IS PREGNANCY

AN UNCOMPROMISED

STATE ?

DatoDr.Ghazali Ismail

Consultant Obstetrician Gynaecologist

Hospital Sultan Ismail, JB

DEFINITION : AN UNCOMPROMISED

STATE

Uncompromised is define as able to function optimally, especially with regard to immune

response, owing to underlying disease,

harmful environmental exposure, or the side

effects of a course of treatment

A person who has an immunodeficiency of any kind is said to be immunocompromised.

An immunocompromised person may be particularly vulnerable to opportunistic

infection in addition to normal infections that

could affect everyone.

The immune system is defined as bodys defense mechanism for fighting disease and infection.

The immune system produces antibodies and special cells that attack viruses and

microorganisms.

The inbuilt immune system within the body enables it to recognize materials as foreign objects and thus

neutralizes, eliminate or metabolize them with or

without injuring its own tissues.

INTRODUCTION

Innate immune system Adaptive immune system

Response is non-specific Pathogen and antigen specific

response

Exposure leads to immediate

maximal response

Lag time between exposure and

maximal response

Cell-mediated and humoral

components

Cell-mediated and humoral

components

No immunological memory Exposure leads to immunological

memory

Found in nearly all forms of life Found only in jawed vetebrates

Components of the immune system

Our immune system is volatile and can be influenced by variety of factors.

Immunity system is suppressed during pregnancy to accept semi-allogenenic fetus

Pregnant woman is more prone to infection and diseases which may have implications on her

own health as well as for the developing fetus

INTRODUCTION Pregnancy is a source of many changes in the body

some of which are sudden and may cause certain

problems

The body is under the influence of drastic changes in the level of certain hormones.

One of the changes that may affect a pregnant woman is weakening of the immune

system.

The risk of getting certain illnesses increases and they require proper care and sometimes

treatment

During pregnancy, the immune system does not work at full capacity.

Because of this, the body's immune system in pregnancy

has a harder time fighting off

Causes and Symptoms of Weakened

Immune System during Pregnancy

Sudden hormonal changes can be blamed for weakening of the

immune.

When fertilized egg is implanted in the uterus further growth and

development of the fetus require

certain hormones.

Placenta- human chorionic gonadotropin (hCG) is responsible for a variety of changes

in the body such as missed periods, mood

changes, morning sickness, fatigue etc.

.

IS PREGNANCY AN

UNCOMPROMISED

STATE ?

The idea that pregnancy is associated with immune suppression has created a myth of

pregnancy as a state of immunological

weakness and, therefore, of increased

susceptibility to infectious diseases.

.is the maternal immune system is a friend or a foe of

pregnancy ?

PREGNANCY AND IMMUNE SYSTEM

During normal pregnancy, the human decidua contains a high number of immune cells, such as

macrophages, uterine natural killer (uNK) cells,

dendritic cells and regulatory T cells (Treg).

During the first trimester, uNK cells, dendritic cells and macrophages infiltrate the decidua and

accumulate around the invading trophoblast

These immune cells in the decidua play an important role in the acceptance of the semi-allogeneic fetus,

implantation and placentation

The presence of immune cells at the implantation site is not

associated with a response to

the foreign fetus but to facilitate and protect the

pregnancy

It is characterized by a reinforced network of recognition,

communication, trafficking and

repair

It is able to raise the alarm, if necessary, to maintain the well-being of the mother and the fetus

The fetus provides a developing active immune system that will modify the way the mother

responds to the environment

Pregnancy is a unique immune condition that is modulated, but not suppressed.

This unique behavior explains why pregnant women respond

differently to the presence of

microorganisms or its products.

1. ALLOGRAFT PARADIGM; TRANSPLANTATION VERSUS

IMPLANTATION

The immunology of pregnancy is the result of the combination of signals and responses originated

from the maternal immune system and the fetalplacental immune system.

The signals originated in the placenta will modulate the way the maternal immune system behave in the

presence of potential

dangerous signals

Integrational view of the

immune system during

pregnancy.

a) The old model conceives

the maternal immune

system as the major

player in response to the

fetus and microorganism

b) New integrational

2. CYTOKINE SHIFT

This theory postulates that pregnancy is an anti-inflammatory response

Implantation and placentation resemble an open wound that requires a strong inflammatory response

Blastocyst has to break through the epithelial lining of the uterus to implant, damage the endometrial tissue to invade

Invasion by the trophoblast endometrium and myometrium to secure an adequate placentalfetal blood

An inflammatory environment is required to secure the adequate repair of the uterine epithelium and the

removal of cellular debris which is responsible for

morning sickness

Three stages of interaction.

1) Recruitment : Trophoblast sends signals to recruit

immune cells towards the implantation site

2) Education: trophoblast influence the differentiation

of immune cells.

3) Response:

factors produced by

trophoblast-educated

immune cells support

placental formation

and function

.

Each stage of pregnancy is characterized by a unique

inflammatory environment.

The 1st and 3rd trimesters are pro-inflammatory (TH1),

whereas the 2nd trimester represents an anti-inflammatory

phase also known TH2 environment

The second immunological phase of pregnancy is the optimal time for the mother.

This is a period of rapid fetal growth and development.

The mother, placenta and fetus are symbiotic, and the predominant

immunological feature is induction of an anti-

inflammatory state.

During the last immunological phase of pregnancy, the fetus has completed its development

All the organs are functional and prepared for the external world.

Now the mother needs to deliver the baby

this is achieved through renewed inflammation.

Parturition is characterized by an influx of immune cells

into the myometrium to

promote recrudescence of

an inflammatory

Active Protection of the Trophoblast

Against Viral Infection

The trophoblast, the cellular unit of the placenta Recognizes microorganisms

Initiates an immune response

May also produce anti-microbial peptides and, therefore, actively protect itself against pathogens

Interlukin (IFN- and SLPI) production by trophoblast cells, in response to a viral infection at

the maternal-fetal interface, prevents placental

transmission of viral infection to the fetus during

pregnancy

MotherPlacentaFetus: A Complex Response to Infection

Fetal inflammatory response syndrome (FIRS) is a condition where, despite an absence of cultivable

microorganisms, neonates with placental infections have

very high circulating levels of inflammatory cytokines,

such as IL-1, IL-6, IL-8 and TNF-.

Cytokines have been shown to affect the CNS and the circulatory system

The presence of FIRS increases the future risk for autism, schizophrenia, neuro-sensorial deficits and

psychosis induced in the neonatal period

There is evidence that the fetal immune response may predispose to diseases in adulthoo

IMMUNO-COMROMISED STATE

IN PREGNANCY

Nutrition deficiency vitamins, mineral

Infection bacterial, virus, fungal

Inflammation SLE, Rheumatoid arthritis, psoariasis

Malignancy

Drugs cytotoxic agent,

Radiation

NUTRITIONAL DEFICIENCY

Pregnancy obviously results in an increased need for vitamins and minerals.

Deficiency or excess of any of a number of nutrients can lead to birth defects and/or

complications during pregnancy

A nutritional deficiency occurs when the body

doesnt absorb the necessary amount of a nutrient.

Nutrition during pregnancy may be a cause of weakening of the immune system.

Inadequate intake all the essential nutrients, vitamins and minerals in optimal amounts become susceptible to many illnesses and infections.

Weakened immune system become prone to different infection and may develop more serious illnesses.

The symptoms and signs of such conditions generally depend on the very disease.

Folic acid helps prevent neural tube birth defects, which affect the brain and spinal cord

Calcium can help prevent from losing her own bone density, as the baby uses calcium for its

own bone growth.

Iron helps blood -- in both the mother and baby -- carry oxygen.

Content of Prenatal vitamins

400 micrograms (mcg) of folic acid.

400 IU of vitamin D.

200 to 300 milligrams (mg) of calcium.

70 mg of vitamin C.

3 mg of thiamine.

2 mg of riboflavin

20 mg of niacin.

6 mcg of vitamin B12.

10 mg of vitamin E.

15 mg of zinc.

17 mg of iron.

INFECTION IN PREGNANCY

Sexually transmitted

disease

Syphilis

Gonorrhoea

Genital herpes

Chlamydia

HIV

Non sexually transmitted

disease

Cytomegalovirus (CMV)

Rubella

Chicken pox

Toxoplasmosis

Viral hepatitis

Listeriosis

Bacterial infections

Pregnancy does not alter womans resistance to infection

The severity and the onset infection in pregnancy, correlates positively with its effect to

the fetus

Indirect effect

Reducing the oxygenation of the placental blood

Altering nutrient exchange thro the placenta

Direct effect

Depends on the ability of the micro-organism to penetrate the placenta and infect the fetus

Exception is Rubella, CMV and herpes simplex infection congenital defects

Most common infections that occur during pregnancy, such as those of the skin and

respiratory tract, cause no serious problems.

However, some infections can be passed to the fetus before or during birth and damage the

fetus or cause a miscarriage or premature birth.

How a Viral Infection Affects the

Fetus and the Pregnancy Outcome ?

Viral infections which are able to reach the fetus by crossing the placenta might have a detrimental effect on

the pregnancy.

It is well accepted that some infection will lead to embryonic and fetal death, induce miscarriage or induce

major congenital

However, even in the absence of placental transmission, the fetus could be adversely affected by the maternal

response to the infection.

An association between viral infections and preterm labor, and fetal congenital anomalies of the central

nervous system and the cardiovascular

Some viral infections may be asymptomatic

Approximately of all preterm deliveries are associated with histologic evidence of inflammation of

the placenta, termed acute chorioamnionitis (or chronic

chorioamnionitis)

A placental infection that is able to elicit the production of inflammatory cytokines will activate the maternal

immune system and lead to placental damage and

abortion or preterm labor

The placenta and the fetus represent an additional immunological organ which affects the global response

of the mother to microbial infections

AUTOIMMUNE DISEASE

..autoimmune disorders occur when our very own

immune systema complex system to begin withbegins to attack our body.

For women who have an autoimmune disease and subsequently become pregnant, pregnancy

can induce amelioration of the mothers disease, such as in rheumatoid arthritis, while

exacerbating or having no effect on other

autoimmune diseases like systemic lupus

erythematosus

Symptoms of an autoimmune disease could improve, worsen, or remain unchanged when a

woman becomes pregnant depending upon her

specific autoimmune disease

The Role of Estrogen

in the Immune System ??

The endocrine system is a target for autoimmune diseases eg pancreas, thyroid

Scientists believe that the female hormone estrogen may be the reason for this.

Estrogen may interplay with certain immune factors that enhance the action of the inflammatory response,

increasing antibodies that attack certain tissues in the

body.

Other studies have shown that during their reproductive years, when estrogen levels are higher, females tend to

have a more vigorous immune response

Some of known Autoimmune disease

Autoimmune Disease

SLE

Rheumatoid arthritis

Multiple sclerosis

Graves disease

Hashimoto thyroiditis

Chron disease

Auoimmmune haemolytic anaemia (AHA)

Idiopathic thrombocytopenia

Affected area

Most tissue,DNA,platelet

Cartilage and joint

Brain and spinal cord

Thyroid

Thyroid

GIT

RBC membrane

Platelet

Most autoimmune diseases, however, do not improve during pregnancy.

A woman with SLE typically has an unpredictable disease course and is at

increased risk for several obstetric complications

(preterm labor, fetal death).

Autoimmune responses in the mother may also target the fetus when autoantibodies cross the

placenta, such as neonatal lupus syndrome

(NLS) and neonatal thyrotoxicosis.

MALIGNANCY IN PREGNANCY

Cancer is the second most common cause of death in women of reproductive age,

complicating between 0.02% and 0.1% of all

This prevalence will likely rise as women are delaying pregnancy until later in life, when the

risk of developing cancer increases.

The most common malignancies associated with pregnancy include breast cancer, cervical

cancer, malignant melanoma, and lymphoma

There is almost always a conflict between optimal maternal therapy and fetal well-

being.

The maternal interest is for an immediate treatment of the recently diagnosed tumor.

Consequently, either maternal or fetal health, or both, will be compromised

Pregnant women with cancer need to be treated in the same fashion as women who are not pregnant, including

receiving chemotherapy, radiation, and surgery, all of

which might be teratogenic to the fetus

Administration of cytotoxic drugs during the second and third trimesters poses minimal hazard to developing

fetuses.

Even when chemotherapy is given in the first trimester, children might be born healthy and have normal

neurodevelopment.1

1. Avils A, Neri N. Hematological malignancies and pregnancy: a

final report of 84 children who received chemotherapy in utero.

Clin Lymphoma. 2001;2(3):1737.

CONCLUSION Placental immune response and its tropism for specific

viruses and pathogens affect the pregnant womans susceptibility to and severity of certain infectious

diseases.

The generalization of pregnancy as a condition of general immune suppression or increased risk is

misleading and prevents the determination of adequate

guidelines for treating pregnant women during

pandemics.

There is a need to evaluate the interaction of each specific pathogen with the fetal/placental unit and its

responses to design the adequate prophylaxis or

therapy.

It is essential to evaluate the presence of maternal viral infections prenatally to prevent

long-term adverse outcomes for the child and

the mother.

Future studies are needed to develop useful biomarkers for viral infections during pregnancy

as a strategy of early detection and prevention

of fetal damage and maternal mortality.

To consider the possibility of placental infection when determining a response to emerging

infectious disease threats.

THANK KIU for your attention