Whilst infections can occur in utero, birth represents an abrupt transition from a highly protected environment to exposure to a vast array of new pathogens ex utero. Parturition also places the baby in direct contact with maternal blood or genital secretions and infections may result, especially if there was prolonged or early rupture of membranes.

At birth, an infant's immune system remains immature. Some protection is provided by maternal antibodies (IgG) crossing the placenta. This process is less complete in the premature baby, especially if markedly premature. If a mother develops a new infection close to the time of birth, she may remain infectious and will not yet have produced any protective IgG, placing the infant at risk of a more severe form of the disease, as in the case of neonatal varicella.

Common neonatal infections

Skin Infection

Skin infections with Staphylococcus aureus are common. Periumbilical skin infections present a special risk because of the possibility of bacteria passing up the umbilical vein, causing thrombophlebitis and even a hepatic abscess. Infection appears as:

• Pustules - singly or in multiples, without associated redness, almost anywhere on the skin. They can cause a problem in the axillae or groin but rarely spread. They should be treated with antiseptic powder to prevent cross-infection.
• Bullous impetigo is less common but potentially far more serious. This presents as large pus-filled blisters that burst to form scabs. Where large areas of skin are involved, the condition is known as scalded skin syndrome. Treatment is with flucloxacillin, IV if necessary, and fluid replacement.
• Paronychia is infection of the nail fold and often involves more than one finger. It may produce pus. Treatment is with an antistaphylococcal cream.
• Acute mastitis is strictly an infection of subcutaneous tissue presenting with swelling, inflammation and fever. Treatment is with flucloxacillin and drainage of the abscess if needed.

An increasing problem is of methicillin-resistant S. aureus (MRSA). These organisms may be transmitted perinatally from the mother's skin or genital tract or nosocomially, particularly among premature or sick infants, or acquired in the community after discharge from hospital.²

Red eye

See separate article on Ophthalmia Neonatorum.

• Simple infective conjunctivitis is often caused by S. aureus, streptococci or Escherichia coli. Swabs should be taken for culture before treatment with a broad spectrum antibiotic, e.g. ofloxacin 0.3% qds.
• Infections that fail to respond fully may be caused by Chlamydia trachomatis passed on from the mother during delivery. Unilateral or bilateral watery discharge develops between 5 to 14 days following birth, becoming copious and purulent later on. Treatment is with tetracycline ointment or oral erythromycin.³
• Conjunctivitis caused by infection with gonorrhoea, acquired from the mother, is potentially sight-threatening. It presents with a purulent conjunctivitis, lid oedema and purulent discharge, typically 3-5 days after birth but sometimes later. There may be associated corneal ulceration and perforation. It is diagnosed by microscopy of pus.
• Neisserial and chlamydial infections are notifiable diseases.

Oral thrush

Candida albicans is a common commensal, but infection may affect the tongue and the rest of the mouth. It can spread to the gastrointestinal tract, causing diarrhoea and vomiting. It presents as a large number of firmly adherent, small, white plaques that may interfere with feeding by making the mouth sore. If the lesions are scraped with a tongue spatula, they will readily shift if they are only milk curds but thrush will be adherent. Treatment is with a topical antifungal such as nystatin suspension.

Viral infections

Congenital or perinatally-acquired viral infections (such as HIV and Hepatitis B and C) may present in the neonate, but symptoms can appear much later. See separate article Congenital HIV Infection and its Prevention. Maternal HIV should be diagnosed before delivery to enable Caesarean delivery and the avoidance of breast-feeding, where possible.⁴ Where a mother is known to be HBsAg positive, hepatitis B vaccine is started at 3 days and an accelerated schedule given to the infant.⁵ There is no hepatitis C vaccine currently available. Other viral infections that may occur perinatally include:

Herpes simplex

Neonatal herpes simplex virus (HSV) infection is rare (approximately 1-2/100, 000 deliveries) but devastating. It is acquired from the mother during vaginal delivery and mainly infects the eye, skin or mouth. It can also cause a systemic infection producing meningo-encephalitis with jaundice and hepatosplenomegaly, and sometimes bleeding.⁶ Neonates with HSV infection acquired perinatally have a 65% mortality rate (untreated), reduced to 25% with treatment. Diagnosis is by viral culture and treatment is with IV aciclovir.

Elective Caesarean section can reduce the risk of infant exposure to infected secretions during birth and has become the standard of care for women with symptomatic lesions. However, most neonatal infections occur with asymptomatic mothers, who are subclinically shedding virus. Studies suggest that giving pregnant women with primary genital herpes infection or recurrences, aciclovir from 36 weeks' gestation prevents recurrence and reduces the risk of peripartum HSV shedding, thereby reducing the need for Caesarean section. The best strategy for detecting pregnant women at risk of peripartum HSV shedding remains controversial and screening is not currently recommended. ⁷

Varicella zoster

Maternal infection in the perinatal period carries a risk of severe neonatal varicella, with a mortality rate of 30%. Approximately a quarter of neonates will develop clinical chickenpox if their mother develops chickenpox or shingles in the month before delivery. However, the highest risk of severe neonatal illness is where the mother develops infection from 5 days before delivery to 2 days afterwards.

Babies of mothers developing perinatal chickenpox from a week before to a week after birth⁸ should receive varicella-zoster immune globulin (VZIG) as it prevents clinically-apparent chickenpox in approximately half of neonates born to mothers with chickenpox around the time of delivery and reduces the severity where the disease is not prevented.⁹ If the baby has developed the varicella rash, VZIG is not helpful and treatment for neonatal chickenpox should be started with aciclovir.

Enteroviruses

• Coxsackie infection of type B appears as sporadic outbreaks in maternity unit with meningo-encephalitis and acute myocarditis.¹⁰
• Echovirus infection often presents with gastroenteritis but can affect any system, with symptoms that range from slight illness to severe sepsis. Usually no treatment is required but immunoglobulins can be used in severe cases.

Serious acute infections¹¹

The incidence of serious acute infections in neonates is around 2/1,000 live births but the figure rises to 8 to 9/1,000 in small babies weighing just 1,000 to 2,000 grams and 26/1,000 in those of less than 1,000 grams. Group B streptococcus (GBS) is the most frequent cause of severe early-onset neonatal infection in neonates and occurs in 0.5/1,000 UK births.

Of early-onset neonatal sepsis, 85% presents in the first 24 hours, 5% between 24 and 48 hours, and the remaining 10% over the next 4 days. Early-onset infections include GBS, E. coli, Haemophilus influenzae, and Listeria monocytogenes and are most likely to have been acquired transplacentally, by ascending or intrapartum infection.

Diagnosis is complicated by the lack of clear clinical features of infection and very poor localising features. The lack of an effective immune response in the neonate means that infection can spread, rapidly causing significant damage to organs

Serious neonatal infections include:

• Septicaemia:
  • In the early neonatal period, the most common organisms causing septicaemia are E. coli and GBS. Later, coagulase-negative staphylococci (frequently methicillin-resistant) predominate.
  • Blind treatment is with a penicillin plus gentamicin or cefotaxime/cefuroxime. Vancomycin plus gentamicin is used in late-onset sepsis if MRSA is found or suspected.
• Meningitis:
  • Typical signs found in older children or adults are not present in a small infant. There may possibly be a bulging fontanelle but this is unreliable and features such as Kernig's sign and neck stiffness are of no value.
  • There may depressed consciousness or convulsions.
  • If there is any doubt, a lumbar puncture should be performed, as failure to treat meningitis has such serious consequences.
  • The implicated organisms are totally different in the neonate from older patients. GBS and E coli are responsible for around two thirds of cases.
• Pneumonia:
  • This may be acquired through aspiration of the micro-organisms during the delivery process.
  • Infection causes pulmonary changes with infiltration, and destruction of bronchopulmonary tissue. Fibrinous exudation into the alveoli leads to inhibition of pulmonary surfactant function and respiratory failure with a presentation very similar to respiratory distress syndrome (RDS).
  • Differentiating RDS from infection in a premature baby can be very difficult. Segmental or lobar atelectasis, seen on chest X-ray, may occur in both.
• Urinary tract infection:
  • Symptoms are similar to the non-specific ones of other serious acute infections.
  • Diagnosis is by examination of a urine sample, if necessary obtained by suprapubic bladder aspiration.
  • Treatment should start immediately in the ill child, purely on clinical suspicion.
  • Use IV cefotaxime or an aminoglycoside with careful monitoring of blood levels.
  • After successful treatment, the urinary tract should be checked for congenital abnormalities.

Presentation

Signs and symptoms are often non-specific and investigation for possible infection should be started on minimum suspicion, as early treatment is essential.

Investigations

These should include:

• FBC. White count is very non-specific and platelets are often low in infection
• Blood culture from peripheral vein
• Urine culture
• Ear, nose and throat swabs
• Swabs from any obvious sites of infection
• Lumbar puncture should be used quite readily
• Chest X-ray with respiratory signs
• U&Es
• Blood gases

Prognosis

Serious neonatal infection has a bad prognostic implication for neuro-development and delay is common.¹⁴ This is especially so if the infant is premature. The inflammatory mediators may have an important role in neurotoxicity. There may also have been hypoxia. Oxygen therapy has to be monitored very carefully in infants, especially if premature, as excessive oxygen can cause retrolental fibroplasia. Any baby that has received an aminoglycoside should have hearing assessed. Premature Babies and their Problems are discussed in a separate article..

Prevention

Preventing neonatal GBS remains controversial:¹⁵

• Routine screening of pregnant women for vaginal carriage is not recommended.
• Prophylactic intrapartum IV antibiotics (penicillin or clindamycin) should be considered when:
  • A woman has had a previous baby affected by GBS disease.
  • There has been incidental detection of vaginal GBS during pregnancy.
  • Where there are 2 or more risk factors (prematurity <37 weeks' gestation, prolonged rupture of membranes >18 hours, fever in labour of >38°C).
• A baby whose mother has had a previous infant with GBS disease, or has other risk factors, should either be clinically evaluated after birth and closely observed for at least twelve hours or treated with antibiotics until blood culture results are available.

Tuberculosis

Tuberculosis can be acquired from the mother very early in life and may present around 6 weeks of life with unwillingness to feed, excessive weight loss, slight fever and hepatosplenomegaly. Chest X-ray is required. Obtaining samples such as sputum is impractical in babies. Remember this possibility in those from high-risk groups. Treatment is with standard anti-tuberculous drugs. If there has been tuberculosis in the family in the past 6 months, BCG is given at 3 days - see separate article Immunisation Schedule (UK).

Document references

1. CEMACH Perinatal Mortality 2007, published June 2009; 5th annual report.
2. Pinter DM, Mandel J, Hulten KG, et al; Maternal-infant perinatal transmission of methicillin-resistant and methicillin-sensitive Staphylococcus aureus. Am J Perinatol. 2009 Feb;26(2):145-51. Epub 2008 Oct 31. [abstract]
3. Di Bartolomeo S, Mirta DH, Janer M, et al; Incidence of Chlamydia trachomatis and other potential pathogens in neonatal conjunctivitis.; Int J Infect Dis. 2001;5(3):139-43. [abstract]
4. McIntyre J; Preventing mother-to-child transmission of HIV: successes and challenges.; BJOG. 2005 Sep;112(9):1196-203. [abstract]
5. No authors listed; What can be done about hepatitis B?; Drug Ther Bull. 2006 Jun;44(6):41-4. [abstract]
6. Kimberlin DW; Neonatal herpes simplex infection. Clin Microbiol Rev. 2004 Jan;17(1):1-13. [abstract]
7. Gupta R, Warren T, Wald A; Genital herpes. Lancet. 2007 Dec 22; 370(9605):2127-37. [abstract]
8. RCOG Green Top Guideline 13, Chickenpox in pregnancy, Sept 2007.
9. Tebruegge M, Pantazidou A, Curtis N; Towards evidence based medicine for paediatricians. How effective is varicella-zoster immunoglobulin (VZIG) in preventing chickenpox in neonates following perinatal exposure? Arch Dis Child. 2009 Jul;94(7):559-61.
10. Bryant PA, Tingay D, Dargaville PA, et al; Neonatal coxsackie B virus infection-a treatable disease? Eur J Pediatr. 2004 Apr;163(4-5):223-8. Epub 2004 Feb 18. [abstract]
11. Anderson-Berry AL; Neonatal Sepsis. eMedicine, November 2008.
12. Feverish illness in children - Assessment and initial management in children younger than 5 years, NICE Clinical Guideline (2007)
13. Ng PC, Lam HS; Diagnostic markers for neonatal sepsis. Curr Opin Pediatr. 2006 Apr;18(2):125-31. [abstract]
14. Adams-Chapman I, Stoll BJ; Neonatal infection and long-term neurodevelopmental outcome in the preterm infant. Curr Opin Infect Dis. 2006 Jun;19(3):290-7. [abstract]
15. RCOG Treen Top Guideline 36, Prevention of early onset neonatal group B Streptococcal Disease, Nov 2003.

Internet and further reading

• O'Connor NR, McLaughlin MR, Ham P; Newborn skin: Part I. Common rashes. Am Fam Physician. 2008 Jan 1;77(1):47-52. [abstract]

Acknowledgements