Birth Defect Causes Infographic Header
04 March 2015

Why Do Most Birth Defects Develop During The First Trimester?

While birth defects can develop at any time during pregnancy, most begin during the first trimester. Why? This is the time when a baby’s organs are first forming – the most crucial part of fetal development. That means babies are most vulnerable to the causes of birth defects during the first trimester, too.

What Causes Birth Defects In First Trimester?

As for what causes birth defects, scientists are unanimous in their belief that birth defects are a result of genetic and environmental factors.

Genetic Mutations

Nearly every cell in the human body carries around between 25,000 and 35,000 genes. In a very real sense, genes serve as the instruction manual for building a person. Genetic information, however, can mutate, changing the instructions and telling fetal cells and tissues to develop abnormally.

Gene Statistics Infographic

Sometimes fetuses inherit genetic mutations from their parents, abnormalities present from the moment of conception. Genes can also mutate during embryonic development, as cells copy their genetic mutation (sometimes making mistakes) over and over to create new cells.

Environmental Factors

When researchers point to “environmental” factors, they usually mean substances in the environment, like airborne toxins, that can be absorbed by a mother’s body, ultimately coming to affect how her unborn child grows. But environment, in this context, actually has a double meaning, since fetuses develop in an environment of their own.

Many substances can change the way a baby develops inside the womb. Tobacco products and alcohol are well-known examples of chemicals that can lead to birth defects. Some pharmaceutical drugs have also been linked to a higher rate of birth defects, leading researchers to suggest that these medications could also be potential causes of congenital abnormalities.

Birth Defect Causes Infographic

Genetics and environment are the two primary causes of birth defects that researchers have identified. Many scientists believe that these factors actually work hand-in-hand. Some, if not most, bits of genetic information need to be turned on, or “expressed,” to alter the course of fetal development. In many cases, a gene is switched on by a nudge from the environment, some chemical signal that tells the gene to activate.

A Baby’s Journey Through The First Trimester

To learn more about what causes birth defects in the first trimester, we’ll have to dig in to the science of being pregnant. In this section, we’ll cover the first five weeks of pregnancy with a focus on the primary causes of birth defects.

The average pregnancy lasts from 40 to 41 weeks. Doctors break pregnancies up into three roughly equal “trimesters,” and it turns out that the first trimester, from fertilization to about 12 weeks, is the most important for a baby’s healthy development.

Fertilization: Weeks 1, 2 & 3

While professionals agree that the clock starts ticking from the first day of your last menstrual period, you’re not technically “pregnant” until after the second week. The first two weeks, though, are extremely important. At the beginning of each menstrual period, the female body gears up to conceive and sustain a growing baby. During ovulation, eggs are released from the ovaries, and then travel down the Fallopian tube. They hang out at the end of this tube for about thirty hours, waiting for sperm.

In the meantime, hormones are ramping up in the mother’s body, as progesterone thickens the uterine lining so it can accept an egg once it’s been fertilized. This process, in which a fertilized egg (or zygote) embeds in the wall of its mother’s uterus, is called implantation. We’ll learn more about that a little later.

Chromosomes & DNA: Genetic Causes Of Birth Defects

But to understand one of the most common causes of birth defects, we’ll have to continue on to the third week of pregnancy and a process called fertilization. This is when an egg and sperm combine to create a single cell. During fertilization, an embryo’s genetic code is determined, and the information contained in this code will determine how the embryo develops. Genes tell cells where to move and how to interact, multiplying and combining to form all of the bodily structures that make up a human being.

When a sperm meets an egg, they become one cell that we call a zygote. Any two cells, including sperm and eggs, that combine like this can also be referred to as gametes.

Fertilization Infographic

At the center of this new cell is a structure called the nucleus, and inside the nucleus are chromosomes. Shaped like little “X”s, chromosomes come wrapped in deoxyribonucleic acid (DNA), a series of amino acids that contain all the genetic information needed to build an embryo into a fetus (and eventually, a baby). DNA determines your baby’s sex and physical appearance, along with personality to a lesser extent. It tells the various body structures how to form themselves, giving directions on where cells should move and how they should interact. Most zygotes contain 42 separate chromosomes, 23 from the mother’s egg and 23 from the father’s sperm.

Birth Defects Can Be Caused By Genetic Factors

Some birth defects begin here, in the chromosomes.

Let’s say that an egg has a little bit of genetic code that “instructs” the cells in a baby’s eyes to be blue. But the sperm has genetic code that says brown. In terms of eye color, the code for brown is “dominant,” and the code for blue is “recessive.” Dominant genes “knock out” recessive ones, in effect overpowering them. Although nothing is certain at this point, it’s far more likely that the baby will continue to develop brown eyes, rather than blue ones. If the baby is in fact born with brown eyes, we can say that the dominant genetic code for brown was “expressed.” The code for blue went “unexpressed.”

As a general rule, recessive genes are only expressed when both gametes have them. If mother and father both have genes for blue, then a baby is likely to be born with blue eyes. Some genes, though, are missing crucial information. Others actively code for anomalies, and both types can tell body structures to form improperly.

Single Gene Birth Defects

Tay-Sachs disease and sickle-cell anemia are two examples of these so-called “single gene” birth defects.

Down syndrome, the most common “chromosomal abnormality” birth defect, can begin even earlier. A type of Down syndrome called “Complete trisomy 21” begins way back when the sperm or egg were created in the first place. In this case, one of the gametes over-copied genetic material, specifically chromosome 21. If a sperm or egg with two copies of chromosome 21 joins with a gamete with one copy, the embryo has three and will eventually be born with Down syndrome.

Cell Division & Genetic Mutation

Genetic information can also cause birth defects a little later. As it travels further down the Fallopian tube, the zygote divides to make more cells. Every time, the unique DNA of each cell is copied, and this copy goes on to dictate the behavior of a new cell.

Embryonic Development Infographic

Sometimes, mistakes are made during the copying process: large segments of DNA can be left out, or entire chromosomes can be forgotten. In either case, cells will lack the normal genetic information necessary to form an anomaly-free fetus.

Implantation & Placentas: Weeks 4 & 5

The second major cause of birth defects, environmental factors, only becomes possible a little later, during weeks four and five.

At this point, a baby is little more than a ball of cells called a blastocyst. Once it reaches the uterus, this ball has divided into two distinct parts. The inside will eventually develop into an embryo, which is what most of us think of as a growing baby. The outer ring, on the other hand, is becoming the amniotic sac, a sphere of nourishing cells that will feed the embryo as it grows.

Inside the uterus, the blastocyst burrows into the uterine wall to seek nourishment from its mother’s body.

Organ Formation

Week five is a big one. Your baby is now becoming an embryo, and its cells are again separating into three distinct layers. Within each layer, a different set of organs is beginning to form: intestines on the inside, bones, muscles and heart in the middle and skin, eyes and connective tissues on the outside.

Meanwhile, the developing embryo continues to rely on nutrients from its mother’s body to grow properly. Linked to its mother by the umbilical cord, the embryo receives a flow of blood that delivers oxygen and other nutrients. It also passes waste products, like carbon dioxide, out through the umbilical cord for the mother’s body to dispose of.

Medications, Habits & Infections: Environmental Causes Of Birth Defects

An organ called the placenta separates the mother’s body from the embryo. The placenta is able to filter the blood an embryo receives, but some harmful substances can get through. Anything that can cross the placental barrier and adversely alter an embryo’s development is called a teratogen.

Teratogen Infographic

Some teratogen’s, like alcohol and cigarettes, are ingested voluntarily. When a mother consumes too much alcohol during pregnancy, the chemical crosses the placental barrier and enters the developing embryo. It can then inhibit the growth of the developing baby’s brain and cause “fetal alcohol syndrome” (FAS). FAS is characterized by stunted growth and a distinct facial appearance.

Certain foods contain teratogens. Fish like swordfish and mackerel contain high levels of mercury, an element that has been linked to developmental delays and brain damage. Infections, especially ones that are transported in the blood, can also be absorbed by a growing embryo and cause birth defects.

Birth Defects Can Be Caused By Prescription Drugs

Many common prescription drugs have also been linked to birth defects. In the 1950s, mothers were often prescribed thalidomide, a sedative to treat morning sickness. Many of these women gave birth to children with phocomelia, a congenital disorder marked by malformed limbs. In 1961, Widukind Lenz, a German pediatrician, proved that these defects were caused by thalidomide. Accutane, a drug for severe cases of acne, is so dangerous during pregnancy that the government requires women to take two forms of birth control while using it.

Unfortunately, we don’t usually learn that a prescription drug may be harmful to fetal development until after pregnant women have started taking it. Ethical concerns prevent researchers from studying the vast majority of drugs during pregnancy, so few prescriptions are explicitly approved for use in pregnant women. It’s not until doctors start prescribing the drug “off-label” to pregnant women that we begin to see warning signs.

In recent years, significant concerns have been raised about the drug ondansetron. Marketed by GlaxoSmithKline as Zofran, ondansetron was approved by the FDA to treat nausea and vomiting that accompanies several cancer treatments, including chemotherapy. Many obstetricians and gynecologists, however, soon began prescribing the drug to pregnant women as a morning sickness treatment. In fact, Zofran is currently the most popular treatment for morning sickness in the United States. But recent studies have found a link between Zofran and severe birth defects, including cleft palate and congenital heart defects. Some families have even filed lawsuits against GlaxoSmithKline, accusing the company of knowing about the drug’s risks but doing nothing to warn pregnant women or doctors.

Genes & Environment: The Primary Causes Of Birth Defects

We’ve now covered the two main causes of birth defects: problems with genetic material and harmful substances that pass from a mother’s body to that of her growing baby. As we’ve seen, these risks are highest during the first trimester because that’s when a developing baby’s organs are undergoing the most crucial stages of formation.

The structures and processes that make birth defects possible appear during the first trimester, but the dangers don’t end after these initial three months are over. Excessive alcohol ingestion, for example, has been linked to birth defects during any of the three trimesters, not just the first. Some prescription drugs may also have similar effects later in pregnancy.