INFECTION AND PREGNANCY LOSS 
Vol 2. No. 9 


by 
Jacob Tangir, M.D. 

Resident
Yale University School of Medicine
Yale-New Haven Hospital

 

Infectious agents has been long recognized as a cause for spontaneous abortion and perinatal mortality (the perinatal period is from the 22nd week of pregnancy to the 28th day after birth). Scientific understanding of this phenomenon has helped in developing effective preventive measures and treatment for many of these infection. It is important for pregnant women to know the basic mechanism of infections that can potentially affect pregnancy outcome, and how to prevent them. 
In general there are three major mechanisms that an infectious agent can affect pregnancy outcome: ascending infections, transplacental infection and infections acquired through the birth canal.  
Ascending infections occur when microorganisms residing in the external genitalia of the pregnant women gain access to the amniotic sac. This event can debilitate the sac and eventually rupture it. The infectious agent then will spread over the amniotic fluid. At this point the fetus can become infected by aspirating the microorganisms to the lungs, by swallowing them or by penetration to the ear canal. Also the inflammatory reaction on the amniotic sac triggered by the infection could initiate labor. 
In cases of transplacental infection the mother must have the infection along with presence of circulating microorganisms in blood. Then they penetrate the placenta and affecting its well functioning and could also invade the fetus. 
Some microorganisms cannot ascend to the amniotic sac nor cross the placenta barrier. They colonize the female external genital tract. However during the delivery the fetus will contaminate by exposure to maternal blood and secretions at the birth canal. 
Other less common routes of neonatal infection include breastmilk, infections acquired in neonatal intensive care units, nurseries etc. 
In terms of the timing, any microorganism that seriously affect the fetus or the mother in the first 20 weeks of pregnancy can cause fetal death and subsequent spontaneous abortion. If the infection occurs between 20 and 37 weeks it can cause preterm labor and delivery. Preterm delivery is associated with low-birth-weigh infants and with increase complication as well as neonatal mortality. Finally, infants that acquire infections during passage through the birth canal can develop neonatal infections and in some cases it spread to produce sepsis and death during the first days of life. 
The following section is a brief review of common infection that can complicate pregnancy outcome. Preventive measures and treatment will also be discuss when appropriate.
 

SYPHILIS: 
 Syphilis is a sexually transmitted disease caused by a microorganism called Treponema pallidum. The incidence of syphilis had been declining since the 1950s after the introduction of penicillin therapy. However, there was an increase in the incidence of in the United States that peaked in 1990 and has slowly decreased since then. Many investigators have reported a strong association of maternal syphilis with drug abuse, lack of prenatal care and race.  
  
 The syphilis infectious agent readily crosses the placenta and infects the fetus causing congenital syphilis. Usually there are multiple fetal internal organs affected like lungs, liver, spleen and pancreas. The frequency of congenital syphilis varies depending on the duration and stage of the maternal infection. Fetus born to mothers with recent infection (primary or secondary) are more likely to be infected that from mothers with latent disease. 
 The complications of untreated syphilis are well described in reports from the pre-antibiotic era. Approximately two third of the cases will be complicated by perinatal death, preterm labor and intrauterine growth retardation. Approximately 40% to 50% of the neonates will have symptomatic congenital syphilis with a variety of symptoms and damages. More recently, an observational study from a large medical center attending inner city population showed a rate of 18.4 cases of congenital syphilis per 10000 births. There were 34% of stillborn and preterm labor was significantly more common than in non affected pregnancies. The resultant perinatal mortality rate in that series was 464 per 1000. 
 Fortunately syphilis is relatively easy to diagnose and to treat if there is adequate prenatal care. Usually the diagnosis is made by demonstrating specific antibodies in serologic testing (obtained from blood sampling), The most common tests is called VDRL. Because of the devastating effects of congenital syphilis and the effectiveness of the treatment, every pregnant woman should have a VDRL test. 
 Syphilis is effectively treated with penicillin. Pregnant women with syphilis and allergic to penicillin should undergo inpatient desensitization to be able to get treatment with penicillin.
 

TOXOPLASMOSIS 
Toxoplasmosis is an infection caused by a protozoan known as Toxoplasma gondii. It is widely distributed in nature and the domestic cat is a very common host. Approximately one third of the adult women in the USA have toxoplasma antibodies which indicates prior infection. Toxoplasma is acquire by eating undercooked meat of animal containing infective tissue cysts or by inhaling or ingesting the microorganism excreted in the feces of domestic cats. It is also transmitted from mother to fetus. It has been shown that transmission to the fetus occur almost only when women acquire the infection during pregnancy. Conversely, women that has been infected before being pregnant have virtually no risks of transmitting the disease to their offspring. One exception is the immunocompromised patients including mothers infected with HIV. 
 Acute toxoplasma infection goes undetected in approximately 90% of cases. The signs and symptoms are so minor and unespecific that patients usually don’t seek medical attention. When symptomatic, acute toxoplasmosis presents with fever, malaise and adenopathy, mostly in head and neck. 
 Transmission of toxoplasma to the fetus can cause abortion or infected fetuses with congenital toxoplasmosis. Approximately 50% to 60% of fetuses whose mothers acquire the infection during the pregnancy will be affected. Three quarter of them will be asymptomatic but will show sequelae later in life. Congenital toxoplasmosis can cause Chorioretinitis, hydrocephalus and microcephalus. Congenital infection is more common after maternal infection during the third trimester but the sequelae less severe. 
 Serology (presence of antibodies against toxoplasma on the serum) is the best method for diagnosis of maternal toxoplasmosis. Unfortunately the inaccuracy of available tests and the low prevalence of acute toxoplasmosis in pregnancy makes routine screening not recommended in the USA. In other countries where maternal toxoplasmosis is a more common disease, routine screening during prenatal visits is mandatory. The American College of Obstetrics and Gynecology recommends that if serologic screening is considered in women of reproductive age, the best time to perform it will be prior to pregnancy. If there is presence of specific antibodies it will indicate prior infection and maternal immunity that will avoid congenital disease. However this approach is not helpful in cases of absence of antibodies prior to conception. Other authors in the USA have advocated for a routine serological screening suggesting that congenital infection is much more common problem and is being under detected because of the lack of routine prenatal testing. 
 In cases where the diagnosis of acute toxoplasma infection is made early in pregnancy, therapeutic abortion has been recommended. Another alternative is treatment with antibiotics. Spiramycin has been widely used in Europe for this purpose. It reduces the frequency of maternal transmission in about 60%. This antibiotic is not currently approved by the FDA for this use in the USA. However, it is available to physicians through the FDA on a case-by-case basis. Combination of other drugs might be more effective but also more Teratogenic in the first trimester.
 

RUBELLA 
Also known as German measles is a disease caused by a virus. In not pregnant women and general population it is a disease of little consequences. It is contagious and could present with fever, rash and neck adenopathy, especially post auricular lymph node enlargement. A large number of cases will present without symptoms. Epidemics of rubella have virtually disappeared in developed countries because of routine vaccination during childhood. 
 In the USA, however, it is estimated that 6% to 25% of women are still susceptible. It has been well documented that rubella acquired during pregnancy has devastating effects to the fetus. One published series of mother who acquired rubella during pregnancy showed that 4% had spontaneous abortion and another 2% had stillbirths. Of the fetus that survived, all of them whose mother were infected before the 11th week had congenital defects but only 36 percent when the infection occurred after the 13th week.  
 The clinical manifestation of congenital rubella varies depending on the timing of maternal infection and the stage of fetal development. It could include eye lesions resulting in blindness, heart diseases, deafness, lung abnormalities, chromosomal abnormalities etc. 
 The main preventive measure is vaccination. However, it is not currently recommended shortly before or during pregnancy because the vaccine is made of live viruses. Therefore it is very important to establish presence of antibodies (which indicates prior infection) in all women of reproductive age before pregnancy. In cases where antibodies are present it will be extremely rare for the mother to infect a fetus if re-exposed. If antibodies could not be demonstrated, vaccination is mandatory. The person should not get pregnant for the next three months. 

MEASLES 
Measles is a viral disease very contagious and common during childhood. It has become a rare disease in developed countries because of routine vaccination during childhood. It usually manifests as fever, malaise, rash, pharingitis and conjunctivitis. It could be more complicated in adults and about 3% will develop pneumonia. Pregnant women does not appeared to have a more complicated course. 
 There are not conclusive studies about the effects of the virus on the fetus probably because of the rarity of the disease on pregnancy . There is consensus, however in that measles can cause an increase rate of abortion and premature. In a recent report of 58 pregnancies complicated by measles, 50% of them ended within 14 days of the onset of measles rash. That included five spontaneous abortion and 11 preterm deliveries. The virus does not appear to be Teratogenic, meaning that fetuses that survived will not have an increased risk of malformations.  
 Measles that is apparent in the first 10 days of life is considered congenital. The mortality rate in those cases is around 30%. The mortality rate in premature infants with congenital measles is approximately 50%. 

PARVOVIRUS  
Human parvoviruses are a group of viruses from which the most common is the B19. It causes a disease known as fifth disease , erythema infectiosum or roseola infantum. It is more common in children, very contagious and generally mild. It could be asymptomatic or present with facial rash (slapped cheek appearance), fever and malaise. In adults rash is not present usually and more commonly will present with fever, arthralgias and adenopathy. In the United States, 50% to 75% of women in reproductive age are immune with antibodies in serum. 
 In cases of primary infection during pregnancy parvovirus B19 can be transmitted to the fetus through the placenta. Fetal infection can cause spontaneous abortion, intrauterine fetal death, fetal anemia and hydrops fetalis. It is not clear, however how frequent this complications will occur. There are a number of series published in the literature showing cases of fetal loss associated with B19 infection but in most of them, the rate of pregnancy loss among women infected during pregnancy was not significantly higher than the normal population. 
 The current recommendation is that women exposed to parvovirus during pregnancy should be screened for presence of antibodies. If IgG is present, meaning prior infection, she can be reassured. If IgG is absent and IgM (reflects acute infection) is also absent, she is susceptible, therefore should reduce the risks of exposure. This is especially important in day care workers and school teachers. If IgG is absent and IgM is present, the mother should be followed closely with serial ultrasounds to detect earlier any fetal abnormality, including hydrops. 

VARICELLA 
 Varicella-zoster virus causes chickenpox. The disease is common in childhood and most adult women are already immune because of previous infection. There are reports that suggest that chickenpox could be especially severe in pregnancy. Pneumonitis, a serious complication, could present more frequently in pregnant women with chickenpox than in non-pregnant affected adults, thus increasing the chances of fetal complications. 
 It is well documented that maternal chickenpox during the first 20 weeks of pregnancy will cause congenital varicella syndrome in about 2% of the cases. This syndrome is characterized by fetal malformations, typically bony defects and scarring in limbs, chorioretinitis, hydronephrosis etc. 
 There has been cases of spontaneous abortion and fetal death after 20 weeks secondary to in-utero varicella infection but it is rare. In a series of 1373 pregnant women with chickenpox, only 1 case of spontaneous abortion at 16 weeks and one case of fetal death at 23 weeks could be proved to be related to in-uterus varicella infection.  

CYTOMEGALOVIRUS 
 Cytomegalovirus (CMV) is a virus that infects about 80% of the population. After the primary infection the virus becomes latent and periodically is reactivated, meaning that there is not effective lifetime immunity after the first infection. Cytomegalovirus infection is a serious health problem only in immuno-supressed people and in fetuses and newborns. 
 Most infections are asymptomatic and in only about 15% of the cases the person will present mononucleosis type symptoms. 
 CMV can be transmitted to the fetus via the placenta and also through the birth canal, since CMV could infect the uterine cervix. There are no reports that suggest that CMV infection in-uterus can cause spontaneous abortion or fetal death. CMV, however can cause congenital cytomegalovirus infection which produces devastating effects in newborns and their family. The syndrome includes intracranial calcifications, chorioretinitis low birthweight resulting in blindness, deafness and mental retardation. It could also cause neonatal death. 
 It is estimated that 0.5% to 2% of all neonates are infected. From those 5% to 10% could have neurologic sequelae. Severe disease thus will occur in 1 every 10000 to 20000 newborns. It has been shown that only fetuses from mothers with primary infection are at risk for severe sequelae, in approximately 25% of those cases. It also more common if the infection occur during the first trimester than in subsequent trimesters. Newborns exposed in utero to recurrent infection has a minor risk of having sequelae and probably have no risk of developing mental retardation. 
 Unfortunately there is no treatment to maternal infection nor there is a way to prevent fetuses to become infected once the mother acquires the infection. While there is ongoing investigation to develop an effective vaccine, the only effective way to reduce this public health problem is by prevention. Most experts will recommend that women in reproductive ages should have their CMV-antibody status determined. This will show if a person has been already infected in which case the risk of having a baby with significant sequelae will be very low in the event of a new infection during a pregnancy. Women who are CMV-seronegative and therefore susceptible to primary infection should be counseled. Once they become pregnant they should avoid contact with urine and saliva from infants and practice careful hygiene. Minimize sharing of glasses and other utensils and avoid sexual contact with a partner with evident mononucleosis like infection, since CMV can also be transmitted sexually. 
 If a primary infection is documented during pregnancy and/or if fetal abnormalities consistent with CMV congenital infection are found, therapeutic termination of the pregnancy should be considered. 

LISTERIOSIS 
Listeriosis is caused by a bacteria called Listeria monocytogenes. Listeria is usually a food-borne pathogen, often found in contaminated, poor or non-pasteurized dairy products. It can also be isolated from soil, water, sewage and human feces.  
 Listeriosis is a rare but catastrophic complication of pregnancy. The infection could presents without symptoms or as a febrile illness that could be confused with influenza or other infectious diseases. Listeria infection in the mother is spread hematogenously (through the blood) to the uterine cavity and the fetus. Although there is no data showing the percentage of fetuses that will be affected, not all fetuses will be infected during maternal Listeriosis. 
 The diagnosis is made by isolation of the bacteria in maternal blood, amniotic fluid, placenta or from the fetus in case of fetal infection. Maternal Listeriosis will cause a high incidence of second and third trimester pregnancy losses. The mortality of a neonate born with congenital Listeriosis is around 50%. 
 There is now scientific evidence that treating the mother with antibiotic combinations intravenously may prevent perinatal mortality.  

SALMONELLOSIS 
Salmonella is a bacteria commonly found contaminating poultry and egg products. Is a major cause of food poisoning, characterized by diarrhea, abdominal pain, cramping, fever etc. Usually is a self-limited infection, requiring no antibiotic treatment.  
There are two major groups of salmonella species: typhy and non-typhoid. Salmonella typhy could spread through the blood and cause a more serious disease known as Typhoid. In pregnant women typhoid could cause pregnancy loss in around 80% of the cases if not treated with appropriate antibiotics. The diagnosis is made by isolation of the bacteria in blood or stools or by serologic testing. 
The incidence of pregnancy losses caused by non-typhoid salmonella is probably much less. However there is no data in the literature to fully illustrate the effect of this specie in pregnancy. 

SHIGELLOSIS 
Shigella is another relatively common cause of food poisoning, characterized by bloody stools, abdominal cramping and general toxicity. Like the majority of the salmonellosis, is a self-limited infection and does not require antimicrobial treatment. The main risk that shigellosis cause in pregnant women is by producing dehydration and electrolyte imbalances secondary to intense secretory diarrhea. 

LYME DISEASE 
Lyme disease is caused by a spirochete that is transmitted by the bite of ticks. Initially the disease is localized, causing a characteristic skin rash and a influenza-type illness and lymph node enlargement. If not treated, the infection may affect other organs like the heart, joints and central nervous system. 
The diagnosis is usually made on clinical findings. Serologic testing (presence of specific antibodies in serum) is also useful. Lyme disease is usually treated with antibiotics with better results if treated earlier. 
The consequences of Lyme disease in pregnancy are not totally known. There are a few case reports of women acquiring Lyme disease during pregnancy resulting in dead fetuses. In these reported cases the spirochetes were isolated from different fetal organs, suggesting that Lyme disease may had a role in those pregnancy loss. More recently, however, a larger series of pregnant women in an area endemic for Lyme disease showed that maternal infection was not associated with fetal death, preterm deliveries or malformation. 
Until more conclusive date is available, preventive intervention, specifically against tick bites, is the best way to avoid Lyme disease.  

HEPATITIS: 
Hepatitis, meaning inflammation of the liver, can occur as result of many different insults to the liver. Here we will focus on hepatitis caused by viruses infection, which is in general the most common form of hepatitis. 
Viral hepatitis is also the most common liver disease in pregnant women. Currently there are five different viruses that can cause hepatitis: A, B, C, D and E. In this discussion we will include the most common ones: Hepatitis A and B 
Hepatitis A is usually benign in well nourished people. The main aspect during the disease is to rest and being able to maintain a good nutrition. There is no data suggesting that Hepatitis A increases the risk of spontaneous abortion more than any other febrile diseases. Nor it increases the risks of fetal malformation. There may be a slightly higher risk of preterm labor during an acute maternal infection. 
The major impact on the mother and fetus could be caused by Hepatitis B. There is no clear evidence that the Hepatitis B virus could be transmitted through the placenta to the fetus. The major mechanism of fetal infection, however, appear to be ingestion by the newborn of infected maternal blood and fluids during the delivery.  
Approximately 80 to 90 percent of newborns of mothers who develop acute hepatitis B in the third trimester will acquire the virus. A small percentage of these will develop fulminant hepatitis and die during the first few months. Another small group may not get infected. The rest, about 80%, will become chronic carries and will be at a higher risk of developing cirrhosis and liver cancer. 
The incidence of spontaneous abortion in first trimester patients with acute hepatitis B is increased. When it occurs during the third trimester there is also an increased incidence of preterm labor. Teratogenic effect has never been demonstrated. 

GONORRHEA 
Gonorrhea, a disease caused by a bacteria known as Neisseria gonnorheae, is a relatively common sexually transmitted disease. Most of the times the infection is limited to the genitals, especially the cervix. In women gonorrhea could be asymptomatic, hence the importance of routine screening especially in pregnant women.  
If the infection is not diagnosed and treated, it increases the risks of spontaneous abortion most likely secondary to cervix inflammation during the first trimester. It also increases the risks of preterm labor and infections of the uterine cavity. 

HIV: 
Transmission of human immunodeficiency virus (HIV) from mother to infant is now well established. Possible routes of transmission include the placenta, by contact of contaminated fluid and blood during the delivery, and post-natally in association with breast feeding. It is not clear however the frequency of each of these mechanism. Approximately 10% to 40% of infants born to sero-positive women will become infected. The average in most series is about 30%. The majority of infants with congenitally acquire HIV will die within the first two years of life. 
Initially it was thought that HIV infection did not interfere with the pregnancy outcome. Recently, however, a report of a series of HIV infected mother showed an increase rate of spontaneous abortion. The rate was higher in mothers that already developed the acquired immunodeficiency syndrome (AIDS) than in asymptomatic mothers. 
The rate of HIV transmission during pregnancy can be successfully diminished with anti-retroviral therapy. Treatment with Zidovudine starting between 18 to 34 week and continued until delivery can decrease the percentage of infected newborns to below 10%. Some authors also recommend delivery by cesarean section to avoid contact of the fetus with contaminated blood and fluid during passage through the birth canal. Breast-feeding should also be avoided because of virus transmission through breast milk. 

HERPES 
Herpes Simplex Virus (HSV) has become one of the most common sexually transmitted disease. The first episode known as the primary infection is usually more sever . Is characterized by multiple fluid-filled lesion in the genitalia associated with extreme pain and discomfort. Is also commonly associated with flu-like symptoms. After the first episode, the virus stays latent and the person remain without symptoms. The recurrences are typically milder and shorter. 
Unfortunately, the benefit of currently known anti-virals is to shorten the active episode but the virus cannot be totally eliminated. 
Transmission of HSV from mother to fetus could have catastrophic consequences. The virus is rarely transmitted through the placenta. The fetus almost always acquires it by passage through the birth canal; or the virus my ascend through ruptured membranes and contaminate the fetus.  
If the herpetic neonatal infection is localized, the outcome is generally good. However in disseminated neonatal infection the mortality is around 50% to 60%. Interestingly the risks of neonatal infection are approximately 50% in cases in which the mother has a primary infection; versus approximately 5% during recurrent infections.  
The evidence of the effect of herpes infection in the pregnancy outcome is controversial. A number of reports have suggested that first-episode infection is associated with some increased risk of spontaneous abortion. However these result are not being reproduced in a several other investigations. There is more agreement in that it increases the risk of premature delivery in the range of 30% to 50%. There is no data to suggest bad pregnancy outcome as a results of recurrent infection.  
If herpes infection is diagnosed during labor, the current recommendation is to deliver by cesarean section. This is to avoid further contact of the newborn with contaminated maternal tissue. It has been recently shown that treating mothers known to have had herpes in the past with Acyclovir (an antiviral ) from the 36th week until delivery will effectively reduce the recurrences, neonatal infections and avoid cesarean sections. 

CHLAMYDIA: 
Lower genital tract infection with Chlamydia trachomatis is currently the most commonly diagnosed sexually transmitted disease. It has been estimated that 20 to 40% of sexually active women in the United States has been infected with chlamydia.  
 The infection can be asymptomatic. It could also caused muco-purulent vaginal discharge and pain. When untreated, it could ascend to upper genital organs and cause Pelvic Inflammatory disease (PID). PID is rare in pregnancy but when it occurs, it can cause pregnancy loss in approximately 50% of the cases. Chlamydia and Gonorrhea are the two most common causes of PID. 
 The effects of chlamydia infection on the newborn are well characterized. Usually if the mother’s genital tract is colonized, he newborn will acquire the infection during the delivery. Conjunctivitis will develop in up to 50% of infected newborns. This complication could potentially lead to blindness if not treated. Ten to 20% will develop pneumonia. 
 What is more debatable is the role of maternal chlamydial infection in the pregnancy outcome. Some reports suggested that chlamydial infection is strongly associated with spontaneous abortion, preterm labor and uterine infection. However there are also investigations that were unable to prove any relationship. More recently it has been shown that only women with evidence of recent infection were at a higher risk of developing premature rupture of membranes and preterm labor. 
 Under current obstetrical practices all pregnant women are routinely checked for chlamydia infection early in the pregnancy. If the culture results are positive treatment with antibiotics is prescribed. 

MYCOPLASMA: 
 Mycoplasma species that colonize the female genital tract include M. hominis and Ureaplasma urealyticum. These microorganism are probably sexually transmitted. They have been cultured from the genital tract in 15% to 75% of sexually active women, being more prevalent in women with more sexual partners. 
 Mycoplasma colonization has been suggested, not without controversy, as a cause of recurrent spontaneous abortion, stillbirth and preterm delivery. Several studies have found mycoplasma in fetal material in significantly larger numbers of spontaneous abortion compared to induced abortion. Similarly several investigators have reported a higher incidence of genital colonization with mycoplasma in women experiencing repetitive spontaneous abortion compare to normal women. These results may suggest an association between mycoplasma genital colonization and spontaneous pregnancy loss. 
 These studies, however are not conclusive enough to establish that mycoplasma has indeed infected the fetus causing its death; it is also possible that the fetus dies from other causes and then becomes more susceptible to be infected by ascending microorganisms. Mycoplasma has also been implicated as a cause of preterm birth. However a recent multi-center report showed that mycoplasma colonization was not correlated with preterm labor, preterm delivery or low birth-weight infants. Similarly, studies investigating the role of routine mycoplasma cultures and even empirical treatment with antibiotics before pregnancy in women with recurrent pregnancy loss have not consistently found to be beneficial. 
 The presence of genital mycoplasma does not appear to cause serious newborn illnesses, even after contact during the birth process. 
 In summary, current scientific data does not support the hypothesis that mycoplasma colonization of the genital tract increases risk of pregnancy loss; nor it recommends routine cultures for mycoplasma or treatment with antibiotics.  
  
GROUP B STREPTOCOCCAL INFECTION: 
Group B Streptococcus (GBS) is a bacteria that commonly colonizes the female genital tract. Between 10 to 30% of pregnant women are colonized with GBS in the vaginal or rectal area. Unfortunately this organism has been recognized as cause of illnesses and death in newborn infants and in parturient women. 
 In the pregnant women GBS can cause urinary tract infection, infection of the uterine cavity, especially after a cesarean section, as well as infection of the surgical wound. In newborns GBS is responsible for infection of different organs (meningitis, pneumonia, cellulitis etc.) that can spread to cause sepsis and death. The risk of sepsis in the United States is about 1.8 per 1000 live birth. The mortality rate is between 5% to 20%.  
 Early reports have suggested that GBS genital colonization was associated to an increase risk of stillbirth, preterm rupture of membranes, and premature deliveries. However data to support this association has been inconsistent. What is more accepted is the association between GBS bacteriuria (presence of the bacteria in urine) and preterm delivery. Bacteriuria is an indicator of heavy genital colonization. In other words, women that are heavy colonized with GBS are at a higher risk of preterm delivery. Women lightly colonized are probably at the same risk than women not colonized. The main route of neonatal contamination thus is the passage through the birth canal. Also important is through ruptured membranes that allow ascending of the bacteria to the uterine cavity. 
 Besides being heavily colonized, there are other risk factors that influence in the rate of newborn GBS infection. These risk factors include rupture of membranes for more than 18 hours before delivery, preterm birth and maternal chorioamnionitis (infection of the uterus and pregnancy related tissues).  
Fortunately, GBS are very susceptible to antibiotic therapy. The main issue is to whom and when to give it in order to prevent neonatal infection. 
Several national agencies have developed guidelines to administer antibiotic to pregnant women close to or in labor. These are basically based on the presence of risk factors. It is well establish that timely administration of antibiotics to colonized women will effectively prevent neonatal complication as well as postpartum infections. draft 

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