Download Teratology and drug use during pregnancy Once it was believed that

Teratology and drug use during pregnancy
Once it was believed that the placenta acted as a protective barrier, keeping dangerous
substances from reaching the fetus. This is not true. Substances that can harm the
fetus "teratogens" do pass through the placenta and can adversely affect the
developing fetus.
Principles of teratology:
1- Drugs ingested during pregnancy can affect the fetus:
- Should be used only when necessary.
- Risk-benefit ratio should justify the use of any drug.
2- Passage of drugs influenced by several factors:
- Lipid-soluble substances passed readily across the placenta.
- Water-soluble substances pass less well.
- Protein bound fraction
only free drugs can cross the placenta.
3- Development defects:
- Drug exposure responsible for 2% to 3%.
- Genetic factors about 25%.
- Unknown etiology in most cases.
FDA Categories:
Category A:
Adequate, well-controlled studies in pregnant women have not shown an increased
risk of fetal abnormalities to the fetus in any trimester of pregnancy.
Controlled studies in women fail to demonstrate a risk to the fetus in the 1st
trimester and the possibility of fetal harm appears remote.
Category B:
Animal studies have revealed no evidence of harm to the fetus; however, there are no
adequate and well-controlled studies in pregnant women.
OR
Animal studies have shown as adverse effect, but adequate and well-controlled studies
in pregnant women have failed to demonstrate a risk to the fetus in any trimester.
Animal studies do not indicate a risk to the fetus and there are no controlled
human studies or animal studies to show an adverse effect on the fetus .
Category C:
Animal studies have shown an adverse effect and there are no adequate and wellcontrolled studies in pregnant women.
OR
No animal studies have been conducted and there are no adequate and well-controlled
studies in pregnant women.
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Studies have shown the drug to have animal teratogenic or embryocidal effects,
but there are no controlled studies of women or no available studies of animals or
women.
Category D:
Adequate well-controlled or observational studies in pregnant women have
demonstrated a risk to the fetus.
However, the benefits of therapy may outweigh the potential risk. For example, the
drug may be acceptable if needed in a life-threatening situation or serious disease for
which safer drugs cannot be used or are ineffective.
Positive evidence of human fetal risk exists, but benefits in certain situations
"e.g. life- threatening situations or serious diseases " may make use of the drug
acceptable despite its risks.
Category X:
Adequate well-controlled or observational studies in animals or pregnant women have
demonstrated positive evidence of fetal abnormalities or risks.
The use of the product is contraindicated in women who are or may become pregnant.
Studies in animals or humans have demonstrated fetal abnormalities,
or there is evidence of fetal risk based on human experience, or both and the risk
clearly outweighs any possible benefit .
Timing of teratogenesis:
Classic teratogenesis period extends from the second to the eighth week, which is
the critical period of organogenesis. This means that early exposure usually results
in all-or-none effect. Later exposure can result in problems.
Breasts milk secretion of drugs often pharmacologically insignificant.
After 11 weeks, the fetus becomes more resistant to damage from teratogens
because the organ systems have been established.
Effects of some therapeutic drugs:
Anticonvulsant:
 Infants of epileptic mothers have 5% risk of major malformations , and
2%to3% risk of epilepsy .
 Phenytoin decreases folate absorption
increased risk of neural tube
defects, microcephaly and developmental delay.
 Carbamazepine, valproic acid
1% risk of neural tube defects.
Anticoagulant:
 Heparin does not cross placenta but Coumadin does.
 Lithium
high rate of cardiovascular anomalies.
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Thyroid and antithyroid drugs:
 Propylthiouracil
causes fetal goiter.
 Thyroxine
safe in pregnancy.
Antiemetic:
 Phenergan is effective and safe.
Analgesics:
 Aspirin:
 No teratogenic effect in the 1st trimester.
 Low dose use may be useful in preventing PIH in high-risk patients.
 Prolonged bleeding time.
 Acamol: safe.
Antibiotics:
 Penicillins , Erythromycin , Isoniazid , Rifampin , Ethambutol and Flagyl
are safe in pregnancy.
 Sulfonamides: increase the risk of hyperbilirubinemia .
 Tetracyclines: inhibit bone growth, can affect enamel of decidual teeth.
Aminoglycosides:
 No teratogenicity in the 1st trimester.
 Increase the incidence of ototoxicity.
Antiasthmatics:
 Aminophylline: safe.
 Epinephrine: slight increase in minor malformations.
Cardiovascular drugs:
 Digoxin , Aldomet and Hydralazine are safe .
 Capoten: not recommended, can result in fetal renal failure, craniofacial
deformities and limb contractures.
Androgens:
 May masculinize a developing female fetus.
Radiation
 High levels of radiation during pregnancy may cause damage to
chromosomes and embryonic cells and can adversely affect fetal physical
growth and cause mental retardation. Consequences of radiation exposure
include stunted growth, deformities, abnormal brain function, or cancer
that may develop sometime later in life.
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Drug in Breast Milk
Rate of transfer depends on lipid solubility, molecular weight and ionization. Dose to
infant is usually 1% to 2% maternal dose.
Secretion into Colostrum is minimal. Generally medications should be taken after
breast-feeding and long-acting preparations should be avoided
Drugs contraindicated during breast-feeding :
 Drugs of abuse e.g. Cocaine, Heroin , marijuana, …
 Lithium, Antianxiety, Antipsychotic, Antidepressants.
 Radioactive isotopes.
Interventions:
Goal: to provide maximum health for the mother and her infant.
Assessment:
 General health status with particular attention to infection and nutrition.
 Obstetrical condition of mother and her fetus.
 Substance being used by the mother.
Diagnosis: is made according to specific teratogenic substance,
Planning: there should be a cooperation between the mother, physician, midwife,
social worker and other health professionals.
Implementation:
 Prenatal health teaching, alcohol and smoking to be stopped.
 Prescribed drugs: used with caution after consultation with physician or
pharmacist.
 Neonates need intensive care and discharge planning with long term
rehabilitation.
Blood Dyscrasias
Of special significance in obstetrics is the typing of blood according to the inherited
presence or absence of certain antigens. The two most important types are the Rh and
A and B antigens.
Rh factors:
 Several forms of Rh antigens exist. Those factors responsible for problems are
D, M, E, c, e & d.
 The D antigen produces the strongest stimulus for antibody production in Rh
negative people. 85% of population is Rh positive. Rh hemolytic disease
occurs when Rh antigens pass through the placenta into the mother’s blood.
 In most situations, exposure of maternal blood to fetal blood occurs during the
third stage of labor at the time of placental separation. The woman’s first child
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is usually unaffected because the maternal antibodies form after the infant’s
birth.
 The woman produces antibodies against the antigens (sensitization).
Sensitization also can occur whenever an Rh negative person receives an Rh
positive blood transfusion.
 The antibodies then pass back into the fetus circulation and destroy the
erythrocytes. The life span of the fetal or neonatal RBCs is shortened.
 The fetus attempts to make up for this destruction by producing increased
numbers of immature RBCs called erythroblast that are unable to carry
oxygen. This is called erythroblastosis.
 The severe hemolytic syndrome is known as erythroblastosis fetalis.
 If treatment is not begun, the anemia resulting from this disorder can cause
severe fetal edema called hydrops fetailis.
 Congestive heart failure may result and profound jaundice called icterus
gravis leading to neurological disorder (damage) called kernicterus.
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Prenatal screening and assessment:
 At the first prenatal visit, a history is taken concerning prior blood
transfusions, abortions, and children born with jaundice and the presence of
medical diseases.
 Blood typing (ABO), Rh factor and Rh antibody screening are done. If the
woman is Rh negative, the father of unborn child is assessed for Rh factor and
blood type.
 Indirect coombs test
for Rh negative woman to determine if she is
sensitized to the Rh antigen. “When baby is Rh positive" The test measures
the antibody amounts in the blood.
 Results are expressed as titer or proportion of antibody to serum.
o A titer of 1: 16 or less indicates that the fetus is not at risk. When titers
are higher than 1:16 a delta optical density ( OD) test of amniotic
fluid is performed at 26 weeks gestation to plan treatment .
 This test a spectrophotometric (color) analysis test that determines the amount
of bilirubin in the amniotic fluid.

OD test results are indicated as zones:
o Zone I indicates a normal neonate (fetus) who can be delivered at term
with good prognosis anticipated.
o Zone II indicates an infant possibly at risk.
o Zone III indicates a seriously affected fetus who may require
intrauterine transfusions every 1-2 weeks until viability at about 32
weeks then cesarean birth is performed .
 Interventions:
o Prentally, if tests indicate a severely affected fetus, plans will be made
for an early delivery .
o Intrauterine transfusions of the fetus may be considered.
o Fresh packed RBCs are introduced through a catheter that passes
through the woman’s abdomen into her intrauterine space, then into the
fetal peritoneal cavity, in which diaphragmatic lymphatics absorb these
RBCs into fetal circulation.
o In the postpartum period, the Rh negative woman whose indirect
cooms titer is negative and who is delivered an Rh positive fetus is
given an IM injection of anti-D gamma globulin such as RhoGAM
within 72 hours.
o This is done so that she does not have time to produce antibodies to
fetal cells that entered her blood stream when the placenta is separated.
This is done to protect future babies if she becomes pregnant again.
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o RhoGAM is given to Rh-negative nonimmunized woman at 28 -32
weeks gestation (as a preventive measure to prevent formation of
active antibodies during the remainder of pregnancy) as well as after
delivery.
o RhoGAM (anti-D) works by coating and destroying fetal cells in the
maternal circulation.
o (RhoGAM) must be given after the birth of every Rh(D)-positive
infant. If the infant is Rh(D) negative, no Rho(D) immune globulin is
necessary.
o RhoGAM is not useful in a woman who has Rh antibodies .
o RhoGAM should be given IM , not in fatty tissue or IV .
o RhoGAM never given to an infant or father .
ABO blood types:
 In the ABO system, there are 2 kinds of antigens A and B
 People who have neither are said to be O (zero).
 The rest of population has type A , B or AB .
 When the fetus inherits a blood type from the father that is different from that
of mother, fetal blood may cross the placenta and sensitize the mother to
antigens of foreign blood type.
 During subsequent pregnancy, another baby with same type as the first infant
might be affected by hostile antibodies in the blood of the mother.
 Note: ABO hemolytic problems almost exclusively A or B infants of O
mothers. The problem may appear in the first pregnancy as well as in the
subsequent ones.
 Kernicterus / anemia are rare.
 To date no immune globulin such as RhoGAM has been developed.
Multiple pregnancies
Introduction of ovulation inducing agents in late 1960s and assisted reproductive
technologies (ART) in the 1970 caused increased number of multiple births.
Much of perinatal mortality and morbidity attributable to multiple births is due to
preterm delivery.
Twin gestation:


1% all births.
Represent a high-risk pregnancy.
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Types of twining:
1) Monozygotic (identical): are identical because they develop from fertilization
of one ovum. "The same sex" occurs at random in about 3 to 4/1000. develop
from one fertilized oocyte (zygote) that divides into equal halves during an
early cleavage phase (series of mitotic cell divisions) of development.
2) Dizygotic (fratermal): twining occurs more frequently in some families
"heredity is important on mother’s side".
- Occurs in response to greater levels of FSH.
- Increased in women greater than 35 years of age and in obese women.
- More common among Africans (10 to 40/1000).
- May be different sexes.
- Always have 2 chorions, 2 amnions.
- Result from fertilization of 2 separate ova.
- Fertility drug use associated with dizygotic twinning such as clomide and
pergonal.
Note: Conjoined twins with shared organs occur as a monozygotic twins through
division of the fertilized ovum after the 13th day post conception.
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Maternal complications:


Greater increase in blood volume, pulse, cardiac output and weight gain.
Increased rate of preterm labor, hypertension, abruption, anemia, hydramnios,
UTI, cesarean section and postpartum hemorrhage.
Infant complications:


Prematurity –average age of delivery is 37 weeks.
Discordance: defined as a difference of greater than 20% to 25% in weight.
Etiology:
- Difference in placental surface area.
- Donor twin→ small, pale, anemia.
- Recipient twin→ large, plethoric, polycythemia, hyperbilirubinemia.
Fetal anomalies occur more often in multiple pregnancies.

Clinical manifestation:
1.
2.
3.
4.
5.
Uterus larger than expected for length of gestation.
Two fetal heart tones can be counted simultaneously.
Abdominal palpation yields many small parts by 6-7 months.
U/S usually used to confirm the diagnosis.
Oversized uterus and increased abdominal pressure often lead to:
- Diagnosis difficulty
- Constipation
- Dyspnea
- Backache
- Hemorrhoids &other varicosities.
Triplets:





Increasing frequency because of ART.
Average weight gains 45 to 50 pounds.
Usual spontaneous time for delivery is 32-34 weeks.
Average weight 1800-1900 grams.
Most delivered by cesarean section.
Quadruplets or more:




Most are a result of ART.
Average weight gains 50 to 55 pounds.
Average gestational age 30 to 31 weeks.
Average weight 1200-1500 grams.
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Multifetal reduction, has been shown to improve perinatal survival rate.
Assessment:
 Initial maternal assessment includes a family history of twinning or use of
fertility drugs.
 At each prenatal visit, assess fundal height, FHR, fetal development.
 U/S to confirm the diagnosis.
 Assessment of physical discomforts such as backache and dyspnea.
 Multiple pregnancies increase the incidence of PIH, prematurity, hydramnios,
abnormal fetal positions and presentations, uterine dysfunction, and postpartum
hemorrhage.
Nursing intervention:
To prevent premature delivery:
 Encourage the woman to keep appointments for more frequent checkups.
 Counsel the woman to rest frequently during the day especially in the third
trimester; assist the family to mobilize support system for this purpose.
 Teach the woman reportable signs and symptoms of premature labor.
 Diet high in protein, iron, calcium, 300 calories added to normal pregnancy.
 Monitor for hypertensive disorders.
 During labor, mother and fetuses are monitored closely.
 Ideally, the largest fetus is delivered through vertex presentation and is the first
to be born. If the first is a breech presentation or the smaller one, delivery is
complicated.
 Cesarean birth is recommended if fetal distress, CPD, placenta previa, or sever
PIH is present or if prior cesarean birth have occurred.
 Following delivery, monitor the woman for postpartum hemorrhage due to over
distended uterus.
Health education:
 Rest frequently on her side.
 Sitting with leg elevated to help relief backache.
 Small frequent meals will aid digestion.
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 Cesarean Delivery
 Is removal of the infant from the uterus through an incision made in the
abdominal wall and in the uterus.
 Indications:
 Cephalopelvic disproportion (CPD).
 Uterine dysfunction, inertia, inability of the cervix to dilate.
 Neoplasm obstruction birth canal or pelvis.
 Malposition and malpresentation.
 Previous uterine surgery (cesarean delivery, hysterotomy …).
 Complete or partial placenta previa.
 Abruption placenta.
 Fetal distress.
 Prolapsed umbilical cord.
 The basic purpose of cesarean delivery is to preserve the life or health of the
mother and her fetus.
 Types of Cesarean Delivery:
 Low Segment (Operation of choice):
 Incision is made transversely in lower uterine segment, in the thinnest portion so
that blood loss is minimal and uterus is easier to open. Lower uterine segment is
also area of least uterine activity.
 Postoperative convalescence is more comfortable.
 Possibility of later rupture is lessened.
 Peritoneal flap is brought over uterine incision, preventing lochia from entering
peritoneal cavity.
 Incidence of postoperative adhesions and danger of intestinal obstruction are
reduced.
 Classic:
 Vertical incision is made directly into the wall of the body of uterus.
 Useful when bladder and lower uterine segment are involved in extensive
adhesions.
 Useful when fetus is in transverse lie.
 Selected when anterior placenta previa exist.
 Rarely used today, the classic cesarean incision is reserved for some cases of
shoulder presentation, placenta previa, and when birth must take place
immediately. Since this type of uterine incision is associated with complications
including considerable blood loss, infection, and uterine rupture with subsequent
pregnancies, women who undergo classic cesarean births may not attempt future
vaginal births.
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
 Extra Peritoneal:
 The tissue around bladder is dissected, providing access to lower uterine
segment without entering into peritoneal cavity.
 Devised to prevent peritonitis.
 Availability of blood and antibiotics has reduced use of this method.
 Cesarean delivery and hysterectomy ( Porro’s operation).
 Cesarean delivery followed by the removal of the uterus.
 Indications for Porro’s operation:
 Hemorrhage due to uterine atony after conservative therapy fails.
 Uncontrollable hemorrhage from placenta previa or abruption placenta.
 Placenta accreta (abnormal attachment of placenta to uterine endometrium).
 Not repairable rupture of the uterus.
 Cross multiple fibromyomas.
 Nursing Intervention:
 Preparations for Emergency cesarean birth:
 Standard preoperative measures include:
 Nothing by mouth (NPO).
 Abdominal and perineal shaved from nipple line to pubis.
 Indwelling catheter to dependent drainage.
 Signed operative permit.
 Two units of whole blood ready for administration.
 I.V. line in place.
 Preoperative medications (atropine), narcotics are avoided.
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 Infant preparations: warmer, resuscitation and suction equipment, and
notification of the pediatrician.
 Promoting Coping Abilities:
 Have the woman discuss her perception of why the cesarean delivery is needed,
correct misinformation and provide further knowledge.
 Have the woman / couple listens to fetal heart sounds to reassure them of the
well being of the fetus.
 Explain postoperative care and procedures:
 Provide Postoperative Care similar to that following abdominal surgery:
 Observe for hemorrhage, inspect perineal pads and abdominal dressing, and
assess vital signs frequently.
 Administer oxytocics as prescribed.
 Check fundus for firmness.
 Continue IV fluid as prescribed.
 Check urinary output from indwelling catheter for amount and evidence of
bleeding.
 Provide medications to relief pain as prescribed.
 Encourage woman to turn frequently from side to side, to breathe deeply and to
cough.
 Assist woman out of bed on first postoperative day.
 As soon as possible, have the woman hold and care for infant to reassure her of
infant's well being.
 Maintain cleanliness and prevent infection.
 Note:
 When a mother who has had cesarean birth wants to deliver vaginally, a trial
labor may be undertaken.
 She must be in a good health, her medical history should be available, and the
fetus should be in vertex position with no CPD or other complications.
 The birthing center must be able to provide fetal and maternal monitoring, blood
transfusions, anesthetic services and physician availability.
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