Lecture - Fetal Development

From Embryology
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Introduction

Size comparison embryo-fetus actual.jpg

The fetal period (9-36 weeks) is about continued differentiation of organs and tissues, most importantly this period is about growth both in size and weight.

<Flowplayer height="400" width="380" autoplay="true">fetal growth.flv</Flowplayer>

The long Fetal period (4x the embryonic period) is a time of extensive growth in size and mass as well as ongoing differentiation of organ systems established in the embryonic period and do so at different times. For example, the brain continues to grow and develop extensively during this period (and postnatally), the respiratory system differentiates (and completes only just before birth), the urogenital system further differentiates between male/female, endocrine and gastrointestinal tract begins to function.

Fetal length and weight changes
  • First Trimester (1 - 12 weeks) - embryonic and early fetal
  • Second Trimester (13 - 24 weeks) - organ development and function, growth
  • Third Trimester (25 - 40 weeks) - organ function and rapid growth


Textbooks

The Developing Human, 8th edn.jpg Moore, K.L. & Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders.
(chapter links only work with a UNSW connection).
Larsen's human embryology 4th edn.jpg Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R. and Francis-West, P.H. (2009). Larsen’s Human Embryology (4th ed.). New York; Edinburgh: Churchill Livingstone.
(chapter links only work with a UNSW connection).
Logo.png Hill, M.A. (2011) UNSW Embryology (11th ed.). Sydney:UNSW.
Fetal Links: fetal | Week 10 | Week 12 | second trimester | third trimester | fetal neural | Fetal Blood Sampling | fetal growth restriction | birth | birth weight | preterm birth | Developmental Origins of Health and Disease | macrosomia | BGD Practical | Medicine Lecture | Science Lecture | Lecture Movie | Category:Human Fetus | Category:Fetal
Historic Embryology  
1940 Fetus Physiology
Carnegie Fetal: 95 | 96 | 142 | 145 | 184 | 211 | 217 | 300 | 362 | 448 | 449 | 538 | 590 | 607 | 625 | 662 | 693 | 847 | 858 | 922 | 928 | 948 | 972 | 1318 | 1388 | 1455 | 1591 | 1597b | 1656 | 1686 | 2250a | 2250b | 3990 | 5652 | 6581 | 7218
Fetal Graphs: Crown-Rump Length (CRL) | Third trimester CRL | Head Circumference | Head Circumference 2nd Trimester | Liver Weight | Pancreas Weight | Thymus Weight | Small Intestine Length | Large Intestine Length | Length and Weight Changes | Fetal Development
Links: Embryology Textbooks
  • Human Embryology (3rd ed.) Larson Chapter 15: Fetal development and the Fetus as Patient p481-499
  • The Developing Human: Clinically Oriented Embryology (8th ed.) Moore and Persaud Chapter 6. The Fetal Period: Ninth Week to Birth
  • Color Atlas of Clinical Embryology (2nd ed.) Moore, Persaud and Shiota Ch3: 9th to 38th weeks of human development p50-68

Fetal Size

Fetal length increases through both the second and third trimesters .

Fetal size change.jpg Fetal length change.jpg


Head Size

Fetal head growth circumference graph02.jpg Fetal head growth circumference graph01.jpg


Fetal Graphs: Crown-Rump Length (CRL) | Third trimester CRL | Head Circumference | Head Circumference 2nd Trimester | Liver Weight | Pancreas Weight | Thymus Weight | Small Intestine Length | Large Intestine Length | Length and Weight Changes | Fetal Development

Fetal Weight

Fetal weight change.jpg

See also Fetal origins hypothesis and Low Birth Weight.

Birth Weight

Birth weight (grams) less 500 500 – 999 1,000 – 1,499 1,500 – 1,999 2,000 – 2,499 2,500 – 2,999 3,000 – 3,499 3,500 – 3,999 4,000 – 4,499 4,500 – 4,999 5,000 or more
Classification Extremely Low Birth Weight Very Low Birth Weight Low Birth Weight Normal Birth Weight High Birth Weight

The primary causes of VLBW are premature birth (born <37 weeks gestation, and often <30 weeks) and intrauterine growth restriction (IUGR), usually due to problems with placenta, maternal health, or to birth defects. Many VLBW babies with IUGR are preterm and thus are both physically small and physiologically immature.

Musculoskeletal

Fetal head (12 weeks)
  • Ongoing process of ossification.
    • endochondral and intramembranous
  • growth in long bone length
  • increased limb length
  • continues postnatally
    • rapid growth during puberty
  • relocation of haemopoietic stem cells to bone marrow
Endochondral ossification 2.jpg

Endochondral ossification

Ossification centre.jpg

Intramembranous ossification

Links: Bone Histology

Fetal Neural

Timeline of events in Human Neural Development

Brain ventricles and ganglia development 03.jpg

Brain fissure development 02.jpg

Human brain at three months (median sagittal section)
Human brain at four months (inferior surface)
Human brain at five months (outer surface)

During the fetal period there is ongoing growth in size, weight and surface area of the brain and spinal cord. Microscopically there is ongoing: cell migration, extension of processes, cell death and glial cell development.

Cortical maturation (sulcation and gyration) and vascularization of the lateral surface of the brain starts with the insular cortex (insula, insulary cortex or insular lobe) region during the fetal period. This cerebral cortex region in the adult brain lies deep within the lateral sulcus between the temporal lobe and the parietal lobe.

  • sulcation - The process of brain growth in the second to third trimester which forms sulci, grooves or folds visible on fetal brain surface as gyri grow (gyration). Abnormalities of these processes can lead to a smooth brain (lissencephaly).
  • gyration - The development of surface folds on the brain (singular, gyrus)

Insular Gyral and Sulcal Development[1]

  • 13-17 gestational weeks - appearance of the first sulcus
  • 18-19 gestational weeks - development of the periinsular sulci
  • 20-22 gestational weeks - central sulci and opercularization of the insula
  • 24-26 gestational weeks - covering of the posterior insula
  • 27-28 gestational weeks - closure of the laeteral sulcus (Sylvian fissure or lateral fissure)


  • Between 29-41 weeks volumes of: total brain, cerebral gray matter, unmyelinated white matter, myelinated, and cerebrospinal fluid (from MRI)
    • grey matter- mainly neuronal cell bodies; white matter- mainly neural processes and glia.
  • total brain tissue volume increased linearly over this period at a rate of 22 ml/week.
  • Total grey matter also showed a linear increase in relative intracranial volume of approximately 1.4% or 15 ml/week.
  • The rapid increase in total grey matter is mainly due to a fourfold increase in cortical grey matter.
  • Quantification of extracerebral and intraventricular CSF was found to change only minimally.

(Text - modified from Huppi etal., (1998) Quantitative magnetic resonance imaging of brain development in premature and mature newborns. Ann Neurol 43(2):224-235.)


Neural development will continue after birth with substantial growth, death and reorganization occuring during the postnatally (MH - postnatal not described in this current lecture)


Links: Neural System - Fetal | Neuroscience - Regional specification of the developing brain

Fetal Cardiovascular

MH - covered in last week's lecture Late Vascular Development.

  • fetal neutrophils, monocytes, and macrophages are produced
  • mononuclear phagocytes do not mature until after birth

Immune System

  • maternal placenta transfer of IgG not other immunoglobulin isotypes.
  • fetal lymphocytes (mature T and B cells) produced not activated

MH - see postnatal lecture - maternal milk IgG and IgA antibodies, leukocytes, secretory IgA, lactoferrin, lysozyme, and oligosaccharides and glycoconjugates that are receptor analogs for microbial adhesins and toxins.

Fetal Respiratory

MH - covered in lecture Respiratory Development.

Month 3-6 - lungs appear glandular, end month 6 alveolar cells type 2 appear and begin to secrete surfactant.

Month 7 - respiratory bronchioles proliferate and end in alveolar ducts and sacs.

Lung Stages

  • week 4 - 5 embryonic
  • week 5 - 17 pseudoglandular
  • week 16 - 25 canalicular
  • week 24 - 40 terminal sac
  • late fetal - 8 years alveolar

Gastrointestinal Tract

Fetal small Intestine length growth graph.jpg Fetal large Intestine length growth graph.jpg
Fetal small Intestine length growth
Fetal large Intestine length growth

Fetal developmental features include:

  • initially herniated outside the ventral body wall
  • the growth and rotation of intestines
  • changes in mesenteries
  • development of the blood supply and tract wall.

Initial functions:

  • amionic fluid swallowing - absorbed through the gastrointestinal tract and respiratory tract epithelium
  • meconium - accumulation of both secretions and swallowed components within the large intestine


Links: Lecture - Gastrointestinal Development | Gastrointestinal Tract Development

Fetal Genital

MH - introduced in the Genital Development lecture.

Gonad Descent

  • Both kidney and gonads develop retroperitoneally, with the gonads moving into the abdomen or eventually into the scrotal sacs.
  • During fetal development the gubernaculum and fetal growth in both male and female, changes the gonads’ relative positions finally reaching their adult locations.


Both female and male gonads undergo anatomical descent.

  • Ovaries ‐ undergo caudal and lateral shifts to be suspended in the broad ligament of the uterus, gubernaculum does not shorten, it attaches to paramesonephric ducts, causing medial movement into the pelvis.
  • Testes ‐ two anatomical phases in descent, transabdominal and transinguinal, under the influence of the shortening gubernaculum.

Testis 001 icon.jpgTestis-descent start.jpgTestis-descent end.jpg

Testis Descent

The testis (white) lies in the subserous fascia (spotted) a cavity processus vaginalis evaginates into the scrotum, and the gubernaculum (green) attached to the testis shortens drawing it into the scotal sac. As it descends it passes through the inguinal canal which extends from the deep ring (transversalis fascia) to the superficial ring (external oblique muscle). Descent of the testes into the scrotal sac begins generally during week 26 and may take several days. The animation shows the path of a single testis.


Incomplete or failed descent can occur unilaterally or bilaterally, is more common in premature births, and can be completed postnatally.

Data from a recent study of male human fetal (between 10 and 35 weeks) gonad position.

  • 10 to 23 weeks - (9.45%) had migrated from the abdomen and were situated in the inguinal canal
  • 24 to 26 weeks - (57.9%) had migrated from the abdomen
  • 27 to 29 weeks - (16.7%) had not descended to the scrotum

Postnatal Genital Development

  • Not completed until puberty.
  • Development of secondary sexual characteristics.
  • Humans - earlier in female than male.
  • Female - commencing menstrual cycle, follicle development, recommence meiosis.
  • Male - decrease in MIS, Leydig cell testosterone, activation of spermatogenesis, begin meiosis.

Fetal Endocrine

HPG Axis

Pituitary Hormones

  • HPA axis established by week 20
  • Pituitary functional throughout fetal development

Thyroid Hormone

  • required for metabolic activity, also in the newborn
  • important for neural development
  • placenta inactivates most of the maternal T4 to reverse T3 (rT3)
  • Fetal to term up to 30% of the fetal thyroid hormones are of maternal origin.

Human thyroid system and neural development.jpg

Parathyroid Hormone

  • newborn has total calcium levels (approx 20 grams) accumulated mainly in the 3rd trimester (weeks 28–40)
  • fetal parathyroid hormone (PTH) potentially available from 10–12 weeks and PTH does not cross the placenta
  • fetus relatively hypercalcemic, active transplacental transport of Ca2+ to fetus
  • maternal serum - calcium ions (Ca2+), inorganic phosphate (Pi) and PTH concentrations are within the non-pregnant normal range throughout pregnancy.
  • maternal bone turnover increases in the 3rd trimester.

(Based on Endocrinology - Materno—fetal calcium balance)

Pancreatic Hormones

  • maternal diabetes can affect fetal pancreas development (increase in fetal islet beta cells).

Gonadal Hormones

  • testosterone - required during fetal development for external genital development and internal genital tract in male.
  • estrogens - secreted inactive precursor converted to active form by placenta.


Links: Endocrinology - Control of steroid production in the fetal gonads | Neuroscience - The Effect of Sex Hormones on Neural Circuitry

Fetal Origins Hypothesis

  • Maternal derived abnormalities relate to lifestyle, environment and nutrition and while some of these directly effect development.
  • Growing evidence that some effects are more subtle and relate to later life health events.
  • Original theory based on the early statistical analysis carried out by Barker of low birth weight data collected in the early 1900's in the south east of England
    • He then compared with these same babies later health outcomes.
    • Theory was therefore originally called the "Barker Hypothesis"
  • recently been renamed as "developmental origins of health and disease" (DOHAD).


Links: Fetal Origins Hypothesis

Premature Birth

Premature infant
Year < 34 weeks % 34-36 weeks % total preterm %
1990 3.3 7.3 10.6
1995 3.3 7.7 11
2000 3.4 8.2 11.6
2005 3.6 9.1 12.7

Table data from: Prevention of preterm birth: a renewed national priority.[2]

Australia Recommendations

Perinatal care at the borderlines of viability: a consensus statement based on a NSW and ACT consensus workshop (February 2005) published in The Medical Journal of Australia 2006.[3]

  • < 23 weeks survival is minimal and the risk of major morbidity is so high that initiation of resuscitation is not appropriate.
  • 23 weeks active treatment may be discussed, but would be discouraged in NSW/ACT neonatal intensive care units.
  • 23 to 25 weeks otherwise normal infant, there is an increasing obligation to treat. However, it is acceptable medical practice not to initiate intensive care if parents so wish, following appropriate counselling.
  • 24 weeks antenatal transfer to a tertiary centre for fetal reasons is indicated. The option of non-initiation of intensive care/resuscitation should be offered.
  • 25 weeks active treatment is usually offered, but the option of non-initiation of intensive care/resuscitation (presence of adverse fetal factors such as twin-to-twin transfusion, intrauterine growth restriction or chorioamnionitis) should also be discussed.
  • 26 weeks + otherwise normal infant the obligation to treat is very high, and treatment should generally be initiated unless there are exceptional circumstances.

Abnormalities

Teratology

How different environmental effects during the pregnancy may influence outcomes. A teratogen (Greek, teraton = monster) is defined as any agent that causes a structural abnormality (congenital abnormalities) following fetal exposure during pregnancy. The overall effect depends on dosage and time of exposure (see critical periods below).

Absolute risk - the rate of occurrence of an abnormal phenotype among individuals exposed to the agent. (e.g. fetal alcohol syndrome)

Relative risk - the ratio of the rate of the condition among the exposed and the nonexposed. (e.g. smokers risk of having a low birth weight baby compared to non-smokers) A high relative risk may indicate a low absolute risk if the condition is rare.

Mutagen - a chemical or agent that can cause permanent damage to the deoxyribonucleic acid (DNA) in a cell. DNA damage in the human egg or sperm may lead to reduced fertility, spontaneous abortion (miscarriage), birth defects and heritable diseases.

Fetotoxicant - is a chemical that adversely affects the developing fetus, resulting in low birth weight, symptoms of poisoning at birth or stillbirth (fetus dies before it is born).

Synergism - when the combined effect of exposure to more than one chemical at one time, or to a chemical in combination with other hazards (heat, radiation, infection) results in effects of such exposure to be greater than the sum of the individual effects of each hazard by itself.

Toxicogenomics - the interaction between the genome, chemicals in the environment, and disease. Cells exposed to a stress, drug or toxicant respond by altering the pattern of expression of genes within their chromosomes. Based on new genetic and microarray technologies.

Critical Periods

Critical periods of development refer to times when genetic or materal effects can impact upon the developmental process. The timing of these effects will impact on different systems at different times.

Conceptus Embryonic development (weeks) Fetal period (weeks)
1
2
3
4
5
6
7
8
9
16
20-36
38
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
Neural
Stage2.jpg Heart
Upper limbs
Lower limbs
Ear
Eye
CSt3.jpg Palate
Teeth
Week2 001 icon.jpg External genitalia
Loss Major abnormalities Functional and Minor abnormalities


Links: Embryonic Development | Timeline human development | Movie - Human Development annotated cartoon | Human - critical periods | Human Abnormal Development


Systems with long periods of development or complex developmental origins are more susceptible to developmental abnormalities.

  • Which systems will take a long time to develop?
  • Which systems are complex in origin?


Co-ordinator Note

Mhicon08.jpg

Dr Mark Hill

ANAT2341 Embryology S2 2011
--Mark Hill 06:47, 20 July 2011 (EST)

Course Content 2011

2011 Timetable: | Embryology Introduction | Fertilization | Cell Division/Fertilization | Week 1 and 2 Development | Week 3 Development | Week 1 to 3 | Mesoderm Development | Ectoderm, Early Neural, Neural Crest | Trilaminar Embryo to Early Embryo | Early Vascular Development | Placenta | Vascular and Placenta | Endoderm, Early Gastrointestinal | Respiratory Development | Endoderm and Respiratory | Head Development | Neural Crest Development | Head and Neural Crest | Musculoskeletal Development | Limb Development | Musculoskeletal | Renal Development | Genital | Kidney and Genital | Sensory | Stem Cells | Stem Cells | Endocrine Development | Endocrine | Heart | Integumentary Development | Heart and Integumentary | Fetal | Birth and Revision | Fetal

Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link

Cite this page: Hill, M.A. (2019, October 16) Embryology Lecture - Fetal Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Fetal_Development

What Links Here?
© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G
  1. <pubmed>17962979<pubmed>
  2. <pubmed>18989136</pubmed>
  3. <pubmed>17137454</pubmed>