Abnormal Development - Environmental

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Human critical periods of development
Human critical periods of development

Materal effects should really be called environmental (in contrast to genetic) removing the association of mother with the deleterious agent. Accepting this caveat, there are several maternal effects from lifestyle, environment and nutrition that can be prevented or decreased by change which is not an option for genetic effects.

Infections, collectively grouped under the acronym TORCH for Toxoplasmosis, Other organisms (parvovirus, HIV, Epstein-Barr, herpes 6 and 8, varicella, syphilis, enterovirus) , Rubella, Cytomegalovirus and Hepatitis. See related pages on maternal hyperthermia, viral and bacterial infections.

Maternal diet the best characterised is the role of low folic acid and Neural Tube Defects (NTDs) see also abnormal neural development and Neural Tube Defects and the sample environmental effects listed below.

Maternal drugs effects either prescription drugs (therapeutic chemicals/agents, thalidomide limb development), non-prescription drugs (alcohol, smoking, herbal drugs), and illegal drugs (Cannabis/Marijuana, Methamphetamine/Amphetamine, Cocaine, Heroin, Lysergic Acid Diethylamide)

Environment (smoking, chemical, heavy metals) and maternal endocrine function (maternal diabetes, thyroid development) and maternal stress.

Different environmental effects can act individually or in combination on the same developing system. For example, neural development can be impacted upon by alcohol (fetal alcohol syndrome), viral infection (rubella) and/or inadequate dietry folate intake (neural tube defects). These effects may also not be seen as a direct effect on a system or systems but result in a reduced birth weight and the potential postnatal developmental effects.

Finally, when studying this topic remember the concept of "critical periods" of development that will affect the overall impact of the above listed factors. This can be extended to the potential differences between prenatal and postnatal effects, for example with infections and outcomes.

This current page provides only a general overview of the topic, use the links below to get detailed information about specific environmental effects.

Environmental Links: Introduction | low folic acid | iodine deficiency | Nutrition | Drugs | Australian Drug Categories | USA Drug Categories | thalidomide | herbal drugs | Illegal Drugs | smoking | Fetal Alcohol Syndrome | TORCH | viral infection | bacterial infection | fungal infection | Zoonotic Infection | Toxoplasmosis | Malaria | Maternal Diabetes | Maternal Hypertension | maternal hyperthermia | Maternal Inflammation | Maternal Obesity | Hypoxia | Biological Toxins | Chemicals | heavy metals | radiation | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Fetal Origins Hypothesis

Bacterial Links: bacterial infection | syphilis | gonorrhea | tuberculosis | listeria | salmonella | TORCH | Environmental | Category:Bacteria
Viral Links: viral infection | TORCH | cytomegalovirus | Hepatitis Virus | HIV | Parvovirus | Polio Virus | rubella virus | Chickenpox | Lymphocytic Choriomeningitis Virus | Zika Virus | rotavirus | vaccination | Environmental
Historic Embryology - Viral 
1941 Rubella Cataracts | 1944 Rubella Defects
Abnormality Links: abnormal development | abnormal genetic | abnormal environmental | Unknown | teratogens | ectopic pregnancy | cardiovascular abnormalities | Coelomic Cavity | endocrine abnormalities | gastrointestinal abnormalities | genital abnormalities | head abnormalities | integumentary abnormalities | musculoskeletal abnormalities | limb abnormalities | neural abnormalities | neural crest abnormalities | renal abnormalities] | respiratory abnormalities | placenta abnormalities | hearing abnormalities | vision abnormalities | twinning | Developmental Origins of Health and Disease | ICD-11
Historic Embryology  
1915 Congenital Cardiac Disease | 1917 Frequency of Anomalies in Human Embryos | 1920 Hydatiform Degeneration Tubal Pregnancy | 1921 Anencephalic Embryo | 1921 Rat and Man | 1966 Congenital Malformations

Some Recent Findings

French regions - Ain, Brittany and Loire-Atlantique
Brindisi, Italy
  • Recurrent pregnancy loss: A summary of international evidence-based guidelines and practice[1] "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. 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). 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."
  • Impact of sample collection participation on the validity of estimated measures of association in the National Birth Defects Prevention Study when assessing gene-environment interactions[2] "To better understand the impact that nonresponse for specimen collection has on the validity of estimates of association, we examined associations between self-reported maternal periconceptional smoking, folic acid use, or pregestational diabetes mellitus and six birth defects among families who did and did not submit buccal cell samples for DNA following a telephone interview as part of the National Birth Defects Prevention Study (NBDPS). Analyses included control families with live born infants who had no birth defects (N = 9,465), families of infants with anorectal atresia or stenosis (N = 873), limb reduction defects (N = 1,037), gastroschisis (N = 1,090), neural tube defects (N = 1,764), orofacial clefts (N = 3,836), or septal heart defects (N = 4,157). Estimated dates of delivery were between 1997 and 2009. ...These findings support the validity of observed associations in gene-environment interaction studies for the selected exposures and birth defects among NBDPS participants who submitted DNA samples.
  • Maternal genetic variation accounts in part for the associations of maternal size during pregnancy with offspring cardiometabolic risk in adulthood[3] "Maternal pre-pregnancy body-mass index (ppBMI) and gestational weight gain (GWG) are associated with cardiometabolic risk (CMR) traits in the offspring. The extent to which maternal genetic variation accounts for these associations is unknown. Maternal genetic risk scores (GRS) were created using a subset of SNPs most predictive of ppBMI, GWG, and each CMR trait, selected among 1384 single-nucleotide polymorphisms (SNPs) characterizing variation in 170 candidate genes potentially related to fetal development and/or metabolic risk."
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches

Search term: Environmental Abnormal Development

Keiko Iwata Mitochondrial Involvement in Mental Disorders; Energy Metabolism, Genetic, and Environmental Factors. Methods Mol. Biol.: 2019, 1916;41-48 PubMed 30535680

Maëlle Wirth, Aurélie Naud, Emmanuelle Schmitt, Isabelle Clerc-Urmès, Jean-Michel Hascoët Visual Maturation at Term Equivalent Age in Very Premature Infants According to Factors Influencing Its Development. Front Physiol: 2018, 9;1649 PubMed 30515105

Cunguang Lou, Chenyao Pang, Congrui Jing, Shuo Wang, Xufeng He, Xiaoguang Liu, Lei Huang, Feng Lin, Xiuling Liu, Hongrui Wang Dynamic Balance Measurement and Quantitative Assessment Using Wearable Plantar-Pressure Insoles in a Pose-Sensed Virtual Environment. Sensors (Basel): 2018, 18(12); PubMed 30513590

M L Hu, S W Xiong, S X Zhu, X X Xue, X D Zhou MicroRNAs in gastric cancer: from bench to bedside. Neoplasma: 2018; PubMed 30509106

Hyun-Na Koo, Seung-Hwan Yun, HyunKyung Kim, Gil-Hah Kim Elucidation of molecular expression associated with abnormal development and sterility caused by electron beam irradiation in Spodoptera litura (F.) (Lepidoptera: Noctuidae). Int. J. Radiat. Biol.: 2018;1-34 PubMed 30499761

Older papers  
  • Work and Pregnancy (UK)[4] "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."
  • Congenital anomalies among live births in a polluted area[5] "Congenital anomalies and their primary prevention are a crucial public health issue. This work aimed to estimate the prevalence of congenital anomalies in Brindisi, a city in southeastern Italy at high risk of environmental crisis. This research concerned newborns up to 28 days of age, born between 2001 and 2010 to mothers resident in Brindisi and discharged with a diagnosis of congenital anomaly. ...Our findings indicated an increased prevalence of Congenital Anomalies (especially congenital heart diseases) in the city of Brindisi. More research is needed in order to analyze the role of factors potentially involved in the causation of congenital anomalies."
  • Environmental factors in axial skeletal dysmorphogenesis[6] "Approximately 1 in 1000 live births is afflicted with an axial skeletal defect. Although many of the known human teratogens can produce axial skeletal defects, the etiology of over half of the observed defects is unknown."
  • The temporal dynamics of vertebrate limb development, teratogenesis and evolution.[7] "Recent genetic and functional analysis of vertebrate limb development begins to reveal how the functions of particular genes and regulatory hierarchies can drastically change over time. The temporal and spatial interplay of the two instructive signalling centres are part of a larger signalling system that orchestrates limb bud morphogenesis in a rather self-regulatory manner. It appears that mesenchymal cells are specified early and subsequently, the progenitors for the different skeletal elements are expanded and determined progressively during outgrowth. Mutations and teratogens that disrupt distal progression of limb development most often cause death of the early-specified progenitors rather than altering their fates."
  • Developmental toxicity of pharmaceuticals using human embryonic stem cells and metabolomics.[8] "Teratogens, substances that may cause fetal abnormalities during development, are responsible for a significant number of birth defects. Animal models used to predict teratogenicity often do not faithfully correlate to human response. Here, we seek to develop a more predictive developmental toxicity model based on an in vitro method that utilizes both human embryonic stem (hES) cells and metabolomics to discover biomarkers of developmental toxicity."

Critical Periods

The table below identifies approximate windows of time, "critical periods", that following exposure to teratogens can lead to developmental abnormalities (anomalies, congenital). In general, the effects for each system are more severe (major anomalies) in the embryonic period during organogenesis in the first trimester. Later teratogen exposure are less severe (minor anomalies) in the fetal period during continued growth and differentiation in the second and third trimester.

Critical Periods of Human Development
Conceptus Embryonic development (weeks) Fetal period (weeks)
Early zygote.jpg Week2 001 icon.jpg Stage9 sem4c.jpg Stage13 sem1c.jpg Stage15 bf1c.jpg Stage17 bf1c.jpg Stage19 bf1c.jpg Stage23 bf1c.jpg
Stage2.jpg Heart
Upper limbs
Lower limbs
CSt3.jpg Palate
Week2 001 icon.jpg External genitalia
Loss Major abnormalities Functional and Minor abnormalities


The potential of a pesticide or biocide to cause adverse effects in the developing embryo or fetus is an important consideration in any health risk assessment for humans and wildlife.

Report of the 8th Berlin Workshop on Developmental Toxicity held in May 2014.[9]

"The main aim of the workshop was the continuing harmonization of terminology and innovations for methodologies used in the assessment of embryo- and feto-toxic findings. The following main topics were discussed: harmonized categorization of external, skeletal, visceral and materno-fetal findings into malformations, variations and grey zone anomalies, aspects of developmental anomalies in humans and laboratory animals, and innovations for new methodologies in developmental toxicology. The application of Version 2 terminology in the DevTox database was considered as a useful improvement in the categorization of developmental anomalies."

Links: DevTox


There is an increasing number of women travelling during pregnancy that may carry some additional environmental risks. The following information is summarised from a recent BMJ article.[10]

  • second trimester of pregnancy is considered the safest in which to travel
  • air travel may carry risk of miscarriage, preterm birth, and thromboembolism
  • obstetric and neonatal care facilities at destinations is varied
  • obtain adequate insurance and check with their airline for restrictions on travel
  • communicable diseases acquired abroad may increase risks of perinatal morbidity


  1. 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
  2. Jenkins MM, Reefhuis J, Herring AH & Honein MA. (2017). Impact of sample collection participation on the validity of estimated measures of association in the National Birth Defects Prevention Study when assessing gene-environment interactions. Genet. Epidemiol. , 41, 834-843. PMID: 29071735 DOI.
  3. Wander PL, Hochner H, Sitlani CM, Enquobahrie DA, Lumley T, Lawrence GM, Burger A, Savitsky B, Manor O, Meiner V, Hesselson S, Kwok PY, Siscovick DS & Friedlander Y. (2014). Maternal genetic variation accounts in part for the associations of maternal size during pregnancy with offspring cardiometabolic risk in adulthood. PLoS ONE , 9, e91835. PMID: 24670385 DOI.
  4. Palmer KT, Bonzini M & Bonde JP. (2013). Pregnancy: occupational aspects of management: concise guidance. Clin Med (Lond) , 13, 75-9. PMID: 23472500
  5. Gianicolo EA, Bruni A, Rosati E, Sabina S, Guarino R, Padolecchia G, Leo C, Vigotti MA, Andreassi MG & Latini G. (2012). Congenital anomalies among live births in a polluted area. A ten-year retrospective study. BMC Pregnancy Childbirth , 12, 165. PMID: 23270371 DOI.
  6. Alexander PG & Tuan RS. (2010). Role of environmental factors in axial skeletal dysmorphogenesis. Birth Defects Res. C Embryo Today , 90, 118-32. PMID: 20544699 DOI.
  7. Zeller R. (2010). The temporal dynamics of vertebrate limb development, teratogenesis and evolution. Curr. Opin. Genet. Dev. , 20, 384-90. PMID: 20537528 DOI.
  8. West PR, Weir AM, Smith AM, Donley EL & Cezar GG. (2010). Predicting human developmental toxicity of pharmaceuticals using human embryonic stem cells and metabolomics. Toxicol. Appl. Pharmacol. , 247, 18-27. PMID: 20493898 DOI.
  9. Solecki R, Rauch M, Gall A, Buschmann J, Clark R, Fuchs A, Kan H, Heinrich V, Kellner R, Knudsen TB, Li W, Makris SL, Ooshima Y, Paumgartten F, Piersma AH, Schönfelder G, Oelgeschläger M, Schaefer C, Shiota K, Ulbrich B, Ding X & Chahoud I. (2015). Continuing harmonization of terminology and innovations for methodologies in developmental toxicology: Report of the 8th Berlin Workshop on Developmental Toxicity, 14-16 May 2014. Reprod. Toxicol. , 57, 140-6. PMID: 26073002 DOI.
  10. Hezelgrave, NL, Whitty, CJM, Shennan, AH, and Chappell, LC. Advising on travel during pregnancy BMJ 2011; 342:d2506 doi: 10.1136/bmj.d2506 (Published 28 April 2011) BMJ


  • Environmental Health Perspectives (EHP) is a monthly journal of peer-reviewed research and news on the impact of the environment on human health. EHP | Pubmed EHP


Sadler TW. (2017). Establishing the Embryonic Axes: Prime Time for Teratogenic Insults. J Cardiovasc Dev Dis , 4, . PMID: 29367544 DOI.

Foster WG, Evans JA, Little J, Arbour L, Moore A, Sauve R, Andrés León J & Luo W. (2017). Human exposure to environmental contaminants and congenital anomalies: a critical review. Crit. Rev. Toxicol. , 47, 59-84. PMID: 27685638 DOI.

Brent RL. (2004). Environmental causes of human congenital malformations: the pediatrician's role in dealing with these complex clinical problems caused by a multiplicity of environmental and genetic factors. Pediatrics , 113, 957-68. PMID: 15060188


Search Pubmed

June 2010 "teratogens" All (25401) Review (3026) Free Full Text (3991) "TORCH Infections" All (183) Review (37) Free Full Text (18)

Search Pubmed: teratogens | TORCH Infections | maternal abnormalities

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

  • REPROTOX - contains summaries on the effects of medications, chemicals, infections, and physical agents on pregnancy, reproduction, and development.
  • DevTox

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Cite this page: Hill, M.A. (2018, December 13) Embryology Abnormal Development - Environmental. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Environmental

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© Dr Mark Hill 2018, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G