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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.

INTRODUCTION

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.

Components of the immune system


Innate immune system
Response is non-specific

Adaptive immune system


Pathogen and antigen specific response

Exposure leads to immediate maximal response


Cell-mediated and humoral components No immunological memory Found in nearly all forms of life

Lag time between exposure and maximal response


Cell-mediated and humoral components Exposure leads to immunological memory Found only in jawed vetebrates

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

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.

INTRODUCTION

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.
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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 fetal placental 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 antiinflammatory 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 antiinflammatory 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 with begins 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 wellbeing. 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