Maternal Infection During Pregnancy

Maternal Infection During Pregnancy

Maddalena Morlando1 and Baskaran Thilaganathan2

1 Prenatal Diagnosis and High Risk Pregnancy Unit, Department of Women and General and Specialized Surgery, University “Luigi Vanvitelli”, Naples, Italy

2 Fetal Medical Unit, St George’s University of London, London, UK

Perinatal infections continue to affect pregnancies in the UK and worldwide. Most perinatal infections are asymptomatic in the mother, but may have serious consequences for the fetus. Pregnant women are exposed to infections prevalent in the community but they are also likely to reside with young children and this represents a significant additional factor in exposure to infectious agents. Most infections in pregnancy resolve spontaneously without therapy or are readily treated with antimicrobial agents. Such infections usually have no effect on the developing fetus. However, the infecting organism may invade the bloodstream and subsequently infect the placenta and fetus. Transplacental spread and invasion of the bloodstream after maternal infection is the usual route by which the fetus is infected. Uncommonly, the fetus may be infected by extension of infection into adjacent maternal tissues and organs, including the peritoneum and the genitalia, during delivery, or as a result of invasive procedures, such as the use of monitors, chorionic villous biopsy, sampling of fetal blood and intrauterine transfusion. Before rupture of fetal membranes, organisms in the genital tract may invade the amniotic fluid and infect the fetus. These organisms can invade the placenta through microscopic defects in the membranes, particularly in devitalized areas overlying the cervical os.

Microorganisms of concern include those identified in the acronym TORCH: toxoplasmosis, rubella, cytomegalovirus, and herpesvirus; the ‘O’ in TORCH originally stood for ‘other infections’. A new acronym should include other well‐described causes of in utero infection: syphilis, hepatitis B, HIV and parvovirus. The UK screening programme for infectious disease in pregnancy advocates routine screening for HIV, hepatitis B, rubella and syphilis. The policy and standards are agreed by the National Screening Committee and published in the National Institute for Health and Care Excellence (NICE) antenatal care guidelines [1]. The prevalence of all four of these infections is still significant in the UK and particularly in inner cities such as London [2] (Table 13.1) and therefore routine antenatal screening is essential to prevent mother‐to‐child transmission of hepatitis B, HIV and syphilis. The screening programme also identifies women for whom postnatal MMR (measles, mumps, rubella) vaccination could protect future pregnancies. The programme stipulates the following.

  1. All pregnant women are offered screening at the booking visit for rubella antibody, syphilis, HIV and hepatitis B as an integral part of their antenatal care during their first and all subsequent pregnancies regardless of immunization history.
  2. Although every woman has the right to decline screening, if screening has been declined at booking, it should be re‐offered at 28 weeks’ gestation.
  3. Pregnant women arriving in labour who have not received antenatal care elsewhere are offered screening for infectious diseases. Priority is given to hepatitis B and HIV screening and presumptive action is taken on a preliminary positive result until the result is confirmed. If an HIV test result is not available, appropriate preventive measures should be offered. In cases where consent for screening is withheld during labour, screening is offered again after delivery.
  4. If there is a screen‐positive result, the current national standards state a second sample should be taken for syphilis, hepatitis B and HIV to confirm the screening result. Following this result the women should be referred for specialist counselling and appropriate follow‐up and management [3].

Table 13.1 Prevalence of infections in London (data based on annual reports).

Infection Prevalence (%) 2011–2012 Prevalence (%) 2012–2013 Prevalence (%) 2013–2014
Syphilis 0.3 0.3 0.3
Hepatitis B 1.1 1.5 0.9
HIV 0.4 0.7 0.3
Susceptibility to rubella 5.1 5.9 6.5

Human immunodeficiency virus

The human immunodeficiency virus type 1 (HIV‐1) pandemic remains one of the greatest public health challenges in the 21st century. The care of HIV‐infected women is more effective than ever and the rates of mother‐to‐child transmission of HIV are lower than ever in communities with access to therapy. Because of widespread implementation of routine antenatal screening for HIV, antiretroviral therapy (ART) during pregnancy, elective caesarean section and avoidance of breastfeeding, transmission of HIV‐1 from mother to child is now a rare occurrence in the UK. However, mother‐to‐child transmission of HIV still represents the most common source of HIV infection among infants and children. In 2014, there were an estimated 103 700 people living with HIV in the UK. The prevalence of HIV in the UK among those aged 15–44 years in 2014 was estimated to be 1.7 per 1000 women. The HIV epidemic remains largely concentrated among gay, bisexual men and men and women of black African ethnicity [4,5].

Pathogenesis and transmission

HIV is a retrovirus that infects and damages T lymphocytes, resulting in immunosuppression and eventually leading to AIDS. Two types of HIV viruses, HIV‐1 and HIV‐2, can cause AIDS in humans. HIV‐1 and HIV‐2 are lentiviruses belonging to the Retroviridae family and have a complex genomic structure [6]. The commonest and most virulent form is HIV‐1, with HIV‐2 being relatively uncommon in Western countries.

HIV can be transmitted through sexual contact or via contaminated blood, for example needle sharing. Mother‐to‐child transmission of HIV can occur in utero, during labour and delivery, or postnatally through breastfeeding. In utero transmission may occur through HIV infection in the placenta or fetal exposure to cell‐free or cell‐associated HIV in the amniotic fluid. Intrauterine transmission occurs in about 20–25% of infections and mostly occurs during the last few weeks before delivery when the vascular integrity of the placenta is disrupted. Intrapartum transmission may occur because of direct exposure of the fetus to infected maternal secretions during birth. Although numerous maternal, obstetric, infant, host genetic, and viral factors may modify perinatal HIV transmission risk, maternal plasma HIV RNA level is the strongest predictor of intrauterine and intrapartum transmission. Other maternal risk factors associated with higher rates of perinatal HIV infection include women with advanced clinical disease, acute HIV infection during pregnancy, and low CD4+ counts. Obstetric risk factors associated with increased risk of transmission include vaginal delivery, prolonged rupture of membranes, chorioamnionitis and invasive obstetric procedures.

In the absence of interventions, postnatal transmission of HIV through breastfeeding can account for one‐third to half of all HIV infections globally and carries an estimated transmission risk of about 15% when breastfeeding is prolonged. Risk factors for breast‐milk HIV transmission include women seroconverting during lactation, high HIV DNA or RNA level in maternal plasma and breast milk, low maternal CD4+ cell count, maternal symptomatic disease or AIDS, prolonged duration of breastfeeding, mixed infant feeding, oral lesions in the infant, abrupt weaning and maternal breast problems.


In England, the routine offer and recommendation policy was implemented in 2000, and similar policies were subsequently adopted elsewhere in the UK. National uptake of antenatal HIV screening was reported to be 95% in 2008. Between 2000 and 2004 the majority of HIV‐infected women diagnosed before delivery were identified through antenatal screening. However, by 2011, over 80% of women diagnosed before delivery were already aware of their infection before they conceived, many of them diagnosed in a previous pregnancy. Pregnant women should be offered screening for HIV infection at their booking appointment because appropriate antenatal interventions can reduce mother‐to‐child transmission of HIV infection. If screening has been declined at booking, it should be offered again at 28 weeks’ gestation. Pregnant women arriving in labour who have not received antenatal care elsewhere should be offered screening for HIV. If an HIV test result is not available, appropriate preventive measures should be offered. In cases where consent is withheld for screening during labour, screening is offered again after delivery [5].


If there is a primary laboratory screen‐positive result (positive ELISA), the samples are referred for testing by a specialist laboratory to confirm the reactivity is specific for HIV (by Western blot) involving at least two further independent assays. Obtaining a CD4 count and a viral load provides the clinician with a useful snapshot of the patient’s status and medication needs when she is first encountered. All women who have confirmed positive test results should be counselled in person and offered specialist counselling and support, which is also available for their partners and family if requested. Women found to be positive are referred for specialist HIV treatment within a multidisciplinary framework. This would involve advice about management of their infection and interventions to reduce the risk of vertical and sexual transmission, including discussions on the use of antiretrovirals and caesarean section, early treatment and care for the child, and decisions about breastfeeding. It also provides an opportunity to reinforce health promotion advice and to discuss arrangements for partner notification and testing of previous children. HIV‐positive results also need to be accessible to members of staff at all times to inform appropriate clinical care, particularly in the delivery suite when the woman arrives in labour. It is also important to ensure that a paediatric care plan is determined prior to the birth to ensure the mother understands and has consented for testing and potential treatment regimens after delivery.

ART has been shown to significantly reduce the rate of vertical transmission. Zidovudine chemoprophylaxis given in the prenatal and intrapartum period and to the newborn reduces vertical transmission from 27.7 to 7.9% [7]. However, zidovudine monotherapy is considered inappropriate in mothers with high viral load or low CD4 counts because it fails to suppress viral replication and increases the risk of development of viral resistance. The British HIV Association [5] recommend the use of combination ART in order to achieve prolonged viral suppression when treatment is indicated, with the aim of reducing the viral load to below detectable levels, and recommend that HIV infection in pregnant women should be treated as infection in non‐pregnant patients. It is therefore recommended that advanced HIV infection in pregnant women should be treated with combination ART, which through more complete suppression of viral replication allows greater and prolonged recovery of immune function. Women requiring ART for their own health should commence treatment as soon as possible, while all pregnant women should have commenced ART by week 24 of pregnancy. Zidovudine monotherapy can be used in women planning a caesarean section who have a baseline viral load of less than 10 000 HIV RNA copies/mL and a CD4 count above 350 cells/μL.

For women with a plasma viral load of less than 50 HIV RNA copies/mL at 36 weeks, and in the absence of obstetric contraindications, a planned vaginal delivery is recommended. Where the viral load is 400 HIV RNA copies/mL or more at 36 weeks, elective caesarean delivery is recommended. Where the indication for caesarean section is the prevention of vertical transmission, delivery should be planned at 38–39 weeks’ gestation. Intrapartum intravenous zidovudine infusion is recommended for women with a viral load above 1000 HIV RNA copies/mL presenting in labour, or with ruptured membranes or who are admitted for planned caesarean section; for untreated women presenting in labour or with ruptured membranes in whom the current viral load is not known; and in women on zidovudine monotherapy undergoing elective caesarean section.

Neonatal post‐exposure prophylaxis (usually oral zidovudine) should be commenced very soon after birth, certainly within 4 hours and should be given for 4 weeks. All mothers known to be HIV positive, regardless of ART and infant prophylaxis, should be advised to exclusively formula feed from birth.

Hepatitis B

Hepatitis B is an infection of the liver caused by the hepatitis B virus (HBV). Many new infections with hepatitis B are subclinical or may manifest as a flu‐like illness. Jaundice only occurs in about 30–50% of adults. The UK is a very low prevalence country, but prevalence of HBsAg varies across the country. The prevalence rates found in antenatal women vary from 0.05 to 0.08% in some rural areas but rise to 1% or more in certain inner city areas. Overall, the prevalence in antenatal women in the UK is around 0.14%. The incidence of acute infection is high among those with certain lifestyle or occupational risk factors. Most reports of acute infection in the UK occur as a result of injecting drug use or sexual exposure [8].

Pathogenesis and transmission

HBV is a well‐characterized, partially double‐stranded DNA virus. The virus is transmitted by parenteral exposure to infected blood or body fluids. Transmission mostly occurs through vaginal or anal intercourse, as a result of blood‐to‐blood contact (e.g. sharing of needles and ‘needlestick’ injuries) or through perinatal transmission from mother to child.

The incubation period ranges from 40 to 160 days (average 60–90 days). Current infection can be detected by the presence of HBsAg in the serum. Blood and body fluids from HBsAg‐positive individuals should be considered to be infectious. In most cases, infection will resolve and HBsAg disappears from the serum, but the virus persists in some patients who become chronically infected. Chronic hepatitis B infection is defined as persistence of HBsAg in the serum for 6 months or more. Individuals with chronic infection are referred to as chronic carriers. Among those who are HBsAg positive, those in whom hepatitis B e‐antigen (HBeAg) is also detected in the serum are the most infectious. Those who are HBsAg positive and HBeAg negative (usually anti‐HBe positive) are infectious but generally of lower infectivity. A proportion of chronically infected people who are HBeAg negative will have high HBV DNA levels, and may be more infectious. Around 20–25% of individuals with chronic HBV infection worldwide have progressive liver disease, leading to cirrhosis in some patients. The risk of progression is related to the level of active viral replication in the liver. Individuals with chronic infection, particularly those with active inflammation and/or cirrhosis, are at increased risk of developing hepatocellular carcinoma.

Perinatal transmission occurs at or near the time of birth because of exposure to cervical secretions and maternal blood. To a minor degree, transplacental transmission might be responsible for perinatal infections, depending on risk factors that include maternal HBeAg positivity, HBsAg titre, and HBV DNA level [6]. Mothers positive for HBeAg and mothers with very high serum DNA levels (e.g. 109 copies/mL) have the greatest risk of transmitting HBV to their offspring. Approximately 70–90% of mothers who are HBeAg positive will transmit the infection to the baby. The rate of transmission is approximately 10% in women with antibody to e antigen (anti‐HBe). Mode of delivery does not influence the likelihood of HBV transmission. Another possible route of HBV transmission is amniocentesis in HBsAg‐positive mothers. Although HBsAg can be detected in the breast milk of HBV‐infected mothers, several studies have shown that there is no additional risk of transmission of HBV to breastfed infants of infected mothers, provided that proper active and passive immunoprophylaxis is carried out.

Clinical manifestations

The clinical manifestations of HBV infection depend on the age of acquisition. The risk of chronic infection is greater than 90% in neonates, and observed in only 5% of adults exposed to HBV. Approximately 6% of infants born to mothers who are positive for anti‐hepatitis B early antibody develop acute hepatitis at 2 months of age. Infants are ill with fever, jaundice and hepatic tenderness. Serum aminotransferases are elevated, and there is active inflammation in the liver biopsy specimen. About one‐third of older children and adolescents with acute HBV develop these classic symptoms. Most infants, children and adolescents have chronic infection (lasting longer than 6 months) of the asymptomatic immunotolerant type. Inactive carriers are characterized by HBsAg positivity, seroconversion of HBeAg to anti‐hepatitis B early antibody, undetectable HBV DNA, and normal serum aminotransferases. Individuals with active hepatitis are at greatest risk for developing cirrhosis and hepatocellular carcinoma.


The diagnosis of HBV is most commonly made by the presence of HBsAg in the serum. UK guidelines recommend that all pregnant women should be offered screening for hepatitis B infection during each pregnancy. Confirmatory testing and testing for HBeAg of those mothers shown to be infected should follow. Where an unbooked mother presents in labour, an urgent HBsAg test should be performed to ensure that vaccine can be given to babies born to positive mothers within 24 hours of birth. Management of the infant should be based on the results of these markers and, if available, HBV viral load testing of the mother.


If a woman is screen‐positive for HBV, she should be referred to an appropriate specialist (hepatologist, gastroenterologist or infectious disease specialist) within 6 weeks of a positive result. There, she should be fully evaluated in terms of any acute management and arrangements made for appropriate postnatal vaccination of the baby. All babies born to these mothers should receive a complete course of vaccine on time. Babies born to highly infectious mothers (e.g. mother HBeAg positive; mother HBeAg positive and anti‐HBeAg negative; HBeAg unknown; acute hepatitis B during pregnancy; HBV DNA level ≥1 × 106 IU/mL) should receive hepatitis B immunoglobulin (HBIG) as well as active immunization. HBIG should preferably be given within 24 hours of delivery, and should be ordered well in advance of the birth. HBIG may be given simultaneously with vaccine but at a different site. There should also be discussion about testing of other family members. Notification of hepatitis B is a legal requirement.


Rubella, although usually causing a minor maternal illness, is one of the most teratogenic infections known. Fortunately, since the introduction of the rubella vaccine, the incidence of rubella and congenital rubella syndrome has decreased substantially. Universal immunization against rubella, using the measles, mumps and rubella (MMR) vaccine, was introduced in the UK in the October 1988. The aim of this policy was to interrupt circulation of rubella among young children, thereby protecting susceptible adult women from exposure. This led to a considerable decline in rubella in young children following the introduction of MMR, with a concomitant fall in rubella infections in pregnant women, from 167 in 1987 to one in 2003 [8]. However, recent data from Health Protection Agency national surveillance systems in the UK have reported a national increase in the number of women susceptible to rubella [3].

Pathogenesis and transmission

Rubella is caused by a togavirus and spread by droplet transmission. Following exposure to the virus via nasopharyngeal secretions, almost 80% of susceptible individuals become infected. Replication occurs in the nasopharynx and regional lymph nodes, and viraemia develops 5–7 days after exposure. Viraemia usually results in placental and fetal infection. The incubation period is 14–21 days, and in most cases a rash develops 14–17 days after exposure. Individuals with rubella are infectious from 1 week before symptoms appear to 4 days after the onset of the rash.

Clinical manifestations

Rubella is a mild disease. There may be a mild prodromal illness involving a low‐grade fever, malaise, coryza and mild conjunctivitis. Lymphadenopathy may precede the rash and usually involves post‐auricular and sub‐occipital glands. The rash is usually transitory, erythematous and mostly located behind the ears and on the face and neck. Clinical diagnosis is unreliable as the rash may be fleeting and is not specific to rubella. Complications include thrombocytopenia and post‐infectious encephalitis. In adults, arthritis and arthralgia may occasionally be seen after rubella infection.

Maternal rubella infection in pregnancy may result in fetal loss or in congenital rubella syndrome (CRS). CRS presents with one or more of the following:

  • cataracts and other eye defects;
  • deafness;
  • cardiac abnormalities;
  • microcephaly;
  • retardation of intrauterine growth;
  • inflammatory lesions of brain, liver, lungs and bone marrow.

Deafness is the most common and sometimes the only manifestation, especially when infection occurs after 16 weeks’ gestation. Cardiac defects include patent ductus arteriosus, pulmonary stenosis, septal defects and coarctation of the aorta. Eye defects include cataracts, microphthalmia, pigmentary retinopathy and glaucoma. Neurological problems include encephalitis, microcephaly, mental handicap and behavioural problems. Other abnormalities include hepatitis, splenomegaly, thrombocytopoenia and growth retardation. Diabetes mellitus occurs frequently in later childhood in those with CRS.

Infection from 8 to 10 weeks of pregnancy results in damage in up to 90% of surviving infants. The risk of damage declines to about 10–20% when infection develops between 11 and 16 weeks’ gestation [9]. The risk of fetal damage is small when infection happens after 16 weeks of pregnancy: only deafness has been reported following infections up to 20 weeks of pregnancy. Some infected infants may appear normal at birth but perceptive deafness may be detected later.


The diagnosis of rubella infection is usually based on serological analysis. Detection of rubella IgM indicates recent infection, although re‐exposure to rubella may induce a reappearance of low‐titre IgM. Following a primary rubella infection, IgM can be detected within 5–7 days and may persist up to 2 months. Specific IgG develops by 2 weeks and persists for life; re‐exposure may increase IgG titres temporarily. A history of exposure to, or possible recent infection with, rubella in early pregnancy is actively sought, particularly in recent immigrants, and the laboratory is informed of a suspicious history so that the appropriate tests for primary rubella infection (IgM and IgG avidity) are performed [10]. If the first specimen has detectable antibody and was obtained within 7–10 days of exposure, there is no risk of infection and further evaluation is unnecessary. Diagnosis of subclinical infection is straightforward if the woman is known to be susceptible, the exposure is recognized, and a serum sample is obtained approximately 28 days after exposure. The diagnosis of subclinical infection is more difficult if the immune status of the woman is unknown. It can be facilitated, however, if the acute‐phase serum specimen is obtained as soon as possible after a recognized exposure that did not occur more than 5 weeks earlier. Testing is considered unnecessary if there is documented evidence of two tests on different blood samples both confirming the presence of rubella‐specific IgG. Rubella immune status should be assessed at first prenatal care visit. Susceptible women should be counselled regarding prevention strategies and be vaccinated post partum.


The management of the pregnant woman exposed to rubella needs to be individualized and depends on when during gestation she was exposed and on her state of immunity. Confirming the diagnosis, counselling about the risks of infection of and damage to the fetus, and discussing all the available options, including the use of immunoglobulin and consideration of termination of pregnancy, require an understanding of the natural history and consequences of rubella in pregnancy. In the case of congenital infection, emphasis is on diagnosis and acute and long‐term management. Isolation may also be important to reduce spread of infection. There is no treatment for rubella and supportive care should be offered. Droplet precautions are recommended for 7 days after the onset of the rash. Human immunoglobulin is not routinely used for post‐protection from rubella since there is no evidence that it is effective. It is not recommended for the protection of pregnant women exposed to rubella, and should only be considered when termination of pregnancy is unacceptable.

There is no evidence that rubella‐containing vaccines are teratogenic. However, as a precaution, MMR vaccine should not be given to pregnant women. If MMR vaccine is given to adult women, they should be advised to guard against pregnancy for 1 month. Termination of pregnancy following inadvertent immunization should not be recommended. Pregnant women who are found to be susceptible to rubella should be immunized with MMR after delivery. Breastfeeding is not a contraindication to MMR immunization, and MMR vaccine can be given to breastfeeding mothers without any risk to their baby [8].


Despite the description of syphilitic infection for more than 500 years and availability of adequate therapy for more than 50 years, syphilis in the adult and neonate still represents a relevant issue for public health providers. The elimination of congenital syphilis from the UK was considered within the framework of the 2013 WHO guidelines for validating the elimination of mother‐to‐child transmission of syphilis. Diagnoses of infectious syphilis in reproductive‐age women fell from 268 in 2010 to 206 in 2013. The uptake of antenatal screening in England rose from 96.6% in 2010 to 97.9% in 2013. Despite the high antenatal screening coverage, concerns have been raised about the effectiveness of case management and control strategies [11].

Pathogenesis and transmission

Treponema pallidum, the causative agent of syphilis, is a Gram‐negative bacterium. Syphilis can be passed horizontally from person to person through direct contact, such as during sexual activity, resulting in acquired syphilis, or vertically from mother to baby, resulting in congenital syphilis. Because sexual contact is the most common mode of transmission for acquired disease, the sites of inoculation are usually the genital organs, but lips, tongue and abraded areas of the skin have been described as well. Such an entry point is identified as the site of the initial ulcerating sore, or chancre. The cervical changes associated with pregnancy, including ectropion, hyperaemia and friability, increase the risk of spirochaete entry. Local replication then occurs and lymphatic dissemination leads to the systemic findings of secondary syphilis. The incubation period averages 3 weeks (3–90 days) depending on inoculum load and host factors. Although transmission of syphilis to the fetus can occur throughout pregnancy, the likelihood of vertical transmission increases with advancing gestation. A newborn occasionally may be infected perinatally, by contact at delivery with an infectious lesion present in the birth canal or perineum. Postnatal transmission from mother to child is rare. The likelihood of vertical transmission is directly related to the maternal stage of syphilis, with early primary syphilis resulting in significantly higher transmission rates than late latent infection. Among pregnant women with untreated primary or secondary early syphilis, the rate of transmission is 60–100% but decreases with later stages of maternal infection to approximately 40% with early latent infection and 8% with late latent infection.

Clinical manifestations

Maternal syphilis infection is staged according to duration and clinical features. Primary syphilis is the initial stage and its characteristic lesion is an erosion called a chancre. It is a typical, indolent, well‐circumscribed, flat ulcer with a yellow‐coated base and an indurated non‐undermined wall. As it causes no symptoms and because of its location on the labia minora, within the vagina or on the cervix or perineum, it is often unrecognized. Two to ten weeks after the primary lesions, an infected woman may experience secondary disease: the time of systemic dissemination with involvement of many major organ systems. Of women with secondary syphilis, 90% have dermatological manifestations. The rash of secondary syphilis appears as rough, red or reddish‐brown spots mostly occurring on the palms, soles and trunk, where they tend to follow skin lines. Plantar and palmar maculopapular target‐like lesions are commonly seen. Patchy alopecia may result when hair follicles are involved. Mucosal lesions called mucous patches will develop in 35% of women. Systemic symptoms are commonly seen in secondary syphilis (70%), with generalized lymphadenopathy, fever, fatigue, weight loss, anorexia, pharyngitis, splenomegaly, sore throat, headache, myalgia and arthralgia (with a noticeable nocturnal pattern). The signs and symptoms of secondary syphilis usually resolve with or without treatment. However, without treatment the infection will progress to the latent stages of disease.

Latent syphilis is defined as the period after infection when patients are seroreactive but demonstrate no clinical manifestations of disease. Early latent syphilis is latent syphilis of less than 12 months’ duration. During this stage, 20–25% of women will relapse. Late latent syphilis is diagnosed after being asymptomatic for more than 12 months. The woman is still infectious during latent stages. Of untreated women, 20–30% will progress to tertiary syphilis. After 15 years, three‐quarters of infected subjects show evidence of tertiary syphilis, 50–80% of whom have cardiovascular complications. In 9% of untreated subjects the gummata of tertiary disease can be found: localized nodules that can have central necrosis. Approximately 15% of untreated infected subjects develop neurosyphilis in the tertiary stage. Mortality from untreated syphilis has been described to be about 8–14% [12].

Clinicians caring for pregnant women should be aware that any ulcer, regardless of location, that is painless, indurated and indolent and which fails to heal within 2 weeks needs exclusion of syphilis. Similarly, any generalized skin eruption, regardless of its morphology, should be viewed as secondary (disseminated) syphilis until proven otherwise.

The extent of damage to a fetus affected by congenital syphilis depends on the stage of development when infection occurs and the elapsed time before treatment. With infection early in pregnancy and in the absence of therapy, fetal demise or late‐term stillbirth occurs, but premature delivery or neonatal death may also occur. In liveborn infants, infection can be clinically recognizable or silent. When symptoms are present, congenital syphilis is characterized by the presence of hepatosplenomegaly, lymphadenopathy, rash, mucocutaneous lesions, haemolytic anaemia or thrombocytopenia, osteochondritis and pseudoparalysis, periostitis, rhinitis and central nervous system (CNS) involvement, all of which usually appear within the first 2–8 weeks of life.

Late congenital syphilis lesions represent the scars induced by initial lesions of early congenital syphilis or reactions to persistent and ongoing inflammation. They usually present after 2 years of life and often in early adolescence, and include Hutchinson teeth, mulberry molars, interstitial keratitis, healed chorioretinitis, secondary glaucoma (uveitis), corneal scarring, eighth nerve deafness, ‘saddle nose’, protuberant mandible, rhagades, mental retardation, arrested hydrocephalus, convulsive disorders, optic nerve atrophy, juvenile general paresis, cranial nerve palsies and sabre shins. Congenital syphilis can be prevented or treated in utero.


All pregnant women should have serological screening for syphilis at their first antenatal assessment. Tests should be repeated later in pregnancy if a woman has been at risk of infection after a negative initial screen. Diagnosis of syphilis in pregnant women is usually performed by a non‐treponemal serological screening test, with a treponemal serological test for confirmation. Non‐treponemal antibody tests consist of the rapid plasma reagin (RPR) and Venereal Disease Research Laboratory (VDRL) assay. Treponemal antibody tests are represented by treponemal enzyme immunoassay (EIA), treponemal chemiluminescent assay (CLIA), T. pallidum haemagglutination assay (TPHA) and fluorescent treponemal antibody absorption test (FTA‐abs).

An EIA/CLIA, preferably detecting both IgM and IgG, is the screening test of choice. Positive screening tests should be confirmed with a different treponemal test (not the FTA‐abs) and a second specimen for confirmatory testing obtained. A quantitative RPR or VDRL should be performed when screening tests are positive as it is recommended for monitoring the serological response to treatment. An initial RPR/VDRL titre above 16 usually indicates active disease and the need for treatment.

The diagnosis of congenital syphilis prenatally is difficult. Sonographic findings may include hydrops fetalis, hepatomegaly, placental thickening and hydramnios, but often the infected fetus will have a normal sonogram. Polymerase chain reaction (PCR) can be performed on amniotic fluid.


Treatment of pregnant women with congenitally transmissible syphilis can significantly reduce the risk of congenital syphilis, stillbirths, premature births, neonatal deaths and severe illness in infancy and beyond. The pregnant woman can also be treated to prevent progression of disease, as well as giving the opportunity of treatment for their sexual partners. Once a screen‐positive result is confirmed, the woman and her family should be referred to a specialist in genitourinary medicine for assessment, counselling and possible treatment.

Where syphilis is treated in the current pregnancy, particularly when this is early infection, maternal referral to fetal medicine is recommended when 26 weeks’ gestation has been reached prior to treatment. Fetal syphilis infection may be suggested by ultrasound detection of non‐immune hydrops or hepatosplenomegaly. Fetal assessment will help planning of antepartum care as well as neonatal treatment.

A single dose of benzathine penicillin G 2.4 million units is effective in most cases. Physiological changes in pregnancy alter drug pharmacokinetics and may cause reduced plasma penicillin concentrations. For this reason, when treatment is initiated in the third trimester, a second dose of benzathine penicillin is recommended 1 week after the first, with careful assessment of the neonate at birth. Up to 50% of women treated for early‐stage syphilis will have a systemic reaction called the Jarisch–Herxheimer reaction. Although transient with only mild constitutional symptoms, preterm labour and fetal distress may complicate treatment. The uterine contractions appear to occur secondary to the development of fever. Fetal heart rate decelerations are also reported, occurring in about 40%, concomitant with maternal fever, and resolve within 24 hours of maternal penicillin treatment.

After treatment, it may take several months to observe a fourfold drop in RPR/VDRL titre and in many pregnancies labour will occur before this period has elapsed. Hence, serological cure may not be demonstrable before birth of the neonate [13].

Sep 7, 2020 | Posted by in GYNECOLOGY | Comments Off on Maternal Infection During Pregnancy
Premium Wordpress Themes by UFO Themes