Pregnancy

Prenatal development – a brief capture

The first eight weeks after conception is the period of embryogenesis. Organ systems are established during this time and develop further in the second and third trimesters. Prenatal testing is carried out in the first and second trimesters to rule out chromosomal anomalies. The mother is able to feel foetal movements known as "quickening" during the second trimester. In the third trimester the foetus gains weight and develops the ability to hear. The last trimester is also the time of development of the foetal respiratory system (Hill, 2020, Embryology.ch, 2008). Infants born at or after 37 weeks of gestation are considered full term infants. Infants born before 37 weeks of gestation are considered preterm infants. Premature infants may be small for gestational age and also have associated growth abnormalities such as low birth weight (Fewtrell et al., 2016). 

Prenatal development – a brief capture


Pregnancy starts on the first day of the last menstrual period. This is known as the "menstrual age" or the "gestational age" (Pardi & Cetin, 2006) and is used to calculate the delivery date. This is approximately 40 weeks after the last menstruation. However, the average duration of pregnancy is approximately 38 completed weeks or 266 days. Gestation is one of the fastest periods of growth and development. It can largely be divided into two phases: the embryonic phase and the foetal phase (Hill, 2020). 

Embryogenesis


The first 56 days or eight weeks after conception are knowns as "embryogenesis". If calculated from the first day of the last menstrual period, it covers the first 10 weeks. This is also known as the time of "organogenesis" – cells differentiate and develop further into various complex organ systems. By the end of this phase, more than 90% of the 4500 designated structures of the adult human body are established and can be distinguished (Embryology.ch, 2008). This is also the most vulnerable period of pregnancy. It is during this time when most deformities are produced. Deformities produced will depend on the developmental stage of the embryo and the type of insult (Hill, 2020).

Fertilisation
Fertilisation occurs approximately 14 days after the last menstrual period and completes the genetic makeup of the infant; gender is also determined at this time (Hill, 2020). The egg starts to divide within 24 hours of fertilisation and stays in the fallopian tube for approximately three days after conception. At this point, the developing embryo is known as the "blastocyst". The blastocyst travels to the uterus via the fallopian tube and attaches to the uterine endometrium via a process known as "implantation". Once the blastocyst implants in the uterine wall it starts producing a hormone known as the "human chorionic gonadotropin" (HCG). As early as the second week of pregnancy, human chorionic gonadotropin starts changing the balance of maternal hormones to stop the menstrual cycle. Pregnancy tests are based on the detection of human chorionic gonadotropin in maternal blood and urine (Hill, 2020).

Week 3 
In the 3rd week of pregnancy an early placenta develops and the embryo divides into three germ layers: ectoderm, endoderm and mesoderm. These three layers are positioned as flat oval shaped disks. The outermost layer, ectoderm, will eventually differentiate to become the central nervous system and skin. The middle layer, mesoderm, will differentiate to become connective tissues, muscles, bones, circulatory system and the urogenital system. The innermost layer, the endoderm, gives rise to the gastrointestinal (GI) tract and the respiratory system (Rubarth & van Woudenberg, 2016). 

Week 4 
In the 4th week, limb buds begin to appear from the trunk and present as "paddle – like" projections. These will eventually develop into the four limbs (Hill, 2020). During this time, cells are dividing rapidly and the flat disc of the embryo bulges and folds over itself (Rubarth & van Woudenberg, 2016). One of the first organs to form is the heart. Until the 3rd week of gestation, the embryo receives oxygen by passive diffusion. Towards the beginning of the 4th week this is no longer enough and the primitive heart tube initiates the first heart beat by the 22nd day of gestation (Tan & Lewandowski, 2020). By the end of the 4th week of gestation, the foetal heart beats 65 times per minute and blood circulation within the foetal system also starts. This is the time when the other systems such as the nervous, the digestive, the urogenital, and the circulatory are all taking shape (Hill, 2020).

Week 5
By the 5th week of gestation, the cells of the endoderm have rolled into a long tube and the primitive digestive system made of the foregut, mid gut and hind gut is already established (Hill, 2020). The foregut will develop into the upper gastrointestinal tract i.e. the oesophagus, stomach, liver and pancreas. The mid gut will develop into the small intestine (duodenum, jejunum and ileum) and also form a major portion of the large intestine. The hind gut will form part of the colon, the anal canal and the rectum (Hill, 2020). The neural tube, a primitive version of the brain is also growing rapidly at this time and structures that will become cerebral hemispheres in the future also appear (Sadler, 2018). Since the development of the neural tube occurs this early during gestation, health authorities all over the world  recommend folic acid ()  supplementation for women trying to conceive (Dolin et al., 2018).

Between the 6th to 8th week
At the start of the 6th week, organs such as kidneys, liver and lungs are taking shape. At the end of the 6th week the heartbeat can usually be detected. During this time the four chambers of the heart are also formed, it is about 5 mm in size and beats at approximately 110-160 beats per minute (Tan & Lewandowski, 2020).
By the end of the 8th week, the embryo is the size of a bean and little folds of skin appear on the side of the face. These little folds will eventually become ears. The embryonic cartilage starts getting replaced by bone. The limbs are continuing to grow, and fingers and toes develop (Embryology.ch, 2008, Hill, 2020). 

Did you know …? 


A tammar wallaby can nurse a joey in its pouch and carry a dormant embryo in her uterus at the same time. When nursing stops, the embryo starts to develop. This is called "delayed birth" or "embryonic diapause" (Labiano-Abello, 1999, Sharp et al., 2017, Sharp et al., 2017). 

Teratogenesis


Approximately 3% of neonates suffer from deformities the causes of which can be genetic, chromosomal or environmental. Agents that cause these defects are known as "teratogens". It is not always possible to know the exact cause of the deformities. However, some well-known teratogens include thalidomide, isotretinoin or retinoic acid (a form of Vitamin A), alcohol, cocaine, pesticides and infections such as rubella or zika virus. Although exposure to teratogens can be harmful for the foetus at any time during gestation, damage is more severe if exposure occurs during embryogenesis i.e. between week 2 and week 8 of development (Vargesson & Rosa Fraga, 2017).

The foetal stage


The last month of the first trimester week 9 to week 12

By the beginning of the 9th week the embryo has grown significantly and is now known as the "foetus". The organ systems established in the first eight weeks continue to grow and gradually begin to function. The placenta also matures significantly during this time and becomes the key avenue of nutrition, waste disposal and oxygen exchange for the foetus (Tan & Lewandowski, 2020). Until approx. 10 weeks of age, gas exchange takes place in the yolk sac of the foetus alone. By the 11th week of gestation, the placenta has taken over this function completely (Tan & Lewandowski, 2020, Sadler, 2018).

The glomerular capillaries within the foetal kidney differentiate and urine production starts by the 10th week of gestation. Nephrons will continue to form until at birth approximately one million nephrons are present in each kidney. By the end of the first trimester, cells of the foetal kidney begin to function and pass urine into the amniotic cavity where it mixes with the amniotic fluid. The foetus regularly swallows amniotic fluid which keeps recycling through the foetal kidneys. However, waste disposal is the responsibility of the placenta and is not yet a function of the developing kidneys (Ryan et al., 2018, Sadler, 2018).

Testing in the first trimester


Every woman is at a risk of carrying a foetus with chromosomal abnormalities. Hence, first prenatal testing is advised towards the end of the first trimester: Blood tests carried out during the first trimester rule out chromosomal anomalies and check for serum beta-human chorionic gonadotropin and pregnancy-associated plasma protein A (PAPP-A). An ultrasound scan is also carried out during this time. Prenatal testing helps to identify anomalies such as trisomy 21 (Down syndrome). Women at high risk of conceiving a foetus with chromosomal abnormalities may also be advised chorionic villus sampling (CVS). Chorionic villus sampling is a test in which a sample of the chorionic villi is removed from the placenta for genetic testing. This sample may either be removed via the cervix or through the abdominal wall. Chorionic villi are part of placental tissues with the same genetic makeup as that of the foetus (Chasen, 2014).

The second trimester


Week 13 to week 26 

From the second trimester onwards, the form of the foetus does not change significantly. This is the time during which all the organ systems established during embryogenesis begin to grow in size and complexity. The foetus starts to gain weight and stretches itself out (Hill, 2020). The foetus can also make faces, suck its thumb, yawn and stretch. Development of the outer and inner ear occur, the facial skeleton gets remodelled and the tongue develops taste pores. Parts of the gastrointestinal system also begin functioning and the pancreas starts to produce the hormones insulin and glucagon, which can be detected in the foetal plasma The foetus's heartbeat can be heard using handheld ultrasound devices also known as "dopplers". It is during this time that genital differences are observed between male and female foetuses (Hill, 2020). 

As the foetus continues to develop muscles and exercises them, the mother may begin to start feeling the movements. The first movement of the foetus feels like a flutter and is known as "quickening". Soft fine hair called "lanugo" grows on the body and "vernix caseosa", a whitish coating, covers the foetal skin (Hill, 2020). Foetuses born prematurely at the end of the second trimester (22-24 weeks) and with access to sophisticated medical care can be viable. However, this degree of prematurity is associated with many comorbidities and complications that may lead to lifelong impairment such as (severe) cerebral palsy (WHO et al., 2012). 

Testing in the second trimester


Chromosomal abnormalities can be more readily identified in the second trimester and blood tests that check for beta-human chorionic gonadotropin, α‑fetoprotein (AFP), free oestriol and inhibin A are performed. These tests are conducted to rule out abnormalities such as neural tube defects and Down syndrome (Chasen, 2014). A comprehensive ultrasound is also carried out between 20 to 22 weeks to check for structural abnormalities. Beyond 15 weeks gestation, amniocentesis may be advised for pregnancies at high risk of chromosomal abnormalities to confirm the presence or absence of foetal defects (Chasen, 2014, Hill, 2020).

The third trimester


Week 27 to week 40 

During the third trimester, rate of growth in length slows down and the foetus gains a substantial amount of weight. By 27 weeks, the foetus is able to hear and will respond if startled by stimulation of the mother's abdomen. Development of teeth occurs and permanent premolars are present at approximately 29 weeks of gestation. In male foetuses, gonads begin to descend by 30 weeks. The nervous system also undergoes rapid development between 33 to 34 weeks of gestation (Hill, 2020). The foetus now regularly swallows the amniotic fluid which contains proteins, carbohydrates, triglycerides and numerous growth factors. This stimulates the secretion of hormones in the foetus' gastrointestinal tract which in turn promotes gut motility and maturation. Propulsive motility develops at approx. 30 weeks of gestation (Avery et al., 2016).
One of the last systems to mature is the respiratory system. It is only at the end of the 6th month that type 2 alveolar cells develop and begin to secrete surfactants. It is during this period of late gestation that the respiratory motions made by the foetus and amniotic fluid together facilitate lung maturation. The third trimester is also the time when in addition to exchange of gases and nutrients, the placenta transfers maternal antibodies to the foetus. The foetus thus gains passive immunity to a number of infectious diseases before being born (Avery et al., 2016).

Any infant born after 37 weeks of gestation is considered a full-term infant. Infants born before 37 weeks gestation are considered preterm infants (Koletzko et al., 2014). A healthy term infant weighs approximately 7.5 pounds or 3 kg at birth depending on gender and ethnicity (Fewtrell et al., 2016).
 

Abnormal foetal growth


Growth abnormalities in the foetus maybe a result of maternal factors such diabetes, obesity, hypertension, poor pregnancy weight gain, preeclampsia, autoimmune diseases etc. Growth abnormalities could also be caused by maternal lifestyle choices such as smoking, drug  or alcohol consumption. Growth is also affected by chromosomal anomalies e.g. Down syndrome or because of placental abnormalities such as reduced blood flow, which may result in intrauterine growth restriction (IUGR) (Mayer & Joseph, 2013). Common growth abnormalities include small for-gestational age, intrauterine growth retardation, large-for-gestational age and macrosomia ()  (Fewtrell et al., 2016). 

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