Embryology · Teratology and prenatal diagnosis

Maternal diabetes and obesity as teratogens !

Teratogen

High maternal sugar in the first weeks can cause heart, spine and neural tube defects; later it makes the baby grow too big.

Updated 2026-11-01

See it in 3D: Sacrum · Coccyx · Interventricular septum · Pulmonary trunk

What it is

Pre-existing diabetes (type 1 or type 2) that is poorly controlled in weeks 3 to 8 is teratogenic: high glucose causes oxidative stress and cell death in the embryo. It increases heart defects, neural tube defects and caudal regression. Later, maternal hyperglycaemia causes fetal hyperinsulinism, macrosomia and neonatal hypoglycaemia. Gestational diabetes arises after the critical period, so it is linked mainly to excess growth.

Key facts

Glucose enters the embryo through GLUT transporters; maternal insulin does not cross the placenta.
Gestational diabetes starts after weeks 3 to 8, so it does not clearly raise major malformations.
Pre-pregnancy obesity roughly doubles the risk of neural tube defects and raises heart defects and omphalocele.
Uncontrolled maternal phenylketonuria causes microcephaly, intellectual disability and heart defects in the child.
Macrosomia raises the risk of shoulder dystocia.

Critical period and mechanism

Critical period: weeks 3 to 8 after fertilization, often before the pregnancy is known.
Hyperglycaemia increases reactive oxygen species, causes embryonic hypoxia and depletes myo-inositol.
The result is apoptosis in forming tissues: caudal mesoderm, neural tube, heart.
In the second and third trimesters maternal glucose drives the fetal pancreas, and excess insulin acts as a growth hormone.

Prevention

Preconception visit with good glucose control before conceiving.
Folic acid supplement before conception; the amount is set by the treating professional.
Addressing weight before pregnancy when there is obesity.

What it does to the embryo and fetus

Congenital heart defects, neural tube defects, caudal regression (in its extreme form, sirenomelia).
Renal agenesis, femoral hypoplasia and craniofacial anomalies.
Macrosomic newborn with hypoglycaemia, polycythaemia, hyperbilirubinaemia and respiratory distress syndrome (insulin delays surfactant).
More stillbirths and neonatal deaths with poor control.

In the lab

Anatomy scan around weeks 18–20 and fetal echocardiography in the second trimester.
Screening for gestational diabetes between weeks 24 and 28.

Test yourself

Think of the answer, then tap the question to see it.

Which malformation is most characteristic of pregestational maternal diabetes?

Caudal regression (sacral agenesis), along with heart defects such as transposition of the great arteries and neural tube defects.

Why does gestational diabetes not clearly raise major malformations?

It appears after the critical period of weeks 3 to 8; it is linked mainly to macrosomia.

Why is the infant of a diabetic mother hypoglycaemic at birth?

The fetal pancreas made excess insulin in response to maternal glucose; once the cord is cut, that insulin persists without the glucose supply.

Add to my cards (3)

See it in 3D

The structures of Durgical's 3D anatomy where it is found.

← All of embryology

Educational content on embryonic development; not a guide to prenatal diagnosis or to medicines in pregnancy and no substitute for a health professional's advice. No doses are given.

Sources: Diabetic Embryopathy (StatPearls Publishing (NCBI Bookshelf), 2023); Langman's Medical Embryology, 13th ed., ch. 9: Birth Defects and Prenatal Diagnosis (Wolters Kluwer, 2015).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.