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Definition
Prenatal development refers to the process in which a baby develops from a single cell after
conception into an embryo and later a fetus.

Description
The average length of time for prenatal development to complete is 38 weeks from the date of
conception. During this time, a single-celled zygote develops in a series of stages into a full-
term baby. The three primary stages of prenatal development are the germinal stage, the
embryonic stage, and the fetal stage.

Germinal stage
The genetic material of the sperm and egg combine to form a single cell called a zygote and
the germinal stage of prenatal development commences. The zygote soon begins to divide
rapidly in a process called cleavage, first into two identical cells, which further divide to four
cells, then into eight, and so on. About sixty hours after fertilization, approximately sixteen
cells have formed to what is called a morula; three days after fertilization, the morula enters
the uterus. The zona pellucida disappears and the morula becomes a blastocyst. At this stage
the blastocyst consists of 200 to 300 cells and is ready for implantation.
Implantation, the process in which the blastocyst implants into the uterine wall, occurs
approximately six days after conception. Implantation marks the end of the germinal stage
and the beginning of the embryonic stage.

Embryonic stage
The embryonic stage begins after implantation and lasts until eight weeks after conception.
Soon after implantation, the cells continue to rapidly divide and clusters of cells begin to take
on different functions (called differentiation). The process of differentiation takes place over
a period of weeks with different structures forming simultaneously. Some of the major events
that occur during the embryonic stage are as follows:
 Illustration of prenatal development, from the two-cell, or zygote, stage through the
embryonic stage, in which the major body systems develop, to the fetal stage, during which
the baby's brain develops and the body adds size and weight.
(Illustration by GGS Information Services.)

 Week 3: Beginning development of the brain, heart, blood cells, circulatory system,
spinal cord, and digestive system.
 Week 4: Beginning development of bones, facial structures, and limbs (presence of
arm and leg buds); continuing development of the heart (which begins to beat), brain,
and nervous tissue.
 Week 5: Beginning development of eyes, nose, kidneys, lungs; continuing
development of the heart (formation of valves), brain, nervous tissue, and digestive
tract.
 Week 6: Beginning development of hands, feet, and digits; continuing development of
brain, heart, and circulation system.
 Week 7: Beginning development of hair follicles, nipples, eyelids, and testes or
ovaries; first evidence of brain waves.
 Week 8: Facial features more distinct, internal organs well developed, the brain can
signal for muscles to move, heart development ends
 By the end of the embryonic stage, all essential external and internal structures have
been formed. The embryo is now referred to as a fetus.
Fetal stage
Prenatal development is most dramatic during the fetal stage. When an embryo becomes a
fetus at eight weeks, it is approximately 3 centimeters (1.2 inches) in length from crown to
rump and weighs about 3 grams (0.1 ounce). By the time the fetus is considered full-term at
38 weeks gestation, he or she may be 50 centimeters (20 inches) or 3.3 kilograms (7.3
pounds). Although all of the organ systems were formed during embryonic development, they
continue to develop and grow during the fetal stage. Examples of some of the major features
of fetal development by week are as follows:

 Weeks 9–12: The fetus reaches approximately 8 cm. (3.2 in.) in length; the head is
approximately half the size of the fetus. External features such as the face, neck,
eyelids, limbs, digits, and genitals are well formed. The beginnings of teeth appear,
and red blood cells begin to be produced in the liver. The fetus is able to make a fist.
 Weeks 13–15: The fetus reaches approximately 15 cm. (6 in.) in length. Fine hair
called lanugo first develops on the head; structures such as the lungs, sweat glands,
muscles, and bones continue to develop. The fetus is able to swallow and make
sucking motions.
 Weeks 16–20: The fetus reaches approximately 20 cm. (8 in.) in length. Lanugo
begins to cover all skin surfaces, and fat begins to develop under the skin. Features
such as finger and toenails, eyebrows, and eyelashes appear. The fetus becomes more
active, and the mother can sometimes begin to feel fetal movements at this stage.
 Weeks 21–24: The fetus reaches approximately 28.5 cm. (11.2 in.) in length and
weighs approximately 0.7 kg (1 lb. 10 oz.). Hair grows longer on the head, and the
eyebrows and eye lashes finish forming. The lungs continue to develop with the
formation of air sac (alveoli); the eyes finish developing. A startle reflex develops at
this time.
 Weeks 25–28: The fetus reaches approximately 38 cm. (15 in.) in length and weighs
approximately 1.2 kg (2 lb. 11 oz.). The next few weeks mark a period of rapid brain
and nervous system development. The fetus gains greater control over movements
such as opening and closing eyelids and certain body functions. The lungs have
developed sufficiently that air breathing is possible.
 Weeks 29–32: The fetus reaches approximately 38–43 cm. (15–17 in.) in length and
weighs approximately 2 kg (4 lb. 6 oz.). Fat deposits become more pronounced under
the skin. The lungs remain immature but breathing movements begin. The fetus's
bones are developed but not yet hardened.
 Weeks 33–36: The fetus reaches approximately 41–48 cm. (16–19 in.) in length and
weighs 2.6–3.0 kg (5 lb. 12 oz. to 6 lb. 12 oz.). Body fat continues to increase, lanugo
begins to disappear, and fingernails are fully grown. The fetus has gained a high
degree of control over body functions.
 Weeks 36–38: The fetus reaches 48–53 cm. (19–21 in.) in length is considered to be
full-term by the end of this period. Lanugo has mostly disappeared and is replaced
with thicker hair on the head. Fingernails have grown past the tips of the fingers. In a
healthy fetus, all organ systems are functioning.

Common problems
Abnormalities arise during prenatal development that are considered congenital (inherited or
due to a genetic abnormality) or environmental (such as material derived abnormalities). In
other cases, problems may arise when a fetus is born prematurely.
Congenital abnormalities
In some cases abnormalities may arise during prenatal development that cause physical
malformations or developmental delays or affect various parts of the body after the child is
born. The cause may be a small mutation in or damage to the genetic material of cells, or a
major chromosomal abnormality (each normal cell has two copies each of 23 strands [called
chromosomes] of genetic material, and abnormalities can arise if there are three copies of a
strand or only one). Sometimes the abnormality is inherited from one or both parents; in other
cases, the defect occurs because of an error in prenatal development.
Some abnormalities are minor and do not affect the long-term prognosis once the child is
born. At the other end of the spectrum, abnormalities may be so severe that fetal demise is
inevitable. Approximately 10 to 15 percent of pregnancies end before the twentieth week, a
process called miscarriage or spontaneous abortion; congenital abnormalities account for a
significant proportion of miscarriages. Genetic abnormalities account for approximately 5
percent of miscarriages.

Maternal derived abnormalities

The age, health status, nutritional status, and environment of the mother are all closely tied to
the health of a growing embryo or fetus. Some examples of environmental factors that may
lead to developmental abnormalities include:

 Age: As of 2004, research showed that babies born to mothers between the ages of
seventeen and thirty-five tend to be healthier. One reason is that the risk of certain
congenital abnormalities such as Down syndrome increases with mother's age
(particularly mothers over forty). Another reason is that the risk of having pregnancy
or birth complications is greater with women over the age of thirty-five.
 Health status: In some cases a mother may pass a viral or bacterial infection to the
fetus, such as in human immunodeficiency virus (HIV). In other cases, a mother's
illness may cause congenital malformations; an example is rubella , which can cause
heart defects, deafness, developmental delays, and other problems in a fetus if the
mother contracts it during pregnancy.
 Nutritional status: A well-balanced diet rich in nutrients such as folic acid , calcium,
iron, zinc, vitamin D, and the B vitamins is recommended for pregnant women.
Certain vitamin and mineral deficiencies can interfere with normal prenatal
development. For example, a deficiency in folic acid during the early stages of
pregnancy may lead to neural tube defects such as spina bifida . Mothers are
recommended to eat approximately 300 additional calories a day (above and beyond a
normal non-pregnancy diet) to support the fetus's growth and development.
 Other environmental factors: Exposure to certain substances called teratogens (agents
that may interfere with prenatal development) during pregnancy may cause embryonic
or fetal malformations. Examples of teratogens include alcohol, thalidomide, cocaine,
certain seizure medications, diethylstilbestrol (DES), and the anti-acne drug Accutane.
 

Causes of developmental disabilities

Developmental disabilities can involve a cognitive or sensory difficulty, social or

communications/language-related problem, a motor impairment, adaptive delay or some
combination of these. The Global Disease Control Priorities Project estimates that 10% to
20% of individuals worldwide have a developmental disability of some kind.

Developmental disabilities may last a lifetime but early recognition of their existence, a
timely diagnosis and an appropriate treatment plan can make a difference for the children and
families involved. When seeing newcomer families, recognize that risk factors are
cumulative. In many parts of the world, suboptimal conditions and care during pregnancy and
childbirth can have a range of impacts on developmental health.

 Consider the spectrum: risks common in developing countries, specific to this family’s
country of origin, and factors that are family- or ethnicity-specific.
 Be ready for diverse attitudes about developmental disabilities. More information
about cultural perspectives on developmental disability is available in this resource.
 Respond quickly and sensitively to early signs of a developmental disability. A timely
intervention will improve developmental outcomes and the family’s adjustment.
Common prenatal and perinatal risk factors to consider when taking a patient or family
history are reviewed here. Information and approaches for conducting a culturally sensitive
patient history are available on this website.

Prenatal risk factors include:

 Preconceptional factors
 Infections
 Exposure to toxins
 Maternal chronic illness
 Maternal nutritional deficiencies
Perinatal causes may include:

 Pregnancy-related complications
 Infections
 Rh isoimmunization
  Prematurity and low birth weight

Prenatal risk factors

Preconceptional factors

Preconceptional causes of developmental disability relate predominantly to genetic disorders

or malformation syndromes. Genetic disorders are the most commonly identified causal
factor for intellectual and other disabilities, and include single gene disorders, multifactorial
and polygenic disorders, and chromosomal abnormalities. Genetic disorders associated with
developmental delay include aneuploidies and inborn errors of metabolism. Consanguinity
increases the prevalence of rare genetic disorders and significantly increases the risk for
intellectual disability and serious birth anomalies, especially in first cousins. Some ethnic
communities (e.g., Ashkenazi Jews) have a higher prevalence of rare genetic mutations and
congenital anomalies affecting development.4

Causes of intellectual disability can be divided into the following categories, listed here with
their associated prevalence:1

 chromosomal abnormalities (30%)

 central nervous system malformations (10% to15%)
 multiple congenital anomalies syndromes (4% to 5%)
 metabolic (3% to 5%)
 acquired (15% to 20%)
 unknown (25% to 38%)

Prenatal infections

When taking a patient history for a newcomer child with signs of developmental disability,
health care providers need to consider the following infections, and screen accordingly.
Women who are pregnant and new to Canada must be screened for HIV, syphilis and rubella.
The results of this information need to be communicated to the infant’s health care provider.

Cytomegalovirus (CMV)

In the developed world, CMV is the most common congenital viral infection, with an overall
prevalence of 0.6%.6 Ten per cent of affected infants show signs  of infection at birth, with a
substantial risk of neurological sequelae such as sensorineural hearing loss (SNHL),
intellectual delay, microcephaly, seizure disorders and cerebral palsy. CMV is the leading
nonhereditary cause of SNHL, which may be progressive, absent at birth, unilateral or
bilateral. More information on hearing screening for newcomer children is available in this
resource. Both hearing loss and visual problems can occur in an otherwise asymptomatic
infant.
CMV is a herpes virus spread by close interpersonal contact with saliva, blood, genital
secretions, urine or breast milk. Maternal transmission to the fetus from a new or reactivated
infection can occur at any gestational age but is highest with a primary infection compared to
a reactivated infection.

There are geographical variations among virus strains and higher CMV rates in South
America, Africa and Asia, and lower rates in Western Europe and the U.S. CMV occurs more
frequently in nonwhites and individuals living in poverty.6

Rubella

There are an estimated 110,000 cases of congenital rubella annually worldwide.  Maternal
infection during pregnancy transmits the rubella virus to the fetus, causing deafness,
congenital cataracts, microcephaly, seizures and intellectual disability.

Figure 1.  Countries using rubella vaccine, 2012.

Source: Reproduced, with the permission of the publisher, from WHO/UNICEF coverage
estimates 2012 revision, July 2013. 194 WHO Member States. Map production:
Immunization Vaccines and Biologicals, (IVB). World Health Organization.
([Link]
active/Rubella_map_schedule.jpg?ua=1, accessed 12 June 2014)

Syphilis

It was estimated in 2008 that over 1.3 million cases of syphilis had occurred in pregnant
women worldwide, with a large proportion being untreated or inadequately treated. While
most countries have antenatal syphilis screening, implementation levels vary dramatically: an
estimated 30% of pregnant women in sub-Saharan Africa receive testing and treatment,
compared with 70% of women in Europe.9 Like all the preventable STIs, syphilis has been
linked to preterm labour, low birth weight and death. Congenital syphilis can cause deafness,
microcephaly, intellectual disability and visual impairment through interstitial keratitis.10

Prenatal toxins

Smoking

Maternal smoking during pregnancy increases the risk of placenta previa, placental abruption,
and preterm labor. It also has adverse affects on fetal growth.

Alcohol

Exposure to alcohol in utero is the most common teratogenic cause of developmental

disabilities, including microcephaly, cognitive disability, learning disabilities, ADHD and
behavioral challenges. Fetal Alcohol Spectrum Disorder (FASD) occurs worldwide in
approximately 1.9 per 1000 live births.11 Alcohol causes interruption of neuronal production
and secondary destruction, with faulty migration of neurons causing microcephaly.

Other drugs

Maternal exposure to other toxins, including recreational drugs and certain medications (e.g.,
valproic acid, phenytoin sodium, isotretinoin [Accutane]), can also cause developmental
disabilities.

Phenylketonuria (PKU)

The amino acid phenylalanine is a neurotoxin to the developing fetal brain. Untreated PKU,
both maternal and postnatal in the infant, causes intellectual disabilities.

Environmental toxins

Exposure to lead, mercury and chemical compounds such as polychlorinated biphenyls (PCB)
and alcohol can be identified as a contributing cause of intellectual disability in 4% to 5% of
cases.12 The dose and timing of exposures are variables in predicting neurotoxic outcomes.

Arsenic is naturally present in high levels in groundwater, which can contaminate water used
for drinking, preparing food and irrigating food crops. Arsenic is also present in soil, and
prenatal exposure is associated from both sources with intellectual disability and
developmental delay.12 The WHO provides detailed information on the early and long-term
health effects of arsenic.

Developing countries are heavily reliant on agriculture for their economy and the use and
disposal of fertilizers and pesticidesis a serious environmental issue. Chronic pesticide
exposure in the occupational setting, especially in poor rural populations, is a problem for all
workers and particularly hazardous for pregnant women and children who work and live near
areas where these chemicals are used.13

Prenatal exposure to the pesticide commonly known as DDT is associated with

neurodevelopmental delays in early childhood. It persists in the environment for years and
accumulates in the food chain and fatty tissues of humans.14 In sub-Saharan Africa, where
malaria control is a significant issue, DDT use is ongoing.  More information about DDT is
available from the WHO.

Figure 2. More than half of the world’s low-birthweight babies are in 10 countries.

Number of infants weighing less than 2,500 grams at birth (thousands), 2008─2012
Source: UNICEF global databases, 2014, based on MICS, DHS and other nationally
representative surveys, 2008─2012, with the exception of
India.  [Link]

Maternal malnutrition, before and during pregnancy, can have a negative impact on infant
birth weight and development. Some 20 million low birth weight infants (<2500 grams) are
born annually, approximately 23.8% of all births, rising to as high as 30% in many
developing countries.17 Birth weight below 1500 grams is associated with a threefold increase
of developmental disability.1 Read more about malnutrition and immigrants/refugee
populations in this resource.

Preterm birth
 Table 1. The 10 countries with the greatest number of preterm births, 2010

India 3 519 100

China 1 172 300

Nigeria 773 600

Pakistan 748 100

Indonesia 675 700

United States of America 517 400

Bangladesh 424 100

The Philippines 348 900

The Democratic Republic of the Congo 341 400

Brazil 279 300

Sources: WHO, 2013. Preterm birth. Fact sheet No.

363: [Link]/mediacentre/factsheets/fs363/en/; Blencowe H,
Cousens S, Oestergaard MZ, et al. National, regional and worldwide
estimates of preterm birth. The Lancet; 379(9832):2162-72.

Preterm birth (<37 weeks’ gestation) is a global problem. Risk factors for preterm delivery
include: multi-fetal pregnancy, uterine abnormalities, placental bleeding, prenatal drug
exposure, chronic maternal illness, hypertensive disorders, chorioamnionitis, prolonged
rupture of the membranes and bacterial vaginosis.

Lack of prenatal care, under-immunization and inadequate treatment for maternal infections
or other medical issues, including STIs, can all contribute to developmental disabilities in a
preterm infant.