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Zika virus acquisition during pregnancy is associated with severe fetal damage. The Zika virus is related to dengue virus and yellow fever virus, yet fetal damage has not been related to dengue or inadvertent vaccination for yellow fever during pregnancy.

We investigated whether excessive retroperitoneal adipose tissue (AT) expansion programmed by maternal obesity (MO) affects adipocyte size distribution and gene expression in relation to adipocyte proliferation and differentiation in male and female offspring (F1) from control (F1C) and obese (F1MO) mothers. Female Wistar rats (F0) ate a control or high-fat diet from weaning through pregnancy and lactation. F1 were weaned onto a control diet and euthanized at 110 postnatal days. Fat depots were weighed to estimate the total AT. Serum glucose, triglyceride, leptin, insulin, and the insulin resistance index (HOMA-IR) were determined. Adipocyte size and adipogenic gene expression were examined in retroperitoneal fat. Body weight, retroperitoneal AT and adipogenesis differed between male and female F1Cs. Retroperitoneal AT, glucose, triglyceride, insulin, HOMA-IR and leptin were higher in male and female F1MO vs. F1C. Small adipocytes were reduced in F1MO females and absent in F1MO males; large adipocytes were increased in F1MO males and females vs. F1C. Wnt, PI3K-Akt, and insulin signaling pathways in F1MO males and Egr2 in F1MO females were downregulated vs. F1C. MO induced metabolic dysfunction in F1 through different sex dimorphism mechanisms, including the decreased expression of pro-adipogenic genes and reduced insulin signaling in males and lipid mobilization-related genes in females.

Maternal metabolic status influences pregnancy and, consequently, the perinatal outcome. Resistin is a pro-inflammatory adipokine predominantly expressed and secreted by mononuclear cells, adipose tissue, and placental trophoblastic cells during pregnancy. Recently, we reported an inverse association between maternal resistin levels and fetal low-density lipoprotein cholesterol (LDL-C). Then, in this work, we used a human placental explant model and the trophoblast cell line JEG-3 to evaluate whether resistin affects placental LDL-C uptake. Resistin exposure induced the transcription factor SREBP-2, LDLR, and PCSK9 mRNA expression, and changes at the protein level were confirmed by immunohistochemistry and Western blot. However, for LDLR, the changes were not consistent between mRNA and protein levels. Using a labeled LDL-cholesterol (BODIPY FL LDL), uptake assay demonstrated that the LDL-C was significantly decreased in placental explants exposed to a high dose of resistin and a lesser extent in JEG-3 cells. In summary, resistin induces PCSK9 expression in placental explants and JEG-3 cells, which could be related to negative regulation of the LDLR by lysosomal degradation. These findings suggest that resistin may significantly regulate the LDL-C uptake and transport from the maternal circulation to the fetus, affecting its growth and lipid profile.

Background/Objectives Fat-mass (FM) assessment since birth using valid methodologies is crucial since excessive adiposity represents a risk factor for adverse metabolic outcomes. Aim: To develop infant FM prediction equations using anthropometry and validate them against air-displacement plethysmography (ADP). Subjects/Methods Clinical, anthropometric (weight, length, body-mass index –BMI–, circumferences, and skinfolds), and FM (ADP) data were collected from healthy-term infants at 1 (n = 133), 3 (n = 105), and 6 (n = 101) months enrolled in the OBESO perinatal cohort (Mexico City). FM prediction models were developed in 3 steps: 1) Variable Selection (LASSO regression), 2) Model behavior evaluation (12-fold cross-validation, using Theil-Sen regressions), and 3) Final model evaluation (Bland-Altman plots, Deming regression). Results Relevant variables in the FM prediction models included BMI, circumferences (waist, thigh, and calf), and skinfolds (waist, triceps, subscapular, thigh, and calf). The R2 of each model was 1 M: 0.54, 3 M: 0.69, 6 M: 0.63. Predicted FM showed high correlation values (r ≥ 0.73, p p > 0.05). Bias were: 1 M −0.021 (95%CI: −0.050 to 0.008), 3 M: 0.014 (95%CI: 0.090–0.195), 6 M: 0.108 (95%CI: 0.046–0.169). Conclusion Anthropometry-based prediction equations are inexpensive and represent a more accessible method to estimate body composition. The proposed equations are useful for evaluating FM in Mexican infants.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from −90% to +30%, were reported in many countries following early COVID-19 pandemic response measures (‘lockdowns’). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95–0.98, P value

ObjectiveTo identify and quantify the effects of maternal characteristics and medical history on the distribution of Placental Growth Factor (PlGF), mean arterial pressure (MAP), and Uterine Artery Mean Pulsatility Index (UtA-PI); and to standardize the expected values for these biomarkers in the first trimester to create unique multiples of the median (MoMs) for Latin-American population.MethodsThis is a prospective cohort built exclusively for research purposes of consecutive pregnant women attending their first-trimester screening ultrasound at a primary care center for the general population in Mexico City between April 2019 and October 2021. We excluded fetuses with chromosomal abnormalities, major fetal malformations, and women delivering in another care center. Linear regression was used on log-transformed biomarkers to assess the influence of maternal characteristics on non-preeclamptic women to create MoM.ResultsOf a total of 2,820 pregnant women included in the final analysis, 118 (4.18%) developed PE, of which 22 (0.78%) delivered before 34 weeks of gestation, 74 (2.62%) before 37 weeks, and 44 (1.56%) from 37 weeks gestation. Characteristics that significantly influenced PLGF were fetal crown rump length (CRL), maternal age, nulliparity, body mass index (BMI), chronic hypertension, Lupus, spontaneous pregnancy, polycystic ovary syndrome (PCOS), hypothyroidism, preeclampsia (PE) in a previous pregnancy, and mother with PE. MAP had significant influence from CRL, maternal age, PE in a previous pregnancy, induction of ovulation, a mother with PE, chronic hypertension, BMI, and hypothyroidism. UtA-PI was influenced by CRL, maternal age, a mother with PE, chronic hypertension, and gestational diabetes mellitus (GDM) in a previous pregnancy.ConclusionPopulation-specific multiples of the median (MoMs) for PlGF, MAP, and UtA-PI in the first trimester adequately discriminate among women developing preeclampsia later in pregnancy.

BACKGROUNDZika virus (ZIKV) is highly teratogenic, in contrast with dengue virus (DENV) or the yellow fever virus vaccine (YFV-17D). The mechanisms employed by ZIKV to cross the placenta need to be elucidated.METHODSParallel infections with ZIKV, DENV and YFV-17D were compared in terms of efficiency, activation of mTOR pathways and cytokine secretion profile in human cytotrophoblastic HTR8 cells (CTB), and monocytic U937 cells, differentiated to M2 macrophages (M2-MØ).RESULTSIn CTB, ZIKV replication was significantly more efficient than DENV or YFV-17D. In M2-MØ, ZIKV replication continued to be more efficient, although differences between strains were reduced. Significantly greater activation of Phospho-S6r and Phospho-AKT/Ser473 fractions in CTB infected with ZIKV than with DENV or YFV-17D, was observed. CTB treated with the mTOR inhibitors rapamycin or AZD8055, showed a 20-fold-reduction in ZIKV yield, versus 5 and 3.5-fold for DENV and YFV-17D, respectively. Finally, we detected that ZIKV infection, but not DENV or YFV-17D, efficiently inhibited the interferon response of CTB cells.CONCLUSIONSThese results suggest that CTB cells are permissive and act favoring ZIKV entry into the placental stroma, over DENV and YFV-17D and that the mTOR complex is a switch that enhances the replication of ZIKV in CTB cells.

Evidence from studies in the general population suggests an association between vitamin D insufficiency/deficiency and COVID-19 susceptibility and disease severity. The present study was performed on 165 third-trimester pregnant women at the time of delivery. Seventy-nine women tested negative for SARS-CoV-2. From 86 women testing positive, 32 were asymptomatic, 44 presented a mild form of the disease, and 10 experienced severe symptoms. Serum 25-OH vitamin D levels were measured on blood samples collected on admission. Low vitamin D levels were detected in symptomatic but not asymptomatic COVID-19 patients compared to healthy women (p = 0.0227). In addition, 20 (45.4%) pregnant women in the mild COVID-19 group and 6 (60%) in the severe group were vitamin D deficient (p = 0.030). On the other hand, lasso regression analysis showed that 25-OH vitamin D deficiency is an independent predictor of severe COVID-19 with an odds ratio (OR) of 5.81 (95% CI: 1.108–30.541; p = 0.037). These results show the relationship between vitamin D deficiency in pregnant women and the severity of COVID-19 infection and support the recommendation to supplement with vitamin D to avoid worse COVID-19 outcomes during pregnancy.

BackgroundPreeclampsia (PE) and COVID-19 share a common vascular–endothelial physiopathological pathway that may aggravate or worsen women's outcomes when both coexist. This study aims to evaluate the association of sFlt-1 levels and adverse maternal outcomes among positive SARS-CoV-2 pregnant women with and without hypertensive disorders of pregnancy (HDP).MethodsWe performed a multicenter retrospective cohort study of pregnant women with confirmed SARS-CoV-2 infection that required hospital admission. The exposed cohort comprised women with a diagnosis of an HDP. The primary outcome was a composite definition of adverse maternal outcome. The association between predictors and the main and secondary outcomes was assessed using an elastic-net regression which comprised a Lasso and Ridge regression method for automatic variable selection and penalization of non-statistically significant coefficients using a 10-fold cross-validation where the best model if automatically chosen by the lowest Akaike information criterion (AIC) and Bayesian information criteria (BIC).ResultsAmong 148 pregnant women with COVID-19, the best predictive model comprised sFlt-1 MoMs [odds ratio (OR): 5.13; 95% CI: 2.19–12.05], and HDP (OR: 32.76; 95% CI: 5.24–205). sFlt-1 MoMs were independently associated with an increased probability of an adverse maternal outcome despite adjusting for HDP.ConclusionsOur study shows that sFlt-1 is an independent predictor of adverse outcomes in women with SARS-CoV-2 despite hypertension status.

Pregnancy makes women more susceptible to infectious agents; however, available data on the effect of SARS-CoV-2 on pregnant women are limited. To date, inflammatory responses and changes in serum metal concentration have been reported in COVID-19 patients, but few associations between metal ions and cytokines have been described. The aim of this study was to evaluate correlations between inflammatory markers and serum metal ions in third-trimester pregnant women with varying COVID-19 disease severity. Patients with severe symptoms had increased concentrations of serum magnesium, copper, and calcium ions and decreased concentrations of iron, zinc, and sodium ions. Potassium ions were unaffected. Pro-inflammatory cytokines IL-6, TNF-α, IL-8, IL-1α, anti-inflammatory cytokine IL-4, and the IP-10 chemokine were induced in the severe presentation of COVID-19 during pregnancy. Robust negative correlations between iron/magnesium and zinc/IL-6, and a positive correlation between copper/IP-10 were observed in pregnant women with the severe form of the disease. Thus, coordinated alterations of serum metal ions and inflammatory markers – suggestive of underlying pathophysiological interactions—occur during SARS-CoV-2 infection in pregnancy.

Assess the usefulness of the sFlt-1/PlGF ratio for the differential diagnosis of uncontrolled chronic hypertension vs. superimposed preeclampsia.We performed a cross-sectional study from 2015 to 2017 and 42 women with initial diagnosis of superimposed preeclampsia were enrolled in the emergency room. After a 12 week follow up patients were grouped as superimposed preeclampsia (Group A) and uncontrolled chronic hypertension (Group B) according to the American College of Obstetricians and Gynecologist criteria. A group of 33 healthy women paired by gestational age were included as controls (Group C). Maternal serum levels of sFlt-1 and PlGF were measured at enrollment, and the ratios of the groups were compared.Superimposed preeclampsia vs. uncontrolled chronic hypertension.After follow-up, group distribution was 30 women in Group A, 12 women in Group B, and 25 women in Group C. The sFlt-1/PlGF ratio was higher in women with superimposed preeclampsia than in women with uncontrolled chronic hypertension (215.5 vs. 9.65, p 0.001). The control group displayed lower ratio values (3.66, p 0.001). The sFlt-1 concentration was higher in Group A than in Group B (7564 vs. 1281 pg/mL, p 0.001) and the PlGF level was lower in Group A (34.39 vs. 169 pg/mL, p 0.001).The sFlt-1/PlGF ratio exhibits good performance for the differential diagnosis of superimposed preeclampsia vs. uncontrolled chronic hypertension.

The aim of this study was to examine the efficacy of intensive medical nutrition therapy (MNT) plus metformin in preventing gestational diabetes mellitus (GDM) among high-risk Mexican women. An open-label randomized clinical trial was conducted. Inclusion criteria were pregnant women with three or more GDM risk factors: Latino ethnic group, maternal age >35 years, body mass index >25 kg/m2, insulin resistance, and a history of previous GDM, prediabetes, a macrosomic neonate, polycystic ovarian syndrome, or a first-degree relative with type 2 diabetes. Women before 15 weeks of gestation were assigned to group 1 (n = 45): intensive MNT-plus metformin (850 mg twice/day) or group 2 (n = 45): intensive MNT without metformin. Intensive MNT included individual dietary counseling, with ≤50% of total energy from high carbohydrates. The primary outcome was the GDM incidence according to the International Association of Diabetes Pregnancy Study Groups criteria. There were no significant differences in baseline characteristics and adverse perinatal outcomes between the groups. The GDM incidence was n = 11 (24.4%) in the MNT plus metformin group versus n = 7 (15.5%) in the MNT without metformin group: p = 0.42 (RR: 1.57 [95% CI: 0.67–3.68]). There is no benefit in adding metformin to intensive MNT to prevent GDM among high-risk Mexican women. Clinical trials registration: NCT01675310.

An altered mitochondrial DNA copy number (mtDNAcn) at birth can be a marker of increased disease susceptibility later in life. Gestational exposure to acute stress, such as that derived from the earthquake experienced on 19 September 2017 in Mexico City, could be associated with changes in mtDNAcn at birth. Our study used data from the OBESO (Biochemical and Epigenetic Origins of Overweight and Obesity) perinatal cohort in Mexico City. We compared the mtDNAcn in the umbilical cord blood of 22 infants born before the earthquake, 24 infants whose mothers were pregnant at the time of the earthquake (exposed), and 37 who were conceived after the earthquake (post-earthquake). We quantified mtDNAcn by quantitative real-time polymerase chain reaction normalized with a nuclear gene. We used a linear model adjusted by maternal age, body mass index, socioeconomic status, perceived stress, and pregnancy comorbidities. Compared to non-exposed newborns (mean ± SD mtDNAcn: 0.740 ± 0.161), exposed and post-earthquake newborns (mtDNAcn: 0.899 ± 0.156 and 0.995 ± 0.169, respectively) had increased mtDNAcn, p = 0.001. The findings of this study point at mtDNAcn as a potential biological marker of acute stress and suggest that experiencing an earthquake during pregnancy or before gestation can have programing effects in the unborn child. Long-term follow-up of newborns to women who experience stress prenatally, particularly that derived from a natural disaster, is warranted.

Background For the developing kidney, the prenatal period may represent a critical window of vulnerability to environmental insults resulting in permanent nephron loss. Given that the majority of nephron formation is complete in the 3rd trimester, we set out to test whether 1) prenatal lead exposure is associated with decreased preadolescent kidney function and 2) whether preadolescent obesity acts synergistically with early life lead exposure to reduce kidney function. Methods Our study included 453 mother–child pairs participating in the PROGRESS birth cohort. We assessed prenatal blood lead levels (BLLs) in samples collected in the 2nd and 3rd trimesters and at delivery, as well as tibial and patellar bone lead measures assessed one-month postpartum. Preadolescent estimated glomerular filtration rate (eGFR) was derived from serum levels of creatinine and/or cystatin C measured at age 8–12 years. We applied linear regression to assess the relationship between prenatal bone and BLL with preadolescent eGFR, and adjusted for covariates including age, sex, BMI z-score, indoor tobacco smoke exposure, and socioeconomic status. We also examined sex-specific associations and tested for effect modification by BMI status. Results We observed null associations between prenatal lead exposure and eGFR. However, in interaction analyses we found that among overweight children, there was an inverse association between BLL (assessed at 2nd and 3rd trimester and at delivery) and preadolescent eGFR. For example, among overweight participants, a one ln-unit increase in 2nd trimester BLL was associated with a 10.5 unit decrease in cystatin C-based eGFR (95% CI: −18.1, −2.8; p = 0.008). Regardless of lead exposure, we also observed null relationships between BMI z-score and eGFR overall, as well as among overweight participants. However, among participants with preadolescent obesity, we observed a significant 5.9-unit decrease in eGFR. We observed no evidence of sex-specific effects. Conclusions Our findings, if confirmed in other studies, suggest a complex interplay between the combined adverse effects of adiposity and perinatal lead exposure as they relate to adolescent kidney function. Future studies will assess kidney function and adiposity trajectories through adolescence to better understand environmental risk factors for kidney function decline.

Background: In healthy pregnancies, components of the Renin-Angiotensin system (RAS) are present in the placental villi and contribute to invasion, migration, and angiogenesis. At the same time, soluble fms-like tyrosine kinase 1 (sFlt-1) production is induced after binding of ANG-II to its receptor (AT-1R) in response to hypoxia. As RAS plays an essential role in the pathogenesis of COVID-19, we hypothesized that angiogenic marker (sFlt-1) and RAS components (ANG-II and ACE-2) may be related to adverse outcomes in pregnant women with COVID-19; Methods: Prospective cohort study. Primary outcome was severe pneumonia. Secondary outcomes were ICU admission, intubation, sepsis, and death. Spearman’s Rho test was used to analyze the correlation between sFlt-1 and ANG-II levels. The sFlt-1/ANG-II ratio was determined and the association with each adverse outcome was explored by logistic regression analysis and the prediction was assessed using receiver-operating-curve (ROC); Results: Among 80 pregnant women with COVID-19, the sFlt-1/ANG-II ratio was associated with an increased probability of severe pneumonia (odds ratio [OR]: 1.31; p = 0.003), ICU admission (OR: 1.05; p = 0.007); intubation (OR: 1.09; p = 0.008); sepsis (OR: 1.04; p = 0.008); and death (OR: 1.04; p = 0.018); Conclusion: sFlt-1/ANG-II ratio is a good predictor of adverse events such as pneumonia, ICU admission, intubation, sepsis, and death in pregnant women with COVID-19.

(1) This study aimed to evaluate characteristics, perinatal outcomes, and placental pathology of pregnant women with or without SARS-CoV-2 infection in the context of maternal PCR cycle threshold (CT) values. (2) This was a retrospective case-control study in a third-level health center in Mexico City with universal screening by RT-qPCR. The association of COVID-19 manifestations, preeclampsia, and preterm birth with maternal variables and CT values were assessed by logistic regression models and decision trees. (3) Accordingly, 828 and 298 women had a negative and positive test, respectively. Of those positive, only 2.6% of them presented mild to moderate symptoms. Clinical characteristics between both groups of women were similar. No associations between CT values were found for maternal features, such as pre-gestational BMI, age, and symptomatology. A significantly higher percentage of placental fibrinoid was seen with women with low CTs (&lt, 25, p &lt, 0.01). Regarding perinatal outcomes, preeclampsia was found to be significantly associated with symptomatology but not with risk factors or CT values (p &lt, 0.01, aOR = 14.72). Moreover, 88.9% of women diagnosed with COVID-19 at &lt, 35 gestational weeks and symptomatic developed preeclampsia. (4) The data support strong guidance for pregnancies with SARS-CoV-2 infection, in particular preeclampsia and placental pathology, which need further investigation.

BACKGROUND AND AIM: Air pollution exposure, especially particulate matter ≤ 2.5 μm in diameter (PM2.5), is associated with poorer kidney function in adults and children. Perinatal exposure may occu...

Background We evaluated: 1) associations of prenatal manganese (Mn) levels with child neurodevelopment at 4 – 6 years; 2) effect modification by maternal anemia and iron deficiency; and 3) sex-specific effects. Methods We measured blood Mn, hemoglobin, and serum ferritin in mothers at the 2nd trimester, 3rd trimester, and at birth, and in cord blood from a prospective birth cohort in Mexico City (n=571). McCarthy Scales of Children’s Abilities were measured at 4 – 6 years. Using linear regression, we estimated associations between prenatal Mn and neurodevelopment, examined anemia and iron deficiency as effect modifiers, and analyzed associations by child sex. Results No direct associations were observed between Mn, anemia, or iron deficiency and McCarthy scales. Second trimester iron deficiency and 3rd trimester anemia modified the effect of Mn on child neurodevelopment. For instance, 2nd trimester Mn was positively associated child memory scores in mother’s with normal ferritin (1.85 (0.02, 3.45), but negatively associated in mother’s with low ferritin (−2.41 (−5.28, 0.47), interaction p value = 0.01), a pattern observed across scales. No effect modification at birth or in cord blood was observed. Conclusions Anemia/iron deficiency during pregnancy may modify Mn impacts on child neurodevelopment, particularly in boys.

Nayeli Martínez-Cruz,1 Agnese Maria Chiara Rapisarda,2 Karla Patricia Soriano-Ortega,3 Lidia Arce-Sánchez,1 Antonio Cianci,2 Carlos Ortega-Gonzalez,1 Ursula Torres-Herrera,1 Salvador Espino-Y-Sosa,3 Guadalupe Estrada-Gutierrez,4 Araceli Montoya-Estrada,5 José Romo-Yañez,5 Enrique Reyes-Muñoz5 1Department of Endocrinology, Instituto Nacional de Perinatología “Isidro Espinosa de los Reyes”, Mexico City, México; 2Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy; 3Division of Clinical Research, Instituto Nacional de Perinatología “Isidro Espinosa de los Reyes”, Mexico City, México; 4Direction of Research, Instituto Nacional de Perinatología “Isidro Espinosa de los Reyes”, Mexico City, México; 5Department of Gynecological and Perinatal Endocrinology, Instituto Nacional de Perinatología “Isidro Espinosa de los Reyes”, Mexico City, MéxicoCorrespondence: Enrique Reyes-MuñozDepartment of Gynecological and Perinatal Endocrinology, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Montes Urales 800 Lomas Virreyes, Miguel, Hidalgo 11000, Mexico CityMexicoTel +52 5555209900 Ext 307Email dr.enriquereyes@gmail.comPurpose: To compare the risk of adverse perinatal outcomes (APO) between pregnant women with mild gestational diabetes mellitus (GDM) diagnosed by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria, on no specific treatment, versus pregnant women without GDM.Patients and Methods: A retrospective cohort study of pregnant women referred to the Instituto Nacional de Perinatología, in Mexico City, for prenatal care and delivery. Eligibility criteria were singleton pregnancy, age >18 years, gestational age 20–28 weeks, and no history of pre-gestational diabetes. The study population was divided into two groups: Group 1, comprising women with mild GDM defined by one abnormal glucose value at the oral glucose tolerance test (OGTT) according to IADPSG criteria [fasting: 5.1–5.2 mmol/L (92–94 mg/dL) or 2h 8.5–8.56 mmol/L (153–154 mg/dL)], who did not receive specific treatment for GDM, and Group 2, comprising women without GDM, matched for maternal age and pre-gestational body mass index (BMI). Women with two or more abnormal OGTT values, pre-gestational diabetes, any chronic disease, or multiple pregnancies were excluded.Results: As many as 282 women were included in each group. There were no significant differences in basal characteristics between groups. APO analysis showed that newborn weight was significantly higher in Group 1 (3042.4±499g) vs Group 2 (2910±565g) p=0.003; conversely, the incidence of large for gestational age (LGA) and macrosomic neonates was similar in both groups (6 vs 5.7% and 2.1 vs 2.2%, respectively). There were no differences in rates of preeclampsia and gestational hypertension, cesarean and preterm delivery, or premature rupture of membranes. A sub-analysis by maternal pre-gestational BMI showed that LGA incidence was significantly higher among babies born to women with pre-gestational BMI ≥30 kg/m2 in both groups.Conclusion: The risk of APO was similar among Mexican women with mild untreated GDM diagnosed by IADPSG criteria, compared to pregnant women without GDM. Pre-gestational BMI was an independent risk factor for LGA.Keywords: gestational diabetes, large for gestational age, IADPSG, hyperglycemia, pregnancy &nbsp

DNA methylation microarrays have been the platform of choice for epigenome-wide association studies in epidemiology, but declining costs have rendered targeted bisulphite sequencing a feasible alternative. Nonetheless, the literature for researchers seeking guidance on which platform to choose is sparse. To fill this gap, we conducted a comparison study in which we processed cord blood samples from four newborns in duplicates using both the Illumina HumanMethylationEPIC BeadChip and the Illumina TruSeq Methyl Capture EPIC Kit, and evaluated both platforms in regard to coverage, reproducibility, and identification of differential methylation. We conclude that with current analytic goals microarrays still outperform bisulphite sequencing for precise quantification of DNA methylation.

Introduction: Lead (Pb) crosses the placenta and can cause oxidative stress, reduced fetal growth and neurological problems. The principal source of oxidative stress in human cells is mitochondria. Therefore, disruption of normal mitochondrial function during pregnancy may represent a primary mechanism behind the adverse effects of lead. We sought to assess the association of Pb exposure during pregnancy with mitochondrial DNA (mtDNA) content, a sensitive marker of mitochondrial function, in cord blood. Materials and methods: This study comprised mother-infant pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a prospective birth-cohort that enrolled 1050 pregnant women from Mexico City who were receiving prenatal care between December 2007 and July 2011. Quantitative PCR was used to calculate relative MtDNA content (mitochondrial-to-nuclear DNA ratio (mtDNA/nDNA)) in cord blood. Lead concentrations in both maternal blood (2nd and 3rd trimester and at delivery day) and in cord blood were measured by ICP-MS. Multivariable regression models adjusting for multiple confounders were fitted with 410 mother-infant pairs for whom complete data for mtDNA content, lead levels, and covariates were available. Results: Maternal blood Pb measured in the second (mean 3.79 μg/dL, SD 2.63; β = 0.059, 95% CI 0.008, 0.111) and third trimester (mean 3.90 μg/dL; SD 2.84; β = 0.054, 95% CI 0.002, 0.107) during pregnancy and PB in cord blood (mean 3.50 μg/dL, SD 2.59; β = 0.050, 95% CI 0.004; 0.096) were associated with increased cord blood mtDNA content (mean 1.46, SD 0.44). In two-way interaction analyses, cord blood Pb marginally interacted with gestational age leading to an increase in mtDNA content for pre-term births (Benjamini-Hochberg False Discovery Rate correction; BH-FDR = 0.08). Conclusion: This study shows that lead exposure in pregnancy alters mtDNA content in cord blood; therefore, alteration of mtDNA content might be a mechanism underlying the toxicity of lead. Keywords: mtDNA content, Lead exposure, Pregnancy, Mitochondrial dysfunction, Cord blood

BACKGROUND: Trace metal concentrations may affect cardio-metabolic risk, but the role of prenatal exposure is unclear. We examined: 1) the relationship between blood metal concentrations during pregnancy and child cardio-metabolic risk factors; 2) overall effects of metals mixture (essential vs. nonessential); and 3) interactions between metals. METHODS: We measured 11 metals in maternal 2(nd) trimester whole blood in a prospective birth cohort in Mexico City. In children 4–6 years old, we measured body mass index (BMI), percent body fat, and blood pressure (N=609); and plasma hemoglobin A1C (HbA1c) , non-high density lipoprotein (HDL) cholesterol, triglycerides, leptin, and adiponectin (N=411). We constructed cardio-metabolic component scores using age- and sex-adjusted z-scores and averaged five scores to create a global risk score. We estimated linear associations of each metal with individual z-scores and used Bayesian Kernel Machine Regression to assess metal mixtures and interactions. RESULTS: Higher total metals were associated with lower HbA1c, leptin, and systolic blood pressure, and with higher adiponectin and non-HDL cholesterol. We observed no interactions between metals. Higher selenium was associated with lower triglycerides in linear (β=−1.01 z-score units per 1 unit ln(Se), 95%CI = −1.84; −0.18) and Bayesian Kernel Machine Regression models. Manganese was associated with decreased HbA1c in linear models (β = −0.32 and 95% CI: −0.61, −0.03). Antimony and arsenic were associated with lower leptin in Bayesian Kernel Machine Regression models. Essential metals were more strongly associated with cardio-metabolic risk than were nonessential metals. CONCLUSIONS: Low essential metals during pregnancy were associated with increased cardio-metabolic risk factors in childhood.

As renal development and maturation processes begin in utero and continue through early childhood, sensitive developmental periods arise during which metal exposures can program subclinical nephrotoxicity that manifests later in life. We used novel dentine biomarkers of established nephrotoxicants including arsenic (As), cadmium (Cd), lead (Pb), chromium (Cr), and lithium (Li), and their mixtures, to identify critical windows of exposure-associated kidney function alterations in preadolescents.Participants included 353 children in the Programming Research in Obesity Growth, Environment and Social Stressors (PROGRESS) longitudinal birth cohort study based in Mexico City. Estimated glomerular filtration rate (eGFR) was assessed in 8-12 year old children using serum cystatin C measures. Pre- and postnatal metal(loid) concentrations were assessed in weekly increments by analyzing deciduous teeth with laser ablation-inductively coupled plasma-mass spectrometry. We used reverse distributed lag models (rDLMs) and lagged Weighted Quantile Sum (L-WQS) regression to examine time-varying associations between weekly perinatal metal(loid) exposure or metal(loid) mixtures and preadolescent eGFR while adjusting for age, sex, BMI z-score, SES and prenatal tobacco smoke exposure.We identified a critical window of susceptibility to Pb exposure, in the late 3rd trimester (5 weeks prior to birth) during which higher Pb exposure was associated with children's increased eGFR. When all elements were assessed as a mixture, we identified late 2nd/early 3rd trimester (weeks 8-17 of gestation) as a window of vulnerability associated with decreased eGFR, with Li and Cr contributing the greatest weights to the association. When stratified by sex, we observed stronger effects among boys than girls.Using tooth-matrix biomarkers, we identified discrete developmental exposure windows wherein Pb and metal(loid) mixtures were associated with altered preadolescent kidney function.

A high-quality diet during pregnancy may have positive effects on fetal growth and nutritional status at birth, and it may modify the risk of developing chronic diseases later in life. The aim of this study was to evaluate the association between diet quality and newborn nutritional status in a group of pregnant Mexican women. As part of the ongoing Mexican prospective cohort study, OBESO, we studied 226 healthy pregnant women. We adapted the Alternated Healthy Eating Index-2010 for pregnancy (AHEI-10P). The association between maternal diet and newborn nutritional status was investigated by multiple linear regression and logistic regression models. We applied three 24-h recalls during the second half of gestation. As the AHEI-10P score improved by 5 units, the birth weight and length increased (β = 74.8 ± 35.0 g and β = 0.3 ± 0.4 cm, respectively, p &lt, 0.05). Similarly, the risk of low birth weight (LBW) and small for gestational age (SGA) decreased (OR: 0.47, 95%CI: 0.27–0.82 and OR: 0.55, 95%CI: 0.36–0.85, respectively). In women without preeclampsia and/or GDM, the risk of stunting decreased as the diet quality score increased (+5 units) (OR: 0.62, 95%IC: 0.40–0.96). A high-quality diet during pregnancy was associated with a higher newborn size and a reduced risk of LBW and SGA in this group of pregnant Mexican women.

The COVID-19 lockdown represents a new challenge for mental health researchers and clinical practitioners. This cross-sectional study aimed to investigate the prevalence of depression, anxiety, and perceived stress in postpartum Mexican women. The study included 293, 4–12-week postpartum women over the age of 18. The Edinburgh Postpartum Depression Scale (EPDS), Trait-State Trait Anxiety Inventory (T-STAI), and Ten Perceived Stress Scale (PSS-10), which are all questionnaires validated for the Mexican population, were applied using a web-based online survey. Prevalence and 95% confidence intervals (CIs) were calculated. The mean ± standard deviation (SD) of the maternal age was 29.9 ± 6.3 years, the EPDS score: 11 ± 6, T-STAI score: 41.7 ± 12.3, and PSS-10 score: 17.1 ± 7. The prevalence (95% CI) of the postpartum depression symptoms was 39.2% (34–45%), trait anxiety symptoms were found among 46.1% (32–43%) of the participants, and moderate and high perceived stress were in 58% (52–64) and 10.9% (7.8–15) of the participants, respectively. The prevalence of depressive symptoms, generalized anxiety, and perceived stress was higher among postpartum Mexican women during the COVID-19 outbreak than before the lockdown. Our findings highlight the importance of monitoring perinatal mental health during pandemics and the need to design effective psychologic interventions for these patients.

Background: During pregnancy, vitamin D requirements are higher due to fetal growth and development. Vitamin D production occurs mainly through sunlight exposure, which is affected by geographic location and lifestyle factors. Methods: This was a case-control study nested within two cohorts of adult pregnant women (n = 298): urban (Mexico City) and rural (Cuetzalan). To reduce confounding, pairs were selected by age, pregestational body mass index, and pregnancy trimester. Generalized linear models were used to assess the two groups according to their vitamin D status. Results: A total of 298 adult women were studied: 149 from a rural area and 149 from an urban area. Vitamin D deficiency and insufficiency were observed in 28% and 38.2% of women, respectively. A trend for higher 25(OH)D concentrations was observed in women from the rural area (27.5 ng/mL vs. 25.8 ng/mL), probably related to the type of job, where women with partial jobs showing less probability of having vitamin D deficiency (OR = 0.26, CI = 0.06–1.16, p = 0.08) and vitamin D insufficiency (OR = 0.24, CI = 0.06–0.99, p = 0.05). Women whose Last Menstrual Period occurred in spring showed lower vitamin D concentration compared to those whose LMP occurred in winter (p &lt, 0.01). Conclusions: A high prevalence of vitamin D deficiency was observed in both rural and urban areas. Women living in rural areas tended to have higher 25(OH)D concentrations, probably related to more sunlight exposure associated with their type of job.

Aims: The authors sought to examine associations between urinary exosomal miRNAs (exo-miRs), emerging biomarkers of renal health, and cardiorenal outcomes in early childhood. Materials & methods: The authors extracted exo-miRs in urine from 88 healthy Mexican children aged 4–6 years. The authors measured associations between 193 exo-miRs and cardiorenal outcomes: systolic/diastolic blood pressure, estimated glomerular filtration rate and urinary sodium and potassium levels. The authors adjusted for age, sex, BMI, socioeconomic status, indoor tobacco smoke exposure and urine specific gravity. Results: Multiple exo-miRs were identified meeting a false discovery rate threshold of q

Clinical manifestations of coronavirus disease 2019 (COVID-19) in pregnant women are diverse, and little is known of the impact of the disease on placental physiology. Severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been detected in the human placenta, and its binding receptor ACE2 is present in a variety of placental cells, including endothelium. Here, we analyze the impact of COVID-19 in placental endothelium, studying by immunofluorescence the expression of von Willebrand factor (vWf), claudin-5, and vascular endothelial (VE) cadherin in the decidua and chorionic villi of placentas from women with mild and severe COVID-19 in comparison to healthy controls. Our results indicate that: (1) vWf expression increases in the endothelium of decidua and chorionic villi of placentas derived from women with COVID-19, being higher in severe cases, (2) Claudin-5 and VE-cadherin expression decrease in the decidua and chorionic villus of placentas from women with severe COVID-19 but not in those with mild disease. Placental histological analysis reveals thrombosis, infarcts, and vascular wall remodeling, confirming the deleterious effect of COVID-19 on placental vessels. Together, these results suggest that placentas from women with COVID-19 have a condition of leaky endothelium and thrombosis, which is sensitive to disease severity.