Obstetric and perinatal infections During pregnancy tissues potentially

Obstetric and perinatal infections

During pregnancy, tissues potentially susceptible to infection -the placenta

The placenta - effective barrier: - protects the fetus from most circulating microorganisms - the fetal membranes shield the fetus from microorganisms in the genital tract. - Perforation of the amniotic sac, for instance, at a late stage of pregnancy, often results in fetal infection.

During pregnancy, certain infections in the mother can be more severe than usual latent viruses can reactivate and infect the fetus after delivery the raw uterine tissue is susceptible to pathogens, causing puerperal sepsis.

During pregnancy, certain infections in the mother can be more severe than usual : ◦ Malaria ◦ Hepatitis ◦ Influenza ◦ UTI. .

The fetus once infected via the placenta, is highly susceptible, but may survive certain pathogens and develop congenital abnormalities; examples include: Rubella, CMV, Toxoplasma gondii and Treponema pallidum. Maternal genital HSV infection cause more serious neonatal disease and is underreported. TORCH: -Toxoplasma -Rubella -CMV(Cytomegalovirus) -Herpes -Others (Sy: Syphilis)

The fetus Bacteria from the vagina, such as -group B streptococci, can cause neonatal septicemia, meningitis and death, and a birth canal infected with -Neisseria gonorrhoeae or Chlamydia trachomatis inoculates the infant to cause neonatal conjunctivitis.

Maternal HIV infection : ◦ abortion ◦ prematurity ◦ low birth weight ◦ If no prophylaxis is applied up to 40% of infants are infected(In resource-poor countries or where maternal infection is undiagnosed) -about one-third in utero -two-thirds perinatally: - from maternal blood - milk

Maternal blood: ◦ hepatitis B (HBV) ◦ hepatitis C(HCV) milk can be a source of HTLV-1 (human T-cell lymphotropic virus type 1)

INFECTIONS OCCURRING IN PREGNANCY Immune and hormonal changes during pregnancy worsen or reactivate certain infections The fetus may be considered as an immunologically incompatible transplant that must not be rejected by the mother. Reasons for the failure to reject the fetus include: the absence or low density of major histocompatibility complex (MHC) antigens on placental cells a covering of antigens with blocking antibody subtle defects in the maternal immune responses.

INFECTIONS OCCURRING IN PREGNANCY The picture is further complicated when there is malnutrition, which in itself impairs host defenses by weakening immune responses, decreasing metabolic reserves and interfering with the integrity of epithelial surfaces.

The fetus has poor immune defenses Once the fetus is infected, it is exquisitely susceptible because: Ig. M and Ig. A antibodies are not produced in significant amounts until the second half of pregnancy There is no Ig. G antibody synthesis Cell-meditated immune responses are poorly developed or absent, with inadequate production of the necessary cytokines.

Most microorganisms have sufficient destructive activity to kill the fetus once it is infected, leading to spontaneous abortion, or stillbirth. They can interfere with fetal development or cause lesions so that a live but damaged baby is born.

CONGENITAL INFECTIONS Intrauterine infection may result in -death of the fetus or -congenital malformations

After primary infection during pregnancy certain microorganisms enter the blood, establish infection in the placenta, and then invade the fetus. The fetus sometimes dies, leading to abortion, but when the infection is less severe, as in the case of a relatively non-cytopathic virus, or when it is partially controlled by the maternal Ig. G response, the fetus survives. It may then be born with a congenital infection, often showing malformations or other pathologic changes.

After primary infection during pregnancy The infant is generally small and fails to thrive. It produces specific antibodies, but often, for instance with CMV, fails to generate an adequate virus-specific cell-mediated immune response, remaining infected for a long period. Hence, the lesions may even progress after birth. It is a striking feature of these infections that they are generally mild or unnoticed by the mother.

Important causes of congenital infections Viruses that induce fetal malformations (i. e. act as teratogens) share certain characteristics with other teratogens such as drugs or radiation. The fetus tends to show similar responses (e. g. hepatosplenomegaly, encephalitis, eye lesions, low birth weight) to different infectious agents, and the diagnosis is difficult on purely clinical grounds. Most of these infections, HSV, rubella, CMV and syphilis, can also, at times, kill the fetus. They generally follow primary infection of the mother during pregnancy, so their incidence depends upon the proportion of non-immune females of childbearing age.

Routine antenatal screening rubella antibody, treponemal antibody (which includes syphilis, yaws, pinta or bejel, which cannot be identified individually by serology), hepatitis B surface antigen and HIV antibody These tests help identify women who are infected with hepatitis B or HIV, infected or have been exposed in the past to treponemal infections, the most important of which is syphilis in this setting, or are susceptible to rubella. Toxoplasma antibody

Routine antenatal screening rubella antibody: ELISA Rubella Ig. G /Ig. M If positive: avidity test treponemal hepatitis HIV antibody: RPR/TP-PA B surface antigen antibody

Routine screening programs lead to clinical management issues for both the mother and child. For example, HIV diagnosis will lead to consideration of -antiretroviral therapy for the mother and, immediately on birth, -the child, offering a caesarean section delivery, and -advising against breast-feeding to reduce the risk of vertical transmission. In addition, the child will then be followed-up for at least 12 months using sensitive tests to determine whether HIV has been transmitted vertically.

Routine screening programs lead to clinical management issues for both the mother and child. Diagnosis of chronic hepatitis B infection will result in determination of the maternal level of infectivity, and subsequently offering an accelerated course of hepatitis B vaccine alone or, if the mother is highly infectious, vaccine and HBV-specific immunoglobulin (HBIG) to the baby. In addition, there antiviral drugs for chronic hepatitis B that might be offered, together with long term follow-up, to the mother.

Routine screening programs lead to clinical management issues for both the mother and child. Rubella susceptible women are offered rubella immunization postnatally. Women found to have been exposed to treponemal infection in pregnancy are offered antibiotic treatment and the baby is followed-up for the first year using serology to identify active infection, as congenital syphilis can result from earlier untreated infection of the mother In the case of CMV, which is not part of routine antenatal screening, a primary infection, reinfection or reactivation of the latent virus during pregnancy, can lead to fetal infection.

The likelihood of fetal infection is increased when the mother develops a poor immune response, when the concentration of infectious agents in her blood is high (primary or secondary syphilis, e antigen positive hepatitis B carrier, HIV), or in a primary infection.

Maternal mumps, influenza or poliovirus infection during pregnancy: no good evidence for harmful effects in the fetus Human parvovirus: fetal damage or death in 5 -10% of cases following maternal infection in early pregnancy. severe anemia with ascites and hepatosplenomegaly (hydrops fetalis) the virus infects progenitor erythroid stem cells. Intrauterine exchange blood transfusion is used to manage hydrops fetalis.

Congenital rubella The fetus is particularly susceptible to rubella infection when maternal infection occurs during the first 3 months of pregnancy At this time, the heart, brain, eyes and ears are being formed and the infecting virus interferes with their development. If the fetus survives, it may show certain abnormalities

Organ involvement and effects in congenital rubella

Congenital rubella Not all fetuses are affected detectable congenital defects were seen: 15. 3% in the first month 24. 6% in the 2 nd month 17. 5% in the 3 rd month 6. 5% in the 4 th month.

Congenital rubella can affect the eye, heart, brain and ear Fetal rubella Ig. M is found in cord and infant blood Congenital rubella is completely preventable by vaccination

RUBELLA Vaccination live attenuated virus vaccine : MMR (mumps, measles and rubella) Contraindication: Pregnancy to vaccination, Safe time during reproductive life is the immediate postpartum period.

Antirubella Ig. G antibodies should be quantitative and ≥ 10 IU/ml shows immunity

CMV Primary maternal infection during pregnancy: ◦ 40% of fetuses are infected ◦ 5% of these show signs at birth. CMV reactivation during pregnancy in women previous CMV exposure, : with ◦ Fetal damage is then uncommon. As many as 1 -2% of infants born in the USA are infected, and up to about 10% of these are symptomatic, with up to 1 million infectious doses of virus present per ml of urine. However, the incidence of congenital CMV infection is likely to be an underestimate worldwide.

Congenital cytomegalovirus infection Microcephaly with associated severe psychomotor retardation and hepatosplenomegaly

Clinical features of congenital CMV include mental retardation, spasticity, eye abnormalities, hearing defects, hepatosplenomegaly, thrombocytopenic purpura and anemia Deafness and mental retardation may not be detectable until later in childhood. Diagnosis: CMV-specific Ig. M antibodies in infant blood (within 2 -3 weeks of delivery) CMV DNA in the blood or urine during this period.

Congenital syphilis As a result of routine serologic screening for syphilis in antenatal clinics and treatment with penicillin, congenital syphilis is now rare, but is more common in resource-poor countries. Clinical features in the infant include rhinitis (snuffles), skin and mucosal lesions, hepatosplenomegaly, lymphadenopathy, and abnormalities of bones, teeth and cartilage (saddle-shaped nose).

Congenital syphilis Pregnancy often masks the early signs of syphilis, but the mother will have serological evidence of treponemal infection, and treponemal Ig. M will be detected in the fetal blood. Vertical transmission most commonly takes place after 4 months of gestation, therefore treatment of the mother before the 4 th month of pregnancy should prevent fetal infection.

Diagnosis of congenital sy in the baby enzyme-linked immunosorbent SY Ig. M and Ig. G assays:

Congenital syphilis is completely preventable if women are screened serologically early in pregnancy (<3 months) and those who are positive are treated with penicillin.

Congenital toxoplasmosis Acute asymptomatic infection by Toxoplasma gondii during pregnancy can cause fetal malformation Approximately 35% of healthy adults have serological evidence of previous Toxoplasma gondii infection. Clinical features of congenital toxoplasmosis in the infant include convulsions, microcephaly, chorioretinitis, hepatosplenomegaly and jaundice, with later hydrocephaly, mental retardation and defective vision There are often no detectable abnormalities at birth, but signs (e. g. chorioretinitis; generally appear within a few years.

Congenital toxoplasmosis Toxoplasma Ig. M Toxoplasma IGG Avidity test if Ig. G/Ig. M is positive PCR (in amniotic fluid)

Avidity A test carried out with spesific positive Ig. G test The strength the antibodies bind with their antigen and shown against being separated. As the antibody matures the avidity increases: Recent infection: Low avidity Past infection(more than 3 months ago): High avidity

Congenital HIV infection Most infections take place during late pregnancy or during delivery, transmission rates are reduced by lowering the HIV load by offering antiretroviral drugs during pregnancy, especially during the last trimester or during labor, ◦ carrying out an elective caesarean section ◦ avoiding breast-feeding. ◦

Congenital HIV infection Ig. G antibodies present in the neonatal blood sample may be maternal in origin and can persist for at least 1 year. The mainstay of laboratory diagnosis therefore involves detection of HIV-1 proviral DNA or HIV-1 RNA by polymerase chain reaction (PCR), although these tests may not be positive until several months after birth,

Congenital and neonatal listeriosis Listeria monocytogenes small Gram-positive rod beta-hemolytic worldwide a great variety of animals including cattle, pigs, rodents and birds, and the bacteria occur in plants and in soil can grow at regular refrigeration temperatures (e. g. 3 -4°C) Transmission to humans is by: contact with infected animals and their feces consumption of unpasteurized milk or soft cheeses or contaminated vegetables.

Congenital and neonatal listeriosis the pregnant woman: mild influenza-like illness Asymptomatic but there is a bacteremia: which leads to infection of the placenta and then the fetus: abortion premature delivery neonatal septicemia The infant can also be infected shortly after birth, for instance from other babies or from hospital staff, and this may lead to a meningitic illness.

VZV Primary infection with varicellazoster virus (VZV) in the first 20 weeks of pregnancy can lead to limb deformities and other severe lesions in the newborn

Fetal infection with herpes simplex must be considered in a baby who is acutely ill within a few weeks of birth HSV generalized infection and severe CNS involvement. Approximately 80% of mothers with primary HSV infection (only about 10% with recurrent HSV) have cervical lesions and about a third of their infants are infected. Babies <4 weeks of age may present with neonatal HSV as acutely ill and 'septic' but classically there are three well-defined clinical presentations.

Treatment could be started at the same time as samples are collected for HSV DNA detection that include swabs of the vesicles, if present, EDTA whole blood samples and cerebrospinal fluid. Morbidity and mortality rates are higher in those with encephalitis and disseminated disease. Gonococci , chlamydia or staphylococci can infect the eye to cause ophthalmia neonatorum. Infection with group B streptococci generally occurs at this time.

Gonococcal ophthalmia neonatorum Signs appear 2 -5 days after birth. The inflammation and edema are more severe than with chlamydia infection

In countries with high hepatitis B carrier rates, maternal blood is a major source of infection during or shortly after birth. More than 90% of infants from carrier mothers become infected and then carry the virus. This is preventable by giving the vaccine plus specific immunoglobulin to the newborn. Hepatitis C, in contrast, is not usually transmitted in this way, and <5% of children with carrier mothers are infected. Human milk may contain rubella virus, CMV, human T-cell lymphotropic virus (HTLV) and HIV. Virus titers are generally low and, except in the case of HTLV and HIV, milk is not thought to be an important source of infection. However, it makes sense to pasteurize milk in human milk banks, just as we pasteurize cows' milk.

Puerperal sepsis After delivery (or abortion), a large area of damaged vulnerable uterine tissue is exposed to infection. Puerperal sepsis (childbed fever) was a major cause of maternal death in Europe in the 19 th century.

Puerperal sepsis Group A beta-hemolytic streptococci nose, throat or skin of hospital attendants Other possible organisms include anaerobes such as Clostridium perfringens or Bacteroides, E. coli and group B streptococci and originate from the mother's own fecal flora.

During the first 1 -2 weeks of life Staphylococci from the noses and fingers of adult carriers staphylococcal conjunctivitis or 'sticky eye‘ skin sepsis in the neonate, and sometimes the staphylococcal 'scalded skin' syndrome due to a specific 'epidermolytic' staphylococcal toxin. Handwashing aseptic techniques.

Poor hygienic in resource-poor countries Clostridium tetani usually because instruments used to cut the cord are contaminated with bacterial spores It can be prevented by immunizing mothers with tetanus toxoid

Tetanus. Risus sardonicus in a newborn infant.

During pregnancy, certain infections can be more severe than usual, and there can be reactivation of certain persistent infections A few infections are able to pass to the fetus via the placenta and cause damage. These infections are generally mild or subclinical in the mother (rubella, CMV, toxoplasmosis), but this is not always the case (syphilis) Once infected, the fetus may die, but more importantly may survive and be born with the infection (HIV, toxoplasmosis), often showing characteristic malformations (rubella, syphilis) Infection of the infant during birth or shortly afterwards can cause local disease (conjunctivitis due to gonococci or chlamydia) or occasionally severe life-threatening illness (E. coli meningitis, herpes simplex virus or group B streptococcal infection) Life-threatening bacterial infection of the mother via the postpartum uterus (puerperal sepsis) used to be common but is now rare in resource-rich countries.