TERATOGENS

http://www.chw.org/medical-care/genetics-and-genomics-program/medicalgenetics/teratogens/
What is a teratogen?
A teratogen is an agent, which can cause a birth defect. It is usually something in
the environment that the mother may be exposed to during her pregnancy. It could
be a prescribed medication, a street drug, alcohol use, or a disease present in the
mother which could increase the chance for the baby to be born with a birth defect.
About 4 to 5 percent of birth defects are caused by exposure to a teratogen.
What are the most sensitive periods for teratogens in pregnancy?
Once the egg is fertilized (conception), it takes about six to nine days for
implantation (anchoring into the uterus) to occur. Once the fertilized egg is
connected to the uterus, a common blood supply exists between the mother and the
embryo. In other words, if something is in the mother's blood, it can now cross
over to the developing fetus. Teratogens are thought to have the ability to effect the
fetus about 10 to14 days after conception.
During the development of a baby, there are certain organs forming at certain
times. If a teratogen has the potential to interfere with the closure of the neural
tube, for example, the exposure to the teratogen must occur in the first 3.5 to 4.5
weeks of the pregnancy, since this is when the neural tube is closing. There are
some organ systems that are sensitive to teratogens throughout the entire
pregnancy, such as the central nervous system. The central nervous system is the
baby's brain and spine. One teratogen that affects the central nervous system is
alcohol. Alcohol, at any time during the pregnancy, has the potential to cause birth
defects and health problems in the baby, since the central nervous system is
sensitive to teratogens the entire nine months of gestation. This is why alcohol
consumption should be avoided in its entirety during pregnancy.
There are many different teratogens that cause birth defects. Listed in the directory
below are some, for which we have provided a brief overview.
Alcohol
Phenytoin (Dilantin)
Varicella
Examples of Non-Teratogenic Agents: Spermicides, Acetaminophen,
Prenatal Vitamins, Using a Microwave to Cook Food
Identifying Teratogens

What causes fetal alcohol syndrome (FAS)?

Many drugs can pass from the mother's blood stream through the placenta to the
fetus. Alcohol is no exception. Alcohol is broken down more slowly in the
immature body of the fetus than in an adult's body. This can cause the alcohol
levels to remain high and stay in the baby's body longer.
The full picture of FAS usually occurs in babies born to alcoholic mothers, or those
who drink more than four to five drinks/day. However, no amount of alcohol is
safe. Even light or moderate drinking can affect the developing fetus.
Why is fetal alcohol syndrome (FAS) a concern?
Alcohol use in pregnancy has significant effects on the fetus and the baby.
Dependence and addiction to alcohol in the mother also cause the fetus to become
addicted. At birth, the baby's dependence on alcohol continues. But since the
alcohol is no longer available, the baby's central nervous system becomes
overstimulated causing the symptoms of withdrawal. Alcohol withdrawal may
begin within a few hours after birth and symptoms may last up to 18 months.
In addition to the acute effects of withdrawal, babies often suffer the teratogenic
(causing abnormalities in formation) effects of alcohol. Specific deformities of the
head and face, heart defects, and mental retardation are seen with fetal alcohol
syndrome (FAS).
What are the symptoms of fetal alcohol syndrome (FAS)?
The following are the most common symptoms of FAS. However, each baby may
experience symptoms differently. Symptoms may include:
Small head, small jaw, and small, flat cheeks.
Malformed ears.
Small eyes, poor development of optic nerve, crossed-eyes.
Upturned nose, low bridge.
Small upper mouth structure and teeth.
Caved-in chest wall.
Umbilical or diaphragmatic hernia.
Limited movement of fingers and elbows.
Extra fingers, abnormal palm creases.
Excessive hair.
Undergrown nails.
Incomplete or lack of development of brain structures.
Heart murmurs, heart defects, abnormalities of large vessels.

Incomplete development of genitalia.

Growth, motor, and mental retardation.
Irritability in infancy and hyperactivity in childhood.
Poor coordination.
The symptoms of FAS may resemble other medical conditions or problems.
Consult a physician for a diagnosis.
How is fetal alcohol syndrome (FAS) diagnosed?
Most often, FAS is diagnosed based on the mother's history and the appearance of
the baby, based on a physical examination by a physician.
Treatment for fetal alcohol syndrome (FAS):
The US Food and Drug Administration (FDA) has designated specific drugs for
treating the symptoms of withdrawal from alcohol in babies. However, there is no
treatment for life-long birth defects and retardation. Babies and children with
alcohol-related damage often need developmental follow-up and, possibly, longterm treatment and care.
Prevention of fetal alcohol syndrome (FAS):
Fetal alcohol syndrome is 100 percent preventable. However, it requires that a
mother stop using alcohol before becoming pregnant. Because no amount of
alcohol is proven safe, women should stop drinking immediately if pregnancy is
suspected.
Phenytoin (Dilantin)
What is Phenytoin (Dilantin)?
Phenytoin (or Dilantin) is a medication used to treat epilepsy (seizure disorder). If
taken by the mother in the first trimester, there is a 10 percent chance for a
combination of birth defects known as the "Fetal Hydantoin Syndrome", and a 33
percent chance that the baby will be born with some of the following health
problems:
Growth deficiency.
Developmental delay.
Cleft palate.
Certain facial characteristics.
Heart defects.
Genitourinary abnormalities.
Abnormalities of the fingers and nails.

Dilantin crosses the placenta in such a way that the developing fetus receives a
much higher dose of the medication than the mother is taking (the drug is
metabolized differently). This is especially true when the medication is used during
the first trimester of pregnancy.
When a woman with epilepsy is planning a pregnancy, it is important for her to
meet with both her neurologist and her obstetrician before conception, to discuss
the specific treatment to be used to control seizures while pregnant.
Varicella
What is varicella?
Varicella (or chickenpox) is a highly infectious disease, usually associated with
childhood. By adulthood, more than 95 percent of Americans have had
chickenpox. Eighty-five to ninety-five percent of pregnant women are immune to
chickenpox, which means that there is no need to be concerned about this during
pregnancy, even if the woman is exposed to someone with chickenpox. Nearly one
to seven women out of 10,000 will develop chickenpox during pregnancy,
however,
because
they
are
not
immune.
The disease is caused by the varicella-zoster virus (VZV) which is a form of the
herpes virus. Transmission occurs from person-to-person by direct contact, or
through the air. Chickenpox is contagious one to two days before the appearance of
the rash until the blisters have dried and become scabs. Once exposed to the virus,
chickenpox may take up to 10 to 21 days to develop.
When a woman has a varicella infection during pregnancy, if during the first 20
weeks, there is a 2 percent chance for the baby to have a group of defects called the
"congenital varicella syndrome", which includes scars, defects of muscle and bone,
malformed and paralyzed limbs, a small head size, blindness, seizures, and mental
retardation. This syndrome is rarely seen if the infection occurs after 20 weeks of
pregnancy.
Another time that there is a concern with a varicella infection is in the newborn
period, if the mother develops the rash from five days before, to two days after
delivery. Up to 25 percent of newborns will be infected in this case, and develop a
rash between five and 10 days after birth. Up to 30 percent of infected babies will
die if not treated. If the mother develops a rash between six and 21 days before
delivery, the baby faces some risk of mild infection.
In 1995, the US Food and Drug Administration (FDA) approved a chickenpox
vaccine. If the baby is treated immediately after birth with an injection of VZIG

(varicella-zoster immune globulin), the infection can be prevented or the severity

lessened.
If a pregnant woman has been exposed to someone with chickenpox, VZIG can be
given within 96 hours to prevent chickenpox, or lessen the severity. It is important
for pregnant women to avoid exposure to anyone with chickenpox if they are not
sure whether they are immune to this infection.
OBAT YANG MEMICU CACAT JANIN
Beberapa obat mungkin cukup aman kita konsumsi ketika mengalami sakit atau
gangguan kesehatan. Namun ketika tengah hamil, beberapa obat yang tadinya aman
dapat menjadi hal yang berbahaya. Penting untuk memperhatikan kandungan obat
pada kemasan yang akan dikonsumsi pada masa kehamilan. Sebisa mungkin lebih
baik menghindari konsumsi obat jika tidak terlalu dibutuhkan, terutama pada usia
kehamilan 0-8 minggu karena ini adalah periode genting pada pertumbuhan calon
janin. Namun jika Anda benar-benar membutuhkannya, sebaiknya berkonsultasilah
dengan dokter Anda. Berikut diantara beberapa kandungan obat yang perlu
diketahui dan kaitannya dengan kehamilan.
Pseudoefedrin
Pseudoefedrin termasuk golongan simptomimetik yang bekerja melegakan
pernapasan yang tersumbat riak lendir dengan merelaksasi otot polos bronkus oleh
stimulasi syaraf simpatik atau adrenergic yang melepaskan norepinefrin endogen.
Kandungan obat ini terdapat pada beberapa obat flu yang beredar di pasaran. Obat
dengan kandungan pseudoefedrin sebaiknya dihindari terutama di awal-awal
kehamilan karena bisa member resiko gangguan pembentukan perut bayi.
Tetracycline
Tetracycline adalah jenis antibiotic dengan spektrum luas yang sering digunakan
untuk mengobati berbagai penyakit akibat bakteri yang lainnya. Obat ini perlu
diwaspadai karena dapat menyebabkan kerusakan pertumbuhan gigi bayi berupa
warna hitam. Kerusakan ini tidak bisa hilang sama sekali, sampai dewasa gigi bayi
akan berwarna hitam.
Retinoic Acid
Retinoic acid atau Asam Retinoat adalah bentuk asam dan bentuk aktif vitamin A
(retinol). Disebut juga tretinoin. Asam retinoat banyak dipakai dalam beberapa
kosmetik. Retinoic acid perlu diwaspadai karena bisa menyebabkan kecacatan pada
bayi. Tapi umumnya pada obat yang diminum.

Thalidomide
Thalidomide termasuk jenis obat yang sama sekali mesti dihindari oleh ibu hamil
baik dalam jumlah kecil atau besar. Hal ini karena thalidomide bisa memberi efek
buruk menyebabkan bayi tidak punya tangan kaki. Jika dikonsumsi pada akhirakhir kehamilan bisa mengakibatkan ada telinganya yang tidak tumbuh. Obat ini
merupakan jenis obat generasi lama yang dipakai untuk mengatasi gejala mual dan
muntah selama kehamilan, kecemasan, serta insomnia.
Streptomisin
Streptomisin adalah termasuk jenis antibiotic yang biasanya ada pada beberapa obat
untuk tuberkolosis (TBC). Penggunaan Streptomisin bisa berbahaya karena dapat
menyebabkan bayi mengalami gangguan pendengaran.
Kabar baiknya ada beberapa obat yang tergolong aman dikonsumsi meski Anda
hamil. Diantaranya semua jenis vitamin dan multivitamin. Semua obat maag dan
paracetamol untuk penghilang nyeri juga cukup memberi lampu hijau. Namun
paracetamol selama tidak dikombinasi dengan komposisi lain, jika dikombinasi,
cermati dulu komposisi lainnya itu. Maka demi keselamatan kehamilan Anda,
jelilah mencermati label obat.
dr. Febriansyah Darus, SpOG
Artikel disunting dan pernah dimuat pada Majalah Parents Guide Edisi
Januari 2012
http://www.kemangmedicalcare.com/kmc-tips/tips-dewasa/1044-5-obat-yang-perludiwaspadai-ibu-hamil.html
KELAINAN KONGENITAL KROMOSOM
Sadler, T. W. 2012. Langman Embriologi Kedokteran Ed 10. Jakarta, EGC.
Kelainan Jumlah Kromosom
Aneuploid merujuk pada semua jumlah kromosom yang bukan euploid, kata ini
biasa digunakan jika terdapat tambahan satu kromosom (trisomi) atau terjadi
kehilingan satu kromosom (monosomi). Kelainan dapat muncul pada saat
pembelahan meotik atau mitotik.
Meiosis normal kromosom membelah menjadi dua individu, shg setiap anak
menerima satu dr pasangan kromosom.
Nondisjunction tidak tjd pemisahan, kedua anggota bergerak ke salah satu sel.
Trisomi dan monosomi. Insidensi meningkat pd usia 35 tahun lebih.

Mitotik disjunction mosaikisme, sebagian sel memiliki kromososm normal, dan

lainnya abnormal.
Translokasi (tidak seimbang) kromosom putus, potongan dari satu kromosom
melekat ke kromosom lain.
Macam Kelainan Kromosom Jumlah
1. Trisomi 21 (Sindrom Down)
Etiologi: 75% krn nondisjunction meiotik saat pembentukan oosit
tambahan salinan kromosom 21. 4% krn translokasi tak seimbang
kromosom 21 dgn kromosom 13, 14, atau 15.
1% karena mosaikisme akibat nondisjunction mitotik.
Klinis: retardasi pertumbuhan, retardasi mental, kelainan kraniofasial
(kelopak mata sipit ke atas. Lipatan epikantus lipatan kulit tambahan di
sudut medial mata, wajah datar, telinga kecil), cacat jantung, hipotonia.
Insidensi: 1 dr 2000 pd wanita <25 th. 1 dr 300 pd usia 35. 1 dr 100 pd usia
>40.
2. Trisomi 18
Klinis: retardasi mental, cacat jantung, telinga letak rendah, fleksi tangan dan
jarinya, sering: mikrognatia, anomali ginjal, sindaktili, malformasi rangka.
Insidens: 1 dr 5000 neonatus.
Prognosis: 85% meninggal pd kehamilan 10 mgg-aterm, yg lahir meninggal
usia 2 bulan.
3. Trisomi 13
Klinis: RM, holoprosensefalus, cacat jantung, tuli, bibir dan langit2 sumbing
(palatoblastokisis), cacat mata (mikroftalmia, anoftalmia, koloboma).
Insidens: 1 dr 20.000 kelahiran hidup.
Prognosis: 90% meninggal 1 bln pertama kelahiran.
4. Sindrom Kinefelter
Etiologi: pd pria, terdeteksi saat pubertas. XXY nondisjunction kromosom
XX. Trdapat satu badan seks (badan Barr yg dibentuk oleh pemadatan
kromosom seks yg mengalami inaktivasi)
Klinis: sterilitas, atrofi testis, hilainisasi tubulus seminiferus, ginekomastia.
5. Sindrom Turner
Ciri: wanita. kromosom 45, pasangan terakhir hanya X monosom dr gamet
pria. Nondisjunction badan kromatin negatif. Atau nondisjunction mitosis
mosaikisme (kelainan struktur).

Klinis: jelas wanita, tdk ada ovariun, perawakan pendek, leher bersayap,
limfedema ekstremitas, kelainan tulang, dada lebar dgn puting trpisah jauh.
Prognosis: 98% abortus spontan.
6. Sindrom Triple-X
Etiologi: XXXY. Dua badan kromatin seks dlm selnya.
Klinis: Infantil, haid sedikit, RM.
Kelainan Kromosom Struktur
Putusnya kromosom virus, radiasi, dan obat.
1. Sindrom Cri-du-chat
Etiologi: delesi kromosom 5
Klinis: menangis spt kucing, mikrosefalus, RM, cacat jantung kongenital.
2. Sindrom Angelman
Etiologi: Mikrodelesi Kromosom 15 (15q11-15q13) pd warisan ibu.
Klinis: RM, tdk bisa bicara, gangguang perkembangan motorik, rentan
tertawa spontan dan berkepanjangan.
3. Sindrom Prader-Willi
Etiologi: mikrodelesi lengan 15 dr gen ayah.
Klinis: hipotonia, obesitas, gonadisme, RM, kriptokidismus.
4. Sindrom Miller-Dieker
Etiologi: genomic imprinting, bisa ayah bisa ibu delesi di 17p13
Klinis: lisensefalus, keterlambatan perkembangan, kejang, kelainan jantung
dan wajah.
5. Sindrom velokardiofasial (Shprintzen)
Etiologi: delesi kromosom 22q11.
Klinis: cacat palatum, cacat jantung konotrunkal, lambat bicara, gangguan
belajar, mirip skizoprenia.
6. Sindrom Fragile-X
Etiologi: bagian kromosom yg mudah pututs dgn manipulasi sel tertentu
fragile sites kromosom X (Xq27).
Klinis: RM, telinga besar, rahang menonjol, iris biru pucat.
Insidens: pria lebih sering 1 dr 1.000. Wanita 1dr 2.000.