Paeds · fetal-neonatal-and-perinatal
Maternal disease, medication and substance effects on the fetus
Also known as Teratogenesis · Fetal teratogenic effects · Maternal medication in pregnancy · Substance use in pregnancy · Fetal alcohol spectrum disorder · Infant of a diabetic mother
Fellowship guide to how maternal medical conditions, therapeutic medications and non-medical substances affect the developing fetus and newborn: principles of teratogenesis and critical windows, the high-yield agents (diabetes, thyroid, antiepileptics, SSRIs, lithium, warfarin, ACE inhibitors, isotretinoin, maternal PKU, alcohol, tobacco, cannabis, stimulants, opioids), folic acid and magnesium sulfate prophylaxis, neonatal adaptation and withdrawal syndromes, and regional guideline differences.
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Red flags
- Never stop an essential maternal medication (epilepsy, psychiatric, anticoagulation) abruptly out of teratogenic fear without specialist advice
- First-trimester isotretinoin exposure carries a high structural teratogenicity risk and warrants immediate referral and detailed fetal anatomy and cardiac assessment
- Oligohydramnios with second or third trimester ACE inhibitor exposure signals fetal renal injury and needs urgent assessment
- Neonatal irritability and tremor must not be assumed to be opioid or SSRI withdrawal until sepsis, hypoglycaemia and metabolic disease are excluded
- A neonate with a large fetal goitre from antithyroid drugs may have airway compromise at birth and needs a planned delivery with EXIT capability
- Maternal phenylalanine above the target range in maternal PKU predicts microcephaly, cardiac defects and intellectual disability in the offspring
- There is no known safe level of alcohol in pregnancy
Life stages
Care settings
Clinical exam formats
Board mappings
- Neonatal medicine
- General and Community Paediatrics
- Current 2026 PREP curriculum — fetal and neonatal consequences of maternal disease and substance use
- Renewed curriculum for first-year trainees from 2027 — essential general paediatrics
- Renewed curriculum for first-year trainees from 2027 — communication with patients, families, and health professionals
- Clinical Applications
- Medical Sciences
- Long Cases
- Short Cases
- Patient management
- Communication
- Health promotion and illness prevention
- Foundation of Practice (FOP)
- Theory and Science (TAS)
- Applied Knowledge in Practice (AKP)
- Clinical
- History
- General Pediatrics Content Outline — Domain 1: Preventive Pediatrics/Well-Child Care
- General Pediatrics Content Outline — Domain 3: Management of the Newborn
- General Pediatrics Content Outline — Universal Task 3: Diagnosis
- General Pediatrics Content Outline — Universal Task 4: Management and Treatment
- Patient Care: newborn management after maternal exposure
- Systems-Based Practice: coordination with obstetric and addiction services
- Interpersonal and Communication Skills: non-stigmatising counselling
- Medical Expert
- Health Advocate
- Communicator
Overview & Definition
A teratogen is any agent — a maternal disease, a drug, a substance, a nutrient imbalance or an infection — that disturbs fetal development and produces a structural, growth, functional or behavioural abnormality. The word hides a subtlety examiners probe: teratogenesis is not one event. It is a timing-dependent process in which the same agent does different harm depending on the gestational window, the dose, and the genetic susceptibility of the fetus. [1]
This topic covers the whole map of maternal-to-fetal harm: how maternal medical conditions injure the fetus (diabetes, thyroid disease, PKU, autoimmune disease), how therapeutic drugs do so (antiepileptics, SSRIs, lithium, warfarin, ACE inhibitors, isotretinoin, antithyroid drugs), and how recreational substances do so (alcohol, tobacco, cannabis, stimulants, opioids). It does not cover the neonatal management of abstinence syndrome in procedural detail, the management of neonatal hypoglycaemia, or perinatal infection screening — those have their own dedicated topics. What it does cover is how each exposure produces its effect, what to look for, what to prevent, and how to counsel a family without stigma. [27] [4]
The framework that organises everything here is the three critical windows of pregnancy: the pre-implantation all-or-none period, the organogenesis window when major structural defects arise, and the fetal period when growth and brain development are the targets. Once that framework is in place, every agent slots into a window, and every named syndrome becomes explicable. [1]
References28ShowHide
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- [2]van Gool JD, Hirche H, Lax H, De Schaepdrijver L Folic acid and primary prevention of neural tube defects: A review. Reproductive Toxicology, 2018.PMID 29777755
- [3]Shepherd ES, Goldsmith S, Doyle LW, Middleton P, et al. Magnesium Sulfate Before Preterm Birth for Neuroprotection: An Updated Cochrane Systematic Review. Obstetrics and Gynecology, 2024.PMID 38830233
- [4]Ye W, Luo C, Zhou J, Liang X, et al. Association between maternal diabetes and neurodevelopmental outcomes in children: a systematic review and meta-analysis of 202 observational studies comprising 56.1 million pregnancies. Lancet Diabetes and Endocrinology, 2025.PMID 40209722
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- [6]Rodolaki K, Pergialiotis V, Iakovidou N, Boutsikou T, et al. The impact of maternal diabetes on the future health and neurodevelopment of the offspring: a review of the evidence. Frontiers in Endocrinology, 2023.PMID 37469977
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- [9]Tomson T, Landmark CJ, Battino D Antiepileptic drug treatment in pregnancy: changes in drug disposition and their clinical implications. Epilepsia, 2013.PMID 23360413
- [10]Vajda FJ, Hitchcock AA, Graham J, O'Brien TJ, et al. The teratogenic risk of antiepileptic drug polytherapy. Epilepsia, 2010.PMID 19817810
- [11]Clayton-Smith J, Bromley R, Dean J, Journel H, et al. Diagnosis and management of individuals with Fetal Valproate Spectrum Disorder; a consensus statement from the European Reference Network for Congenital Malformations and Intellectual Disability. Orphanet Journal of Rare Diseases, 2019.PMID 31324220
- [12]Cummings C, Stewart M, Stevenson M, Morrow J, et al. Neurodevelopment of children exposed in utero to lamotrigine, sodium valproate and carbamazepine. Archives of Disease in Childhood, 2011.PMID 21415043
- [13]Hegde A, Kaur A, Sood A, Dhanorkar M, et al. Fetal Hydantoin Syndrome. Journal of Pediatrics, 2017.PMID 28578158
- [14]Bérard A, Sheehy O, Zhao JP, et al. SSRI and SNRI use during pregnancy and the risk of persistent pulmonary hypertension of the newborn. British Journal of Clinical Pharmacology, 2017.PMID 27874994
- [15]Patorno E, Huybrechts KF, Bateman BT, Cohen JM, et al. Lithium Use in Pregnancy and the Risk of Cardiac Malformations. New England Journal of Medicine, 2017.PMID 28591541
- [16]Chan KY, Gilbert-Barness E, Tiller G Warfarin embryopathy. Pediatric and Developmental Pathology, 2003.PMID 14692224
- [17]Barr M Jr, Cohen MM Jr ACE inhibitor fetopathy and hypocalvaria: the kidney-skull connection. Teratology, 1991.PMID 1771591
- [18]Deva M, Kara T ACE inhibitor fetopathy: a case series and survey of opinion amongst New Zealand paediatricians, obstetricians, neonatologists, and nephrologists. New Zealand Medical Journal, 2012.PMID 22960716
- [19]Cha EH, Kim N, Kwak HS, Han HJ, et al. Pregnancy and neonatal outcomes after periconceptional exposure to isotretinoin in Koreans. Obstetrics and Gynecology Science, 2022.PMID 35193174
- [20]Verduci E, Tosi M, Zuvadelli J, Giorda S, et al. The First 1000 Days of PKU: A Narrative Review of Maternal PKU and Early Life Management After Positive Newborn Screening. Nutrients, 2026.PMID 41599812
- [21]Lange S, Probst C, Gmel G, Rehm J, et al. Global Prevalence of Fetal Alcohol Spectrum Disorder Among Children and Youth: A Systematic Review and Meta-analysis. JAMA Pediatrics, 2017.PMID 28828483
- [22]Popova S, Lange S, Shield K, Mihic A, et al. Comorbidity of fetal alcohol spectrum disorder: a systematic review and meta-analysis. Lancet, 2016.PMID 26777270
- [23]Abraham M, Alramadhan S, Iniguez C, Duijts L, et al. A systematic review of maternal smoking during pregnancy and fetal measurements with meta-analysis. PLoS One, 2017.PMID 28231292
- [24]Corrêa ML, Soares PSM, da Silva BGC, et al. Maternal smoking during pregnancy and intelligence quotient in offspring: A systematic review and meta-analysis. Neurotoxicology, 2021.PMID 34004235
- [25]Lo JO, Shaw B, Robalino S, Ayers CK, et al. Cannabis Use in Pregnancy and Neonatal Outcomes: A Systematic Review and Meta-Analysis. Cannabis and Cannabinoid Research, 2024.PMID 36730710
- [26]Kalaitzopoulos DR, Chatzistergiou K, Amylidi AL, Kokkinidis DG, et al. Effect of Methamphetamine Hydrochloride on Pregnancy Outcome: A Systematic Review and Meta-analysis. Journal of Addiction Medicine, 2018.PMID 29509557
- [27]Coyle MG, Brogly SB, Ahmed MS, Patrick SW, et al. Neonatal abstinence syndrome. Nature Reviews Disease Primers, 2018.PMID 30467370
- [28]Jansson LM, Patrick SW Neonatal Abstinence Syndrome. Pediatric Clinics of North America, 2019.PMID 30819342