the risk of obstetric complications associated with placental insufficiency.


Author(s):  
Yusuf Abisowo Oshodi ◽  
Kabiru Afolarin Rabiu ◽  
Agbara Joy Onyinyechi ◽  
Akinlusi Fatimat Motunrayo ◽  
Kuye Olufunmilayo Taiwo ◽  
...  

Background: Adipocytokines have been recently implicated in the pathogenesis of preeclampsia. Visfatin is one of such adipokines. Objective: To determine the association between serum visfatin levels and preeclampsia. Methods: A prospective, case-control study was carried out in 160 pregnant women consisting of 80 pre-eclamptics and 80 normotensive controls, matched for age and parity during the third trimester. Maternal serum visfatin levels were determined in both groups using a visfatin (Human) enzyme- linked immunosorbent assay. Serum Visfatin levels were compared between the groups and correlated to the blood pressure, proteinuria, fetal birth weight and Apgar scores. Results: The mean serum visfatin level was significantly higher (10.3±6.9 ng/ml) in preeclampsia than (7.4±4.4 ng/ml) in the control group (p=0.001). The mean serum visfatin level was higher in severe pre-eclamptics (10.8±8.9 ng/ml) compared to (9.6±5.8ng/ml) in mild preeclamptics and this was statistically significant (p=0.021). Visfatin levels showed a negative and non-significant correlation with both systolic (r= -0.011 and p=0.924), diastolic blood pressure (r= -0.012, p=0.913) and body mass index (r= -0.142, p=0.209) in both study and control groups. Mean birth weight was significantly lower in the preeclampsia (2.8±0.25 kg) compared to the control group (3.2±0.31 kg) P=0.000. the mean birth weight was lower in severe preeclampsia (2.7±0.25 kg compared to 2.9±0.39 in mild preeclamsia. There was no significant correlation between the visfatin levels and Apgar score at 5minutes and birth weights in both groups (P=>0.05). Conclusion: This study showed a significant increase in the level of visfatin in preeclampsia compared to their normo-tensive controls. However, this increased level was not consistent with the severity of the disease.


2020 ◽  
Author(s):  
Marisol Castillo-Castrejon ◽  
Ivana V Yang ◽  
Elizabeth J Davidson ◽  
Sarah J Borengasser ◽  
Purevsuren Jambal ◽  
...  

ABSTRACT Background Preconceptional maternal small-quantity lipid-based nutrient supplementation (SQLNS) improved intrauterine linear growth in low-resource countries as demonstrated by the Women First Preconception Maternal Nutrition Trial (WF). Fetal growth is dependent on nutrient availability and regulated by insulin-like growth factor 1 (IGF-1) through changes in placental transfer capacity, mediated by the mechanistic target of rapamycin (mTOR) pathway. Objectives Our objective was to evaluate the role of placental mTOR and IGF-1 signaling on fetal growth in women from 2 low-resource countries with high rates of stunting after they received preconceptional SQLNS. Methods We studied 48 women from preconception through delivery who were from Guatemala and Pakistan and received SQLNS or not, as part of the WF study. Placental samples were obtained at delivery (control, n = 24; SQLNS, n = 24). Placental protein or mRNA expression of eukaryotic translation initiation factor binding protein-1 (4E-BP1), ribosomal protein S6 (rpS6), AMP-activated protein kinase α (AMPKA), IGF-1, insulin-like growth factor receptor (IGF-1R), and pregnancy associated plasma protein (PAPP)-A, and DNA methylation of the IGF1 promoter were determined. Maternal serum IGF-1, insulin-like growth factor binding protein (IGFBP)-3, IGFBP-4, IGFBP-5, PAPP-A, PAPP-A2, and zinc were measured. Results Mean ± SEM maternal prepregnancy BMI differed between participants in Guatemala (26.5 ± 1.3) and Pakistan (19.8 ± 0.7) (P &lt; 0.001). In Pakistani participants, SQLNS increased the placental rpS6(T37/46):rpS6 ratio (1.5-fold) and decreased the AMPKA(T172):AMPKA ratio. Placental IGF1 mRNA expression was positively correlated with birth length and birth weight z-scores. Placental PAPP-A (30-fold) and maternal serum zinc (1.2-fold) increased with SQLNS. In Guatemalan participants SQLNS did not influence placental mTOR signaling. Placental IGF-1R protein expression was positively associated with birth length and birth weight z-scores. SQLNS increased placental PAPP-A (40-fold) and maternal serum IGFBP-4 (1.6-fold). Conclusions In Pakistani pregnant women with poor nutritional status, preconceptional SQLNS activated placental mTOR and IGF-1 signaling and was associated with improved fetal growth. In contrast, in Guatemalan women SQLNS did not activate placental nutrient-sensing pathways. In populations experiencing childhood stunting, preconceptional SQLNS improves placental function and fetal growth only in the context of poor maternal nutrition. This trial was registered at clinicaltrials.gov as NCT01883193.


2018 ◽  
Vol 45 (2) ◽  
pp. 614-624 ◽  
Author(s):  
Yong-Ping Lu ◽  
Christoph Reichetzeder ◽  
Cornelia Prehn ◽  
Liang-Hong Yin ◽  
Chen Yun ◽  
...  

Background/Aims: Impaired birth outcomes, like low birth weight, have consistently been associated with increased disease susceptibility to hypertension in later life. Alterations in the maternal or fetal metabolism might impact on fetal growth and influence birth outcomes. Discerning associations between the maternal and fetal metabolome and surrogate parameters of fetal growth could give new insight into the complex relationship between intrauterine conditions, birth outcomes, and later life disease susceptibility. Methods: Using flow injection tandem mass spectrometry, targeted metabolomics was performed in serum samples obtained from 226 mother/child pairs at delivery. Associations between neonatal birth weight and concentrations of 163 maternal and fetal metabolites were analyzed. Results: After FDR adjustment using the Benjamini-Hochberg procedure lysophosphatidylcholines (LPC) 14: 0, 16: 1, and 18: 1 were strongly positively correlated with birth weight. In a stepwise linear regression model corrected for established confounding factors of birth weight, LPC 16: 1 showed the strongest independent association with birth weight (CI: 93.63 - 168.94; P = 6.94×10-11 ). The association with birth weight was stronger than classical confounding factors such as offspring sex (CI: -258.81- -61.32; P = 0.002) and maternal smoking during pregnancy (CI: -298.74 - -29.51; P = 0.017). Conclusions: After correction for multiple testing and adjustment for potential confounders, LPC 16: 1 showed a very strong and independent association with birth weight. The underlying molecular mechanisms linking fetal LPCs with birth weight need to be addressed in future studies.


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