NORMAL FETAL DEVELOPMENT

FACT FILE 2A

http://commons.wikimedia.org

In gaining a full understanding of the normal biology of the neonates in our care, the best place to start is at the beginning of human life when we commence care at the point of their delivery into the world. Many important and fundamantal stages of development have occurred in-utero which are relevant to the presenting condition after birth and the introduction to ex-utero life.

This information file covers the normal stages of embryonic (from conception to the end of week 8) and fetal life (week 9 onwards). Stages described are approximate.

THE EMBRYO – (i) WEEKS 1-4

After fertilisation of ovum and sperm, the zygote develops into a 16 cell morula around 3 days (Figure 1). When uterine fluid passes into the spaces between the cells, a blastocyst forms (Figure 2) at 4-5 days which then differentiates into an external layer (trophoblast) and the inner cells (embryoblast). At 6-7 days implantation occurs giving rise to the epiblast.

FIGURE 1; http://commons.wikimedia.org/wiki/File:Gray9.png

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FIGURE 2; http://commons.wikimedia.org/wiki/File:Blastocyst_English.svg

Blastomeres isolated from the inner cell mass of the mammalian embryo are also known as embryonic stem (ES) cells. These pluripotenpluripotentt cells can give rise to all three germ layers (ectoderm, endoderm, and mesoderm) of the body .

In the second week, the amnion encloses the epiblast, and both a primitive and uteroplacental circulation are established. In addition, the embryonic disc forms from which there is subsequent rapid development of the embryo during the next 6 weeks . The primitive streak appears during the third week which differentiates into the endoderm, mesoderm and ectoderm.

Neurulation or the formation of the neural plate, neural folds and neural tube occurs during the third week of embryonic life, later forming the central nervous system. In addition, the primitive cardiovascular system is starting to develop and is the first system to reach a functional state. The circulation of blood starts by the end of the third week as the tubular starts to beat.

Primary chorio nic villi soon begin to branch so that by the end of the third week (Figure 3) a primitive has formed that involves the entire surface of the chorionic sac and endometrium.

FIGURE 3; http://commons.wikimedia.org/wiki/Embryo

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This period is a very important stage of embryonic development as the beginnings of all major external and internal structures appear during these five weeks. By the end of week 8, all major organ systems have begun development but function is minimal.

Important events that occur are; • Folding of the embryo, with a cylindrical curved shape by end of week 4. • Primitive gut differentiates into the foregut, midgut, hindgut and the cloaca. • Differentiation of the 3 germ layers into various tissues and organs. • Development of early limb buds, primitive eye pits, cervical sinuses, digits and ears. Midgut herniation is prominent in week 7. • At the start of week 8, the limbs and digits are prominent and eyes are evident. • By the end of week 8, the embryo undoubtedly has many human characteristics.

It can be seen that within this very short time period, a great deal has happened in relation to human and system development. Due to the fact that the basic systems and associated organs are formed during weeks 4-8, this period is a critical period of human development. During this period, any interruption to this process can result in congenital malformations.

http://en.wikipedia.org/wiki/File:Fetus_amniotic_sac.jpg

WEEKS 9-40 THE FETUS Development now moves from embryonic to fetal growth. In addition, development also moves from the first trimester to the second which continues now up until the age of ‘viability’ to 24 weeks. During this time, the main events concern the growth of the body, development and differentiation of the tissues and organs that have already formed. There are no formal stages but the following important events that occur in the mid-trimester are;

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• Primary ossification with clear visualisation of skeleton by 16 th week. • External genitalia in males and females are similar during the 9 th week and reach their mature fetal form by end of week 12. • Intestinal loops are visible within the at nine weeks but have re- entered the abdomen by week 11. • Erythropoesis occurs in the liver and later at week 12 in the spleen. This continues via the spleen until the bone marrow takes over at approximately 28 weeks. • Urine formation begins during weeks 9-12. • Rapid body growth with head changing in size in proportion with the body. By 21-25 weeks, the body is better proportioned overall. • Differentiation of the ovaries occurs by 16 weeks. • Eyes are now placed anteriorly and ears are in their definitive positions by 16 weeks. • Fetal movements are evident and felt by the mother from 16 -18 weeks, perhaps earlier (variations occur). • Vernix appears by 20 weeks, a white protective skin coating comprising fatty secretions from fetal sebaceous glands and dead epidermal cells. Lanugo hair is also present at this time. • Brown fat starts to form from week 17. • From 21 weeks, the skin is thin, wrinkled and pink or red from visible capillaries. • By 24 weeks, the secretory epithelial cells or type 2 pneumocytes in the interalveolar walls of the lungs have begun to secrete surfactant.

The third and final trimester is a period where reserves of fat and other nutrients are laid down. Subcutaneous fat increases under the skin and continues, resulting in smoother skin and a more chubby appearance of the body and limbs by 34 weeks. In addition, the lungs are now capable of breathing air as the primitive alveoli and pulmonary vasculature have developed to provide gaseous exchange should the neonate be born prematurely before the end of the third trimester. Function however will be limited depending on the gestation at delivery. The central nervous system has matured sufficiently to direct rhythmic breathing movements.

At 34 weeks, important milestones are reached which have significant clinical relevance to those working in neonatal units caring for neonates born within this latter stage of pregnancy. Fetuses have a firm grasp and exhibit an orientation to light. They exhibit physiological flexion and good tone of their limbs which are now tucked centrally in the mid-line in the characteristic fetal position. The germinal matrix within the ventricles of the brain has now involuted and strengthened so there is less a propensity to bleeding should the neonate be born prematurely during this latter stage. The vascularisation of the retina of the eyes is complete, again rendering damage from harmful stimuli such as oxygen much less likely. The neonate if born during this time should exhibit a coordinated suck-swallow reflex from 34 weeks; this is usually weaker than term neonates but nonetheless has implications for feeding ability within the neonatal unit. Lung maturity is now well into the alveolar stage of development resulting in an ability to self ventilate effectively providing no other risk factors are present.

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Image purchased from Dreamstime.com Photographer: © Marceloregalado

THE PLACENTA The placenta is a fetomaternal organ since it is formed from both tissues. The primitive placenta forms during the second week and by the end of week 12, two components are evident – the fetal villous and the maternal ‘decidua basalis’, both held together by anchoring villi. The placental membrane separates the fetal blood in the capillaries of the chorionic villi from the maternal blood in the intervillous spaces. Oxygenated blood from t he mother enters the intervillous spaces in the deciduas basalis and blood pressure if optimum, directs the blood to the chorionic plate for transfer to the fetus via the . Deoxygenated blood then leaves the fetus via the umbilical arteries r eaching the fetal surface and dividing into branches of the chorionic villi for re -oxygenation and removal of carbon dioxide. The placenta imparts many essential functions; Gaseous exchange , transfer of vital nutrients to the fetus and excretion of waste p roducts back to the mother, protection, s torage of some nutrients and hormonal production.

http://commons.wikimedia.org/wiki/File:Placenta.svg

Page | 5 J Petty THE AMNION The amnion forms a sac enclosing the embryo containing amniotic fluid. This fluid originates from maternal blood as well as, later in pregnancy, contributions from the fetus by the excretion of urine into the cavity. Amniotic fluid is swallowed by the fetus and absorbed by the fetal digestive tract. It then passes into the fetal blood and waste products cross the placental membrane into maternal blood. Excess water is excreted by fetal kidneys into the amniotic cavity. The amniotic fluid acts as a protective buffer and provides room for the fetus to move while assisting in the regulation of fetal temperature.

THE UMBILICAL CORD This contains two arteries (from the fetus to the placenta) and one vein (from the placenta to the fetus) surrounded by a mucoid connective tissue.

Abnormal fetal development will be covered in Unit 3A

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KEY READING

http://embryology.med.unsw.edu.au/embryo.htm http://www.uic.edu/com/surgery/embryo/links.htm Embryological Development of the Human website http://www.visembryo.com/baby The Visible Embryo website http://embryo.soad.umich.edu The Multi Dimensional Human Embryo http://www.embryo.chronolab.com http://www.embryology.ch/indexen.html

The - http://www.frca.co.uk/Documents/Foetal%20circulation.pdf http://en.wikipedia.org/wiki/Adaptation_to_extrauterine_life http://www.frca.co.uk/Documents/Foetal%20circulation.pdf http://www.youtube.com/watch?v=uwswhoKfkmM&feature=related

Harding R and Bocking A (2001) (eds) Fetal Growth and development Cambridge Uni Press, Cambridge

Mitchell B and Sharma R (2009) Embryology- An illustrated colour text (2 nd edition) Churchill Livingstone, Oxford

Moore KL and Persaud TVN (2007) The Developing Human: Clinically Oriented Embryology with Student Consult online access (8 th edition) Saunders, Philadelphia

Moore KL and Persaud TVN (2008) Before we are Born; Essentials of Embryology and Birth Defects (7 th Edition) Saunders, Philadelphia

Sadler TW (2009) Langmans Medical Embryology (11 th edition) Lippincott Williams and Wilkins, New York, London

Schoenwof GC, Bleyl SB, Brauer PR and Francis West PH (2008) Larsens Human Embryology; with student Consult online access (4 th edition) Churchill Livingstone, Oxford

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