**2.1. Staging of human embryonic development**

Carnegie stage 13: Four limb buds and optic vesicle appear

32 days after fertilization

CRL (crown-rump length): 5 mm

At this stage, two upper and two lower limb buds become visible. The optic vesicle can be easily recognized and the lens placode begins to differentiate. Although more than 30 pairs of somites have formed by this time, the number of somites becomes increasingly difficult to determine and therefore will no longer be used for staging henceforth.

Carnegie stage 17: Nasofrontal groove become distinct, and finger rays exhibited

Congenital Anomalies in Human Embryos http://dx.doi.org/10.5772/intechopen.72628 23

In comparison with the previous stage, the auricular hillocks and nasofrontal (nasolacrimal) grooves have become more distinct, and the trunk has straightened. The hand plates have come to exhibit conspicuous digital rays, and the foot has acquired a rounded digital plate

Carnegie stage 18: Elbows become discernible, toe rays appear, and eyelid folds appear

The body shape has become more cuboidal by this time. Both cervical and lumbar flexures are denoted, the elbows are discernible and interdigital notches begin to appear in the hand plates. Toe rays are observed in the foot plate. As for the facial features, eyelid folds start appearing, and the auricular hillocks transform into specific parts of the external ear. Furthermore, ossi-

The trunk begins its elongation and straightening. Simultaneously, the eyes and external ears become distinct. As a result of the growing size of the brain, the eyes get positioned in the front part of the face. The upper and lower limbs are approximately parallel, with preaxial borders being cranial, and postaxial borders caudal. Moreover, intestines have developed and parts of them can be observed in normal umbilical cord (physiological umbilical hernia).

The angle of the cervical flexure becomes smaller, and the head is directed upwards. Vascular plexus starts to appear in the superficial tissues of the head. Meanwhile, the coiled intestine finishes its development. Spontaneous movements are recognized at this stage. The upper limbs have increased in length at this time, and it is flexed at the elbows and hand joints.

40 days after fertilization

42 days after fertilization

44 days after fertilization

46 days after fertilization

48 days after fertilization

fication may begin in some skeletal structures.

Carnegie stage 19: Trunk elongation and straightening

Carnegie stage 20: Longer upper limb bends at elbow

Fingers can be observed over the chest, in a slight curve.

Carnegie stage 21: Fingers grow longer, hands approach each other

CRL: 11 mm

CRL: 13 mm

CRL: 16 mm

CRL: 19 mm

CRL: 21 mm

by this stage.

Carnegie stage 14: Lens pit and optic cup appear

34 days after fertilization

CRL: 6 mm

The lens pit begins to invaginate into the optic cup, although its closure remains incomplete at this stage. On the other hand, the optic vesicle emerges from the endolymphatic appendage and becomes easy to define. The upper limb buds elongate and taper, while the cephalic and cervical flexures become prominent in terms of the internal features; the future cerebral hemispheres and cerebellar plates differentiate at this point. The dorsal and ventral pancreatic buds have become noticeable, along with the development of the ureteric bud, which acquires a metanephrogenic blastema.

Carnegie stage 15: Lens vesicles are covered by surface ectoderm, nasal pit and hand plates form

34 days after fertilization

CRL: 8 mm

Lens vesicles have closed and are covered by the surface ectoderm at this time, while the nasal plate invaginates forming a nasal pit. At this stage, auricular hillocks arise, and hand plates begin to form. In the meantime, the foramen secundum develops in the heart while the lung buds begin to branch into lobar buds. The primary urogenital sinus completes its formation by the end of this stage.

Carnegie stage 16: Nasal pit faces ventrally, retinal pigment becomes visible, foot plates emerge

38 days after fertilization

CRL: 10 mm

Nasal pits deepen and start to face ventrally, while the retinal pigment becomes externally visible. In the meantime, hand plates become distinct and foot plates start to emerge. Furthermore, the nasolacrimal groove forms between the frontal and maxillary processes.

Carnegie stage 17: Nasofrontal groove become distinct, and finger rays exhibited

40 days after fertilization

CRL: 11 mm

**2. Normal development of human embryos**

Carnegie stage 13: Four limb buds and optic vesicle appear

determine and therefore will no longer be used for staging henceforth.

Carnegie stage 14: Lens pit and optic cup appear

At this stage, two upper and two lower limb buds become visible. The optic vesicle can be easily recognized and the lens placode begins to differentiate. Although more than 30 pairs of somites have formed by this time, the number of somites becomes increasingly difficult to

The lens pit begins to invaginate into the optic cup, although its closure remains incomplete at this stage. On the other hand, the optic vesicle emerges from the endolymphatic appendage and becomes easy to define. The upper limb buds elongate and taper, while the cephalic and cervical flexures become prominent in terms of the internal features; the future cerebral hemispheres and cerebellar plates differentiate at this point. The dorsal and ventral pancreatic buds have become noticeable, along with the development of the ureteric bud, which acquires

Carnegie stage 15: Lens vesicles are covered by surface ectoderm, nasal pit and hand

Lens vesicles have closed and are covered by the surface ectoderm at this time, while the nasal plate invaginates forming a nasal pit. At this stage, auricular hillocks arise, and hand plates begin to form. In the meantime, the foramen secundum develops in the heart while the lung buds begin to branch into lobar buds. The primary urogenital sinus completes its formation

Carnegie stage 16: Nasal pit faces ventrally, retinal pigment becomes visible, foot plates

Nasal pits deepen and start to face ventrally, while the retinal pigment becomes externally visible. In the meantime, hand plates become distinct and foot plates start to emerge. Furthermore, the nasolacrimal groove forms between the frontal and maxillary processes.

**2.1. Staging of human embryonic development**

32 days after fertilization

34 days after fertilization

a metanephrogenic blastema.

34 days after fertilization

38 days after fertilization

CRL: 6 mm

plates form

CRL: 8 mm

by the end of this stage.

emerge

CRL: 10 mm

CRL (crown-rump length): 5 mm

22 Congenital Anomalies - From the Embryo to the Neonate

In comparison with the previous stage, the auricular hillocks and nasofrontal (nasolacrimal) grooves have become more distinct, and the trunk has straightened. The hand plates have come to exhibit conspicuous digital rays, and the foot has acquired a rounded digital plate by this stage.

Carnegie stage 18: Elbows become discernible, toe rays appear, and eyelid folds appear

42 days after fertilization

CRL: 13 mm

The body shape has become more cuboidal by this time. Both cervical and lumbar flexures are denoted, the elbows are discernible and interdigital notches begin to appear in the hand plates. Toe rays are observed in the foot plate. As for the facial features, eyelid folds start appearing, and the auricular hillocks transform into specific parts of the external ear. Furthermore, ossification may begin in some skeletal structures.

Carnegie stage 19: Trunk elongation and straightening

44 days after fertilization

CRL: 16 mm

The trunk begins its elongation and straightening. Simultaneously, the eyes and external ears become distinct. As a result of the growing size of the brain, the eyes get positioned in the front part of the face. The upper and lower limbs are approximately parallel, with preaxial borders being cranial, and postaxial borders caudal. Moreover, intestines have developed and parts of them can be observed in normal umbilical cord (physiological umbilical hernia).

Carnegie stage 20: Longer upper limb bends at elbow

46 days after fertilization

CRL: 19 mm

The angle of the cervical flexure becomes smaller, and the head is directed upwards. Vascular plexus starts to appear in the superficial tissues of the head. Meanwhile, the coiled intestine finishes its development. Spontaneous movements are recognized at this stage. The upper limbs have increased in length at this time, and it is flexed at the elbows and hand joints. Fingers can be observed over the chest, in a slight curve.

Carnegie stage 21: Fingers grow longer, hands approach each other

48 days after fertilization

CRL: 21 mm

The head becomes round and the superficial vascular plexus spreads to surround the head. Meanwhile, the tail becomes rudimentary. At this time, the hands are slightly flexed at the wrists and are placed closely over the cardiac prominence.

Carnegie stage 22: Eyelids and external ears develop

50 days after fertilization

CRL: 23 mm

The vascular plexus of the head becomes more distinct at this stage. The eyelids start to thicken and encroach into the eyes. In the meantime, the tragus and antitragus of the external ear assume a more definite form, as the external ear repositions higher on the head. The tail is about to disappear.

Carnegie stage 23: The end of embryonic period

52 days after fertilization

CRL: 30 mm

At this stage, the head would be observed with a more rounded appearance and the trunk with a more mature shape. The eyelids and ear auricles have become conspicuous, the limbs have increased in length, and the forearms have ascended toward the level or higher than that of the shoulders. Meanwhile, the vascular plexus approaches the vertex of the head. Although external sex differences are not yet apparent, the external genitalia have developed relatively well by this time. The tail is no longer observed at this stage.
