Talk:Human Abnormal Development

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Cite this page: Hill, M.A. (2021, June 15) Embryology Human Abnormal Development. Retrieved from

Lead effects PMID 20562053


Elias D, Campaña H, Poletta F, Heisecke S, Gili J, Ratowiecki J, Gimenez L, Pawluk M, Santos MR, Cosentino V, Uranga R, Rittler M & Lopez Camelo J. (2020). A graph theory approach to analyze birth defect associations. PLoS ONE , 15, e0233529. PMID: 32442191 DOI.

A graph theory approach to analyze birth defect associations

Birth defects are prenatal morphological or functional anomalies. Associations among them are studied to identify their etiopathogenesis. The graph theory methods allow analyzing relationships among a complete set of anomalies. A graph consists of nodes which represent the entities (birth defects in the present work), and edges that join nodes indicating the relationships among them. The aim of the present study was to validate the graph theory methods to study birth defect associations. All birth defects monitoring records from the Estudio Colaborativo Latino Americano de Malformaciones Congénitas gathered between 1967 and 2017 were used. From around 5 million live and stillborn infants, 170,430 had one or more birth defects. Volume-adjusted Chi-Square was used to determine the association strength between two birth defects and to weight the graph edges. The complete birth defect graph showed a Log-Normal degree distribution and its characteristics differed from random, scale-free and small-world graphs. The graph comprised 118 nodes and 550 edges. Birth defects with the highest centrality values were nonspecific codes such as Other upper limb anomalies. After partition, the graph yielded 12 groups; most of them were recognizable and included conditions such as VATER and OEIS associations, and Patau syndrome. Our findings validate the graph theory methods to study birth defect associations. This method may contribute to identify underlying etiopathogeneses as well as to improve coding systems.


Hh signaling from de novo organizers drive lgl neoplasia in Drosophila epithelium

Dev Biol. 2019 Sep 23. pii: S0012-1606(19)30322-7. doi: 10.1016/j.ydbio.2019.09.011. [Epub ahead of print]

Bajpai A1, Sinha P2. Author information 1 Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, 208 016, India. Electronic address: 2 Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, 208 016, India. Electronic address:

The Hedgehog (Hh) morphogen regulates growth and patterning. Since Hh signaling is also implicated in carcinogenesis, it is conceivable that de novo Hh-secreting organizers, if formed in association with oncogenic hit could be tumor-cooperative. Here we validate this hypothesis using the Drosophila model of cooperative epithelial carcinogenesis. We generate somatic clones with simultaneous loss of tumor suppressor, Lgl, and gain of the posterior compartment selector, Engrailed (En), known to induce synthesis of Hh. We show that lgl UAS-en clones in the anterior wing compartment trigger Hh signaling cascade via cross-talk with their Ci-expressing wild type cell neighbors. Hh-Dpp signaling from clone boundaries of such ectopically formed de novo organizers in turn drive lgl carcinogenesis. By contrast, Ci-expressing lgl clones transform by autocrine and/or juxtracine activation of Hh signaling in only the posterior compartment. We further show that sequestration of the Hh ligand or loss of Dpp receptor, Tkv, in these Hh-sending or -receiving lgl clones arrested their carcinogenesis. Our results therefore reveal a hitherto unrecognized mechanism of tumor cooperation by developmental organizers, which are induced fortuitously by oncogenic hits.

Copyright © 2019 Elsevier Inc. All rights reserved. KEYWORDS: Developmental organizer; Hh signaling; Tumor cooperation; lgl PMID: 31557471 DOI: 10.1016/j.ydbio.2019.09.011


Pattern and outcome of prenatally diagnosed major congenital anomalies at a Nigerian Tertiary Hospital

Niger J Clin Pract. 2018 May;21(5):560-565. doi: 10.4103/njcp.njcp_210_17.

Akinmoladun JA1, Ogbole GI1, O Oluwasola TA2.

The prevalence of major congenital anomalies (CAs) shows wide variations depending on geographical location and may range from <1% to 8% and it causes between 20% and 30% of perinatal deaths. In Nigeria, the prevalence of CAs may be underestimated with the general reliance on mostly livebirths ranging between 0.5% and 2.8% exempting cases of miscarriage and abortions. The purpose of this study was to determine the epidemiologic pattern and outcome of major CAs detected prenatally at the University College Hospital, Ibadan, Nigeria, over a 4-year period. METHODS: This hospital-based descriptive study highlights the prevalence and pattern of prenatally diagnosed fetal anomalies among the pregnant women who presented for routine prenatal ultrasound screening within the study period. Demographic details, associated risk factors, and fetal anomaly type in the fetuses were recorded using a prepared pro forma and were analyzed. RESULTS: Prenatal ultrasound screening for fetal anomalies was performed on 989 fetuses (including 15 sets of twins and 1 set of triplets) during the study period, out of which 62 (6.3%) had CAs. Of the 62 with CAs, 37 (59.7%) were major and 25 (40.3%) were minor. Majority of the fetuses with major anomalies were found among women aged 30-34 years and most were detected during the routine 18-22 weeks' anomaly scan. The major anomalies were most common in central nervous system. Nine (14.5%) pregnancies were terminated before term and 8 (29.6%) babies had different postnatal surgical interventions. Eleven (17.7%) of the fetuses with anomalies died in the perinatal period. CONCLUSION: CAs remain a major contributor to perinatal morbidity and mortality in Nigeria. Since most are idiopathic, early prenatal detection with ultrasound may facilitate improved diagnosis and the reduction of overall perinatal morbidity and mortality in the Nigerian setting. KEYWORDS: Congenital abnormalities; major; pattern; prevalence PMID: 29735854 DOI: 10.4103/njcp.njcp_210_17

Recurrent pregnancy loss: A summary of international evidence-based guidelines and practice

Hong Li Y & Marren A. (2018). Recurrent pregnancy loss: A summary of international evidence-based guidelines and practice. Aust J Gen Pract , 47, 432-436. PMID: 30114870

Hong Li Y1, Marren A2. Author information Abstract BACKGROUND: Recurrent pregnancy loss (RPL) is defined as two or more pregnancy losses. It affects <5% of couples. There are many proposed causes; however, in a significant proportion of cases, the cause is unknown. OBJECTIVE: The aim of this paper is to provide a summary of the aetiology, investigations and management of RPL, which is based on the three most recent international guidelines on RPL (European Society of Human Reproduction and Embryology, 2017; American Society for Reproductive Medicine, 2012; and the Royal College of Obstetricians and Gynaecologists, 2011). DISCUSSION: Management of RPL should occur in a specialised clinic. Appropriate investigations include karyotyping of parents and products of conception, two-dimensional/three-dimensional ultrasonography with sonohysterography, thyroid function tests, and antibodies and testing for acquired thrombophilias. Management options encompass some lifestyle modifications for smoking, alcohol, illicit drug use and caffeine consumption. Acquired thrombophilias should be treated with unfractionated heparin and low-dose aspirin. PMID: 30114870


Health Worker Roles in Providing Safe Abortion Care and Post-Abortion Contraception

Health Worker Roles in Providing Safe Abortion Care and Post-Abortion Contraception. Geneva: World Health Organization; 2015. Available from:

An assessment of sex bias in neurodevelopmental disorders

Genome Med. 2015 Aug 27;7:94. doi: 10.1186/s13073-015-0216-5.

Polyak A1, Rosenfeld JA2,3, Girirajan S4,5,6.

BACKGROUND: Neurodevelopmental disorders such as autism and intellectual disability have a sex bias skewed towards boys; however, systematic assessment of this bias is complicated by the presence of significant genetic and phenotypic heterogeneity of these disorders. METHODS: To assess the extent and characteristics of sex bias, we analyzed the frequency of comorbid features, the magnitude of genetic load, and the existence of family history within 32,155 individuals ascertained clinically for autism or intellectual disability/developmental delay (ID/DD), including a subset of 8,373 individuals carrying rare copy-number variants (CNVs). RESULTS: We find that girls were more likely than boys to show comorbid features within both autism (P = 2.9 × 10(-6), OR = 1.34) and ID/DD (P = 7.2 × 10(-4), OR = 1.08) cohorts. The frequency of comorbid features in ID/DD was higher in boys (1q21.1 deletion, 15q11.2q13.1 duplication) or girls (15q13.3 deletion, 16p11.2 deletion) carrying specific CNVs associated with variable expressivity while such differences were the smallest for syndromic CNVs (Smith-Magenis syndrome, DiGeorge syndrome). The extent of the male sex bias also varied according to the specific comorbid feature, being most extreme for autism with psychiatric comorbidities and least extreme for autism comorbid with epilepsy. The sex ratio was also specific to certain CNVs, from an 8:1 male:female ratio observed among autistic individuals carrying the 22q11.2 duplication to 1.3:1 male:female ratio in those carrying the 16p11.2 deletion. Girls carried a higher burden of large CNVs compared to boys for autism or ID/DD, and this difference diminished when severe comorbidities were considered. Affected boys showed a higher frequency of neuropsychiatric family histories such as autism (P = 0.01) or specific learning disability (P = 0.03), while affected girls showed a higher frequency of developmental family histories such as growth abnormalities (P = 0.02). CONCLUSIONS: The sex bias within neurodevelopmental disorders is influenced by the presence of specific comorbidities, specific CNVs, mutational burden, and pre-existing family history of neurodevelopmental phenotypes. PMID: 26307204 PMCID: PMC4549901 DOI: 10.1186/s13073-015-0216-5



Ten-Year Review of Major Birth Defects in VLBW Infants

Pediatrics. 2013 Jun 3. [Epub ahead of print]

Adams-Chapman I, Hansen NI, Shankaran S, Bell EF, Boghossian NS, Murray JC, Laptook AR, Walsh MC, Carlo WA, Sánchez PJ, Van Meurs KP, Das A, Hale EC, Newman NS, Ball MB, Higgins RD, Stoll BJ; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Source Department of Pediatrics, Emory University School of Medicine, and Children's Healthcare of Atlanta, Atlanta, Georgia;


OBJECTIVE:Birth defects (BDs) are an important cause of infant mortality and disproportionately occur among low birth weight infants. We determined the prevalence of BDs in a cohort of very low birth weight (VLBW) infants cared for at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers over a 10-year period and examined the relationship between anomalies, neonatal outcomes, and surgical care.METHODS:Infant and maternal data were collected prospectively for infants weighing 401 to 1500 g at NRN sites between January 1, 1998, and December 31, 2007. Poisson regression models were used to compare risk of outcomes for infants with versus without BDs while adjusting for gestational age and other characteristics.RESULTS:A BD was present in 1776 (4.8%) of the 37 262 infants in our VLBW cohort. Yearly prevalence of BDs increased from 4.0% of infants born in 1998 to 5.6% in 2007, P < .001. Mean gestational age overall was 28 weeks, and mean birth weight was 1007 g. Infants with BDs were more mature but more likely to be small for gestational age compared with infants without BDs. Chromosomal and cardiovascular anomalies were most frequent with each occurring in 20% of affected infants. Mortality was higher among infants with BDs (49% vs 18%; adjusted relative risk: 3.66 [95% confidence interval: 3.41-3.92]; P < .001) and varied by diagnosis. Among those surviving >3 days, more infants with BDs underwent major surgery (48% vs 13%, P < .001).CONCLUSIONS:Prevalence of BDs increased during the 10 years studied. BDs remain an important cause of neonatal morbidity and mortality among VLBW infants. KEYWORDS: Neonatal Research Network, birth defects, low birth weight, prematurity

PMID 23733791

Pregnancy: occupational aspects of management: concise guidance

Clin Med. 2013 Feb;13(1):75-9.

Palmer KT, Bonzini M, Bonde JP; Multidisciplinary Guideline Development Group; Health and Work Development Unit,; Royal College of Physicians; Faculty of Occupational Medicine. Collaborators (9)

Medical Research Council Lifecourse Epidemiology Unit, University of Southampton.


Most pregnant women are exposed to some physical activity at work. This Concise Guidance is aimed at doctors advising healthy women with uncomplicated singleton pregnancies about the risks arising from five common workplace exposures (prolonged working hours, shift work, lifting, standing and heavy physical workload). The adverse outcomes considered are: miscarriage, preterm delivery, small for gestational age, low birth weight, pre-eclampsia and gestational hypertension. Systematic review of the literature indicates that these exposures are unlikely to carry much of an increased risk for any of the outcomes, since small apparent effects might be explicable in terms of chance, bias, or confounding, while larger and better studies yield lower estimated risks compared with smaller and weaker studies. In general, patients can be reassured that such work is associated with little, if any, adverse effect on pregnancy. Moreover, moderate physical exercise is thought to be healthy in pregnancy and most pregnant women undertake some physical work at home. The guidelines provide risk estimates and advice on counselling.

PMID 23472500


Congenital malformations in perinatal autopsies - a study of 100 cases

J Clin Diagn Res. 2012 Dec;6(10):1726-30. doi: 10.7860/JCDR/2012/4686.2651. Epub 2012 Nov 22.

Andola US, Am A, Ahuja M, Andola SK. Source Professor, Department of Obstetrics and Gynecology, MR Medical College and Basaveshwar Teaching and General Hospital , Gulbarga, Karnataka, India. Abstract BACKGROUND: Congenital malformations remain a common cause of perinatal deaths and even though ultrasonogram can give fairly accurate diagnosis, perinatal autopsy is essential to confirm the diagnosis and look for associated malformations. OBJECTIVES: To emphasize the importance of perinatal autopsy in diagnosing congenital malformations and to compare the same with the prenatal ultrasound findings. METHODS: The present study comprises 100 consecutive perinatal autopsies conducted after obtaining the approval from the Institutional Ethics Committee. In cases where prenatal ultrasound findings were available they were compared with the autopsy findings. RESULTS: Out of 100 perinatal autopsies, 44 cases were congenital anomalies with M:F = 1:1.5. Majority of the fetuses with congenital malformations (36.36%) were therapeutically terminated, Cental nervous system malformations being the commonest indication. The most common timing of therapeutic termination being 20 -24weeks. Congenital malformations were common between 35-39 weeks gestational age and birth weight range 350- 1000g. The malformations involving the central nervous system were commonest, seen in 15 cases (34.09%) followed by renal anomalies in 9 cases (20.45%) and multiple malformations in 7cases ( 15.91%). Autopsy confirmed the prenatal ultrasound findings in 50% of the cases, added to diagnosis in 29.54%, while it completely changed the primary diagnosis in 9.09% of the cases. CONCLUSION: This study highlights the importance of perinatal autopsy in confirming the diagnosis of congenital anomalies by prenatal ultrasound findings. PMID 23373038

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Prevalence of birth defects in korean livebirths, 2005-2006

J Korean Med Sci. 2012 Oct;27(10):1233-40. doi: 10.3346/jkms.2012.27.10.1233. Epub 2012 Oct 2.

Kim MA, Yee NH, Choi JS, Choi JY, Seo K. Source Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.


We investigated the livebirths prevalence and occurrence pattern of birth defects in Korea. After the survey on birth defects was done in 2,348 medical institutions around the nation, the birth defect prevalence of livebirths in 2005-2006 was calculated. This study was based on the medical insurance claims database of the National Health Insurance Corporation. The number of livebirths in Korea was 883,184 from 2005-2006, and 25,335 cases of birth defects were notified to our study, equivalent to a prevalence of 286.9 per 10,000 livebirths. Anomalies of the circulatory system were the most common defects, accounting for 43.4% of birth defects with a prevalence of 124.5 per 10,000 livebirths. It was followed by the musculoskeletal system anomalies, the digestive system anomalies, and the urinary system anomalies. The five major birth defects based on the ranking of prevalence were atrial septal defect, ventricular septal defect, hydronephrosis, patent ductus arteriosus, and cleft lip/palate. Birth defects in livebirths were associated with a high proportion of low birthweight, prematurity, multiple births and advanced maternal age. The prevalence of birth defects in Korea is similar to or lower than those reported in developed countries. Our study suggests baseline data to explain the current status of birth defects and to establish a registry system of birth defects in Korea.

PMID 23091323


Registries of congenital anomalies: EUROCAT

Environ Health Perspect. 1993 Jul;101 Suppl 2:153-7.

Lechat MF, Dolk H. Source Department of Epidemiology and Preventive Medicine, Catholic University of Louvain, Brussels, Belgium.


Congenital anomalies are one of the potential adverse effects of the environment on reproductive health. Registries of congenital anomalies are useful to detect abnormal frequencies, clusters, and trends. Such registries should meet a number of conditions, including an appropriate population denominator, an efficient system for collecting information, standardized diagnostic procedures, postmortem examinations of still-births, and linkage of records. The EUROCAT (European Registration of Congenital Anomalies and Twins) program is a Concerted Action of the Commission of the European Communities initiated in 1979. One of its objectives is the surveillance of congenital anomalies as related to environmental hazards. This surveillance system covers at present 350,000 births per year in 15 countries. A number of problems encountered in the development of EUROCAT and in the course of ongoing activities are reviewed: populations coverage, classification of malformations, coding, definition and coverage of late fetal death, registration of induced abortion, validation of diagnostic information, registration of late diagnosed cases, and maintenance of motivation in data collection. The issue of confidentiality and the need for strict safeguards for the protection of individual privacy are emphasized.

PMID 8243386

Australia - Advisory Committee on Prescription Medicines

The Australian Drug Evaluation Committee (ADEC) was established in 1963 following the thalidomide experience and in 2010 this committee was replaced by the Advisory Committee on Prescription Medicines (ACPM). The new ACPM advises and makes recommendations to the Therapeutic Goods Administration (TGA) on prescription medicines listed on the Australian Register of Therapeutic Goods (ARTG), established under the Therapeutic Goods Act 1989. There were approximately 54,000 products on the Australian Register of Therapeutic Goods as at 23 May 2008.

Advisory Committee on Prescription Medicines

  • inclusion of a prescription medicine on the Australian Register of Therapeutic Goods (the Register)
  • changes to an entry of a prescription medicine on the Register
  • removal or retention of a prescription medicine on the Register
Links: Advisory Committee on Prescription Medicines

Cytomegalovirus infection in pregnancy.

Australian Congenital Anomalies Monitoring System (ACAMS)

USA (2004–2006)

National estimates for 21 selected major birth defects, 2004–2006

CDC Birth Defects - Data & Statistics

Birth Defects Cases per Births Estimated Annual Number of Cases
Anencephaly 1 in 4,859 859
Spina bifida without anencephaly 1 in 2,858 1,460
Encephalocele 1 in 12,235 341
Anophthalmia/microphthalmia 1 in 5,349 780
Common truncus 1 in 13,876 301
Transposition of great arteries 1 in 3,333 1,252
Tetralogy of Fallot 1 in 2,518 1,657
Atrioventricular septal defect 1 in 2,122 1,966
Hypoplastic left heart syndrome 1 in 4,344 960
Cleft palate without cleft lip 1 in 1,574 2,651
Cleft lip with and without cleft palate 1 in 940 4,437
Esophageal atresia/tracheoesophageal fistula 1 in 4,608 905
Rectal and large intestinal atresia/stenosis 1 in 2,138 1,952
Reduction deformity, upper limbs 1 in 2,869 1,454
Reduction deformity, lower limbs 1 in 5,949 701
Gastroschisis 1 in 2,229 1,871
Omphalocele 1 in 5,386 775
Diaphragmatic hernia 1 in 3,836 1,088
Trisomy 13 1 in 7,906 528
Trisomy 21 (Down syndrome) 1 in 691 6,037
Trisomy 18 1 in 3,762 1,109

Birth Defects Cases per Births (1 in ...) Estimated Annual Number of Cases
Anencephaly 4,859 859
Spina bifida without anencephaly 2,858 1,460
Encephalocele 12,235 341
Anophthalmia/microphthalmia 5,349 780
Common truncus 13,876 301
Transposition of great arteries 3,333 1,252
Tetralogy of Fallot 2,518 1,657
Atrioventricular septal defect 2,122 1,966
Hypoplastic left heart syndrome 4,344 960
Cleft palate without cleft lip 1,574 2,651
Cleft lip with and without cleft palate 940 4,437
Esophageal atresia/tracheoesophageal fistula 4,608 905
Rectal and large intestinal atresia/stenosis 2,138 1,952
Reduction deformity, upper limbs 2,869 1,454
Reduction deformity, lower limbs 5,949 701
Gastroschisis 2,229 1,871
Omphalocele 5,386 775
Diaphragmatic hernia 3,836 1,088
Trisomy 13 7,906 528
Trisomy 21 (Down syndrome) 691 6,037
Trisomy 18 3,762 1,109

Original Page Links

Australian Statistics | Abnormalities by Systems | Prenatal Diagnosis | Fetal Origins Hypothesis | Intrauterine Growth Retardation | Twinning | Genetic Abnormalities | Down Syndrome | Edwards Syndrome | Fragile X | Lesch-Nyhan Syndrome | | Maternal Factors | Maternal Diabetes | Maternal Hyperthermia | Neural Tube Defects | Fetal Alcohol Syndrome | Smoking | Chemical | Drugs | Illegal Drugs | Radiation | Heavy Metal | Iodine Deficiency | Viral Infection | Rubella | Polio | Parvovirus | Varicella | Bacterial Infection | Malaria | Toxoplasmosis | Autism |

Abnormalities by System

Abnormalities Links: Introduction | Genetic | Environmental | Unknown | Teratogens

The links below take you to the related systems abnormality page in each section of Notes. Additional pages relating to specific abnormalities will also be linked from these introductory pages.

Neural Development | Heart / Cardiovascular | Musculoskeletal | Musculoskeletal - Limb | Gastrointestinal Tract | Head and Neck | Coelomic cavity Respiratory | Neural Crest | Senses - General Eye, Ear, Nose | Senses - Ear | Senses - Eye | Urogenital | Genital | Endocrine | Endocrine - Adrenal | Integumentary

Cardiovascular | Coelomic Cavity | Endocrine | Gastrointestinal Tract | Genital | Head | Integumentary | Musculoskeletal | Neural | Neural Crest | Renal | Respiratory | Sensory |

Birth defects in Victoria

Fetal lead exposure and infant mental development index. Ronchetti R. Environ Health Perspect. 2007 Apr;115(4):A186; author reply A186-7. No abstract available. PMID: 17450196 | PMC1852654 This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose

Hu H, Téllez-Rojo MM, Bellinger D, Smith D, Ettinger AS, Lamadrid-Figueroa H, et al. Fetal lead exposure at each stage of pregnancy as a predictor of infant mental development. Environ Health Perspect. 2006;114:1730–1735. doi: 10.1289/ehp.9067. [Online 19 July 2006]

Western Australia

A retrospective population-based study of childhood hospital admissions with record linkage to a birth defects registry