A Comprehensive Guide to Fetal Development: From First Trimester to Birth

During weeks 9-12 of pregnancy, significant changes occur in the development of the fetus. At the beginning of the ninth week, the head makes up half of the crown-rump length (CRL). As the weeks progress, the body length grows rapidly, resulting in the crown-rump length doubling by the end of the 12th week. However, the head remains disproportionately large compared to the body, despite its growth slowing down.

At nine weeks, the face is wide, the eyes are widely spaced, and the eyelids are fused. By the end of the first 12 weeks, the primary ossification centers appear in the skull and long bones.

In terms of limb development, the legs are short with small toes in the ninth week. On the other hand, the upper limbs have almost reached their final relative length by the end of the 12th week, while the lower limbs are still less developed and smaller in comparison.

The external male and female genital organs start to appear by the end of the ninth week, but their mature overall shape is not established until the 12th week.

The intestinal loops are clearly visible at the proximal end of the umbilical cord until the middle of the 10th week. By the 11th week, these loops are typically incorporated into the abdomen.

During this period, the liver plays a crucial role in erythropoiesis (formation of fetal red blood cells). However, by the end of the 12th week, this activity decreases in the liver and starts in the spleen instead. Additionally, urine formation begins between the 9th and 12th weeks, with the fetus excreting urine into the amniotic fluid. The fetus also starts reabsorbing some of the amniotic fluid by swallowing it. Fetal metabolic products are transferred into the fetal circulation by passing through the placental membrane.

The second trimester of pregnancy, specifically weeks 13-16, is characterized by rapid growth. By the 16th week, the head size is smaller compared to the 12-week size, while the lower limbs have increased in length. Limb movements, which start at 8 weeks, become coordinated by the 14th week, although they are too small for the mother to feel.

During this period, skeletal ossification is active, but the bones are not visible on the mother's abdominal X-rays until the beginning of the 16th week. At the 16th week, the ovaries begin to differentiate and contain primordial follicles with oogonia. The fetus starts to resemble a human, with the eyes positioned more anteriorly than anterolaterally, and the ears almost in their final position on the sides of the head.

Moving on to weeks 17-20, growth slows down, but the crown-rump length reaches approximately 50 mm. The lower limbs reach their relative final proportions. It is during this period that the mother starts feeling the first movements of the fetus. The time between the mother's detection of fetal movements and birth is typically around 147 ± 15 days.

During this period, several significant developments occur in the fetus's body. Firstly, the skin becomes covered in a protective substance called vernix caseosa, which is a combination of dead epidermal cells and a greasy substance secreted by the sebaceous glands. This substance, similar to cheese, serves to safeguard the delicate skin of the fetus.

Around 19 weeks, fine hair called lanugo starts to cover the bodies of the fetuses. Lanugo helps to retain the vernix caseosa on the skin. Additionally, at 20 weeks, eyebrows and scalp hair become visible.

Between weeks 17-20, adipose tissue begins to develop, particularly in specific areas such as the base of the neck, behind the sternum, and in the perirenal area. This adipose tissue, known as Gerota's protective fat, is predominantly brown and generates heat through the oxidation of fatty acids. It also contains a high concentration of mitochondria.

By 18 weeks, the uterus has formed, and the process of vaginal canalization has commenced. At this stage, numerous primordial ovarian follicles, which contain oogonia, start to form.

From week 20, the testicles begin their descent, although they are still located in the posterior abdominal wall, similar to the position of the ovaries in female fetuses.

During weeks 21-25 of pregnancy, there are notable changes and developments in the fetus. The baby experiences a significant increase in weight during this time. The fetus becomes well-proportioned, with wrinkled skin that appears slightly translucent and pinkish in color of blood in the capillaries.

At 21 weeks, the fetus begins to exhibit rapid eye movements. Around 22-23 weeks, the baby even starts to blink after a vibroacoustic source is applied to the mother's abdomen.

By 24 weeks, the secretory epithelial cells, known as type II pneumocytes, in the interalveolar wall of the lungs start producing surfactant. This surfactant is crucial for the development of the alveoli. Additionally, at 24 weeks, the nails on the baby's hands begin to form.

It is worth noting that a <> between 22-25 weeks can have a chance of survival with intensive therapy. However, their underdeveloped respiratory system poses a risk, and they may not survive.

The third trimester of pregnancy begins at week 27, marking the end of the second trimester. At this stage, premature births at 24 weeks or even earlier can survive, but generally, births induced in the third trimester have high survival rates for the fetus. This is because the respiratory system has started maturing and undergoing alveolarization.

However, in some cases, additional investigations may be performed to assess the development of the respiratory system and the amount of alveolar surfactant. This is particularly important before 34 weeks of gestation to prevent hyaline membrane disease and fetal death due to the collapse of the pulmonary alveoli (atelectasis). When there is a lack of pulmonary surfactant, the high surface tension at the air-water interface causes the alveoli to collapse during expiration.

During weeks 26-29, a prematurely born fetus can survive because its lungs are now capable of breathing air. The lungs and pulmonary vascularization have developed enough to support respiratory gas exchange. Additionally, the fetus's toenails become visible, subcutaneous fat increases, and the skin wrinkles smooth out. The fetal spleen also becomes an important site of hematopoiesis during this period, but this function is transferred to the bone marrow at 28 weeks.

During weeks 30-34 of pregnancy, the fetus reaches several important milestones. At 30 weeks, the pupillary light reflex is present, indicating that the fetus can respond to light. Additionally, the nervous system is developing further, allowing for the control of certain integration functions.

At this stage, most fetuses have a chubby appearance. By week 38, the head circumference is similar to the abdominal circumference, although the abdomen may become larger afterward. As the term approaches, the growth rate slows down. On average, normal fetuses have a crown-to-rump length of 360 mm and weigh around 3400 grams at term. Fat makes up about 16% of the fetal weight, with an average daily fat gain of 14 grams during the final weeks of gestation. Male fetuses tend to be longer and heavier at birth compared to female fetuses.

At week 38, which is considered full term, there are some noticeable changes in the fetus. The skin takes on a pinkish-blue color, and the chest becomes more prominent. Both male and female fetuses may have slightly protruding breasts. The testicles, which begin descending into the scrotum between weeks 28-32, are usually in place for full-term male infants. However, premature male infants may have undescended testicles.

Although the head is relatively smaller than the rest of the body at birth, it remains one of the largest regions of the fetus, facilitating its passage through the birth canal. From head to toes, they are approximately the size of a pumpkin, weighing around 6 to 7 pounds (2.7 to 3.2 kilograms) and measuring about 19 to 21 inches (48 to 53 centimeters) in length.

Approximately one-third of infants will be weighing less than 2500 grams and are considered small for gestational age, meaning they have not reached their expected growth potential in the womb. This can be due to placental insufficiency, where the placenta is small or poorly attached, resulting in reduced oxygen and nutrient supply to the fetus. It is important to differentiate between infants who are small for gestational age and those who are born prematurely. Small for gestational age infants have delayed fetal growth, while premature infants have a shorter gestation period.

Delayed fetal growth can be caused by various factors such as placental insufficiency, multiple pregnancies, infections, cardiovascular issues, poor maternal nutrition, hormonal imbalances, teratogenic factors, and genetic factors. These infants often have wrinkled skin due to a lack of subcutaneous fat.

The timing of birth is determined by the estimated due date, which is either 266 days or 38 weeks after fertilization, or 280 days or 40 weeks after the first day of the last menstrual period. It is worth noting that about 12% of children are born two weeks before the estimated due date, while 5-6% are born 2-3 weeks after. Prolonged pregnancies can lead to postmaturity syndrome in some children, characterized by weakness, dry skin, a higher weight than normal, absence of lanugo and vernix caseosa, long nails, and restlessness. Delays in birth for more than 3 weeks can significantly increase mortality rates, so induction of delivery is recommended in such cases.

The most common method used to determine the probable date of birth is Naegele's rule. This involves counting three months back from the first day of the last menstrual period, and then adding one year and seven days. This method is fairly accurate for women with regular cycles, but errors of 2-3 weeks can occur if the cycle is irregular. Additionally, some pregnant women may experience implantation bleeding around the time of their expected menstrual period, which can lead to incorrect calculations of the due date if mistaken for a menstrual cycle. For a more accurate result, an ultrasonographic examination of the fetus and measurement of the crown-rump length between gestational weeks 9-12 is recommended.

Factors influencing fetal growth include the need for oxygen and nutrients, which are transferred from the mother to the fetus through the placenta. Glucose is the main source of energy for fetal metabolism and growth, while amino acids are also essential. The fetal pancreas secretes insulin for glucose metabolism, but only small amounts of maternal insulin can reach the fetus due to the placental membrane's limited permeability to this hormone. Fetal growth appears to be stimulated by insulin, human growth hormone, and certain small polypeptides like somatomedin C.

Various factors can affect fetal growth, including maternal, fetal, and environmental factors. Harmful factors that persist throughout the entire pregnancy, such as smoking and alcohol consumption, tend to result in delays in fetal growth and weight gain. On the other hand, factors that act in the last trimester of pregnancy, such as maternal malnutrition, can lead to the birth of low birth weight babies with normal length and dimensions.

Delayed fetal growth is caused by various factors, including smoking, maternal malnutrition, multiple pregnancies, social drug use, reduction in intraplacental blood flow, placental insufficiency, and genetic factors.

Smoking during pregnancy is a well-known cause of delayed fetal growth. Mothers who smoke experience lower rates of fetal growth during the last 6-8 weeks of pregnancy. The weight of a child whose mother has heavily smoked during pregnancy is typically 200 grams lower than normal, and there is an increased risk of perinatal mortality.

Maternal malnutrition resulting from a severely deficient diet also leads to reduced fetal weight.

In the case of multiple pregnancies, such as twins or triplets, the weight of the individuals is generally lower compared to those resulting from a single pregnancy. This is because the demand for nutrients that pass through the placenta is higher during the third trimester in multiple pregnancies.

The use of social drugs, such as alcohol, marijuana, and narcotic drugs like heroin, can cause delayed fetal growth and other obstetric complications. Children born to alcoholic mothers may present with fetal alcohol syndrome, which is associated with delayed fetal growth.

Reduction in intraplacental blood flow, which can be caused by small chorionic or umbilical vessels, severe hypotension, and kidney diseases, can result in "fetal starvation" and delayed growth.

Placental insufficiency, which can be caused by placental dysfunction or defects, is another factor that can lead to fetal growth restriction. Placental abnormalities reduce the exchange of nutrients between the fetus and the placenta. It can be challenging to distinguish between the effects of reduced exchange and reduced placental blood flow. In cases of maternal chronic diseases, faulty exchange is often the primary effect, and placental defects are secondary.

Genetic factors can also contribute to growth restriction. Repeated cases of growth restriction within a family indicate that recessive genes can cause abnormal growth. This is seen in children with Down syndrome and trisomy 18, where growth is disrupted due to genetic factors.

Defining fetal age is typically done by calculating the date of birth as either 266 days after the approximate date of fertilization or 280 days after the first day of the last menstrual period. During the embryonic period (up to 8 weeks), age is measured in days, while after that it is measured in weeks.

When there are uncertainties about the age of the fetus, ultrasound measurements can be used to estimate the probable date of birth. This estimation takes into account two factors: the start of the last normal menstrual period and the approximate day of fertilization. It is important to consider the type of months used, whether they are calendar months (between 28 and 31 days) or lunar months (28 days).

In clinical practice, gestation is divided into three trimesters, each lasting three calendar months. By the end of the first trimester, all major systems of the fetus are developed, and its crown-rump length is approximately the width of a palm. At the end of the second trimester (26 weeks from the start of the last normal menstrual period or 24 weeks from the approximate date of fertilization), the fetus is usually not mature enough to survive, even if its length is approximately equal to the length of a hand.

Estimating fetal age involves multiple measurements and external characteristics. One commonly used measurement is the crown-rump length, although it should be noted that fetal length can vary significantly for a given age, similar to child length. The length of the legs, in correlation with the crown-rump length, is particularly useful in determining the age of incomplete or macerated fetuses.

Fetal weight is another criterion used, although there can sometimes be a discrepancy between fetal age and weight, especially when the mother has metabolic disorders during pregnancy, such as diabetes. In these cases, the fetal weight may exceed the values considered normal for the crown-rump length.

Different appearances can in newborn fetuses and those who died shortly before abortion or birth. Newborn fetuses have a shiny, translucent appearance, while those who died a few days before abortion or birth have a dull appearance.

Ultrasound measurements provide fetal dimensions that are similar to those obtained from aborted fetuses, with an accuracy of ± two days. Measurements of the biparietal diameter and trunk size can be obtained. Between weeks 9 and 10, the head is still larger than the trunk. Determining the dimensions of the fetus, particularly the head, is highly valuable for obstetricians and patients, especially for women with a small pelvis and/or fetuses with congenital anomalies.

References

1. Anatomia Omului, Volumul I: Embriologie; Semestrul I; Prof. univ. dr. med. Andrei Motoc; Editura „Victor Babeș”, Timișoara, 2018

2. Embriologie - Sinteze didactice; Romeo Chiriac, Anca Indrei ;Editura Fundatiei Chemarea, Iasi, 1997

3. Embriologie Umană; Lidia Chircor, Loredana Surdu;Editura Ex Ponto, Constanța, 2014

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