Congenital infection
Timing of transmission In-utero Shortly before or at delivery or postnatally
Neonatal infection
Route of infection
Time of presentation At birth or
months/years later First few weeks of life
– early-onset (<72 h) or late-onset (>72 h) infection
Months or years later
Examples
CMV Rubella Parvovirus VZV
Toxoplasmosis Syphilis Malaria (rare) TB (rare)
Group B streptococcus Gram-negative organisms Listeria monocytogenes Coagulase negative staphylococcus Chlamydia Gonococcus
HSV VZV Enterovirus
Candida Fungal HIV
Hepatitis B Hepatitis C HPV HTLV-1 Transplacental
Viral Others
Transplacental/birth canal/nosocomial/breast milk
Bacteria Viral
Fig. 11.1 Congenital and neonatal infections. (CMV – cytomegalovirus; VZV – varicellazoster virus; HSV – herpes simplex virus; HPV – human papilloma virus; HTLV‐1 – human T‐cell leukemia virus 1.)
Diagnosis (Table 11.1)
Table 11.1 Diagnosis of congenital infection.
Antenatal Postnatal
Maternal Infant
History (e.g. rash, ‘flu‐like’ illness, contact) Culture/PCR – blood, urine, CSF, stool, nasopharyngeal aspirate, saliva, skin lesions Screening serology – seroconversion (IgG, IgM, IgA),
or low avidity IgG to identify if infection was recent
CT or MRI head – for calcification, microcephaly Ophthalmologic assessment – for retinitis Culture/PCR of lesion, e.g. cervical herpes, blood,
urine
Paired serology – for comparison with maternal titers (IgG, IgM, etc.), but production of IgM may be delayed in the neonate
Fetal Placenta
Ultrasound or fetal MRI scanning for anomalies Histology/microscopic dark‐field examination for spirochetes in syphilis, culture/PCR Amniocentesis for fluid or fetal blood sample for
serology/platelet count/PCR PCR, polymerase chain reaction.
Key points
• Although clinicians sometimes refer to TORCH (toxoplasmosis, other, rubella, cytomegalovirus, herpes) screening, a range of different tests is required.
• Collect samples as soon as possible after birth to optimize chances of diagnosis.
Congenital infection 23
Clinical features
Congenital infections may precipitate pregnancy loss or preterm delivery. The clinical features of the symptomatic infant are shown in Fig. 11.2.
Congenital cytomegalovirus (CMV) infection
• Commonest congenital infection in the US and UK (0.5–1/1000 live births).
• 1–2% of mothers seroconvert during pregnancy.
• Overall mother‐to‐infant transmission rate is 40%.
• May be reactivated during pregnancy
• May be transmitted postnatally in breast milk or blood transfusions.
Infected infants
• 5–10% severely affected (Fig. 11.2). Poor prognosis for abnor- malities detectable on prenatal ultrasound/in utero MRI. These include significant intrauterine growth restriction (IUGR), central
nervous system abnormalities (including ventriculomegaly), renal abnormality and oligohydramnios. In infants, on postnatal CT or MRI scan, they include microcephaly and periventricular calcifica- tion (Fig. 11.4),
• 80–90% asymptomatic at birth, but 10–15% of them are at risk of sensorineural hearing loss.
• Most common infectious cause of sensorineural hearing loss.
Diagnosis
• Viral DNA (by PCR amplification) from amniotic fluid, fetal blood, or infant’s blood, urine, CSF or saliva collected at less than 3 weeks of age.
Treatment
For infants with CNS involvement, antiviral therapy with oral val- ganciclovir for 6 months has been shown to improve hearing and neuroevelopmental outcome in a randomized controlled trial.
Intrauterine growth restriction Intracerebral calcification
Hydrocephalus
Pneumonitis
Hepatomegaly Jaundice Hepatitis
Heart defects – cardiomegaly
– patent ductus arteriosus Microcephalus
Deafness
Splenomegaly
Bone abnormalities
Rash (see Fig. 11.3) Cataracts
Microphthalmia Retinitis
Anemia Neutropenia Thrombocytopenia
Fig. 11.2 The symptomatic infant.
Fig. 11.3 Blueberry muffin rash in rubella and sometimes CMV.
Key point
It is not possible to reliably differentiate between CMV, toxo- plasmosis, rubella or syphilis either by prenatal ultrasound or physical examination of the neonate.
Other points
• No vaccine yet for seronegative mothers.
• Infected infants may excrete CMV in urine for many months.
• All infected infants should be followed regularly for late‐onset sensorineural hearing loss until school age.
Congenital toxoplasmosis
• Usually after primary maternal infection in pregnancy.
• Seronegative mothers are most at risk from poorly cooked meat.
Small risk from handling feces of recently infected cats or ingest- ing contaminated soil from unwashed vegetables.
• The transmission rate and treatment are shown in Table 11.2 though this is controversial. The earlier in pregnancy the mother is infected the more severely the fetus is affected.
• The clinical features of the symptomatic infant are shown in Fig. 11.2. Subclinical disease includes retinitis (Fig. 11.5), epilepsy and learning difficulties.
• Treatment of infants with congenital infection – pyrimethamine and sulfadiazine plus folinic acid for prolonged duration.
Rubella
• Prevented by maternal vaccination. Now very rare in immunized populations.
• The earlier in pregnancy the mother is infected the more severely the fetus is affected.
• Clinical features are shown in Fig. 11.2.
• There is no effective treatment.
Congenital syphilis
In the US, a marked increase in incidence occurred in the 1980s, especially among drug users, but it has since declined. In the UK it is extremely rare. Antenatal screening on maternal blood is per- formed routinely. If active infection is diagnosed or suspected, the mother should be treated. Treatment more than 4 weeks before delivery prevents congenital infection.
• Transmission rate during primary infection in pregnancy is 100%.
• Without treatment there is 40% abortion/stillbirth/perinatal death.
• Prenatally, is associated with severe IUGR in developing countries.
• Clinical features are shown in Fig. 11.2. Those specific to con- genital syphilis include a characteristic rash and desquamation on the soles of the feet (Fig. 11.6) and hands (Fig. 11.7) and bone lesions (Fig. 11.8).
Table 11.2 Transmission rate and treatment of toxoplasmosis.
Trimester
Transmission
rate (%) Clinical features Treatment
First 15 35% die before birth,
40% severely affected
Preventative – maternal spiramycin if
<18 weeks
Second 40 90% subclinical
disease at birth;
clinical
manifestations may present years later
If severely affected – with antibiotics (pyrimethamine and sulfadiazine) and folinic acid
Question
Should babies with congenital CMV infection be isolated when on the neonatal unit?
No. About 1% of infants in newborn nurseries excrete CMV, but most are asymptomatic. Pregnant staff are potentially at risk, though most are immune. Attention to hand‐washing is the key to preventing infection of caregivers, and should be strictly adhered to when touching any baby.
Fig. 11.5 Retinitis from toxoplasmosis. This may present many years later.
Fig. 11.4 Postnatal CT scan of the brain showing intracranial calcifica- tion from congenital CMV infection. The calcification may be identified on antenatal ultrasound.
Congenital infection 25
• Treatment antenatally and/or postnatally is with penicillin.
Effectiveness of treatment is monitored serologically.
• If the mother has not received adequate treatment or if there is physical, laboratory or radiographic evidence of disease, treat. If there is any doubt, treat directly.
Varicella: chickenpox, varicella zoster virus (VZV) infection
Primary maternal infection in pregnancy is uncommon as more than 90% of mothers are immune.
Early in pregnancy
• Intrauterine infection is rare (2% risk).
• Can lead to eye and CNS damage, skin scarring (Fig. 11.9) and limb hypoplasia.
• 1% risk of herpes zoster (shingles) in infancy.
Late in pregnancy
Infants born to mothers who develop chickenpox between 5 days before or 5 days after delivery should be given varicella zoster immune globulin (VZIG). This reduces but does not eliminate the risk of neonatal varicella zoster virus (VZV).
They should be closely monitored, and should be started on aciclovir (intravenous) if any signs of infection develop.
Parvovirus B19
• 50% of pregnant women are susceptible to infection.
• Transmission rate is 20–30%.
• In most cases there is a normal outcome of pregnancy but rarely infection in pregnancy leads to severe fetal anemia (aplastic anemia), causing hydrops fetalis (edema and ascites from heart failure). Anemia is associated with an abnormally elevated middle cerebral artery velocity on Doppler ultrasound. Can lead to intrauterine death, but if identified and treated by intrauterine transfusion prognosis is usually good.
Fig. 11.6 Characteristic rash and desquamation on the feet in congenital syphilis. (Courtesy of Dr Hermione Lyall.)
Fig. 11.9 Skin scarring from maternal VZV infection early in pregnancy.
This is rare.
Fig. 11.7 Characteristic rash and desquamation on hands in congenital syphilis. (Courtesy of Dr Hermione Lyall.)
Fig. 11.8 X‐rays in congenital syphilis showing bilateral metaphyseal lucency of the long bones and destruction of the medial proximal metaphysis of the left tibia.
Neonatology at a Glance, Third Edition. Edited by Tom Lissauer, Avroy A. Fanaroff, Lawrence Miall and Jonathan Fanaroff.
© 2016 John Wiley & Sons, Ltd. Published 2016 by John Wiley & Sons, Ltd.
The transition from intrauterine to extrauterine life involves a complex sequence of physiologic changes that begin before birth.
Remarkably, although infants experience some degree of intermit- tent hypoxemia during labor, most undergo this transition smoothly and uneventfully. If not, cardiorespiratory depression requires prompt and appropriate resuscitation.
Physiologic changes in fetal–neonatal transition
• Before birth, the lungs are filled with fluid. Oxygen is supplied by the placenta. On reaching the right atrium, some of the oxygen- ated blood from the placenta flows directly to the left atrium via the patent foramen ovale, bypassing the lungs. This ensures that the most oxygenated blood goes to the heart and brain. In addition, the blood vessels that supply and drain the lungs are constricted (providing high pulmonary vascular resistance), so most blood from the right side of the heart bypasses the lungs and flows through the ductus arteriosus into the lower aorta (Fig. 12.1a).
• Shortly before and during labor, lung liquid production is reduced.
• During descent through the birth canal, the infant’s chest is squeezed and some lung liquid exudes from the trachea.
• Multiple stimuli (thermal, chemical, tactile) initiate breathing.
Serum cortisol, ADH (antidiuretic hormone), TSH (thyroid‐
stimulating hormone) and catecholamines dramatically increase.
• The first gasp is usually within a few seconds of birth. A negative intrathoracic pressure is generated to achieve this. Most lung liquid is absorbed into the bloodstream or lymphatics within the first few minutes of birth.
• Aeration of the lungs is accompanied by increased arterial oxygen tension; the pulmonary artery blood flow increases and the pulmonary vascular resistance falls.
• Contraction of the umbilical arteries restricts access to the low resistance placental circulation. This results in increased peripheral vascular resistance and an increase in systemic blood pressure.
• The fall in pulmonary vascular resistance and the rise in systemic vascular resistance result in near equalization of pressures across the duct and virtual cessation of ductal flow and also closure of the foramen ovale (Fig. 12.1b).
Abnormal transition from fetal to extrauterine life The transition may be altered by a variety of antepartum or intrapartum events, resulting in cardiorespiratory depression, asphyxia or both (Table 12.1).