Fetal Development Research Articles

Recent advances in extracellular matrix manipulation for kidney organoid research

The kidney plays a crucial role in maintaining the body’s microenvironment homeostasis. However, current treatment options and therapeutic agents for chronic kidney disease (CKD) are limited. Fortunately, the advent of kidney organoids has introduced a novel in vitro model for studying kidney diseases and drug screening. Despite significant efforts has been leveraged to mimic the spatial-temporal dynamics of fetal renal development in various types of kidney organoids, there is still a discrepancy in cell types and maturity compared to native kidney tissue. The extracellular matrix (ECM) plays a crucial role in regulating cellular signaling, which ultimately affects cell fate decision. As a result, ECM can refine the microenvironment of organoids, promoting their efficient differentiation and maturation. This review examines the existing techniques for culturing kidney organoids, evaluates the strengths and weaknesses of various types of kidney organoids, and assesses the advancements and limitations associated with the utilization of the ECM in kidney organoid culture. Additionally, it presents a discussion on constructing specific physiological and pathological microenvironments using decellularized extracellular matrix during certain developmental stages or disease occurrences, aiding the development of kidney organoids and disease models.

Maternal Nutritional Factors Enhance Birthweight Prediction: A Super Learner Ensemble Approach

Birthweight (BW) is a widely used indicator of neonatal health, with low birthweight (LBW) being linked to higher risks of morbidity and mortality. Timely and precise prediction of LBW is crucial for ensuring newborn health and well-being. Despite recent machine learning advancements in BW classification based on physiological traits in the mother and ultrasound outcomes, maternal status in essential micronutrients for fetal development is yet to be fully exploited for BW prediction. This study aims to evaluate the impact of maternal nutritional factors, specifically mid-pregnancy plasma concentrations of vitamin B12, folate, and anemia on BW prediction. This study analyzed data from 729 pregnant women in Tarragona, Spain, for early BW prediction and analyzed each factor’s impact and contribution using a partial dependency plot and feature importance. Using a super learner ensemble method with tenfold cross-validation, the model achieved a prediction accuracy of 96.19% and an AUC-ROC of 0.96, outperforming single-model approaches. Vitamin B12 and folate status were identified as significant predictors, underscoring their importance in reducing LBW risk. The findings highlight the critical role of maternal nutritional factors in BW prediction and suggest that monitoring vitamin B12 and folate levels during pregnancy could enhance prenatal care and mitigate neonatal complications associated with LBW.

Hypoprolactinemia, a neglected endocrine disorder.

This special issue of Reviews in Endocrine and Metabolic Disorders is dedicated to hypoprolactinemia. Prolactin is known for its actions on the mammary gland including development, preparation for postpartum lactation, as well as synthesis and maintenance of milk secretion. However, prolactin has many other physiological effects on reproduction, embryonic and fetal development, homeostasis, neuroprotection, behavior, and immunoregulation. In clinical practice, physiopathology and clinical consequences of increased prolactin secretion are generally well understood, and medical treatment to decrease prolactin levels is available and effective in most cases. Unlike prolactin excess, hypoprolactinemia has been a neglected endocrine disorder and nospecific replacement therapy is commercially available. Prolactin is the only anterior pituitary hormone not addressed by clinical hypopituitarism guidelines. In recent years, human studies have revealed that hypoprolactinemia is associated with metabolic, sexual and neuropsychologic alterations. Therefore, this special issue of Reviews in Endocrine and Metabolic Disorders is aimed to enhance our incomplete understanding of hypoprolactinemia. A total of 17 articles were authored by respected scientists and clinicians from a variety of disciplines including adult and pediatric endocrinology, pathology, gynecology, reproductive medicine, oncology, and neurosurgery.

Probiotic-rich fermented milk from Lactiplantibacillus plantarum IIA-1A5: Effects on pregnancy health in the animal model

Previous studies of Lactiplantibacillus plantarum IIA-1A5 have shown its potential as a probiotic in modulating gut microbiota and providing health benefits; however, its effects during pregnancy remain underexplored. The aim of this study was to assess the safety of fermented milk enriched with L. plantarum IIA-IA5 in pregnant mice. An experimental study was conducted at Universitas Andalas, Padang, Indonesia. Two groups of pregnant mice (Mus musculus L.) were used, each with six mice. The control group received sterilized milk (10 mL/kg body weight (BW)), while the intervention group was given fermented milk containing L. plantarum IIA-1A5 (107 colony forming unit (CFU)/mL). The evaluated outcomes included maternal weight changes, fetal counts and measurements, and assessments of fetal morphology and skeletal development. Results indicated that the morphology of fetuses showed no significant differences between the control and intervention groups; both groups demonstrated normal development with no detected resorption sites, growth retardation, or hemorrhage. For skeletal development, both groups had the same bone counts, including frontal, parietal, intraparietal, exoccipital, supraoccipital, nasal, pre-maxilla, mandibular, thoracal, lumbar, sternum, and extremities. This study highlights that L. plantarum IIA-1A5-enriched fermented milk was safe, as no significant morphological or bone developmental abnormalities were observed, indicating its potential as a dietary supplement to support pregnancy health. However, further studies involving larger sample sizes may be needed to provide a more comprehensive assessment of its outcomes and safety.

Prenatal exposure to ambient fine particulate matter and child lung function in the CANDLE cohort

Background Ambient fine particulate matter (PM2.5) exposure adversely impacts child airway health; however, research on prenatal PM2.5 exposure, and child lung function is limited. We investigated these associations in the ECHO-PATHWAYS Consortium, focusing on the role of exposure timing during different phases of fetal lung development. Methods We included 675 children in the CANDLE cohort born between 2007 and 2011 in Memphis, TN, USA. Prenatal exposure to ambient PM2.5 was estimated using a spatiotemporal model based on maternal residential history and averaged over established prenatal periods of lung development. Forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) were measured by spirometry at age 8–9 years. We used linear regression and Bayesian Distributed Lag Interaction Models (BDLIM) to estimate associations between exposure and lung function z-scores, adjusting for maternal/child characteristics, prenatal/postnatal tobacco exposure, and birth year/season, and evaluating effect modification by child sex and allergic sensitization. Results The average ambient concentration of PM2.5 during pregnancy was 11.1 µg/m3 (standard deviation:1.0 µg/m3). In the adjusted linear regression and BDLIM models, adverse, but not statistically significant, associations were observed between exposure during the pseudoglandular (5–16 weeks of gestation) and saccular (24–36 weeks) phases of lung development and FEV1 and FVC. The strongest association was between a 2 μg/m3 higher concentration of PM2.5 during the saccular phase and FEV1 z-score (−0.176, 95% Confidence Interval [CI]: −0.361, 0.010). The FEV1/FVC ratio was not associated with PM2.5 in any exposure window. No effect modification by child sex or allergic sensitization was observed. Conclusions We did not find strong evidence of associations between prenatal ambient PM2.5 exposure and child lung function in a large, well-characterized study sample. However, there was a suggested adverse association between FEV1 and exposure during late pregnancy. The saccular phase of lung development might be an important window for exposure to PM2.5.

Sex-bias metabolism of fetal organs, and their relationship to the regulation of fetal brain-placental axis.

The placenta plays influential role in the fetal development of mammals. But how the metabolic need of the fetal organs is related to that of the placenta, and whether this relationship is influenced by the sex of the fetus remain poorly understood. This study used pigs to investigate metabolomic signatures of male and female fetal organs, and determine the relevance of gene expression of the placenta and brain to the metabolism of peripheral organs. Untargeted metabolomics analysis was performed with the day-45 placenta, kidney, heart, liver, lung and brain of male and female pig fetuses to model sex differences in themetabolism of the peripheral organs relative to that of the brain and placenta. Transcriptomic analysis was performed to investigate the expression of metabolic genes in the placenta and fetal brain of both sexes. The results of this study show that the fetoplacental metabolic regulation was not only influenced by the fetal sex but also dependent on the metabolic requirement of theindividual organs of the fetus. Neural network modeling of metabolomics data revealed differential relationship of the metabolic changes of the peripheral organs with the placenta and fetal brain between males and females. RNA sequencing further showed that genes associated with themetabolism of the peripheral organs were differentially expressed in the placenta and fetal brain. The findings of this study suggest a regulatory role of the fetal brain and placenta axis in the sex-bias metabolism of the peripheral organs.

Trisomy 26 in a Holstein calf with disorders of sex development.

Hypospadias occurs sporadically in male livestock and is characterized by a non-fused urethra during fetal development. In this study, perineal hypospadias, a bifid scrotum, penile hypoplasia, and bilateral abdominal cryptorchidism were diagnosed in a neonatal Holstein male calf. Septicemia was also suspected due to hypothermia, blurred conjunctivae, and loss of sucking and swallowing reflexes. Gross pathology revealed that both testicles were located intraabdominally caudally to the kidneys. Histopathological examination of the hypospadias showed a urothelium-lined mucosal fold and parts of the corpus cavernosum penis and prepuce in the subcutis. Whole genome sequencing was performed on the affected calf. Analysis of short-read coverage depth along the chromosomes identified an entire extra copy of chromosome 26. Based on the comparison of available variant calling data from the sire, the identified trisomy 26 is due to non-disjunction of homologous chromosomes during the generation of paternal gametes. We have shown for the first time an association between bovine hypospadias and trisomy 26, which adds to the understanding of variation in fetal male sexual development.

Analysis of the relationship between neonatal birth weight and meconium metabolites based on birth cohort metabolomics

Neonatal birth weight is a crucial indicator of intrauterine growth and development with important implications for child development and adult health. The birth weight of a newborn is closely linked to the nutrition and health of the mother during pregnancy as well as genetic factors. Therefore, assessing the metabolic status of the fetus in utero is greatly significant for understanding the mechanisms responsible for abnormal birth weight. While previous studies often analyzed the impact of maternal metabolism on fetal development using umbilical cord blood from pregnant women, such blood may not accurately reflect the actual intrauterine environment owing to the barrier function of the placenta; moreover, obtaining biological samples during the fetal period is challenging. Meconium, the first feces excreted by a newborn, provides ideal biological material for studying maternal and infant health. Metabolomics can reveal metabolic changes in living organisms by analyzing small molecules in biological samples; hence studying meconium samples using metabolomics technology is expected to reveal fetal metabolic changes during pregnancy, thereby providing new insights into fetal nutritional intake, growth, and development, as well as metabolic pathways related to birth weight. To gain a deeper understanding of the metabolic changes associated with birth weight, this study collected metabolomic data from the meconium of 484 newborns in the established Xiaogan birth cohort using an untargeted metabolomics technique based on liquid chromatography-high resolution mass spectrometry (LC-HRMS) and analyzed the association between meconium metabolites and birth weight. This cohort exhibited incidence rates of low birth weight (<2500 g) and macrosomia (>4000 g) of 3.3% and 7.2%, respectively, which were roughly equivalent to the national average. Orthogonal partial least squares discriminant analysis revealed significant differences between the meconium metabolomes of the low birth weight and macrosomic groups when compared to the normal weight group. We discovered significant distinctions between the differential metabolites of newborns of low birth weight and those of normal weight, as well as between macrosomic and normal weight newborns that point to disparate biological pathways. Newborns with low birth weight exhibited significantly lower levels of critical amino acids, such as glutamate and proline, compared to the normal weight group, which may be associated with placental dysfunction and maternal nutritional deficiencies. Conversely, the meconium of macrosomic newborns contained significantly elevated levels of hormone metabolites such as estrone that reflected the pathophysiological state associated with maternal metabolic diseases or excessive placental hormone levels. Our study suggests that the metabolomic profile of the meconium reflects the metabolic pathways and regulatory mechanisms at play during fetal growth and development, and offers potential metabolic biomarkers and directions for future in-depth research into diseases related to fetal development. However, this study was based solely on the Xiaogan birth cohort, which was limited to specific regions and populations. A multicenter, multiethnic, and multiregional study is expected to help validate the universality of our research findings.

An inhalation exposure assessment of Hexafluoroisobutylene in pregnant rats.

Hexafluoroisobutylene (HFIB) is an important compound widely used in semiconductor lithography materials, refrigerants, fluorine coatings, and pharmaceutical intermediates in the fluorination industry. Owing to its toxicity, the occupational exposure in the workplace, especially for pregnant woman is the concern and there is still lack of the data of HFIB toxicity on pregnancy and fetal development. Here, for the first time, we investigated the effects of HFIB on pregnant rats and fetal development. The pregnant rats were exposed to different doses of HFIB (0 ppm, 27.2 ppm, 53.5 ppm, 105.6 ppm) via whole-body inhalation for the period of organogenesis, which from implantation (gestation day 5) to the day prior to scheduled caesarean section (gestation day 19). The results showed that the pregnant rats exposed to 105.6 ppm HFIB displayed systemic toxicity, including a decrease in body weight and food consumption, as well as tracheal inflammation, pulmonary interstitial inflammation and renal tubular swelling. Moreover, reduced fetal and placental weights, delayed ossification, and a reduced number of ossification centers were observed in fetuses delivered by pregnant rats exposed to 105.6 ppm. These effects were attributed to severe maternal weight loss. In addition, it would be useful to note that no whole-body, visceral or skeletal congenital malformations were observed. However, HFIB exposure at 53.5 ppm showed no significant adverse effects on pregnant rats and fetuses. These findings demonstrate that 105.6 ppm HFIB is a toxic concentration, while 53.5 ppm HFIB is the no-observed-adverse-effect concentration (NOAEC) for both pregnancy and fetal development. This study for the first time to provide evidence for the health risk of HFIB exposure on pregnancy and fetal development.

Phthalate exposure and reproductive effects in rodents: a model for approaches on the protective role of natural products.

This review article summarizes the experimental findings in rodents published between 2014 and 2024 concerning phthalates exposure and reproductive outcomes. Rodents were chosen for this review since most studies that have developmental aspects in different phases of exposure and that address more in-depth reproductive mechanisms have been carried out in mice and rats. The evidence of adverse effects of phthalates on fetal development and human and animal reproduction is extensive, with impacts ranging from gene expression to physiological alterations. Despite the large volume of scientific papers pointing out the harmful effects of exposure to phthalates, isolated or in mixtures, at different developmental periods, most of them are associated with the maternal exposure and long-term effects in the offspring. Regular vegetables, fruits, fish, dairy products, and whole grains intake rich in bioactive compounds can mitigate the adverse effects of EDCs in humans and animals at different developmental periods. Various food bioactive compounds (FBCs) such as genistein, resveratrol, lycopene, vitamin E, curcumin, selenium, and plant secondary metabolites (PSMs) present antioxidant, anti-inflammatory, anti-tumor, and other biological properties with the potential to reduce of deleterious effects of phthalates on the reproductive tract. In this review, we aimed to summarize the main studies produced in the last decade about phthalate exposure and reproductive disorders in males and females (at different developmental critical windows). Additionally, we proposed some FBCs and PSMs that could attenuate the main adverse effects caused by phthalate exposure on male reproduction since there is a lack of studies with females.

Effects of Mimosa pudica Extract on Asthma Biomarkers and Fetal Development in Pregnant Rats

Effects of Mimosa pudica Extract on Asthma Biomarkers and Fetal Development in Pregnant Rats

FGF8-mediated gene regulation affects regional identity in human cerebral organoids.

The morphogen FGF8 establishes graded positional cues imparting regional cellular responses via modulation of early target genes. The roles of FGF signaling and its effector genes remain poorly characterized in human experimental models mimicking early fetal telencephalic development. We used hiPSC-derived cerebral organoids as an in vitro platform to investigate the effect of FGF8 signaling on neural identity and differentiation. We found that FGF8 treatment increases cellular heterogeneity, leading to distinct telencephalic and mesencephalic-like domains that co-develop in multi-regional organoids. Within telencephalic domains, FGF8 affects the anteroposterior and dorsoventral identity of neural progenitors and the balance between GABAergic and glutamatergic neurons, thus impacting spontaneous neuronal network activity. Moreover, FGF8 efficiently modulates key regulators responsible for several human neurodevelopmental disorders. Overall, our results show that FGF8 signaling is directly involved in both regional patterning and cellular diversity in human cerebral organoids and in modulating genes associated with normal and pathological neural development.

The Importance of Optimal Nutritional Intake for The Health of Pregnant Women in Indonesia: Key Challenges and Strategic Solutions

Optimal nutrition during pregnancy plays a vital role in ensuring maternal health and healthy fetal development. Appropriate nutritional needs, including macronutrients and micronutrients, are essential to support fetal growth, prevent pregnancy complications, and reduce the risk of premature birth and low birth weight. In Indonesia, maternal nutrition is still a major challenge, with a high prevalence of anemia and chronic energy deficiency. Factors such as economic constraints, unequal access to health services, lack of education about the importance of nutrition, and socio-cultural influences on diet, exacerbate this condition. The challenge in meeting the nutritional needs of pregnant women is also related to the low awareness and knowledge of nutrition among the community, especially in remote areas. To overcome this problem, a multi-sectoral approach is needed involving government intervention, community empowerment, and increasing access to health services. Continuous education and targeted nutritional assistance programs can be effective solutions in improving the nutritional status of pregnant women in Indonesia. Thus, strong cooperation is needed between various stakeholders to ensure optimal maternal health, which will ultimately improve the quality of future generations.

COVID-19 and Its Potential Impact on Children Born to Mothers Infected During Pregnancy: A Comprehensive Review

Pregnancy is a vulnerable period of time during which pregnant people are prone to infections like COVID-19, which can increase risks for both the mother and fetus. These infections may lead to complications such as preterm birth, developmental delays, and congenital abnormalities. While COVID-19 poses additional risks like placental dysfunction and neonatal infections, studies on long-term effects remain limited. Ongoing research and monitoring are essential to understand and mitigate potential cognitive and developmental challenges in children born to mothers infected with COVID-19. This review aims to guide clinicians in managing these risks throughout childhood. Maternal COVID-19 infection during pregnancy can have significant implications for fetal development, even if the newborn is not infected at birth. The release of inflammatory cytokines may cross the placental barrier, potentially disrupting fetal brain development and increasing the risk of long-term cognitive and behavioral issues, such as ADHD or autism. Placental dysfunction, caused by inflammation or thrombosis, can lead to intrauterine growth restriction (IUGR), preterm birth, or hypoxia, affecting both neurological and respiratory health in newborns. Furthermore, a compromised fetal immune system can increase susceptibility to autoimmune conditions and infections. The early diagnosis and management of infections during pregnancy are crucial in mitigating risks to both the mother and fetus. Swift intervention can prevent complications like preterm birth and long-term developmental challenges, ensuring better health outcomes for both the mother and child. Long-term monitoring of children born to mothers infected with COVID-19 is necessary to understand the full extent of the virus’s impact. This review evaluates the long-term systemic effects of maternal COVID-19 infection during pregnancy on fetuses, newborns, and children, focusing beyond vertical transmission. It highlights the broader impacts on fetal development, offering insights to help clinicians manage potential issues that may arise later in life.

Study of Masanumasika Garbha Vikas Krama (Monthwise Devlopment during Pregnancy) in Context to Embryogenesis and Foetal Development

Sushruta Samhita is a significant Ayurvedic text on human anatomy and physiology. It provides detailed information on Garbha Vriddhi and Vikas Krama (Growth and Development) Various texts express different opinions regarding Garbha Utpatti (Fertilization) and Garbha Vriddhi. Acharyas have explained Garbhini Lakshana (Gravida symptoms) also. Which are helpful in early pregnancy diagnosis. Charaka has explained month wise symptoms in Garbhini during pregnancy. Now days, obstetrics is a fundamental field of study dealing with human reproduction, offering comprehensive information on fetal growth and development. Contemporary obstetrics has undergone extensive research and development. Neonatal mortality and fetal fatality are always the causes of concern. Samhitas provide pertinent resources on these topics. Acharyas have discussed about these in the reference of Garbhini. It takes a great deal of research and debate to comprehend the old Garbha Utpatti or Garbhavkranti notion. Examining both contemporary and Ayurvedic literature will aid in learning more about this. The goal of this study is to compare and clarify the concepts of embryogenesis from antiquity to the present

Ethanol consumption during gestation promotes placental alterations in IGF-1 deficient mouse placentas

Background During pregnancy, the placenta is an extremely important organ as it secretes its own hormones, e.g. insulin-like growth factor 1 (IGF-1), to ensure proper intrauterine fetal growth and development. Ethanol, an addictive and widely used drug, has numerous adverse effects during pregnancy, including fetal growth restriction (FGR). To date, the molecular mechanisms by which ethanol triggers its toxic effects during pregnancy, particularly in the placenta, are not entirely known. For this reason, a murine model of partial IGF-1 deficiency was used to determine ethanol alterations in placental morphology and aspartyl/asparaginyl β-hydroxylase (AAH) expression. Methods Wild type (WT, Igf1 +/+) and heterozygous (HZ, Igf1 +/-) female mice were given 10% ethanol in water during 14 days as an acclimation period and throughout pregnancy. WT and HZ female mice given water were used as controls. At gestational day 19, pregnant dams were sacrificed, placentas were collected and genotyped for subsequent studies. Results IGF-1 deficiency and ethanol consumption during pregnancy altered placental morphology, and decreased placental efficiency and AAH expression in placentas from all genotypes. No differences were found in Igf1, Igf2, Igf1r and Igf2r mRNA expression in placentas from all groups. Conclusions IGF-1 deficiency and ethanol consumption throughout gestation altered placental development, suggesting the crucial role of IGF-1 in the establishment of an adequate intrauterine environment that allows fetal growth. However, more studies are needed to study the precise mechanism to stablish the relation between both insults.

Intrapartum Electronic Cigarette Use and Birth Outcomes: Evidence from a Population-Based Study

The harms of combustible cigarette (CC) use in pregnancy for fetal development are well studied. Less understood are the potential impacts of newer non-combustible cigarette alternatives, including electronic cigarettes (ECs). Our goal was to examine whether EC use during pregnancy predicts increased risk of adverse birth outcomes. This retrospective cohort study used data from the Obstetrics Initiative (OBI), a statewide collaborative of 70 maternity hospitals. OBI’s clinical registry of data on nulliparous, term, singleton, and vertex fetal presentation pregnancies were from medical records. Three groups of pregnancy cigarette users (Controls (n = 26,394), CC (n = 2216), and EC (n = 493)) were compared on birth outcomes, controlling for background differences. Controls were defined as nonsmokers of ECs or CCs. Compared to the controls, the EC group had significantly lower birth weight, while the CC group had reduced birthweight and greater rates of arterial cord pH &lt; 7.1. Compared to EC users, CC users had higher rates of neonates requiring antibiotics and NICU admission. Growing evidence suggests ECs are not safer alternatives to CCs and use during pregnancy should be discouraged. Additional research is needed, as non-significant trends for increased risk of several adverse neonatal outcomes following EC use were found, potentially significant in larger studies with average risk for adverse pregnancy outcomes and when frequency and timing of EC exposure are considered.

ATUAÇÃO DO ENFERMEIRO NA ASSISTÊNCIA AO PRÉ-NATAL DE ALTO RISCO NAS UNIDADES DE SAÚDE

The assistance provided by nurses to pregnant women, especially those at high risk, is crucial to guarantee maternal health and good fetal development. Prenatal care is an essential tool in the identification, treatment and control of possible pathologies during pregnancy and postpartum, aiming to reduce morbidity and mortality rates. Recent studies show that, in 2020, approximately 60% of pregnancy-related deaths could have been avoided with adequate prenatal care, especially in high-risk pregnancies. In the state of Acre, between 2016 and 2021, 89 deaths related to pregnancy, childbirth and the postpartum period were recorded, reinforcing the need for prevention policies and specialized care. This study focuses on the role of nurses in basic health units, addressing the complexities of monitoring high-risk pregnancies and presenting the role of this professional in interpreting events and managing frailties. The method applied was a literature review, based on articles and journals from databases such as Scielo, Google Scholar and LILACS. The results demonstrated the importance of prenatal care in UBS and highlighted the protocols followed by nurses to humanize care and improve the quality of care. It is concluded that the continuous training of nurses is vital to guarantee satisfactory results in prenatal care, promoting and preventing complications in the mother-baby binomial.

Prenatal exposure to air pollution during the early and middle stages of pregnancy is associated with adverse neurodevelopmental outcomes at ages 1 to 3 years

BackgroundA large body of data shows that fetal brain development is vulnerable to disruption by air pollution experienced by the mother during pregnancy, adversely affecting cognitive and psychomotor capabilities during childhood (De Asis-Cruz et al., Biol Psychiatry 7:480–90, 2022; Morgan ZEM et al., Environ Health 22:11, 2023). This study has sought to identify gestational windows of susceptibility to prenatal exposure to air pollution.Methods470 African American and Latina mother/child pairs participated in a prospective cohort study based in the low-income communities of Northern Manhattan and the South Bronx, New York City. Gestational exposure to respirable particulate matter (PM2.5) and nitrogen dioxide (NO2) was assessed through validated models in relation to cognitive and motor development assessed at ages 1, 2, and 3 years using the Bayley-II Scales. Multiple linear regression models and distributed lag models (DLM) were used to identify critical windows of exposure by trimester and week of pregnancy.ResultsBy linear regression, average exposures to NO2 during the first and second trimesters and the entire pregnancy were significantly and negatively associated with the mental developmental index (MDI) at age 1. Average exposures to PM2.5 during the second trimester and the entire pregnancy were also significantly, inversely associated with age 1 MDI. No significant associations were found between these exposures and MDI at age 2. NO2 exposure during the first trimester was significantly negatively associated with MDI at age 3. Using DLM, exposures to NO2 at lags 29–30 weeks (within the first trimester) and PM2.5 at lags 17–18 weeks (second trimester) were significantly and inversely associated with MDI at age 1. Significant, inverse associations were found between exposures to NO2 at lag 29 weeks and PM2.5 at lags 27–29 weeks and children’s MDI at age 3. No significant associations were found between psychomotor index (PDI) and prenatal exposures to NO2 or PM2.5 at ages 1, 2 or 3.ConclusionsOur finding that prenatal exposure to air pollution in the first and second trimesters was associated with lower scores for cognitive development at ages 1 and 3 is of concern because of the potential consequences of these outcomes for long-term functioning. They underscore the need for stronger policies to protect pregnant individuals and offspring, particularly during vulnerable, early life-stage of development.

Reverse epidemiology of obesity paradox: Fact or fiction?

Obesity paradox refers to the clinical observation that when acute cardiovascular decompensation occurs, patients with obesity may have a survival benefit. This apparently runs counter to the epidemiology of obesity, which may increase the risk for non-communicable diseases (NCDs). The scientific community is split on obesity paradox, with some supporting it, while others call it BMI paradox. This review: (a) defines the obesity paradox, and its proposed role in overall mortality in NCDs; (b) delineates evidence for and against obesity paradox; (c) presents the importance of using different indices of body mass to assess the risk in NCDs; (d) examines the role of metabolically healthy obesity in obesity paradox, and emerging importance of cardio-respiratory fitness (CRF) as an independent predictor of CVD risk and all-cause mortality in patients with/without obesity. Evidence suggests that the development of obesity and insulin resistance are influenced by genetic (or ethnic) make up and dietary habits (culture) of the individuals. Hence, this review presents lean diabetes, which has higher total CVD and non-CVD mortality as compared to diabetics with obesity and the possibility of maternal factors programming cardiometabolic risk during fetal development, which may lead to a paradigm shift in our understanding of obesity.