Maternal Metabolic Syndrome Research Articles

Gestational weight gain below recommendations and adverse maternal and child health outcomes for pregnancies with overweight or obesity: a United States cohort study

BackgroundThe current Institute of Medicine (IOM) pregnancy weight gain guidelines were developed using the best available evidence but were limited by substantial knowledge gaps. Some have raised concern that the guidelines for individuals affected by overweight or obesity are too high and contribute to short- and long-term complications for the mother and child. ObjectivesTo determine the association between pregnancy weight gain below the lower limit of the current IOM recommendations and risk of 10 adverse maternal and child health outcomes among individuals with overweight and obesity. MethodsWe used data from a prospective cohort study of United States nulliparae with prepregnancy overweight (n = 955) or obesity (n = 897) followed from the first trimester to 2–7 y postpartum. We used multivariable Poisson regression to relate pregnancy weight gain z-scores with a severity-weighted composite outcome consisting of ≥1 of 10 adverse outcomes (gestational diabetes, preeclampsia, unplanned cesarean delivery, maternal postpartum weight increase >10 kg, maternal postpartum metabolic syndrome, infant death, stillbirth, preterm birth, small-for-gestational age birth, and childhood obesity). ResultsPregnancy weight gain z-scores below, within, and above the IOM-recommended ranges occurred in 5%, 13%, and 80% of pregnancies with overweight and 17%, 13%, and 70% of pregnancies with obesity. There was a positive association between pregnancy weight gain z-scores and all adverse maternal outcomes, childhood obesity, and the composite outcome. Pregnancy weight gain z-scores below the lower limit of the recommended ranges (<6.8 kg for overweight, <5 kg for obesity) were not associated with the severity-weighted composite outcome. For example, compared with the lower limit, adjusted rate ratios (95% confidence interval) for z-scores of −2 standard deviations in pregnancies with overweight (equivalent to 3.6 kg at 40 wk) and obesity (−2.8 kg at 40 wk) were 0.99 (95% confidence interval [CI]: 0.91, 1.06) and 0.97 (95% CI: 0.87, 1.07). ConclusionsThese findings support arguments to decrease the lower limit of recommended weight gain ranges in these prepregnancy body mass index groups.

Preconceptional maternal hyperandrogenism and metabolic syndrome risk in male offspring: a long-term population-based study.

There is limited research on the effects of maternal hyperandrogenism (MHA) on cardiometabolic risk factors in male offspring. We aimed to compare the risk of metabolic syndrome (MetS) in sons of women with preconceptional hyperandrogenism (HA) to those of non-HA women in later life. Using data obtained from the Tehran Lipid and Glucose Cohort Study, with an average of 20years follow-up, 1913 sons were divided into two groups based on their MHA status, sons with MHA (n = 523) and sons without MHA (controls n = 1390). The study groups were monitored from the baseline until either the incidence of events, censoring, or the end of the study period, depending on which occurred first. Age-scaled unadjusted and adjusted Cox regression models were utilized to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MHA and MetS in their sons. There was no significant association between MHA and HR of MetS in sons with MHA compared to controls, even after adjustment (unadjusted HR (95% CI) 0.94 (0.80-1.11), P = 0.5) and (adjusted HR (95% CI) 0.98 (0.81-1.18),P = 0.8). Sons with MHA showed a HR of 1.35 for developing high fasting blood sugar compared to controls (unadjusted HR (95% CI) 1.35 (1.01-1.81), P = 0.04), however, after adjustment this association did not remain significant (adjusted HR (95% CI) 1.25 (0.90-1.74), P = 0.1). The results suggest that preconceptional MHA doesn't increase the risk of developing MetS in sons in later life. According to this suggestion, preconceptional MHA may not have long-term metabolic consequences in male offspring.

Periconceptional Serum Creatinine and Risk of Childhood Autism Spectrum Disorder: A Research Letter.

Autism spectrum disorder (ASD) is a neurodevelopmental condition that manifests in early childhood, in which the maternal metabolic syndrome may be a risk factor. The kidney is a barometer of maternal metabolic syndrome duration and severity. The main objective of this study is to determine whether periconceptional kidney function is associated with ASD in early childhood. This retrospective population-based cohort study was completed in Ontario, Canada. Included were singleton children born in an Ontario hospital between April 2007 and March 2021, who were alive at age 48 months and whose mother had a recorded prepregnancy body mass index (BMI) and a measured serum creatinine (SCr) between 120 days preconception and 28 days postconception. The main study outcome was a diagnosis of ASD between ages 24 and 48 months. Relative risks (RRs) of ASD in association with periconceptional SCr were generated using modified Poisson regression and adjusted for several confounders. The cohort comprised 86 054 women, who had 89 677 liveborn children surviving to at least 48 months of age. There was no significant association between periconceptional SCr and ASD (RR: 0.86; 95 % confidence interval: [0.67, 1.10]). Selection bias may have arisen had SCr been ordered on clinical grounds. Further study is warranted to determine whether prepregnancy glomerular hyperfiltration is a marker of ASD and other behavioral conditions in childhood. To do so, a more accurate measure of hyperfiltration is needed than SCr.

THE EFFECT OF ENOS GENE POLYMORPHISM AND NITRIC OXIDE METABOLISM INDICATORS ON THE NEONATAL CONSEQUENCES IN PREMATURE BABIES BORN FROM MOTHERS WITH METABOLIC SYNDROME

Metabolic syndrome is considered to be a cluster of disorders that directly contribute to the development of cardiovasculardisease and are characterized by chronic systemic infl ammation. Numerous epidemiological data indicate that an adverseintrauterine environment, caused by the peculiarities of the nutritional status or placental insuffi ciency in a woman with metabolic syndrome, can “program” the susceptibility of the fetus to further development of cardiovascular and metabolic diseases, has an impact on cognitive and behavioral development. Nitric oxide (NO) plays a critical role in the pathogenesis of components of the metabolic syndrome. Children born prematurely have a high incidence of brain damage, which can lead to motor, cognitive, behavioral, social and sensory disorders.The purpose the research was the study of the effect of the eNOS gene polymorphism and indicators of nitric oxidemetabolism on the neonatal consequences in prematurely born children from mothers with metabolic syndrome.Material and methods. A study was conducted in which 100 premature infants were included. Two groups were formed: the main group (n=34), which included preterm infants (birth weight 2145.29±148.19 g and gestational age 33.18±0.55 weeks) of mothers with metabolic syndrome, and the comparison group (n=66), which included preterm infants (birth weight 2295.99±101.45 and gestational age 34.03±0.45 weeks) of mothers without metabolic syndrome. The children underwent a genetic study – determination of the polymorphism of the eNOS gene, as well as the level of nitrites, nitrates and nitrosothiols in the urine.By decision of the bioethics commission No. 217 dated 12.06.2023, the materials of the scientifi c work comply with the Rulesof Humane Treatment of Patients.Traditional methods of parametric and nonparametric statistics were used; nonparametric methods were used to analyzequalitative characteristics expressed mainly in percentages. The methods of parametric statistics were used to check the normality of the distribution of quantitative characteristics using the Kolmogorov- Smirnov criterion.Statistical processing of the obtained results was carried out using the package of application programs EXCEL-2003® andSTATA version 11 for Windows (StataCorp, Texas, USA).The work was carried out as part of the scientifi c and experimental work of the Department of Pediatrics #1 with Neonatologyof the Poltava State Medical University “To develop clinical and laboratory criteria, methods of predicting and preventingmetabolic disoders in young children (state registration number 0120U102856).Results. The most common diseases in the infants of the studied groups were the consequences of intrauterine hypoxia(44.1%) and respiratory failure requiring artifi cial lung ventilation (50.0%), although no signifi cant diff erences were foundin the prevalence of these conditions. We identifi ed the presence of signifi cant associations between the consequences ofintrauterine hypoxia and the levels of nitrates (OR 1.19; 95% CI 1.01-1.40; p=0.042), nitrosothiols (OR 1.19; 95% CI 0.99-1.42;p=0.050) and the polymorphic genotype 4aa/ab of the eNOS gene (OR 0.28; 95% CI 0.12-0.67; p=0.004). Analysis of systemichemodynamics revealed no signifi cant diff erences in baseline values between preterm infants with and without intrauterinehypoxia, but we did observe an association with urine output on day 3 of life.To fi nally clarify the complex infl uence of indicators of nitrate metabolism on the development of intrauterine hypoxia andto predict the development of consequences of this condition in premature infants, the following indicators are included in theregression prognostic model: the level of nitrates, nitrites, 4aa/4ab genotype and urine output on the third day of life. As theresearch results show, there is a direct reliable relationship with nitrates and an inverse relationship with nitrites, 4aa/4abgenotype and urine output. This prediction model has high operating characteristics – the area under the ROC curve is 0.8168.Some mechanisms of the infl uence of maternal metabolic syndrome on the development of relevant disorders in newborns areknown, including disorders of nitric oxide synthesis, endothelial dysfunction, and oxidative stress. In our study, the consequences of intrauterine hypoxia were reliably associated with an increase in the concentration of urinary nitrates and a decrease in nitrites, as well as the absence of the 4aa/ab genotype, which is associated with reduced release of nitric oxide. There is evidence that nitric oxide can have both protective and deleterious eff ects, depending on factors such as nitric oxide synthase isoform and duration of exposure to hypoxia.Conclusions. In preterm infants born to mothers with metabolic syndrome, elevated urinary nitrate levels and the absenceof the eNOS 4aa/ab genotype increase the likelihood of suff ering the consequences of intrauterine hypoxia.

Epigenetic implications in maternal diabetes and metabolic syndrome-associated risk of orofacial clefts.

Orofacial clefts (OFCs) are one of the most common types of structural birth defects. The etiologies are complicated, involving with genetic, epigenetic, and environmental factors. Studies have found that maternal diabetes and metabolic syndrome are associated with a higher risk of OFCs in offspring. Metabolic syndrome is a clustering of several disease risk factors, including hyperglycemia, dyslipidemia, obesity, and hypertension. Metabolic disease during pregnancy can increase risk of adverse outcomes and significantly influence fetal development, including orofacial formation and fusion. An altered metabolic state may contribute to developmental disorders or congenital defects including OFCs, potentially through epigenetic modulations, such as histone modification, DNA methylation, and noncoding RNA expression to alter activities of critical morphogenetic signaling or related developmental genes. This review summarizes the currently available evidence and underlying mechanisms of how the maternal metabolic syndrome is associated with OFCs in mostly human and some animal studies. It may provide a better understanding of the interactions between intrauterine metabolic status and fetal orofacial development which might be applied toward prevention and treatments of OFCs.

Maternal metabolic syndrome in pregnancy and child development at age 5: exploring mediating mechanisms using cord blood markers

BackgroundThere is limited evidence on how the classification of maternal metabolic syndrome during pregnancy affects children’s developmental outcomes and the possible mediators of this association. This study uses a cohort sample of 12,644 to 13,832 mother–child pairs from the UK Born in Bradford Study to examine the associations between maternal metabolic syndrome classification (MetS) and child development outcomes at age 5, using cord blood markers as candidate mediators.MethodsMaternal cardiometabolic markers included diabetes, obesity, triglycerides, high-density lipoprotein cholesterol, blood pressure, hypertension, and fasting glucose during pregnancy. Cord blood markers of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, leptin, and adiponectin were used as child mediators. Child outcomes included two starting school variables: British Picture Vocabulary Scale (BPVS) and the Letter Identification Assessment (LID), and five developmental milestone domains from a national UK framework: (1) communication and language (COM); (2) personal, social, and emotional (PSE); (3) physical development (PHY); (4) literacy (LIT); and (5) mathematics (MAT). Mediation models were used to examine the associations between the classification of maternal metabolic syndrome and child developmental milestones. Models were adjusted for potential maternal, socioeconomic, and child confounders such as maternal education, deprivation, and gestational age.ResultsIn mediation models, significant total effects were found for MetS associations with children’s development in the LIT domain at age 5. MetS predicted individual cord blood mediators of lower HDL and increased leptin levels in both adjusted and unadjusted models. Total indirect effects (effects of all mediators combined) for MetS on a child’s COM and PSE domain were significant, through all child cord blood mediators of LDL, HDL, triglycerides, adiponectin, and leptin for adjusted models.ConclusionsThe results support the hypothesis that maternal metabolic syndrome classification during pregnancy is associated with some child developmental outcomes at age 5. After adjusting for maternal, child, and environmental covariates, maternal metabolic syndrome classification during pregnancy was associated with children’s LIT domain through direct effects of maternal metabolic health and indirect effects of cord blood markers (total effects), and COM and PSE domains via changes only in a child’s cord blood markers (total indirect effects).

The association of preconception paternal metabolic syndrome on early childhood emergency department visits and hospitalizations.

Increasing preconception paternal comorbidity has been associated with adverse pregnancy outcomes. However, whether the father's health impacts the child after birth is uncertain. In the present study, we examined the association of preconception paternal metabolic syndrome status with childhood emergency department visits and hospitalizations. This is a longitudinal cohort study of children (295,355 boys and 278,735 girls) born to linked pairs of fathers and mothers in the United States between 2009 and 2016 within the IBM MarketScan Research database. Associations between paternal and maternal metabolic syndrome component diagnoses and subsequent hospitalizations and emergency department visits for offspring within the first 2 years of life were determined. Note that, 35.5% (203,617/574,090) of children had at least one emergency room visit and 6.1% (35,141/574,090) of children had an inpatient admission. After adjustment, the odds of inpatient admission and emergency department visits increased in a dose-dependent fashion among fathers with higher comorbidities. Similar trends were seen for emergency department visit utilization. Increasing paternal preconception comorbidity is associated with a higher risk that a child requires the emergency department and inpatient care in the first years of life. An opportunity exists to engage men in preconception counseling to optimize their and their offspring's health.

First-Trimester Maternal Serum Adiponectin/Leptin Ratio in Pre-Eclampsia and Fetal Growth.

The serum adiponectin/leptin ratio (A/L ratio) is a surrogate marker of insulin sensitivity. Pre-eclampsia (PE) is associated with maternal metabolic syndrome and occasionally impaired fetal growth. We assessed whether the A/L ratio in first-trimester maternal serum was associated with PE and/or birth weight. Adiponectin and leptin were quantitated in first-trimester blood samples (gestational week 10+3−13+6) from 126 women who later developed PE with proteinuria (98 mild PE; 21 severe PE; 7 HELLP syndrome), and 297 controls, recruited from the Copenhagen First-Trimester Screening Study. The A/L ratio was reduced in PE pregnancies, median 0.17 (IQR: 0.12−0.27) compared with controls, median 0.32 (IQR: 0.19−0.62) (p < 0.001). A multiple logistic regression showed that PE was negatively associated with log A/L ratio independent of maternal BMI (odds ratio = 0.315, 95% CI = 0.191 to 0.519). Adiponectin (AUC = 0.632) and PAPP-A (AUC = 0.605) were negatively associated with PE, and leptin (AUC = 0.712) was positively associated with PE. However, the A/L ratio was a better predictor of PE (AUC = 0.737), albeit not clinically relevant as a single marker. No significant association was found between A/L ratio and clinical severity of pre-eclampsia or preterm birth. PE was associated with a significantly lower relative birth weight (p < 0.001). A significant negative correlation was found between relative birth weight and A/L ratio in controls (β = −0.165, p < 0.05) but not in PE pregnancies), independent of maternal BMI. After correction for maternal BMI, leptin was significantly associated with relative birth weight (β = 2.98, p < 0.05), while adiponectin was not significantly associated. Our findings suggest that an impairment of the A/L ratio (as seen in metabolic syndrome) in the first trimester is characteristic of PE, while aberrant fetal growth in PE is not dependent on insulin sensitivity, but rather on leptin-associated pathways.

Effectiveness of a nurse practitioner-led cardiovascular prevention clinic at reduction of metabolic syndrome following maternal complications of pregnancy: a preliminary analysis

AimMaternal complications of pregnancy, including hypertensive disorders of pregnancy, gestational diabetes mellitus, intrauterine growth restriction, preterm labour, and placental abruption, are associated with increased risk of future cardiometabolic disease. Lifestyle interventions that focus on preventative strategies for this young, high-risk population of women may assist in cardiometabolic disease risk reduction. The aim of this preliminary registry analysis was to observe the change in maternal metabolic syndrome status after receiving a nurse practitioner-led lifestyle intervention delivered soon after a complicated pregnancy.MethodThis preliminary analysis included 64 eligible women who had attended both baseline (approximately 6 months postpartum) and review (approximately eighteen months postpartum) appointments at the postpartum lifestyle clinic after an index pregnancy complicated by at least one maternal complication of pregnancy. Metabolic syndrome status at both appointments was assessed.ResultsAt the baseline appointment, 22 (34.4%) women met the criteria for metabolic syndrome. This number reduced at the review appointment to 19 (29.7%). This difference was not statistically significant. There were some modest improvements in the individual cardiometabolic risk factors, as well as marked improvements in the women who had recovered from metabolic syndrome over twelve months.ConclusionThere was a high percentage of metabolic syndrome present early in the postpartum period. The results of this preliminary analysis highlight the importance of continuing preventative care and ongoing research for this group of high-risk women.

Effects of Probiotic Supplementation during Pregnancy on the Future Maternal Risk of Metabolic Syndrome.

Probiotics are live microorganisms that induce health benefits in the host. Taking probiotics is generally safe and well tolerated by pregnant women and their children. Consumption of probiotics can result in both prophylactic and therapeutic effects. In healthy adult humans, the gut microbiome is stable at the level of the dominant taxa: Bacteroidetes, Firmicutes and Actinobacteria, and has a higher presence of Verrucomicrobia. During pregnancy, an increase in the number of Proteobacteria and Actinobacteria phyla and a decrease in the beneficial species Roseburia intestinalis and Faecalibacterium prausnitzii are observed. Pregnancy is a “window” to the mother’s future health. The aim of this paper is to review studies assessing the potentially beneficial effects of probiotics in preventing the development of diseases that appear during pregnancy, which are currently considered as risk factors for the development of metabolic syndrome, and consequently, reducing the risk of developing maternal metabolic syndrome in the future. The use of probiotics in gestational diabetes mellitus, preeclampsia and excessive gestational weight gain is reviewed. Probiotics are a relatively new intervention that can prevent the development of these disorders during pregnancy, and thus, would reduce the risk of metabolic syndrome resulting from these disorders in the mother’s future.

Adverse Maternal Fetal Environment Partially Mediates Disparate Outcomes in Non-White Neonates with Major Congenital Heart Disease

To determine whether differential exposure to an adverse maternal fetal environment partially explains disparate outcomes in infants with major congenital heart disease (CHD). Retrospective cohort study utilizing a population-based administrative California database (2011-2017). Primary exposure: Race/ethnicity. Primary mediator: Adverse maternal fetal environment (evidence of maternal metabolic syndrome and/or maternal placental syndrome). Composite of 1-year mortality or severe morbidity and days alive out of hospital in the first year of life (DAOOH). Mediation analyses determined the percent contributions of mediators on pathways between race/ethnicity and outcomes after adjusting for CHD severity. Included were 2747 non-Hispanic White infants (reference group), 5244 Hispanic, and 625 non-Hispanic Black infants. Hispanic and non-Hispanic Black infants had a higher risk for composite outcome (crude OR: 1.18; crude OR: 1.25, respectively) and fewer DAOOH (-6 & -12days, respectively). Compared with the reference group, Hispanic infants had higher maternal metabolic syndrome exposure (43% vs 28%, OR: 1.89), and non-Hispanic Black infants had higher maternal metabolic syndrome (44% vs 28%; OR: 1.97) and maternal placental syndrome exposure (18% vs 12%; OR, 1.66). Both maternal metabolic syndrome exposure (OR: 1.21) and maternal placental syndrome exposure (OR: 1.56) were related to composite outcome and fewer DAOOH (-25 & -16days, respectively). Adverse maternal fetal environment explained 25% of the disparate relationship between non-Hispanic Black race and composite outcome and 18% of the disparate relationship between Hispanic ethnicity and composite outcome. Adverse maternal fetal environment explained 16% (non-Hispanic Black race) and 21% (Hispanic ethnicity) of the association with DAOOH. Increased exposure to adverse maternal fetal environment contributes to racial and ethnic disparities in major CHD outcomes.

The Intersection of Maternal Metabolic Syndrome, Adverse Pregnancy Outcomes, and Future Metabolic Health for the Mother and Offspring.

The prevalence of obesity is ∼40% in the United States, and the prepregnancy prevalence of obesity in females is ∼30%. This has in part fueled an increase in metabolic syndrome (MetS) among females who are currently pregnant, have been pregnant, or are planning to become pregnant. Importantly, MetS in pregnancy is associated with increased pregnancy complications. Moreover, MetS in pregnancy may have long-lasting adverse cardiovascular and metabolic health implications for the mother and her offspring. To complicate matters, many adverse pregnancy outcomes seem to increase the risk of MetS in the mother after pregnancy. Herein, we describe the potential mechanisms behind the intersection of MetS, adverse pregnancy outcomes, and subsequent long-term disease in the mother and offspring. Because MetS is a cluster of coexisting conditions, it is challenging to identify mediators that can serve as biomarkers for early diagnosis and targets for MetS prevention and therapy.

Zac1 and the Imprinted Gene Network program juvenile NAFLD in response to maternal metabolic syndrome.

Background and Aims:Within the next decade, NAFLD is predicted to become the most prevalent cause of childhood liver failure in developed countries. Predisposition to juvenile NAFLD can be programmed during early life in response to maternal metabolic syndrome (MetS), but the underlying mechanisms are poorly understood. We hypothesized that imprinted genes, defined by expression from a single parental allele, play a key role in maternal MetS-induced NAFLD, due to their susceptibility to environmental stressors and their functions in liver homeostasis. We aimed to test this hypothesis and determine the critical periods of susceptibility to maternal MetS.Approach and Results:We established a mouse model to compare the effects of MetS during prenatal and postnatal development on NAFLD. Postnatal but not prenatal MetS exposure is associated with histological, biochemical, and molecular signatures of hepatic steatosis and fibrosis in juvenile mice. Using RNA sequencing, we show that the Imprinted Gene Network (IGN), including its regulator Zac1, is up-regulated and overrepresented among differentially expressed genes, consistent with a role in maternal MetS-induced NAFLD. In support of this, activation of the IGN in cultured hepatoma cells by overexpressing Zac1 is sufficient to induce signatures of profibrogenic transformation. Using chromatin immunoprecipitation, we demonstrate that Zac1 binds the TGF-β1 and COL6A2 promoters, forming a direct pathway between imprinted genes and well-characterized pathophysiological mechanisms of NAFLD. Finally, we show that hepatocyte-specific overexpression of Zac1 is sufficient to drive fibrosis in vivo.Conclusions:Our findings identify a pathway linking maternal MetS exposure during postnatal development to the programming of juvenile NAFLD, and provide support for the hypothesis that imprinted genes play a central role in metabolic disease programming.

Maternal inositol supplementation modulates offspring liver metabolism in a pregnant murine model of metabolic syndrome

Consumption of high-fat diet induces liver and metabolic complications such as metabolic syndrome (MS). We previously reported that maternal MS and hypertension (HTN) dysregulate fetal and placental glucose homeostasis, which was ameliorated by inositols (INO) supplementation during pregnancy. 5' AMP-activated protein kinase (AMPK) pathway plays a key role in maintaining energy balance and glucose metabolism at liver level. We aim to investigate the effect of INO supplementation on AMPK pathway in female offspring born to a murine model of MS.

Abstract 9331: Adverse Maternal Fetal Environment Partially Mediates Disparate Outcomes in Hispanic and Non Hispanic Black Infants With Critical Congenital Heart Disease

Introduction: Etiologies of racial and ethnic disparities in critical congenital heart disease (CCHD) outcomes are not fully understood. We sought to determine whether differential exposure to an adverse maternal fetal environment (AMFE) partially explains disparate outcomes. Methods: We included infants with CCHD in a population-based administrative California database (2011-2017). Primary exposure was race/ethnicity. Primary mediator was AMFE, defined as maternal metabolic syndrome (MMS: any diabetes, abnormal BMI, or hyperlipidemia) or maternal placental syndrome (MPS: pre-eclampsia/ eclampsia, gestational hypertension, or placental abruption). Outcomes: days alive out of hospital in first year of life (DAOOH); composite of 1-year mortality or severe morbidity (e.g., ECMO, cardiac arrest, BPD, etc.). Mediation analyses (CCHD severity-adjusted) determined % contribution to outcome for each mediator on pathways between race/ethnicity and outcomes. Results: Included were 2,747 Non-Hispanic (NH) White [REF group], 5,244 Hispanic, and 625 NH Black infants. Hispanic and NH Black infants had higher risk for composite outcome (crude OR, 1.18; crude OR, 1.25 respectively) and fewer DAOOH (-6 &amp; -12 days, respectively). Relative to NH White infants (MMS 28%; MPS 12%), Hispanic infants had higher MMS exposure (43%, OR, 1.89), while NH Black infants had higher MMS (44%, OR, 1.97) &amp; MPS exposure (18%, OR, 1.66). Both MMS exposure (OR, 1.21) and MPS exposure (OR 1.56) were related to composite outcome and fewer DAOOH (-25 &amp; -16 days, respectively). AMFE explained 25% of relationship between NH Black race and composite outcome, and 18% of relationship between Hispanic ethnicity and composite outcome. AMFE explained 16% (NH Black race) and 21% (Hispanic ethnicity) of the association with DAOOH (Table). Conclusions: Increased exposure to AMFE contributes to disparate outcomes in NH Black and Hispanic infants with CCHD. This novel finding merits clinical attention.

PD29-02 THE ASSOCIATION OF PRECONCEPTION PATERNAL METABOLIC SYNDROME ON EARLY CHILDHOOD EMERGENCY DEPARTMENT VISITS AND HOSPITALIZATION: ANALYSIS OF U.S. CLAIMS DATA

You have accessJournal of UrologyInfertility: Epidemiology & Evaluation II (PD29)1 Sep 2021PD29-02 THE ASSOCIATION OF PRECONCEPTION PATERNAL METABOLIC SYNDROME ON EARLY CHILDHOOD EMERGENCY DEPARTMENT VISITS AND HOSPITALIZATION: ANALYSIS OF U.S. CLAIMS DATA Tony Chen, Chiyuan Zhang, Shufeng Li, Gary Shaw, Alan Schroeder, and Michael Eisenberg Tony ChenTony Chen More articles by this author , Chiyuan ZhangChiyuan Zhang More articles by this author , Shufeng LiShufeng Li More articles by this author , Gary ShawGary Shaw More articles by this author , Alan SchroederAlan Schroeder More articles by this author , and Michael EisenbergMichael Eisenberg More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002030.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Increasing preconception paternal comorbidity has been associated with adverse pregnancy outcomes including pregnancy loss and preterm birth. However, the relationship between a father’s health on the child after birth remains uncertain. In the present study, we examined the association of preconception paternal health with emergency department (ED) visits and hospitalizations of the children. METHODS: The IBM Marketscan Research database comprises of inpatient and outpatient healthcare claims from private, employer-insured individuals. Family groups were generated within Marketscan linking children born to paired fathers and mothers covering within the United States between 2009–2016. Within these groups, relevant ICD-9, ICD-10, CPT, and Diagnosis Related Group codes were used to query paternal and maternal metabolic syndrome (MetS) component diagnoses (hypertension, diabetes, hyperlipidemia, and obesity), and hospitalization and ED visit rates for offspring within the first two years of life. Models were adjusted for birth year, region, offspring sex, maternal and paternal age, maternal MetS, prematurity, NICU requirement, low birth weight, time of follow-up, and parental smoking status. All analyses were performed in SAS software version 9.4 (SAS Institute). RESULTS: During the observation period, 295,355 boys and 278,735 girls were born with 34.9% of children having at least one emergency room visit and 6.0% of children having an inpatient admission. After adjustment, the odds of inpatient admission and ED visits increased in a dose-dependent fashion among fathers with higher comorbidities. The child of a father with two MetS components was 13% more likely to require hospitalization in the first two years of life (95% CI 1.08-1.19) compared to the child of a father with no MetS components. Similarly, the child of a father with three or more MetS components was 22% more likely to have at least one emergency room visit (95% CI, 1.15-1.29) and 48% more likely to have had three or more ED visits (95% CI, 1.36-1.61) compared to a father with no components of MetS. Moreover, the association persists across maternal health strata. CONCLUSIONS: Increasing paternal preconception comorbidity is associated with a higher risk that a child requires ED and inpatient care in the first years of life. Whether the association is due to biologic, lifestyle, or a combination of factors, an opportunity exists to engage men in preconception counseling to optimize health. Source of Funding: National Institutes of Health National Center for Advancing Translational Science Clinical and Translational Science Award (UL1 TR001085) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e526-e526 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tony Chen More articles by this author Chiyuan Zhang More articles by this author Shufeng Li More articles by this author Gary Shaw More articles by this author Alan Schroeder More articles by this author Michael Eisenberg More articles by this author Expand All Advertisement Loading ...

Gestational metabolic syndrome and neonatal anthropometric indices: a prospective cohort study

Background and aim There is limited knowledge about the effect of maternal metabolic syndrome (MetS) on the anthropometric parameters of newborns. Therefore, the authors aimed to evaluate the association between MetS in the first trimester of pregnancy with weight and height of the newborn. Methods This prospective cohort study was conducted on 455 pregnant women in Tehran during their first trimester of pregnancy. MetS was defined as the coexistence of three or more of the following criteria: fasting blood sugar (FBS) level ≥92 mg/dl, blood pressure ≥130.85 mm/hg, triglyceride ≥150 mg/dl, high density lipoprotein ≤50 mg/dl, and body mass index (BMI) ≥30 kg/m2. All participants were followed up to childbirth. After birth, the baby's weight and height data were collected from the birth certificate. Results Linear regression analysis showed FBS (ß: 0.100, p-value: 0.038), BMI (ß: 0.139, p-value: 0.004), and MetS (ß: -0.122, p-value: 0.015) were significantly associated with birth weight but no statistically significant results were found for birth height. Conclusion MetS and some of its components in pregnancy can affect birth weight of neonates.

Effects of single and combined gestational phthalate exposure on blood pressure, blood glucose and gestational weight gain: A longitudinal analysis

Few studies have investigated the association of gestational exposure to phthalate with metabolic risk and have reached inconsistent conclusions. Based on the Ma’anshan Birth Cohort, 3273 women were included in the present study. All participants provided up to three urine samples for 7 phthalate metabolite measurements. The hazard index (HI) was used to evaluate the cumulative risk of multiple phthalate coexposures. The outcomes of interest included hypertensive disorders of pregnancy (HDOP), gestational diabetes mellitus (GDM), and gestational weight gain (GWG). The incidences of HDOP, GDM, and excessive GWG were 5.93%, 13.09%, and 28.95%, respectively. Exposure to a single phthalate metabolite or a specific diester during the first trimester of pregnancy elevated blood pressure (BP) and fasting plasma glucose (FPG) in the third trimester and body weight gain throughout pregnancy. However, inverse relationships were revealed for some phthalate metabolites, which were inconsistent with the results of their diesters. The HI value during the first trimester was positively associated with subsequent BP, FPG, and GWG. In addition, HI during the first trimester increased the risks of GDM [odds ratio (OR) = 1.34, 95% confidence intervals (CIs) = 1.02–1.75)] and excessive GWG (OR = 1.76, 95% CIs = 1.41–2.19) in a linear manner thereafter. Notably, phthalates might directly increase maternal blood glucose and pressure, and these changes were secondary effects of the obesiogenic effects of certain phthalates. In conclusion, exposure to single and multiple phthalates during the first trimester of pregnancy increased the risks of maternal metabolic syndrome components. However, the conflicting findings between phthalates and their metabolites need to be interpreted carefully.

Maternal metabolic syndrome induces liver injury and promotes tumor growth in the offspring

Abstract Objective Obesity is a growing disease entity affecting a third of women of reproductive age. Epidemiological studies show that children of obese mothers suffer from obesity, long-term morbidity and an increased rate of childhood cancers. However, the mechanisms of disease transmission remain unknown. The aim of this study is to test this hypothesis in a mouse model and shed light on the involved mechanisms of vertical transmission. Methods Female mice were fed a high fat or standard diet (HFD/SD) for 16 weeks before being mated with mice fed a normal diet. Corresponding diet was continued until weaning, all offspring were thereafter fed a SD. Metabolic profile, weight gain, liver enzymes and the gut microbiota profile were assessed in the offspring (n = 24). Additional groups of offspring (n = 48) were injected with a carcinogen (diethylnitrosamine) at week two, tumor characteristics were assessed by computed tomography scan at week 36. Results Mothers fed HFD developed obesity and non-alcoholic fatty liver disease (NAFLD). Female offspring of mothers fed HFD gained significantly more weight (+33.7%, p = 0.001), had increased alanine transaminase levels (62 vs 18 IU/L, p = 0.003) and a significantly altered liver histology exemplified by an increased NAFLD activity score (3.8 vs 0.6, p = 0.016). Expression levels of several candidate genes were studied of which FGF21 showed the largest differential expression between HFD and SD offspring (9 vs 1 2^ΔΔCT, p = &amp;lt;0.001). However, epigenetic analysis of FGF21 in the liver revealed no changes in methylation level between HFD and SD offspring. Furthermore, offspring of HFD mothers had a distinctly altered gut microbiome with lower proportions of Bacteroides caccae, Bacteroidales and Parasutterella excrementihominis. Interestingly, the proportion of female offspring developing tumors was significantly higher in offspring of HFD mothers (83 vs 44%, p = 0.011), the average total tumor volume was larger (234 vs 3.5mm3, p = 0.022) and the offspring developed more tumors (3.5 vs 0.6, p = 0.010). Conclusion Maternal obesity promotes liver tumor growth in the offspring, alters metabolic patterns and induces liver suffering in the progeny in a sex-dependent manner. The gut microbiome seems to play a role in this transmission of disease. Yet further research is needed to determine the vectors of transmission and evaluate preventive interventions in obese mothers.

Prenatal and perinatal metabolic risk factors for autism: a review and integration of findings from population-based studies.

Given the ongoing rise in prevalence of autism spectrum disorder (ASD) and the challenges in developing and administering interventions to significantly alleviate ASD symptoms, there is an urgent need to identify modifiable risk factors for ASD. The goal of this review is to systematically evaluate the current evidence for an association between conditions related to maternal metabolic syndrome and risk for ASD in offspring focusing on methodically rigorous studies. In recent years, multiple studies explored the association between various conditions related to maternal metabolic syndrome (obesity, hypertension, or diabetes prior to, or with onset during pregnancy) and ASD risk in the offspring. Examining large, sufficiently powered, population-based epidemiological studies that explored the association between maternal metabolic syndrome and ASD, we found consistent evidence for an association between maternal preeclampsia and risk for ASD. Other conditions that are part of maternal metabolic syndrome, including maternal obesity, gestational weight gain, diabetes and gestational diabetes, should be studied further with careful attention paid to potential synergistic effects between different metabolic conditions. These findings highlight the need for rigorous, large, population-based epidemiological studies of potentially modifiable ASD risk factors that could inform public health interventions.