Fetal brain and placental programming in maternal obesity: A review of human and animal model studies

Both human epidemiologic and animal model studies demonstrate that prenatal and lactational exposure to maternal obesity and high-fat diet are associated with adverse neurodevelopmental outcomes in offspring. Neurodevelopmental outcomes described in offspring of obese women include cognitive impairment, autism spectrum disorder (ASD), attention deficit hyperactivity disorder, anxiety and depression, disordered eating, and propensity for reward-driven behavior, among others. This review synthesizes human and animal data linking maternal obesity and high-fat diet consumption to abnormal fetal brain development, and neurodevelopmental and psychiatric morbidity in offspring. It highlights key mechanisms by which maternal obesity and maternal diet impact fetal and offspring development, and sex differences in offspring programming. In addition, we review placental effects of maternal obesity, and the role the placenta might play as an indicator vs mediator of fetal programming.     

Maternal obesity and neurodevelopmental and psychiatric disorders in offspring

There is a growing body of evidence from both human epidemiologic and animal studies that prenatal and lactational exposure to maternal obesity and high-fat diet are associated with neurodevelopmental and psychiatric disorders in offspring. These disorders include cognitive impairment, autism spectrum disorders, attention deficit hyperactivity disorder, cerebral palsy, anxiety and depression, schizophrenia, and eating disorders. This review synthesizes human and animal data linking maternal obesity and high-fat diet consumption to abnormal fetal brain development and neurodevelopmental and psychiatric morbidity in offspring. In addition, it highlights key mechanisms by which maternal obesity and maternal diet might impact fetal and offspring neurodevelopment, including neuroinflammation; increased oxidative stress, dysregulated insulin, glucose, and leptin signaling; dysregulated serotonergic and dopaminergic signaling; and perturbations in synaptic plasticity. Finally, the review summarizes available evidence regarding investigational therapeutic approaches to mitigate the harmful effects of maternal obesity on fetal and offspring neurodevelopment. © 2016 John Wiley & Sons, Ltd.     

Short- and long-term outcomes of gestational diabetes and its treatment on fetal development

Globally the prevalence of gestational diabetes mellitus (GDM) is rising mainly due to the increase in maternal obesity. A number of different methods to screen for and diagnose GDM have been described although consensus on the preferred methods does not yet exist. GDM has significant short- and long-term health risks for the mother, developing fetus and the children born to mothers with GDM. Short-term risks for the fetus include macrosomia (excessive birthweight), shoulder dystocia, birth trauma, and hypoglycaemia in the immediate postpartum period. Long-term risks for offspring born to mothers with GDM include increased rates of childhood and adulthood obesity and an increased cardiometabolic risk. A number of pharmacological treatments for GDM have been identified, these include insulin and oral glucose-lowering drugs metformin and glibenclamide. Whilst these oral glucose-lowering drugs show similar short-term childhood outcomes to insulin there is increasing evidence that these drugs may have adverse long-term outcomes on children and adults exposed to the drugs in utero. Future research on treatments for GDM should include long-term follow- up of children exposed to glucose lowering medication in utero to determine the long-term cardiometabolic risk in the offspring born to mothers with GDM.     

Effects of maternal diet and host quality on oviposition patterns and offspring performance in a seed beetle (Coleoptera: Bruchidae)

In seed beetles, oviposition decisions may influence the offspring phenotype because eggs constitute the initial resources available for larval development. We tested the effects of host quality variations (small vs. large seeds of the host plant Calystegia sepium, Convolvulaceae) on oviposition patterns and offspring performance of the seed beetle Megacerus eulophus. We also manipulated the maternal diet: high diet quality vs. low diet quality to evaluate possible interactive effects of the maternal nutritional environment and host quality on oviposition patterns. We further assessed the consequences of egg size variation in offspring size. Female M. eulophus fed with high-quality diet (H-diet) laid more eggs and lived longer than females fed with low-quality diet (P-diet). Fecundity decreased under a low-quality host for both maternal diets. The occurrence of maternal environmental effects on egg size plasticity was detected. Under conditions of low-quality host, mothers fed with the high-quality diet produced bigger eggs in comparison with a high-quality host, whereas females fed with the low-quality diet produced smaller ones. Regardless of these differences observed in egg size depending on the maternal diet, progeny emerging from small seeds (low-quality host) showed a similar performance at emergence. Offspring traits were only significantly affected by host quality. Beetles emerging from large seeds had greater body weight and length than those reared on small seeds. Variations in oviposition patterns in response to host quality are discussed.     

Maternal thyroid disease and its effects on the fetus and perinatal outcomes

Thyroid disease is common in women of childbearing age and can have significant effects on the development of the fetus and perinatal outcomes. Maternal thyroid hormone is critical for proper fetal neurodevelopment, and the fetus relies on thyroid hormone from its mother for the first half of pregnancy. Both overt maternal hypothyroidism and overt maternal hyperthyroidism have been shown to be associated with adverse effects on central nervous system gray matter and neurocognitive development of offspring as well as increased obstetrical risks. Treatment of overt thyroid conditions improves outcomes. Subclinical maternal hypothyroidism may increase adverse neurocognitive and obstetrical outcomes although data are conflicting. To date, treatment of subclinical hypothyroidism has not shown benefit. Subclinical hyperthyroidism is well tolerated in pregnancy. Thyroid autoantibodies alone may also affect neurodevelopment and obstetrical outcomes; however, recent data have shown no improvement with levothyroxine treatment. Several rare maternal genetic thyroid conditions can affect the fetus including a thyroid-stimulating hormone receptor mutation leading to hypersensitivity to human chorionic gonadotropin and thyroid hormone resistance. The thyroid plays a crucial role in fetal health and understanding it is important for optimal care.     

大气PM2.5及高脂饮食对哮喘发病影响的研究进展

大气PM_2.5暴露与呼吸系统疾病密切相关,高脂饮食是哮喘的诱因之一.近年来,哮喘发病率在我国呈上升趋势.对大气PM_2.5、高脂饮食及二者协同作用对哮喘发病的影响进行探讨,为哮喘的干预和治疗提供新思路.总结了PM_2.5暴露与高脂饮食对哮喘的影响以及哮喘的发病机制:①颗粒物暴露可引发机体炎症反应,增加哮喘发病风险;②高脂饮食可通过代谢活化机体内免疫相关信号通路,导致炎症发生;③二者均会通过MyD88/TLRs信号通路和Th1/Th2机制对哮喘炎症产生影响.研究显示,PM_2.5与高脂饮食对哮喘的作用机制具有一致性,二者对人群的健康影响可能具有协同作用.      

Product service systems as systemic cures for obese consumption and production

Many environmental and social problems emerged from our modern production and consumption habits are comparable with the symptoms of physical obesity. Based on this metaphor, effective approaches in obesity treatment can serve as a good reference in order to respond to over-consumption problems. Instead of stressing consumers to change their behaviours, we can attract them by means of providing appropriately designed PSS offers and giving them the opportunities to become aware of better alternatives. Successful examples seem to document support for the hypothesis that, ‘the multidimensional and dynamic approaches are the most promising diet solutions, which can lead to a leaner production and consumption figure.’     

Effects of paternal phenotype and environmental variability on age and size at maturity in a male dimorphic mite

Investigating how the environment affects age and size at maturity of individuals is crucial to understanding how changes in the environment affect population dynamics through the biology of a species. Paternal phenotype, maternal, and offspring environment may crucially influence these traits, but to my knowledge, their combined effects have not yet been tested. Here, I found that in bulb mites (Rhizoglyphus robini), maternal nutrition, offspring nutrition, and paternal phenotype (males are fighters, able to kill other mites, or benign scramblers) interactively affected offspring age and size at maturity. The largest effect occurred when both maternal and offspring nutrition was poor: in that case offspring from fighter sires required a significantly longer development time than offspring from scrambler sires. Investigating parental effects on the relationship between age and size at maturity revealed no paternal effects, and only for females was its shape influenced by maternal nutrition. Overall, this reaction norm was nonlinear. These non-genetic intergenerational effects may play a complex, yet unexplored role in influencing population fluctuations—possibly explaining why results from field studies often do not match theoretical predictions on maternal effects on population dynamics.     

Treatment of poor placentation and the prevention of associated adverse outcomes – what does the future hold?

Poor placentation, which manifests as pre-eclampsia and fetal growth restriction, is a major pregnancy complication. The underlying cause is a deficiency in normal trophoblast invasion of the spiral arteries, associated with placental inflammation, oxidative stress, and an antiangiogenic state. Peripartum therapies, such as prenatal maternal corticosteroids and magnesium sulphate, can prevent some of the adverse neonatal outcomes, but there is currently no treatment for poor placentation itself. Instead, management relies on identifying the consequences of poor placentation in the mother and fetus, with iatrogenic preterm delivery to minimise mortality and morbidity. Several promising therapies are currently under development to treat poor placentation, to improve fetal growth, and to prevent adverse neonatal outcomes. Interventions such as maternal nitric oxide donors, sildenafil citrate, vascular endothelial growth factor gene therapy, hydrogen sulphide donors, and statins address the underlying pathology, while maternal melatonin administration may provide fetal neuroprotection. In the future, these may provide a range of synergistic therapies for pre-eclampsia and fetal growth restriction, depending on the severity and gestation of onset. © 2014 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.     

Red cell alloimmunization: A 2020 update

Management of maternal red cell alloimmunization has been revolutionized over the last 60 years. Advances in the prevention, screening, diagnosis, and treatment of alloimmune-induced fetal anemia make this condition an exemplar for contemporary practice in fetal therapy. Since survival is now an expectation, attention has turned to optimization of long-term outcomes following an alloimmunized pregnancy. In this review, the current management of red cell alloimmunization is described. Current research and future directions are discussed with particular emphasis on later life outcomes after alloimmune fetal anemia.     

Maternal metabolomic profiling and congenital heart disease risk in offspring: A systematic review of observational studies

Aetiological understanding and screening methods for congenital heart disease (CHD) are limited. Maternal metabolomic assessment offers the potential to identify risk factors and biomarkers. We performed a systematic review (PROSPERO CRD42022308452) investigating the association between fetal/childhood CHD and endogenous maternal metabolites. Ovid-MEDLINE, Ovid-EMBASE and Cochrane Library were searched between inception and 06/09/2022. Case control studies included analysing maternal blood or urine metabolites in pregnancy or postpartum where there was foetal/childhood CHD. Risk of bias assessment utilised the Scottish Intercollegiate Guidelines Network methodology checklist and narrative synthesis was performed. A total of 134 records were screened with eight eligible studies (n = 3242 pregnancies, n = 842 CHD-affected offspring). Five studies performed metabolomic analysis in pregnancy. Metabolites distinguishing case and control groups spanned lipid, glucose and amino-acid pathways, with the development of sensitive risk prediction models. No single metabolite consistently distinguished cases and controls across studies. Three studies performed targeted analysis postnatally with altered lipid and amino acid metabolites and raised homocysteine and markers of oxidative stress identified in cases. Included studies reported small sample sizes, analysing different biosamples at variable time points using differing techniques. At present, there is not enough evidence to confidently associate maternal metabolomic profiles with offspring CHD risk. However, several identified pathways warrant further investigation.     

First-trimester maternal factors and biomarker screening for preeclampsia

Preeclampsia (PE), which affects about 2% of pregnancies, is a major cause of maternal and perinatal morbidity and mortality. PE can be subdivided into early onset PE with delivery <34 weeks' gestation and late onset PE with delivery ≥34 weeks. Early onset PE is associated with a higher incidence of adverse outcome. This review illustrates that effective screening for the development of early onset PE can be provided in the first-trimester of pregnancy. Screening by a combination of maternal risk factors, mean arterial pressure, uterine artery Doppler, maternal serum pregnancy-associated plasma protein-A and placental growth factor can identify about 95% of cases of early onset PE for a false-positive rate of 10%. © 2014 John Wiley & Sons, Ltd.     

Sex-biased investment in yolk androgens depends on female quality and laying order in zebra finches (Taeniopygia guttata)

The Trivers–Willard hypothesis predicts sex biases in parental investment according to parental condition. In addition, parents may need to sex bias their investment if there is an asymmetry between the sexes in offspring fitness under different conditions. For studying maternal differential investment, egg resources are ideal subjects because they are self contained and allocated unequivocally by the female. Recent studies show that yolk androgens can be beneficial to offspring, so here we test for sex-biased investment with maternal investment of yolk testosterone (T) in zebra finch (Taeniopygia guttata) eggs. From the Trivers–Willard hypothesis, we predicted females to invest more in male eggs in optimum circumstances (e.g. good-condition mother, early-laid egg), and more in female eggs under suboptimal conditions (e.g. poor-condition mother, late-laid egg). This latter prediction is also because in this species there is a female nestling disadvantage in poor conditions and we expected mothers to help compensate for this in female eggs. Indeed, we found more yolk T in female than male eggs. Moreover, in accordance with our predictions, yolk T in male eggs increased with maternal quality relative to female eggs, and decreased with laying order relative to female eggs. This supports our predictions for the different needs and value of male and female offspring in zebra finches. Our results support the idea that females may use yolk androgens as a tool to adaptively manipulate the inequalities between different nestlings.     

Advanced paternal age,infertility, and reproductive risks: A review of the literature

Advanced paternal age (APA) is associated with infertility and other reproductive risks. Studies looking at APA and outcomes have used different paternal age cut-offs, which has complicated systematic evaluations of reproductive risk associated with paternal aging. This review of the literature suggests that the impact of paternal aging on adverse reproductive outcomes is small, but significant. Studies suggest the incidence of paternal age effect disorders attributed to de novo autosomal dominant mutations is less than 0.5%. Other risks associated with APA include infertility, miscarriage, birth defects, poor neurodevelopmental outcomes, and childhood cancer. Although the increasing prevalence of APA has mirrored the rise in maternal age, this topic has not received similar attention. In this review, we summarize the available literature on the reproductive risks associated with APA to provide a framework for comprehensive genetic counseling and evidence-based management of APA pregnancies.     

海底重燃油对海胆繁殖及其子代发育的影响

利用室内流水式粘油砾石柱模拟实际环境中的海底重燃油,研究了重燃油污染的孔隙水对成年海胆繁殖力、配子质量及子代胚胎发育的影响.结果表明,暴露结束后（7d）,暴露组海胆的排配子率显著降低（P=0.033）,同时雌海胆繁殖力也显著降低（P=0.036,（1957917±811471）个卵细胞）;卵细胞的直径和精子的受精能力并未受到海底重燃油的影响.子代继续暴露48h,发现亲代暴露加剧了子代胚胎畸形程度,表明亲代暴露的毒性可传递给子代.进一步利用整合毒性指数（ITI）检测毒性传递的性别差异发现,与母本效应相比（24和48h子代的ITI分别为0.54~1.45和1.1~2.57）,父本效应（24和48h子代的ITI分别为0.82~1.95和1.89~4.04）在毒性传递过程中起着关键作用.     

Maternal genetic disorders and fetal development

With improvements in early diagnosis and management of genetic diseases, more women with genetic disorders are reaching reproductive age and becoming pregnant. While pregnancy can have a significant impact on a woman's health when there is an underlying genetic disorder, there can also be fetal effects, including embryopathy, fetal growth restriction, and brain injury. Some maternal genetic disorders are associated with adverse perinatal outcomes, including a high risk of perinatal loss and preterm birth. In this article, we review several maternal genetic disorders associated with fetal risk that are important for clinicians and patients to understand and manage appropriately. These include phenylalanine hydroxylase (PAH) deficiency and other inborn errors of metabolism, tuberous sclerosis complex, myotonic dystrophy, cystic fibrosis, Turner syndrome, sickle cell disease, and connective tissue disorders.     

Intrauterine growth restriction (IUGR): biometric and Doppler assessment

Intrauterine growth restriction (IUGR) is a common complication in pregnancy and influences morbidity and mortality at all stages of life. Historically, the management of IUGR has been dependent on antenatal biophysical testing and umbilical artery Doppler studies. With recent Doppler studies of the fetal central circulation, including intracardiac flows and the ductus venosus, better timing of delivery to minimize morbidity may be possible. This review will provide the reader with tools to diagnose IUGR, more accurately date the IUGR pregnancy with poor dating criteria, and better assess the condition of the IUGR fetus. A brief review of animal models of IUGR is presented to demonstrate research directions for answering human clinical questions and potentially carrying therapeutic intervention from the bench to the bedside. Copyright © 2002 John Wiley & Sons, Ltd.     

Mercury in aquatic fauna contamination: A systematic review on its dynamics and potential health risks

Mercury is an important pollutant, released into aquatic ecosystems both naturally and by anthropogenic action. This element is transferred to aquatic organisms in different ways, causing potential health risks. In addition, mercury can be accumulated by humans, especially through the consumption of contaminated food. This systematic review aims to present mercury pathways, the major routes through which this element reaches the aquatic environment and its transformations until becoming available to living animals, leading to bioaccumulation and biomagnification phenomena. The key biotic and abiotic factors affecting such processes, the impact of mercury on animal and human health and the issue of seafood consumption as a source of chronic mercury contamination are also addressed. A total of 101 articles were retrieved from a standardized search on three databases (PubMed, Emabse, and Web of Science), in addition to 28 other studies not found on these databases but considered fundamental to this review (totaling 129 articles). Both biotic and abiotic factors display fundamental importance in mediating mercurial dynamics, i.e., muscle tropism, and salinity, respectively. Consequently, mercurial contamination in aquatic environments affects animal health, especially the risk of extinction species and also on human health, with methylmercury the main mercury species responsible for acute and chronic symptomatology.     

A review of fetal and neonatal consequences of maternal systemic lupus erythematosus

Systemic lupus erythematosus (SLE) primarily affects women of childbearing age and is commonly seen in pregnancy. The physiologic and immunologic changes of pregnancy may alter the course of SLE and impact maternal, fetal, and neonatal health. Multidisciplinary counseling before and during pregnancy from rheumatology, maternal fetal medicine, obstetrics, and pediatric cardiology is critical. Transplacental passage of autoantibodies, present in about 40% of women with SLE, can result in neonatal lupus (NL). NL can consist of usually permanent cardiac manifestations, including conduction system and myocardial disease, as well as transient cutaneous, hematologic, and hepatic manifestations. Additionally, women with SLE are more likely to develop adverse pregnancy outcomes such as preeclampsia, fetal growth restriction, and preterm birth, perhaps due to an underlying effect on placentation. This review describes the impact of SLE on maternal and fetal health by trimester, beginning with prepregnancy optimization of maternal health. This is followed by a discussion of NL and the current understanding of the epidemiology and pathophysiology of anti-Ro/La mediated cardiac disease, as well as screening, treatment, and methods for prevention. Finally discussed is the known increase in preeclampsia and fetal growth issues in women with SLE that can lead to iatrogenic preterm delivery.     

SARS-CoV-2 in the context of past coronaviruses epidemics: Consideration for prenatal care

Since December 2019, the novel SARS-CoV-2 outbreak has resulted in millions of cases and more than 200 000 deaths worldwide. The clinical course among nonpregnant women has been described, but data about potential risks for women and their fetus remain scarce. The SARS and MERS epidemics were responsible for miscarriages, adverse fetal and neonatal outcomes, and maternal deaths. For COVID-19 infection, only nine cases of maternal death have been reported as of 22 April 2020, and pregnant women seem to develop the same clinical presentation as the general population. However, severe maternal cases, as well as prematurity, fetal distress, and stillbirth among newborns have been reported. The SARS-CoV-2 pandemic greatly impacts prenatal management and surveillance and raise the need for clear unanimous guidelines. In this narrative review, we describe the current knowledge about coronaviruses (SARS, MERS, and SARS-CoV-2) risks and consequences on pregnancies, and we summarize available current candidate therapeutic options for pregnant women. Finally, we compare current guidance proposed by The Royal College of Obstetricians and Gynaecologists, The American College of Obstetricians and Gynecologists, and the World Health Organization to give an overview of prenatal management which should be utilized until future data appear.