Prenatal Stages Research Articles

Risk factors of postpartum hemorrhage due to uterine atony: a retrospective cohort study

Background: Postpartum hemorrhage (PPH) continues to be a significant global burden leading to high maternal mortality and morbidity rates. Uterine atony is the most prevalent cause of postpartum hemorrhage, accounting for 75% to 90% of cases.
 Aim: Research uterine atony related PPH at Hospital of Hue University of Medicine and Pharmacy’s Department of Obstetrics and Gynecology.
 Materials and methods: In this study, we conducted a retrospective case-control study to determine the risk factors for PPH among a cohort of women who gave birth between August 2020 and June 2021 at the Department of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy Hospital. PPH was defined as an estimated blood loss ≥500 mL. Logistic regression analysis was used to identify independent risk factors for PPH.
 Results: After the vaginal deliveries, we collected data from 147 patients, including 49 women with PPH caused by uterine atony and 98 without PPH. Maternal characteristics significantly associated with PPH included: pre-delivery anemia (adjusted OR [aOR] 4.0, 95% Confidence interval [CI]: 1.7 - 11.2), macrosomia (aOR = 4.3; 95%CI 1.1 - 16.8) and grand parity (aOR = 4.7; 95%CI: 1.7 - 13.9).
 Conclusions: All pregnant women should have their risks associated with postpartum hemorrhage evaluated and monitored during their pregnancies’ prenatal, labor, and postpartum stages.

A homozygous EVC mutation in a prenatal fetus with Ellis-van Creveld syndrome.

Ellis-van Creveld (EvC) syndrome, caused by variants in EVC, is a rare genetic skeletal dysplasia. Its clinical phenotype is highly diverse. EvC syndrome is rarely reported in prenatal stages because its presentation overlaps with other diseases. A Chinese pedigree diagnosed with EvC syndrome was enrolled in this study. Whole-exome sequencing (WES) was applied in the proband to screen potential genetic variant(s), and then Sanger sequencing was used to identify the variant in family members. Minigene experiments were applied. WES identified a homozygous variant (NM_153717.3:c.153_174 + 42del) in EVC which was inherited from the heterozygous parents and confirmed by Sanger sequencing. Further experiments demonstrated that this variant disrupts the canonical splicing site and produces a new splicing site at NM_153717.3: c.-164_174del, which ultimately leads to a 337 bp deletion at the 3' end of exon 1 and loss of the start codon. This is the first reported case of EvC syndrome based on a splicing variant and detailed delineation of the aberrant splicing effect in the fetus. Our study demonstrates the pathogenesis of this new variant, expands the spectrum of EVC mutations, and demonstrates that WES is a powerful tool in the clinical diagnosis of diseases with genetic heterogeneity.

Prenatal maternal depressive symptoms are associated with neonatal left amygdala microstructure in a sex-dependent way.

Exposures to prenatal maternal depressive symptoms (PMDS) may lead to neurodevelopmental changes in the offspring in a sex-dependent way. Although a connection between PMDS and infant brain development has been established by earlier studies, the relationship between PMDS exposures measured at various prenatal stages and microstructural alterations in fundamental subcortical structures such as the amygdala remains unknown. In this study, we investigated the associations between PMDS measured during gestational weeks 14, 24 and 34 and infant amygdala microstructural properties using diffusion tensor imaging. We explored amygdala mean diffusivity (MD) alterations in response to PMDS in infants aged 11 to 54 days from birth. PMDS had no significant main effect on the amygdala MD metrics. However, there was a significant interaction effect for PMDS and infant sex in the left amygdala MD. Compared with girls, boys exposed to greater PMDS during gestational week 14 showed significantly higher left amygdala MD. These results indicate that PMDS are linked to infants' amygdala microstructure in boys. These associations may be relevant to later neuropsychiatric outcomes in the offspring. Further research is required to better understand the mechanisms underlying these associations and to develop effective interventions to counteract any potential adverse consequences.

ULTRASOUND FEATURES OF ANTENATAL MIDGUT VOLVULUS PRESENTING AS AN OBSTRUCTION IN 24 WEEKS FETUS: A RARE CASE REPORT

Mid- gut volvulus is an embryological abnormal xation of small bowel mesentery that commonly occurs during fetal development leading to ischemia of the involved intestine if not intervened. It is a rare and life-threatening condition that is difcult to diagnose in the prenatal stage. It is usually diagnosed at 27 weeks of gestation, but our case is reported at 24 weeks of gestation. A fetus of 26 years old primigravida with 24 weeks of gestation was discovered to have mid-gut volvulus with small bowel obstruction and absence of peristalsis on ultrasonographic examination antenatally. Ultrasonographic signs showed the presence of extensively dilated loops of bowel in a coffee bean shape and anatomic position reversed between the superior mesenteric vein (SMV) and superior mesenteric artery (SMA), as a sign of malrotation. Moreover, the presence of a "whirlpool sign” (wrapping of SMV and mesentery around SMA) was evaluated on color doppler. Close prenatal follow-up, appropriate delivery, and timing of therapeutic intervention may signicantly lower morbidity and mortality.

Pregnant Women Kesti: Assistance Program "Pregnant Women Know Stunting" as an Effort to Prevent Stunting and Accidents in Bandengan, Pekalongan City

The prevalence of stunted growth among toddlers in Indonesia is a significant factor contributing to its fifth-place ranking globally, with 38% of the total number of toddlers affected by this condition. The prevalence of stunting in Pekalongan City remains considerably high, as evidenced by the recorded figure of 1,421 under-five children who were found to be stunted during the year 2021. The 1000 HPK program is an initiative aimed at preventing stunts. This 1000-day window presents an opportunity to prioritize the nutritional status, health, and psychosocial stimulation of the child during the prenatal, breastfeeding, and complementary feeding stages. The mother's involvement is crucial, as is the role of the husband or other close family members. The Bandengan sub-district region is pertinent in the context of stunting prevention, a chronic nutritional issue that arises from prolonged insufficient nutrient intake, leading to growth impairments in children, specifically a below-average height or dwarfism relative to their age standard. Support is provided through educational interventions aimed at identifying growth and development, nutritional education for expectant mothers, physical exercises, and educational strategies for expectant mothers who are breastfeeding. The outcomes of the mentoring program entail the execution of counseling sessions aimed at enhancing awareness and comprehension of maternal health and balanced nutrition during pregnancy. The objective is to emphasize the significance of fulfilling a healthy and balanced diet to prevent early childhood stunting among pregnant women

The socio-demographic profile associated with perinatal depression during the COVID-19 era

BackgroundCoronavirus disease 2019 (COVID-19) has caused an increase in perinatal depression. The aim of this research was to identify which sociodemographic variables are related to the increase in perinatal depression due to the pandemic. In addition to estimating to what extent they predict perinatal depression, differentiating the prenatal and postnatal periods.MethodsThe sample consisted of 3,356 subjects, 1,402 in the prenatal period and 1,954 in the postnatal period. The Edinburgh Postnatal Depression Scale was used to assess depressive symptomatology. A subset of 14 questions was included to collect demographic data. Items from the Spanish version of the Coronavirus Perinatal Experiences Survey were also included.ResultsExperiencing the change of environment due to COVID-19 as negative and having a history of mental health predict perinatal depression, otherwise having higher education decreases the risk. In the prenatal stage having symptoms compatible with COVID-19 is a predictor of perinatal depression and having more than 3 years living together with the partner and being a housewife decreases the risk. In the postnatal stage being unemployed is a predictor of prenatal depression and being a first-time mother decreases the risk.ConclusionsThis study highlights the relevance of sociodemographic status. It is essential to be aware of the risk factors of perinatal depression, to make adequate prevention, and to create health policies to alleviate the consequences of the pandemic.

Humanized childbirth, a link to humanitarian treatment, synonymous with quality obstetric care at the 1st level of care in Mexico

Bringing a new being into the world is a relevant and transcendent event in a woman's life, which will be marked for the rest of her life. However, it can be experienced as a painful and traumatic experience. Objective: Analyze the most effective actions to improve the quality of humanized delivery care in low-risk pregnant women in hospitals of 1st and 2nd level of care. Methodology: A narrative review was carried out that includes a critical, reflective analysis of humanized childbirth. The review of: original articles, revision of doctoral and master's theses was carried out. The adopted search strategy included keywords or descriptors, connected by means of the boolean operator and. The keywords used were "humanization", "delivery", "human needs", and breastfeeding, these being identified through Medical Subject Headings 2020 Serach MeSH, in this way the referred articles, descriptors in language were used for the search. Spanish and English. The search was carried out in various databases. Information collection time 6 months, (August 2022 to February 2023). Results: The review allowed us to analyze in a standardized way the historical evolution of humanized childbirth and the transcultural significance that it represents and to a large extent to be carried out, and how it will reinforce the multidisciplinary health team that cares for women in this process, to offer different strategies. to be this stage an unforgettable and humanistic experience that you will never forget. Conclusions: Humanized childbirth is translated into a birth with a humanistic character which includes: the prenatal stage, labor, delivery and the puerperium, where the protagonists are the pregnant woman and the newborn, receiving dignified, free treatment. of violence and based on human and ethical rights

Teratoma nasofaríngeo inmaduro con diagnóstico prenatal: reporte de un caso y revisión de la literatura

To report the case of a pregnant woman with prenatal diagnosis of fetal immature nasopharyngeal teratoma, and to conduct a review of the literature describing the prognosis of this condition. We report the case of a 27-year-old pregnant woman who received care at the Obstetrics and Gynecology Unit of a reference hospital in Bogotá (Colombia) because of a finding during a prenatal visit of evidence of polyhydramnios, secondary to a nasopharyngeal teratoma. A literature search was conducted in the Medline vía PubMed, Scopus, SciELO and ScienceDirect databases, restricted by language (English and Spanish) and date of publication (January 2001 to January 2021). Case reports and case series covering the prognosis of this condition were included. Overall, 168 titles were retrieved, 55 of which met the inclusion criteria. Perinatal outcomes for a total of 58 fetuses with a diagnosis of immature nasopharyngeal teratoma detected during the prenatal stage were reported. In the identified cases, perinatal mortality was 25.4 % and the percentage of fetal demise was close to 3.6 %. Immature nasopharyngeal teratoma is an infrequent condition. The available literature suggests that fetal prognosis depends on the degree of compromise of intracranial structures and the possibility of resecting the lesion. Further studies are needed to assess the prognosis of fetuses with immature nasopharyngeal teratoma.

Development of the primary and secondary jaw joints in the mouse

This study assesses the morphogenesis of the primary and secondary jaw joints. A collection of 11 murine heads, ranging from prenatal stage E13.5 to postnatal stage P10, were prepared as histological serial sections (thickness 8–10 µm) and stained conventionally in order to examine them with light microscopy. Next, the regions of the developing temporomandibular joint and the middle ear ossicles were three dimensionally reconstructed using AnalySIS® software. This study gained new insight into the spatio-temporal development of the temporomandibular joint and the auditory ossicles. Furthermore, we newly visualized in 3D that during the developmental period from stages E16 to P4 two morphologically well-functional joints (the primary and secondary jaw joints) exist on either side and are mechanically connected via Meckel’s cartilage. Potential separation mechanisms of these two joints are discussed and options for mathematical analysis are suggested.

Genetic susceptibility for schizophrenia after adjustment by genetic susceptibility for smoking: implications in identification of risk genes and genetic correlation with related traits.

Prevalence of smoking in schizophrenia (SCZ) is larger than in general population. Genetic studies provided some evidence of a causal effect of smoking on SCZ. We aim to characterize the genetic susceptibility to SCZ affected by genetic susceptibility to smoking. Multi-trait-based conditional and joint analysis was applied to the largest European SCZ genome-wide association studies (GWAS) to remove genetic effects on SCZ driven by smoking, estimated by generalized summary data-based Mendelian randomization. Enrichment analysis was performed to compare original v. conditional GWAS. Change in genetic correlation between SCZ and relevant traits after conditioning was assessed. Colocalization analysis was performed to identify specific loci confirming general findings. Conditional analysis identified 19 new risk loci for SCZ and 42 lost loci whose association with SCZ may be partially driven by smoking. These results were strengthened by colocalization analysis. Enrichment analysis indicated a higher association of differentially expressed genes at prenatal brain stages after conditioning. Genetic correlation of SCZ with substance use and dependence, attention deficit-hyperactivity disorder, and several externalizing traits significantly changed after conditioning. Colocalization of association signal between SCZ and these traits was identified for some of the lost loci, such as CHRNA2, CUL3, and PCDH7. Our approach led to identification of potential new SCZ loci, loci partially associated to SCZ through smoking, and a shared genetic susceptibility between SCZ and smoking behavior related to externalizing phenotypes. Application of this approach to other psychiatric disorders and substances may lead to a better understanding of the role of substances on mental health.

De novo mutations disturb early brain development more frequently than common variants in schizophrenia.

Investigating functional, temporal, and cell-type expression features of mutations is important for understanding a complex disease. Here, we collected and analyzed common variants and de novo mutations (DNMs) in schizophrenia (SCZ). We collected 2,636 missense and loss-of-function (LoF) DNMs in 2,263 genes across 3,477 SCZ patients (SCZ-DNMs). We curated three gene lists: (a) SCZ-neuroGenes (159 genes), which are intolerant to LoF and missense DNMs and are neurologically important, (b) SCZ-moduleGenes (52 genes), which were derived from network analyses of SCZ-DNMs, and (c) SCZ-commonGenes (120 genes) from a recent GWAS as reference. To compare temporal gene expression, we used the BrainSpan dataset. We defined a fetal effect score (FES) to quantify the involvement of each gene in prenatal brain development. We further employed the specificity indexes (SIs) to evaluate cell-type expression specificity from single-cell expression data in cerebral cortices of humans and mice. Compared with SCZ-commonGenes, SCZ-neuroGenes and SCZ-moduleGenes were highly expressed in the prenatal stage, had higher FESs, and had higher SIs in fetal replicating cells and undifferentiated cell types. Our results suggested that gene expression patterns in specific cell types in early fetal stages might have impacts on the risk of SCZ during adulthood.

How prenatal cortisol levels relate to grandmother-mother relationships among a cohort of Latina women.

As part of the human reproductive strategy, mothers receive childcare assistance from others. For kin, allomothers are adaptively incentivized to provide assistance due to inclusive fitness benefits. Previous studies across a broad range of populations identify grandmothers as particularly consistent allomothers. Minimal attention has been paid to the possibility that allomothers may begin investing in offspring quality during the prenatal stage of life. Here, we innovate within the area of grandmother allocare research by examining the prenatal stage of life and biopsychosocial mechanisms by which prenatal grandmother effects may be enacted. Data derive from the Mothers' Cultural Experiences study, a cohort of 107 pregnant Latina women in Southern California. At <16 weeks' gestation, we administered questionnaires, collected morning urine samples, and measured cortisol by enzyme-linked immunosorbent assay, correcting for specific gravity. We measured the soon-to-be maternal and paternal grandmothers' relationship quality, social support, frequency of seeing each other, communicating, and geographic proximity to pregnant mothers, that is, their daughters and daughters-in-law. These measures were self-reported by the pregnant mothers. We assessed how grandmother constructs related to the pregnant women's depression, stress, anxiety, and cortisol levels. We observed benefits conferred by maternal grandmothers for mothers' prenatal mental health and lower cortisol levels. Paternal grandmothers also conferred mental health benefits to pregnant daughters-in-law, but higher cortisol levels. Our results suggest that grandmothers, especially maternal grandmothers, are able to improve their inclusive fitness by caring for pregnant daughters, and allomother support may positively impact prenatal health. This work extends the traditional cooperative breeding model by identifying a prenatal grandmother effect, and, by examining a maternal biomarker.

Genome-wide association study identifies 12 new genetic loci associated with growth traits in pigs

Growth traits are among the most important economic traits in pigs and are regulated by polygenes with complex regulatory mechanisms. As the major indicators of growth performance, the backfat thickness (BFT), loin eye area (LEA), and days to 100 kg (D100) traits are commonly used to the genetics improvement in pigs. However, the available genetic markers for these traits are limited. To uncover novel loci and candidate genes associated with growth performance, we collected the phenotypic information of BFT, LEA, and D100 in 1,186 pigs and genotyped all these individuals using the Neogen GGP porcine 80K BeadChip. We performed a genome-wide association study (GWAS) using 4 statistical models, including mixed linear models (MLM), fixed and random model circulating probability unification (FarmCPU), settlement of MLM under progressively exclusive relationships (SUPER), Bayesian-information and linkage-disequilibrium Iteratively nested keyway (Blink), and identified 5, 3, and 6 high-confidence single nucleotide polymorphisms (SNPs) associated with BFT, LEA, and D100, respectively. Variant annotation and quantitative trait locus (QTL) mapping analysis suggested that 6 genes (SKAP2, SATB1, PDE7B, PPP1R16B, WNT3, and WNT9B) were potentially associated with growth performance in pigs. Transcriptome analysis suggested that the expression of Src Kinase Associated Phosphoprotein 2 (SKAP2) was higher in prenatal muscles than in postnatal muscles, and the expression of Phosphodiesterase 7B (PDE7B) continuously increased during the prenatal stages and gradually decreased after birth, implying their potential roles in prenatal skeletal muscle development. Overall, this study provides new candidate loci and genes for the genetic improvement of pigs.

Sexuality and affectivity after a grieving process for an antenatal death: a qualitative study of fathers' experiences

The loss of an infant at the prenatal stage is one of the most traumatic events parents can experience. Prenatal losses have several negative implications for parents’ physical, psychological, and social well-being, including intimacy and sexuality. Fathers who suffer from this experience have to cope not only with their grief, but also with the physical and emotional suffering of their partners. The social context gives the father a masculine role of strength, insensitivity, and protection of the mother, with the result that his pain and grief become invisible. The objective of this study is to understand fathers’ experience of affective-sexual relationships after a grieving process for an antenatal death; A qualitative study based on interviews with 11 fathers in Spain who have experienced an antenatal death was conducted. Data were analyzed with the help of ATLAS.ti software to discover emerging themes. 6 sub-themes were developed from the analysis, grouped into two main themes: the invisibility of grieving fathers and the relationships between the grieving parents are influenced by the death of their infants. The sexuality of fathers who suffer an antenatal death is altered. Gender stereotypes and the lack of social and professional awareness make their grief invisible. Fathers need to express their emotions to cope with their own grief and break the stereotypical gendered bereavement. In most cases, the couple’s relationship is altered, from a close union to a more distant relationship, in addition to a decrease in sexual desire and arousal. However, other fathers experienced greater closeness and intimacy in the couple. A communication based on sincerity, exposing their own grief, feelings, emotions and needs could help the couple’s relationship.

Естественный и искусственный интеллект: точки соприкосновения

The study concerns the problem of the natural intelligence specificity which is cor­related with the prenatal stage of mind forming. At the same time, only those as­pects of the system’s functioning are the subject of consideration in research that become visible from the methodological perspective. These are the modes of non-duality and integrity of the very space of existence, in which not only the main po­tentialities of natural intelligence are laid, but the peculiarities of the contents that have their source in a given period are established also. When person becomes conscious such contents (and mechanisms for their provision) move into the un­conscious sphere. However, they continue to influence the entire universe of hu­man cognition in a significant way: they determine not only the nature and styles of thinking, but also set the cognition’s dynamics that are permissible in such a space of opportunity. In a generalized form, these contents can be characterized as intensional ones, while contents with which the dissociated mind of technocratic culture adult person deals are mainly extensional. Artificial intelligence, that has no knowledge of a non-dual mode of becoming, deals with the extensional facet of the natural mind modeling. To make an approximation to the potentials of natu­ral intelligence functioning more achievable, it is proposed to modify the structure of artificial intelligence systems’ “experience” by adding a mode of free navigation in the space provided for data analysis. Also it seems useful to modify the concept of rationality, by expanding it with two types of contents, whose genesis was corre­lated with non-dual-holistic mode of the mind functioning.

Hepatitis B and C in Pregnancy and Children: A Canadian Perspective.

In 2016, the World Health Organization released a plan to eliminate viral hepatitis as a public health threat by 2030. For Canada to achieve the recommended decreases in HBV- and HCV-related new diagnoses and deaths, an increase in services is urgently required. Identifying those at risk of, or who have acquired HBV and HCV, remains a challenge, especially with the emergence of new priority populations such as pregnant persons and children. Importantly, prenatal, and pediatric care are times when individuals are often already engaged with the healthcare system, leading to the potential for opportunistic or co-localized care and interventions. At present, Canada may not be maximizing all available virologic tools that could lead to increases in prevention, identification, improved management, or even cure. Here, we describe the continuum of care that includes preconception, prenatal, postpartum, and pediatric stages; and identify current global and Canadian recommendations, findings, and opportunities for improvement.

High cardiomyocyte diversity in human early prenatal heart development

Cardiomyocytes play key roles during cardiogenesis, but have poorly understood features, especially in prenatal stages. Here, we characterized human prenatal cardiomyocytes, 6.5-7weeks post-conception, by integrating single-cell RNA sequencing, spatial transcriptomics, and ligand-receptor interaction information. Using a computational workflow developed to dissect cell type heterogeneity, localize cell types, and explore their molecular interactions, we identified eight types of developing cardiomyocyte, more than double compared to the ones identified in the Human Developmental Cell Atlas. These have high variability in cell cycle activity, mitochondrial content, and connexin gene expression, and are differentially distributed in the ventricles, including outflow tract, and atria, including sinoatrial node. Moreover, cardiomyocyte ligand-receptor crosstalk is mainly with non-cardiomyocyte cell types, encompassing cardiogenesis-related pathways. Thus, early prenatal human cardiomyocytes are highly heterogeneous and develop unique location-dependent properties, with complex ligand-receptor crosstalk. Further elucidation of their developmental dynamics may give rise to new therapies.

Histopathological and Immunohistochemical Features of Small to Big Satellite Nevus Uncover the Nevogenesis of Large/Giant Congenital Melanocytic Nevus.

The nevogenesis of large/giant congenital melanocytic nevus (lgCMN) is a complex biological process including several integral prenatal stages. Limited by ethical concerns, the debate of whether lgCMN develops from the epidermis to the dermis or in the opposite direction remains controversial. With the present study of the accompanying satellite nevi, we tend to support that lgCMN develops from epidermis to dermis. The satellite nevi were divided into 3 groups: big (diameter >10 mm), medium (>5 mm but ≤10 mm), and small (≤5 mm). Hematoxylin and eosin and immunohistochemical staining (SOX10, Ki67, and p16) were performed to compare the nevocyte infiltration depth as well as the positively stained rates among these satellite nevi. Compared to big satellite nevi, less deeply the nevocytes infiltrated the dermis, as well as more cells expressed SOX10 and Ki67 in the epidermis and fewer cells expressed p16 in the dermis of small satellite nevi. Additionally, two specimens were obtained from each of 4 patients who underwent serial resections of lgCMN at an average interval of 1.75 years to examine the histopathological changes. In the present study, satellite nevi of different sizes represent different stages of lgCMN from early to late, deepening our comprehension of the sequential stages of lgCMN nevogenesis. Initially, abnormal nevocytes seeded, proliferated, and spread along the epidermis. At rete ridges that protrude from the papillary dermis within the epidermis, some nevocytes formed nests and gradually penetrated into the dermis. Eventually, the nevocytes infiltrated the dermis and entered a homeostatic state. This study provides new evidence supporting the theory of epidermal-to-dermal nevogenesis in lgCMN.

Bonding Goes Back to the Dawn of Cosmos

Bonding is more than a lifelong process. It is a process that begins long before conception. In a broader context, this process begins with the dawn of the cosmos itself. Bonding is the linking process that bridges the prenatal and postnatal stages and prepares the child to connect securely and meaningfully with the world and life on earth. This article highlights aspects of bonding in the pre-conception and conception periods, as well as in pregnancy and birth, so that connections can be made to pre-, gestational, then peri-, and postnatal growth. A list of bonding support issues accompanies the consideration of parent and child development within the psychocultural, spatial, and temporal environments so that taking responsibility for personal health and growth at different stages becomes possible. In summary, bonding is about strengthening the life-enhancing polarity over the life-diminishing polarity.

Overlapping pathogenic de novo CNVs in neurodevelopmental disorders and congenital anomalies impacting constraint genes regulating early development.

Neurodevelopmental disorders (NDDs) and congenital anomalies (CAs) are rare disorders with complex etiology. In this study, we investigated the less understood genomic overlap of copy number variants (CNVs) in two large cohorts of NDD and CA patients to identify de novo CNVs and candidate genes associated with both phenotypes. We analyzed clinical microarray CNV data from 10,620 NDD and 3176 CA cases annotated using Horizon platform of GenomeArc Analytics and applied rigorous downstream analysis to evaluate overlapping genes from NDD and CA CNVs. Out of 13,796 patients, only 195 cases contained 218 validated de novo CNVs. Eighteen percent (31/170) de novo CNVs in NDD cases and 40% (19/48) de novo CNVs in CA cases contained genomic overlaps impacting developmentally constraint genes. Seventy-nine constraint genes (10.1% non-OMIM entries) were found to have significantly enriched genomic overlap within rare de novo pathogenic deletions (P value = 0.01, OR = 1.58) and 45 constraint genes (13.3% non-OMIM entries) within rare de novo pathogenic duplications (P value = 0.01, OR = 1.97). Analysis of spatiotemporal transcriptome demonstrated both pathogenic deletion and duplication genes to be highly expressed during the prenatal stage in human developmental brain (P value = 4.95 X 10-6). From the list of overlapping genes, EHMT1, an interesting known NDD gene encompassed pathogenic deletion CNVs from both NDD and CA patients, whereas FAM189A1, and FSTL5 are new candidate genes from non-OMIM entries. In summary, we have identified constraint overlapping genes from CNVs (including de novo) in NDD and CA patients that have the potential to play a vital role in common disease etiology.