54 BEFORE WE ARE BORN ESSENTIALS OF EMBRYOLOGY AND BIRTH DEFECTS
fourth weeks (Fig. 6-5A), their measurements indicate the greatest length. The sitting height, or crown–rump length, is used to estimate the age of older embryos (see Fig. 6-5B and C). Standing height, or crown–heel length, is some- times measured during weeks 14 to 18 (see Fig. 6-5D).
The Carnegie Embryonic Staging System is used interna- tionally for comparison (see Table 6-1).
HIGHLIGHTS OF THE FOURTH TO
C H A P T E R 6 FOuRTH TO EIGHTH WEEkS OF HuMAN DEvELOPMENT 55
Table 6–1 Criteria for Estimating Developmental Stages in Human Embryos AGE
(days) FIGURE
REFERENCE CARNEGIE
STAGE NUMBER
OF SOMITES LENGTH
(mm)* MAIN EXTERNAL CHARACTERISTICS†
20–21 6-1A1 9 1–3 1.5–3.0 Flat embryonic disc. Deep neural groove and prominent
neural folds. Head fold is evident.
22–23 6-8A, C 10 4–12 2.0–3.5 Embryo is straight or slightly curved. Neural tube is
forming or has formed opposite somites, but is widely open at the rostral and caudal neuropores. First and second pairs of pharyngeal arches are visible.
24–25 6-9A 11 13–20 2.5–4.5 Embryo is curved owing to head and tail folds. Rostral
neuropore is closing. Otic placodes are present. Optic vesicles have formed.
26–27 6-7B
6-10A
12 21–29 3.0–5.0 Upper limb buds appear. Rostral neuropore is closed.
Caudal neuropore is closing. Three pairs of pharyngeal arches are visible. Heart prominence is distinct. Otic pits are present.
28–30 6-6
6-11A
13 30–35 4.0–6.0 Embryo has C-shaped curve. Caudal neuropore is closed.
Four pairs of pharyngeal arches are visible. Lower limb buds appear. Otic vesicles are present. Lens placodes are distinct.
31–32 6-12A 14 ‡ 5.0–7.0 Lens pits and nasal pits are visible. Optic cups are present.
33–36 15 7.0–9.0 Hand plates have formed; digital rays are present. Lens
vesicles are present. Nasal pits are prominent. Cervical sinuses are visible.
37–40 16 8.0–11.0 Foot plates have formed. Pigment is visible in the retina.
Auricular hillocks are developing.
41–43 6-13A 17 11.0–14.0 Digital rays are clearly visible in hand plates. Auricular
hillocks outline the future auricle of the external ear.
Cerebral vesicles are prominent.
44–46 18 13.0–17.0 Digital rays are clearly evident in foot plates. Elbow
region is visible. Eyelids are forming. Notches are between the digital rays in the hands. Nipples are visible.
47–48 19 16.0–18.0 Limbs extend ventrally. Trunk is elongating and
straightening. Midgut herniation is prominent.
49–51 20 18.0–22.0 Upper limbs are longer and are bent at the elbows. Fingers
are distinct but webbed. Notches are between the digital rays in the feet. Scalp vascular plexus appears.
52–53 21 22.0–24.0 Hands and feet approach each other. Fingers are free and
longer. Toes are distinct but webbed. Stubby caudal eminence (tail) is present.
54–55 22 23.0–28.0 Toes are free and longer. Eyelids and auricles of the
external ears are more developed.
56 6-14A 23 27.0–31.0 Head is more rounded and shows human characteristics.
External genitalia still have undifferentiated appearance.
Midgut herniation is still present. Caudal eminence has disappeared.
*The embryonic lengths indicate the usual range. In stages 9 and 10, the measurement is greatest length; in subsequent stages, crown–rump measurements are given.
†Based on O’Rahilly R, Müller F: Developmental Stages in Human Embryos. Washington, DC, Carnegie Institute of Washington, 1987; and Gasser RF: Digitally Reproduced Embryonic Morphology DVDs. Computer Imaging Laboratory, Cell Biology and Anatomy. New Orleans, LA, Louisiana State University Health Sciences Center, 2002–2006.
‡At this stage and subsequent stages, the number of somites is difficult to determine and so is not a useful criterion.
Fourth Week
Major changes in body form occur during the fourth week. At the beginning, the embryo is almost straight.
In the fourth week the somites produce conspicuous surface elevations and the neural tube is open at the rostral and caudal neuropores (Fig. 6-7A and Fig. 6-8C and D). By 24 days, the pharyngeal arches have appeared (see Fig. 6-7A to C). The embryo is now slightly curved
because of the head and tail folds. The early heart pro- duces a large ventral prominence and pumps blood (Fig.
6-9 and Fig. 6-10). The rostral neuropore is closing at 24 days (see Fig. 6-9B).
At 26 days, the forebrain produces a prominent eleva- tion of the head and the long, curved caudal eminence (tail-like structure) is present (see Fig. 6-10B). At 28 days, upper limb buds are recognizable as small swellings on the
56 BEFORE WE ARE BORN ESSENTIALS OF EMBRYOLOGY AND BIRTH DEFECTS
Figure 6–6 Endovaginal scan of embryos. A, Endovaginal scan of a 5-week embryo (crown–
rump length [CRL] 10 mm [calipers]) surrounded by the amniotic membrane (arrow). B, Coronal scan of a 7-week embryo (CRL 22 mm [calipers]). Amnion seen anterior (arrow). Umbilical vesicle (yolk sac) anterior.
A B
1
1
Figure 6–7 A, B, and C, Lateral views of older embryos, showing 16, 27, and 33 somites, respectively. The rostral neuropore is normally closed by 25 to 26 days, and the caudal neuro- pore is usually closed by the end of the fourth week.
Third pharyngeal
arch Fourth pharyngeal
arch
C
Rostral neuropore closing
Heart prominence
First pharyngeal arch
Otic pit (primordium
of ear)
Second pharyngeal arch
Somites Caudal eminence
A 24-day embryo = 3.5 mm 26-day embryo = 4.0 mm 28-day embryo = 5.0 mm Caudal
neuropore open
Forebrain prominence
B
Lens placode (primordium of lens)
Lower limb bud
Upper limb bud
ventrolateral body walls (Fig. 6-11A and B). At 26 days, the otic pits (primordia of internal ears) are also visible (see Fig. 6-10B). Ectodermal thickenings called lens plac- odes, indicating the future lenses of the eyes, are visible on the sides of the head. The fourth pair of pharyngeal arches and the lower limb buds are visible by the end of the fourth week (see Fig. 6-7C and Fig. 6-12). By the end of the fourth week, the caudal neuropore is usually closed (see Fig. 6-10). Rudiments of many organ systems, espe- cially the cardiovascular system, are established.
Fifth Week
Changes in body form are minor during the fifth week compared with those that occurred during the fourth week. Growth of the head exceeds that of other regions (see Fig. 6-12A and B), which is caused mainly by the rapid development of the brain and facial prominences.
The face soon contacts the heart prominence. The meso- nephric ridges indicate the site of the mesonephric kidneys (see Fig. 6-12B), which are the primordia of the perma- nent kidneys (see Fig. 6-12A and B).
C H A P T E R 6 FOuRTH TO EIGHTH WEEkS OF HuMAN DEvELOPMENT 56.e1
(Courtesy E. A. Lyons, MD, Professor of Radiology and Obstetrics and Gynecology, Health Sciences Centre and University of Mani- toba, Winnipeg, Manitoba, Canada.)
C H A P T E R 6 FOuRTH TO EIGHTH WEEkS OF HuMAN DEvELOPMENT 57
Figure 6–8 A, Dorsal view of a five-somite embryo at Carnegie stage 10, approximately 22 days. Observe the neural folds and neural groove. The neural folds in the cranial region have thickened to form the primordium of the brain. B, Drawing of the structures shown in A. Most of the amniotic and chorionic sacs have been cut away to expose the embryo. C, Dorsal view of an older embryo at Carnegie stage 10, approximately 23 days. The neural folds have fused opposite the somites to form the neural tube (primordium of spinal cord in this region). The neural tube is in open communication with the amniotic cavity at the cranial and caudal ends through the rostral and caudal neuropores, respectively. D, Diagram of the structures shown in C. The amniotic fluid provides a buoyant medium that supports the delicate tissues of the early embryo.
B
Neural groove
Neural fold in region of developing brain
Umbilical vesicle
First pairs of somites
Connecting stalk Cut surface
of amnion
Neural fold in region of developing spinal cord Neural groove
Location of primitive streak
Rostral neuropore
Neural folds in region of developing brain
Neural tube
Remnant of amniotic sac Site of fusion of neural folds
(23-day embryo) = 3.0 mm Somites
Caudal neuropore
A
C D
(22-day embryo) = 2.5 mm
58 BEFORE WE ARE BORN ESSENTIALS OF EMBRYOLOGY AND BIRTH DEFECTS
Seventh Week
The limbs undergo considerable change during the seventh week. Notches appear between the digital rays in the hand plates, partially separating the future digits.
Communication between the primordial gut and the umbilical vesicle is now reduced to a relatively slender duct, the omphaloenteric duct (see Fig. 6-1C2).
Eighth Week
At the beginning of this final week of the embryonic period, the digits of the hand are separated, but noticeably webbed (see Fig. 6-13B). Notches are clearly visible between the digital rays of the feet. The scalp vascular plexus has appeared and forms a characteristic band around the head. At the end of the fetal period, the digits have lengthened and are separated (Fig. 6-14A and B). Coordinated limb movements first occur during this week. Primary ossification begins in the femur. All evidence of the tail-like caudal eminence has disappeared by the end of the eighth week.
Sixth Week
Embryos in the sixth week show spontaneous move- ments, such as twitching of the trunk and limbs. Embryos at this stage show reflex responses to touch. The primor- dia of the digits (fingers)—the digital rays—begin to develop in the hand plates (Fig. 6-13A and B). Develop- ment of the lower limbs occurs 4 to 5 days later than that of the upper limbs.
Several small swellings—auricular hillocks—develop and contribute to the formation of the auricle of the external ear. The eyes are now obvious largely because retinal pigment has formed. The head is much larger rela- tive to the trunk and is bent over the large heart promi- nence. This head position results from bending in the cervical (neck) region. The trunk then begins to straighten.
During the sixth week, the intestines enter the extraem- bryonic coelom in the proximal part of the umbilical cord. This umbilical herniation is a normal event in the embryo, occurring because the abdominal cavity is too small at this stage to accommodate the rapidly growing intestines (see Chapter 12, Fig. 12-11C).
Figure 6–9 A, Dorsal view of a 13-somite embryo at Carnegie stage 11, approximately 24 days. The rostral neuropore is closing, but the caudal neuropore is wide open. B, Illustration of the structures shown in A. The embryo is curved because of folding of the cranial and caudal ends.
A B
Rostral neuropore closing
Forebrain
1st pharyngeal arch
Amnion Heart prominence
Somites
Connecting stalk
(24-day embryo) = 3.5 mm Neural tube in
region of developing spinal cord
Caudal neuropore
C H A P T E R 6 FOuRTH TO EIGHTH WEEkS OF HuMAN DEvELOPMENT 59
Figure 6–10 A, Lateral view of a 27-somite embryo at Carnegie stage 12, approximately 26 days. The embryo is curved, especially its tail-like caudal eminence. Observe the lens placode (primordium of lens of eye). The otic pit indicates early development of the internal ear.
B, Illustration of the structures shown in A. The rostral neuropore is closed, and three pairs of pharyngeal arches are present. (A, From Nishimura H, Semba H, Tanimura T, Tanaka O:
Prenatal Development of the Human with Special Reference to Craniofacial Structures: An Atlas.
Washington, DC, National Institutes of Health, 1977.) Forebrain
Site of otic pit (primordium of internal ear) 1st, 2nd, and 3rd pharyngeal arches
Somites
(26-day embryo) = 4.0 mm Caudal eminence
Site of lens placode Stomodeum (primordial mouth)
Heart prominence
A B
Figure 6–11 A, Lateral view of an embryo at Carnegie stage 13, approximately 28 days.
The primordial heart is large and is divided into a primordial atrium and a ventricle. The rostral and caudal neuropores are closed. B, Drawing indicating the structures shown in A. The embryo has a characteristic C-shaped curvature, four pharyngeal arches, and upper and lower limb buds.
(A, From Nishimura H, Semba H, Tanimura T, Tanaka O: Prenatal Development of the Human with Special Reference to Craniofacial Structures: An Atlas. Washington, DC, National Institutes of Health, 1977.)
B
Site of midbrain
1st, 2nd, 3rd, and 4th pharyngeal (branchial) arches
Left atrial prominence of heart
Upper limb bud
Somites
(28-day embryo) = 5.0 mm Mesonephric
ridge Site of
lens placode
Umbilical cord
Caudal eminence Lower limb bud Site of nasal placode Left ventricular prominence of heart
A
60 BEFORE WE ARE BORN ESSENTIALS OF EMBRYOLOGY AND BIRTH DEFECTS
the eyelids are closing. By the end of the eighth week, the eyelids begin to unite by epithelial fusion. The intestines are still in the proximal portion of the umbilical cord (see Chapter 12, Fig. 12-11C). The auricles of the external ears begin to assume their final shape, but are still low-set The hands and feet each approach each other ventrally.
At the end of the eighth week, the embryo has visually distinct human characteristics; however, the head is still disproportionately large, constituting almost half of the embryo (see Fig. 6-14). The neck region is established and
Figure 6–12 A, Lateral view of an embryo at Carnegie stage 14, approximately 32 days.
The second pharyngeal arch has overgrown the third arch, forming the cervical sinus. The mesonephric ridge indicates the site of the mesonephric kidney, an interim functional kidney.
B, Illustration of the structures shown in A. The upper limb buds are paddle-shaped, whereas the lower limb buds are flipper-like. (A, From Nishimura H, Semba H, Tanimura T, Tanaka O:
Prenatal Development of the Human with Special Reference to Craniofacial Structures: An Atlas.
Washington, DC, National Institutes of Health, 1977.)
A B
4th ventricle of brain Midbrain
1st pharyngeal groove
Cervical sinus Heart prominence
Upper limb bud
Mesonephric ridge Somites
(32-day embryo) = 6.0 mm 1st, 2nd, and 3rd pharyngeal arches
Lens pit Nasal placode Umbilical cord Caudal eminence
Lower limb bud
Figure 6–13 A, Lateral view of an embryo at Carnegie stage 17, approximately 42 days.
Digital rays are visible in the hand plate, indicating the future site of the digits (fingers). B, Illustration of the structures shown in A. The eye, auricular hillocks, and external acoustic meatus are now obvious. (From Moore KL, Persaud TVN, Shiota K: Color Atlas of Clinical Embryology, 2nd ed. Philadelphia, Saunders, 2000.)
B
Auricular hillocks forming auricle of external ear
External acoustic meatus (ear canal)
Heart prominence
Digital rays of hand plate
(42-day embryo) = 12.5 mm Pigmented eye
Nasolacrimal groove
Umbilical cord
Foot plate
A
C H A P T E R 6 FOuRTH TO EIGHTH WEEkS OF HuMAN DEvELOPMENT 61
2. When does the embryo become a human being?
3. Can the sex of embryos be determined by ultra- sonography? What other methods can be used to determine sex?
The answers to these questions are at the back of this book.
on the head. Although sex differences exist in the appear- ance of the external genitalia, they are not distinctive enough to permit accurate sex identification.
CLINICALLY ORIENTED QUESTIONS 1. There is little apparent difference between an 8-week
embryo and a 9-week fetus. Why do embryologists give them different names?
Figure 6–14 A, Lateral view of an embryo at Carnegie stage 23, approximately 56 days (end of embryonic period). B, Illustration of the structures shown in A. (A, From Nishimura H, Semba H, Tanimura T, Tanaka O: Prenatal Development of the Human with Special Reference to Craniofacial Structures: An Atlas. Washington, DC, National Institutes of Health, 1977.)
Eyelid Scalp vascular plexus
Auricle of external ear
Lower jaw
Arm
(56-day embryo) = 29.0 mm Nose
Mouth
Umbilical cord Toes separated
A B
C H A P T E R 6 FOuRTH TO EIGHTH WEEkS OF HuMAN DEvELOPMENT 61.e1
Answers to Chapter 6 Clinically Oriented Questions
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63
C H A P T E R
Fetal Period:
The Ninth Week to Birth
7
Highlights of Fetal Period 64 Nine to Twelve Weeks 64 Thirteen to Sixteen Weeks 65 Seventeen to Twenty Weeks 65 Twenty-One to Twenty-Five Weeks 65 Twenty-Six to Twenty-Nine Weeks 66 Thirty to Thirty-Eight Weeks 67 Expected Date of Delivery 67 Factors Influencing Fetal Growth 67 Procedures for Assessing Fetal Status 68
Ultrasonography 68
Diagnostic Amniocentesis 68
Chorionic Villus Sampling 69 Cell Cultures 69
Percutaneous Umbilical Cord Blood Sampling 69
Magnetic Resonance Imaging 69 Fetal Monitoring 70
Alpha-Fetoprotein Assay 70 Noninvasive Prenatal Diagnosis 70 Neonatal Period 70
Clinically Oriented Questions 70
evelopment during the fetal period is concerned primarily with body growth and dif- ferentiation of tissues, organs, and systems. Rudimentary organ systems were formed during the embryonic period. The rate of body growth during the fetal period is rapid, and fetal weight gain is phenomenal during the terminal weeks (Table 7-1). Ultrasonographic measurements of the crown–rump length (CRL) can be used to determine fetal size and probable age (Fig. 7-1). The intrauterine period may be divided into days, weeks, or months (Table 7-2), but confusion arises if it is not stated whether the age is calculated from the last normal menstrual period (LNMP) or from the fertilization age. Unless otherwise stated, fetal age in this book is calculated from the estimated time of fertilization, and months refer to calendar months. Clinically, the gestational period is divided into three trimesters, each lasting 3 months. Various measurements and external characteristics are useful for estimating fetal age (see Table 7-1). Measurement of the CRL is the method of choice for estimating fetal age until the end of the first trimester.
D
64 BEFORE WE ARE BORN ESSENTIALS OF EMBRYOLOGY AND BIRTH DEFECTS
Figure 7–1 Endovaginal scan of a 9-week fetus with a crown–
rump length of 41.7 mm (calipers). Chorionic cavity (CC) has low-level echoes normally, while the amniotic cavity (AC) is echo-free.
1
CC AC
Table 7–1 Criteria for Estimating Fertilization Age during the Fetal Period AGE
(weeks) CROWN–RUMP
LENGTH (mm)* FOOT LENGTH
(mm)* FETAL
WEIGHT (g)† MAIN EXTERNAL CHARACTERISTICS Previable Fetus
9 50 7 8 Eyelids are closing or have closed. Head is rounded. External
genitalia are still not distinguishable as male or female.
Intestinal herniation is present.
10 61 9 14 Intestine is in the abdomen. Early fingernail development.
12 87 14 45 Sex is distinguishable externally. Well-defined neck.
14 120 20 110 Head is erect. Lower limbs are well developed. Early toenail
development.
16 140 27 200 Auricles of the ears stand out from the head.
18 160 33 320 Vernix caseosa covers the skin. Fetal movement (quickening) is
felt by the mother.
20 190 39 460 Head and body hair (lanugo) are visible.
Viable Fetus‡
22 210 45 630 Skin is wrinkled and red.
24 230 50 820 Fingernails are present. Lean body.
26 250 55 1000 Eyes are partially open. Eyelashes are present.
28 270 59 1300 Eyes are open. Most fetuses have scalp hair. Skin is slightly
wrinkled.
30 280 63 1700 Toenails are present. Body is filling out. Testes are descending.
32 300 68 2100 Fingernails extend to fingertips. Skin is smooth.
36 340 79 2900 Body is usually plump. Lanugo is almost absent. Toenails extend
to the toe tips. Flexed limb; firm grasp.
38 360 83 3400 Prominent chest; breasts protrude. Testes in the scrotum or
palpable in the inguinal canals. Fingernails extend beyond fingertips.
*These measurements are averages, and dimensional variations increase with age.
†These weights refer to fetuses that have been fixed for approximately 2 weeks in 10% formalin. Fresh specimens usually weigh approximately 5% less.
‡There is no sharp limit of development, age, or weight at which a fetus automatically becomes viable or beyond which survival is ensured, but experience has shown that it is uncommon for an infant to survive if its weight is less than 500 g or if its fertilization age or developmental age is less than 22 weeks.