Altered placental iron transport and putative ferroptosis pathways in pregnancies with excessive gestational weight gain: A prospective cohort study.
Excessive gestational weight gain (GWG) is associated with various adverse pregnancy outcomes, including disruption of placental function and fetal development. Iron transport through the placenta is crucial for fetal growth, and transferrin receptor 2 (TfR2) plays a key role in iron homeostasis. However, the effect of excessive GWG on placental TfR2 expression and neonatal iron parameters remains unclear. This study aimed to investigate the effect of excessive GWG on placental TfR2 expression and its association with neonatal iron levels, including cord blood serum iron levels and total iron-binding capacity. A prospective study was conducted with 90 pregnant women divided into 2 groups: 45 with normal weight gain and 45 with excessive GWG. Placental TfR2 expression was assessed via immunohistochemistry, whereas neonatal iron parameters were analyzed in umbilical cord blood using biochemical assays. Additionally, in silico analyses were performed to explore the molecular pathways linking TfR2 expression and iron homeostasis. Placental TfR2 expression was significantly increased in the excessive GWG group compared to controls, with high immunoreactivity observed in the trophoblastic layer, capillaries, and villous connective tissue. Neonates from mothers with excessive GWG had significantly higher cord blood serum iron levels (P = .025) and lower total iron-binding capacity levels (P = .017). Bioinformatics analysis revealed that TfR2 is involved in iron homeostasis regulation, and ferroptosis emerged as a potentially relevant pathway. Excessive GWG may be associated with altered placental iron transport and increased TfR2 expression, which could contribute to iron overload and involvement of ferroptosis-related pathways. However, the lack of direct ferroptosis markers such as GPX4, ACSL4, reactive oxygen species levels, or cell-death assays limits mechanistic confirmation. Further studies are required to validate the role of ferroptosis in this context.
119
- 10.3390/ijms20133283
- Jul 4, 2019
- International journal of molecular sciences
39
- 10.1016/j.fertnstert.2022.08.014
- Sep 6, 2022
- Fertility and Sterility
7
- 10.1016/j.bpobgyn.2023.102407
- Aug 23, 2023
- Best Practice & Research Clinical Obstetrics & Gynaecology
22
- 10.1016/j.earlhumdev.2011.12.030
- Feb 18, 2012
- Early Human Development
2709
- 10.1038/s41422-020-00441-1
- Dec 2, 2020
- Cell Research
41
- 10.1186/s12943-024-01999-9
- May 3, 2024
- Molecular cancer
48
- 10.1111/apha.13795
- Feb 15, 2022
- Acta Physiologica
47
- 10.1111/bjh.14194
- Jul 21, 2016
- British Journal of Haematology
5
- 10.1089/omi.2024.0061
- May 1, 2024
- Omics : a journal of integrative biology
3
- 10.1186/s12903-024-04413-4
- Jul 12, 2024
- BMC Oral Health
- Research Article
335
- 10.1074/jbc.c600197200
- Sep 1, 2006
- The Journal of biological chemistry
HFE and transferrin receptor 2 (TFR2) are membrane proteins integral to mammalian iron homeostasis and associated with human hereditary hemochromatosis. Here we demonstrate that HFE and TFR2 interact in cells, that this interaction is not abrogated by disease-associated mutations of HFE and TFR2, and that TFR2 competes with TFR1 for binding to HFE. We propose a new model for the mechanism of iron status sensing that results in the regulation of iron homeostasis.
- Abstract
- 10.1016/j.ajog.2012.10.401
- Dec 27, 2012
- American Journal of Obstetrics and Gynecology
236: Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) expression in adipose tissue of women with excessive versus normal gestational weight gain during pregnancy
- Research Article
20
- 10.1038/jp.2014.22
- Feb 27, 2014
- Journal of Perinatology
To assess the prognostic validity of the Institute of Medicine/National Research Council (IOM/NRC) week-specific cutoff values for inadequate or excessive total gestational weight gain (GWG) by 4-week intervals. We merged data from two German cohorts (LMU cohort (all maternal-weight categories) and PEACHES cohort (obese women)) to provide information on GWG for 749 women (365 normal weight, 199 overweight and 185 obese). We calculated the prognostic values for suboptimal and excessive GWG according to the IOM/NRC cutoff values. The positive predictive values for excessive total GWG for those who experienced excessive GWG early in pregnancy was 70.1% (95% confidence interval (CI) 60.5; 78.6) as of week 12/1 to 16/0 in normal-weight women, 89.5% (95% CI 75.2; 97.1) and 95.2 (76.2; 99.9) 95.2% (95% CI 76.2; 99.9) as of week 8/1 to 12/0 for overweight and obese women, respectively. In absence of excessive GWG as of week 12/1 to 16/0, normal-weight women had 77.5% (95% CI 77.1; 83.1) probability of not experiencing excessive total GWG (negative predictive value). In overweight and obese women, the negative predictive value was considerably lower up to week 24/1 to 28/0 (60.0% (95% CI 48.8; 70.5) in week 20/1 to 24/0 and 50.6% (95% CI 39.3; 61.9) in week 24/1 to 28/0). Most women with inadequate GWG in the first and second trimester had adequate total final GWG (positive predictive value for total inadequate GWG <50% up to week 16/1 to 20/0 in all groups). As women with excessive weight gain can be identified with high confidence if the GWG exceeds the IOM/NRC week-specific cutoff values, interventions may be initiated early in pregnancy.
- Research Article
51
- 10.1111/j.1552-6909.2009.01036.x
- Jul 1, 2009
- Journal of Obstetric, Gynecologic & Neonatal Nursing
Risk Factors for Excessive or Inadequate Gestational Weight Gain Among Hispanic Women in a U.S.-Mexico Border State
- Research Article
7
- 10.1097/md.0000000000016414
- Jul 1, 2019
- Medicine
The gestational weight gain is determined by food habits, environmental and genetic factors.The aims of this paper were to establish relationships between maternal gene polymorphisms (patatin-like phospholipase domain-containing protein 3 rs738409 [PNPLA3 rs738409], glucokinase regulatory protein rs780094 [GCKR rs780094], and guanine nucleotide-binding protein rs5443 [GNB3 rs5443]) and mothers’ gestational weight gain, but also neonatal outcomes (birth weight, length, and ponderal index [PI]).We performed a cross-sectional study in a sample of 158 mothers and their product of conception’ in an Obstetrics-Gynecology Clinic from Romania. We divided the pregnant women according to the Institute of Medicine recommendations into 3 subgroups: (1) insufficient gestational weight gain; (2) normal gestational weight gain; and (3) excessive gestational weight gain.The gestational weight gain among pregnant women included in this study was classified as insufficient (10.1%), normal (31%), and excessive (58.9%). We found a tendency towards statistical significance for mothers that were overweight or obese before pregnancy to present an excessive gestational weight gain as compared to the normal weight ones. Similarly, we identified a tendency for statistical significance regarding the association between the variant genotype of GNB3 rs5443 and excessive gestational weight gain. We noticed differences that tended to be statistical significant concerning aspartate aminotransferase values between the 3 subgroups, mothers with excessive gestational weight gain having higher values than mothers with normal gestational weight gain (median, IQR: 22.89[17.53; 31.59] for mothers with excessive gestational weight gain versus 22.71[18.58; 27.37] for mothers with normal gestational weight gain). In mothers with excessive gestational weight gain, we found a significant association between the variant genotype of PNPLA3 rs738409 polymorphism and neonatal PI noticing a decrease of this index in case of newborns from mothers carrying the variant genotype.Excessive gestational weight gain was noticed in pregnant women that were obese and overweight before pregnancy. We found a positive association between the variant genotype of GNB3 rs5443 polymorphism and excessive gestational weight gain. Similarly, the presence of variant genotype of PNPLA3 rs738409 in mothers was associated with a lower PI in their newborns. Our study pointed out the most important factors that influence gestational weight gain and related birth outcomes.
- Research Article
1
- 10.1016/j.jogc.2020.10.022
- Dec 14, 2020
- Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
Does Excess First- or Second-Trimester Weight Gain Predict Excess Total Gestational Weight Gain? A Multicentre Prospective Cohort Study.
- Research Article
- 10.1016/j.jogc.2019.02.185
- Apr 15, 2019
DOES EXCESS FIRST TRIMESTER WEIGHT GAIN PREDICT EXCESS TOTAL GESTATIONAL WEIGHT GAIN?
- Research Article
- 10.1016/j.ajogmf.2023.101247
- Dec 5, 2023
- American journal of obstetrics & gynecology MFM
Severity of excessive gestational weight gain and risk of severe maternal morbidity
- Abstract
1
- 10.1016/j.ajog.2009.10.414
- Dec 1, 2009
- American Journal of Obstetrics and Gynecology
549: Gestational weight gain in consecutive pregnancies
- Research Article
5
- 10.3760/cma.j.cn112338-20210126-00072
- Nov 10, 2021
- Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi
Objective: To explore the effects of maternal pre-pregnancy body mass index (BMI) and gestational weight gain and its subtypes on the risk of preeclampsia. Methods: Pregnant women delivered in the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Shanxi Medical University from March 2012 to September 2016 were selected as the research subjects. According to the inclusion and exclusion criteria, 9 274 pregnant women were included. 901 preeclampsia pregnant women were selected as the case group, and 8 373 non-preeclampsia pregnant women were selected as the control group. General demographic characteristics, pre-pregnancy weight, height, lifestyle during pregnancy, reproductive history, and disease history of pregnant women were collected, and pre-pregnancy BMI and gestational weight gain were calculated. Unconditional logistic regression was used to analyze the relationship between pre-pregnancy BMI and weight gain during pregnancy and PE and its clinical subtypes. Results: Among the 901 preeclampsia after inclusion and exclusion, 401 cases were diagnosed as early-onset PE (EOPE), 500 cases were late-onset PE (LOPE), 178 cases were Mild PE (MPE), and 723 cases were severe PE (SPE). There were statistically significant differences between PE and non-PE pregnant women in terms of maternal age, residence, parity, family history of gestational diabetes and hypertension (P<0.05). After adjusting for the above factors, the logistic regression analysis results showed that pre-pregnancy BMI<18.5 kg/m2 and inadequate gestational weight gain were protective factors for PE (OR=0.74, 95%CI: 0.56-0.98; OR=0.78, 95%CI: 0.62-0.99), while pre-pregnancy BMI≥24.0 kg/m2 and excessive gestational weight gain were risk factors for PE (OR=1.82, 95%CI: 1.54-2.14; OR=1.82, 95%CI: 1.54-2.15). After subtype analysis on PE, the results showed that pre-pregnancy BMI<18.5 kg/m2 was a protective factor for EOPE and MPE (OR=0.52, 95%CI: 0.32-0.83; OR=0.47, 95%CI: 0.23-0.97), while pre-pregnancy BMI≥24.0 kg/m2 and excessive gestational weight gain were risk factors for clinical subtypes of PE. After stratification according to pre-pregnancy BMI, excessive gestational weight gain was the risk factor for PE (OR=1.86, 95%CI: 1.51-2.30; OR=1.90, 95%CI: 1.39-2.60) in pregnant women 18.5 kg/m2≤BMI<24.0 kg/m2 and ≥24.0 kg/m2. Inadequate gestational weight gain (OR=0.55, 95%CI: 0.34-0.89) was a protective factor for PE in pregnant women with pre-pregnancy BMI≥24.0 kg/m2. Excessive gestational weight gain (OR=4.05, 95%CI: 1.20-13.69) was a risk factor for EOPE in pregnant women with pre-pregnancy BMI<18.5 kg/m2. Excessive gestational weight gain was a risk factor for the clinical subtype of PE in pregnant women 18.5 kg/m2≤BMI<24.0 kg/m2 before pregnancy. Inadequate gestational weight gain was a protective factor for EOPE and MPE (OR=0.39, 95%CI: 0.19-0.80; OR=0.29, 95%CI: 0.11-0.77) in pregnant women with pre-pregnancy BMI≥24.0 kg/m2. Excessive weight gain was a risk factor for EOPE, LOPE and SPE (OR=1.60, 95%CI: 1.06-2.42;OR=2.20, 95%CI: 1.44-3.37;OR=2.28, 95%CI: 1.58-3.29). Conclusions: Pre-pregnancy BMI and gestational weight gain affect the risk of preeclampsia and its clinical subtypes. In contrast, the influence of gestational weight gain on preeclampsia varies among different pre-pregnancy BMI groups. Therefore, it is recommended to pay attention to the changes in pre-pregnancy BMI and gestational weight gain simultaneously to reduce preeclampsia.
- Research Article
11
- 10.1055/s-0041-1730363
- Jun 3, 2021
- American Journal of Perinatology
This study aimed to determine whether specific factors of the built environment related to physical activity and diet are associated with inadequate and excessive gestational weight gain (GWG). This analysis is based on data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be, a prospective cohort of nulliparous women who were followed from the beginning of their pregnancies through delivery. At each study visit, home addresses were recorded and geocoded. Locations were linked to several built-environment characteristics such as the census tract National Walkability Score (the 2010 Walkability Index) and the number of gyms, parks, and grocery stores within a 3-km radius of residential address. The primary outcome of GWG (calculated as the difference between prepregnancy weight and weight at delivery) was categorized as inadequate, appropriate, or excessive based on weight gained per week of gestation. Multinomial regression (generalized logit) models evaluated the relationship between each factor in the built environment and excessive or inadequate GWG. Of the 8,182 women in the analytic sample, 5,819 (71.1%) had excessive GWG, 1,426 (17.4%) had appropriate GWG, and 937 (11.5%) had inadequate GWG. For the majority of variables examined, built environments more conducive to physical activity and healthful food availability were associated with a lower odds of excessive or inadequate GWG category. For example, a higher number of gyms or parks within 3 km of a participant's residential address was associated with lower odds of having excessive (gyms: adjusted odds ratio [aOR] = 0.93 [0.89-0.96], parks: 0.94 [0.90-0.98]) or inadequate GWG (gyms: 0.91 [0.86-0.96]; parks: 0.91 [0.86-0.97]). Similarly, a higher number of grocery stores was associated with lower odds of having excessive GWG (0.94 [0.91-0.97]). Among a diverse population of nulliparous women, multiple aspects of the built environment are associated with excessive and inadequate GWG. · There are little data on the association between the built environment and pregnancy outcomes.. · Multiple aspects of the built environment are associated with excessive and inadequate GWG.. · These results suggest the role that neighborhood investment may play in improving pregnancy outcomes..
- Research Article
- 10.1016/j.preghy.2017.07.123
- Jul 1, 2017
- Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health
P 45 Does apolipoprotein B (apo B) level in early pregnancy predict excessive gestational weight gain and adverse pregnancy outcome?
- Research Article
2
- 10.1186/s13098-023-01239-y
- Jan 13, 2024
- Diabetology & Metabolic Syndrome
AimsTo identify the gestational weight gain (GWG) patterns in women with gestational diabetes mellitus (GDM) and evaluate their association with offspring weight status from birth to 40 months.Materials and methodsThis study included 2,723 GDM-mother–child pairs from the Beijing Birth Cohort Study. The association between GWG trajectories identified by the latent class model and offspring weight outcomes from birth to 40 months were evaluated, after adjustment for maternal age, parity, pre-pregnancy body mass index, maternal height, and blood glucose levels.ResultsThree GWG rate groups, including the non-excessive GWG group (1,994/2,732), excessive GWG group (598 /2,732), and excessive early GWG group (140/2,732), were identified in women with GDM, respectively. Compared to the non-excessive GWG group, the adjusted OR (aOR) and 95% CI were 1.83 (1.35–2.47) and 1.79 (1.06–3.01) for macrosomia, 1.33 (1.07–1.66) and 1.48 (1.01–2.17) for large for gestational age (LGA) in the excessive GWG group and excessive early GWG group. Excessive GWG was also associated with an increased risk of BMI-for-age at 40 months (aOR = 1.66, 95% CI 1.14–2.42).ConclusionsBoth excessive GWG and excessive early GWG increased the risk of macrosomia and LGA in women with GDM, but only the excessive GWG was associated with childhood overweight/obesity. The results suggest the long-term impact of GWG on offspring weight status in women with GDM and the potential benefits of GWG restriction after GDM diagnosis.
- Research Article
4
- 10.3390/ijerph17186452
- Sep 1, 2020
- International Journal of Environmental Research and Public Health
There is a dearth of information on the risk of inadequate and excess gestational weight gain (GWG) among different generations of Hispanic women in the United States. Therefore, the objective of this study was to understand the relationship of GWG and immigration across three generations of Hispanic women. The study was conducted using data from National Longitudinal Survey of Youth 1979 (NLSY79). The study sample included 580 (unweighted count) women (148 first-generation, 117 second-generation, and 315 third-/higher-generation). Sociodemographic and immigration data were extracted from the main NLSY79 survey, and pregnancy data were extracted from the child/young adult survey following the biological children born to women in NLSY79. Covariate adjusted weighted logistic regression models were conducted to assess the risk of inadequate and excess GWG among the groups. Average total GWG was 14.98 kg, 23% had inadequate GWG, and 50% had excess GWG. After controlling for the covariates, there was no difference in the risk of inadequate GWG between the three generations. First-generation women (OR = 0.47, p = 0.039) and third-/higher-generation women (OR = 0.39, p = 0.004) had significantly lower risk of excess GWG compared to second-generation women. It is important to recognize the generational status of Hispanic women as a risk factor for excess GWG.
- Research Article
24
- 10.1097/aog.0000000000003234
- May 1, 2019
- Obstetrics & Gynecology
To evaluate whether inadequate or excessive gestational weight gain before the third trimester is associated with adverse pregnancy outcomes, and to evaluate the association of weight gain in the third trimester with fetal growth. This was a retrospective cohort study of all eligible overweight and obese women with singleton pregnancies delivered at an academic institution between 2012 and 2014. Our primary exposure was inadequate or excess gestational weight gain during the first and second trimesters. Outcomes included small- (SGA) or large- (LGA) for-gestational-age birth weight as well adverse maternal outcomes and composite neonatal morbidity. Multivariable logistic regression was used to assess the relationship between weight gain and perinatal outcomes, and stratified analyses evaluated the relationship between third trimester weight gain and birth weight category. Of the 5,814 women, 1,280 (22%) had adequate, 1,428 (24.6%) had inadequate, and 3,106 (53.4%) had excessive weight gain in the first and second trimesters. Women with inadequate early gestational weight gain were more likely to deliver an SGA neonate (adjusted odds ratio [aOR] 1.59, 95% CI 1.23-2.06) and less likely to deliver an LGA neonate (aOR 0.73, 95% CI 0.54-0.98), whereas those with excessive early gestational weight gain were less likely to deliver an SGA neonate (aOR 0.66, 95% CI 0.52-0.85) and more likely to deliver an LGA neonate (aOR 1.66, 95% CI 1.32-2.1). Higher weight gain in the third trimester was associated with increased risk for LGA birth weight, but third trimester weight gain was not related to SGA birth weight. Early gestational weight gain is associated with birth weight category. Modifying weight gain in the third trimester may limit the risk for LGA birth weight, but higher weight gain in late gestation does not alter the association between inadequate early weight gain and the risk for SGA.
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