INTRODUCTION —
Chlamydia trachomatis is the most common bacterial sexually transmitted infection in the United States. Infants born vaginally to infected mothers with genital disease are at risk for acquiring C. trachomatis, which can present as conjunctivitis and/or pneumonia.
This topic will review the clinical features, diagnosis, and treatment of C. trachomatis conjunctivitis and pneumonia in newborns and young infants.
Related topics include:
●(See "Epidemiology of Chlamydia trachomatis infections".)
●(See "Gonococcal infection in the newborn".)
MICROBIOLOGY —
There are 15 serotypes of C. trachomatis. Neonatal infection is usually caused by C. trachomatis serotypes D through K, which are the primary serotypes causing genital disease in adults [1]. The microbiology of C. trachomatis is discussed in greater detail separately. (See "Epidemiology of Chlamydia trachomatis infections", section on 'Microbiology'.)
EPIDEMIOLOGY —
Perinatally acquired C. trachomatis infection is transmitted from an infected birthing parent to the infant during vaginal birth [2]. The implementation of routine screening and treatment of pregnant individuals has dramatically reduced the incidence of perinatally acquired C. trachomatis infection in the United States and Canada. (See "Prenatal care: Initial assessment", section on 'Chlamydia'.)
●Prevalence in pregnancy – Chlamydia prevalence correlates with age and sexual activity. The highest prevalence rate in pregnancy occurs in adolescent and young adults <25 years of age. The prevalence and risk factors for C. trachomatis infection in women in the general population are discussed elsewhere. (See "Epidemiology of Chlamydia trachomatis infections".)
Reported prevalence rates of C. trachomatis among pregnant individuals vary by region and age of the cohort, ranging from as low as 2 percent to as high as 20 percent [2-8].
Risk factors for C. trachomatis infection in sexually active adults include multiple sex partners, non-use of barrier contraceptives, concurrent or prior sexually transmitted disease, and anatomic factors (eg, cervical friability or cervical ectopy). (See "Epidemiology of Chlamydia trachomatis infections", section on 'General risk factors'.)
●Neonatal infection – In the United States and Canada, routine screening and treatment of C. trachomatis infection during pregnancy have resulted in a dramatic decrease in perinatal chlamydial infections [2,9]. In the contemporary era, C. trachomatis is a rare cause of neonatal conjunctivitis or pneumonia in the United States. The estimated prevalence of C. trachomatis infection among infants <1 year of age in the United States is 7 to 9 cases per 100,000 live births [10].
In a retrospective study that reviewed all infant C. trachomatis eye cultures submitted to one laboratory from 1986 to 2002, the positivity rate fell from 15.6 percent prior to implementation of routine prenatal screening (1986 to 1993) to 1.8 percent after implementation of screening (1994 to 2002) [9]. A similar study conducted in a community with a high prevalence of Chlamydia among pregnant individuals assessed C. trachomatis seropositivity rates in young children before and after implementing a prenatal screening program [2]. The seropositivity rate fell from 18.5 percent before implementing prenatal screening to 0 percent after implementing screening.
However, in countries where prenatal screening is not routinely offered (eg, the Netherlands, China, Republic of Ireland, United Kingdom, and many other European countries), perinatally transmitted C. trachomatis remains a common cause of neonatal conjunctivitis and respiratory illness [11-13]. In one study from Ireland, C. trachomatis was the most common cause of ophthalmia neonatorum in infants referred to a tertiary center from 2013 through 2018, accounting for 20 percent of cases [13]. In another study from the Netherlands, C. trachomatis was detected in 7 percent of infants <6 months old who presented with respiratory complaints and had nasopharyngeal swab specimens collected [12].
TRANSMISSION —
Most perinatally-acquired C. trachomatis infections are transmitted from an infected birthing parent to the infant during vaginal birth. There is a small risk of acquiring infection during cesarean delivery, particularly if there is premature rupture of membranes [1].
For infants delivered vaginally to a birthing parent with active chlamydial infection, the risk of acquiring C. trachomatis infection is approximately 50 to 70 percent [1,14]. Approximately one-half of perinatally-acquired C. trachomatis infections are symptomatic and one-half are asymptomatic (ie, serologic evidence of infection only or positive nasopharyngeal culture without any clinical manifestation) [1,2,14]. Among infants with symptomatic infection, conjunctivitis is the most common manifestation, accounting for approximately 60 to 90 percent of symptomatic cases. Pneumonia accounts for approximately 10 to 40 percent of symptomatic cases and is often preceded by conjunctivitis [1,14].
CLINICAL MANIFESTATIONS
Conjunctivitis — The most frequent clinical manifestation of C. trachomatis infection newborns and young infants is conjunctivitis.
The incubation period for C. trachomatis conjunctivitis is 5 to 14 days after delivery. Presentation before five days is unusual but has been reported to occur earlier if the prenatal course was complicated by premature rupture of the membranes [2].
Clinical findings of conjunctivitis range from mild swelling with a watery eye discharge, which becomes mucopurulent (picture 1), to marked swelling of the eyelids with red and thickened conjunctivae (chemosis). A pseudomembrane may form as the exudate adheres to conjunctiva. The conjunctivae may also be very friable, resulting in bloody discharge. In a retrospective study of 90 infants from with conjunctivitis, bloodstained eye discharge was found to have high specificity and positive predictive value for chlamydial conjunctivitis [15]. A membrane of granulation tissue (micropannus) may form, especially if the patient is untreated for more than two weeks [16].
Treatment of conjunctivitis usually results in healing without complications. However, untreated infection may persist for months and may rarely cause corneal and conjunctival scarring.
By contrast, recurrent C. trachomatis ocular infection (trachoma), which can be transmitted in resource-limited regions in areas of poor hygiene, causes chronic keratoconjunctivitis and is the leading cause of blindness in the world. Trachoma is discussed separately. (See "Trachoma".)
Pneumonia — Pneumonia accounts for approximately 10 to 40 percent of symptomatic C. trachomatis infections in newborns and young infants [1,14]. In otherwise healthy infants, C. trachomatis pneumonia is generally a mild illness, sometimes referred to as "afebrile pneumonia of infancy." Approximately one-half of affected infants have a history of conjunctivitis.
●Timing of presentation – C. trachomatis pneumonia usually presents between four to eight weeks of age, though it can present as early as two weeks or as late as three to four months of age. Some infants may have upper respiratory tract symptoms as early as two weeks of age. Affected infants may have a protracted or gradual progression of symptoms before presenting to medical attention. In one report, the mean duration of symptoms prior to admission was eight days [17].
In preterm infants, C. trachomatis has been isolated from tracheal secretions as early as the first week after birth [18,19].
●Signs and symptoms – The most common presenting signs are nasal congestion, cough, and tachypnea. The cough characteristically has a staccato quality that may occur in paroxysms, though this is not universal. Most infected infants lack significant nasal discharge, although occasionally thick nasal secretions may be present [20]. Patients usually are afebrile or have minimal fever. Preterm infants may present with apneic spells. Rales are often present on auscultation of the lungs; wheezing is uncommon. Mild to moderate hypoxemia may be noted [1]. (See "Management of apnea of prematurity" and "Bronchopulmonary dysplasia (BPD): Clinical features and diagnosis".)
●Laboratory and radiographic findings – Peripheral eosinophilia is a characteristic laboratory finding; however, the total white blood cell count is typically normal [17,21].
The chest radiograph typically shows hyperinflation with diffuse interstitial infiltrates (image 1) [21].
DIAGNOSIS
Indications for testing — C. trachomatis should be suspected in a newborn or young infant with conjunctivitis if there is the possibility of exposure to the organism, specifically if the birthing parent has a history of untreated C. trachomatis infection or no prenatal care. If there has been no prenatal care or a maternal history of Neisseria gonorrhoeae, the exudate also should be tested for N. gonorrhoeae by NAAT. All the currently available NAATs for C. trachomatis are duplexed with N. gonorrhoeae. (See "Gonococcal infection in the newborn".)
The diagnosis of C. trachomatis infection should be considered in an infant less than three months of age with pneumonia if the mother has a history of untreated infection or no prenatal care.
Specimens — Newborns and young infants with suspected chlamydial infection should have both conjunctival and nasopharyngeal samples taken.
Conjunctival specimens for C. trachomatis testing should be obtained by swabbing the everted eyelid using aluminum-shafted Dacron-tipped swab or a swab specified by the manufacturer's test kit. The specimens must include conjunctival epithelial cells because C. trachomatis is an obligate intracellular organism. Exudates are not adequate for testing.
Respiratory specimens for C. trachomatis testing should be obtained from the nasopharynx. Tracheal aspirates can be sent in patients who are intubated.
Diagnostic methods
Nucleic acid amplification tests — Nucleic acid amplification tests (NAATs) are the standard method for diagnosing chlamydial infections, including neonatal infections [22]. NAAT methodology consists of amplifying C. trachomatis DNA or RNA sequences. Studies investigating the performance of NAATs in the setting of genital and extragenital (pharynx, rectum) infections in sexually active men and women have found that, compared with culture, NAATs have higher sensitivity and comparable specificity [22-25]. There are several commercially available NAAT assays for detection of C. trachomatis that are approved by the FDA for use in extragenital sites (pharynx and rectum), though none is approved specifically for use in conjunctival or nasopharyngeal specimens from infants [26]. Nevertheless, many laboratories in the United States will perform this testing on a conjunctival specimen provided the laboratory has verified the procedure according to Clinical Laboratory Improvement Amendments (CLIA) standards. If NAAT testing is not available, other options include culture or an alternative nonculture method (eg, direct fluorescent antibody test) [26]. (See 'Culture' below and "Clinical manifestations and diagnosis of Chlamydia trachomatis infections in adults and adolescents", section on 'Other diagnostic techniques'.)
Infants with C. trachomatis conjunctivitis usually have very high numbers of organisms present, and it is easy to obtain an adequate specimen. As a result, NAATs perform well in this setting [27,28].
Most NAATs are laboratory based, and results are typically not immediately available [24,25]. Point-of-care tests for Chlamydia have been developed, but they do not play a role in the evaluation of suspected infection in infants. (See "Clinical manifestations and diagnosis of Chlamydia trachomatis infections in adults and adolescents", section on 'Rapid tests for chlamydia'.)
Culture — Chlamydia culture, performed in tissue culture, is a sensitive and specific method for detection of neonatal chlamydial infections. However, it is labor intensive and expensive and very few laboratories perform Chlamydia culture in contemporary practice.
Testing for Neisseria gonorrhoeae — A diagnosis of C. trachomatis in a neonate should prompt evaluation for possible N. gonorrhoeae infection [22]. Treatment for N. gonorrhoeae is indicated only if testing is positive. (See "Gonococcal infection in the newborn".)
TREATMENT
When to initiate — The decision of when to initiate treatment depends on the type of infection:
●Conjunctivitis – Initial treatment for chlamydial conjunctivitis should be based upon a positive diagnostic test.
●Pneumonia – Initial therapy for chlamydial pneumonia is presumptive until diagnostic test results are available [22]. A presumptive diagnosis is based upon characteristic clinical and radiographic findings, particularly in an infant born to a birthing parent with untreated chlamydial infection. Other features that help distinguish chlamydial pneumonia from other respiratory infections in young infants and thus may prompt consideration of diagnostic testing and empiric treatment include conjunctivitis (either prior to or concurrent with respiratory symptoms), protracted illness, staccato cough, eosinophilia, and bilateral interstitial infiltrates on chest radiograph (image 1).
Choice of antibiotic — Erythromycin base or ethylsuccinate (50 mg/kg per day in four divided doses given orally for 14 days) is the preferred treatment for neonatal C. trachomatis conjunctivitis and pneumonia. Oral azithromycin (20 mg/kg per day given orally once daily for three days) is an acceptable alternative [2,22,29].
The dosing regimen is the same for both indications [2].
Data on the effectiveness of azithromycin in treating C. trachomatis infections in infants are limited [30,31]. In a case series of 13 infants with C. trachomatis conjunctivitis, three of five infants treated with single dose of azithromycin therapy became culture negative with resolution of symptoms [31]. Of the eight infants treated once daily for three days, six had resolution of symptoms with negative cultures, one had improved symptoms though cultures remained positive until erythromycin was given, and one, was lost to follow-up.
Topical therapy for chlamydial conjunctivitis is not effective, and there is a high failure rate compared with oral therapy in eradicating conjunctival infection. In addition, topical therapy does not eradicate nasopharyngeal infection, and thus infants treated with only topical therapy may develop recurrent infection and/or pneumonia [32].
Risk of pyloric stenosis — Both azithromycin and erythromycin are associated with increased risk of infantile hypertrophic pyloric stenosis (IHPS), particularly in infants younger than two weeks [33]. Parents/caregivers should be advised about the potential risk for IHPS, and infants should be observed closely for signs of intestinal obstruction. (See "Infantile hypertrophic pyloric stenosis", section on 'Macrolide antibiotics'.)
Treatment of the birthing parent — The infant's birthing parent and sexual partner(s) should be evaluated and treated for C. trachomatis infection. They also should be evaluated for other sexually transmitted diseases. (See "Treatment of Chlamydia trachomatis infection in adults and adolescents".)
PREVENTION
Screening during pregnancy — In the United States, routine screening for Chlamydia is recommended for all pregnant individuals <25 years of age and individuals ≥25 years of age with risk factors for sexually transmitted infection (table 1) [22,34]. In Canada, screening is suggested for all pregnant individuals [35]. Routine screening and treatment during pregnancy has resulted in a dramatic decrease in perinatal chlamydial infections. However, prenatal screening is not routinely offered in many parts of the world (eg, the Netherlands, China, Republic of Ireland, United Kingdom, most other European countries), and C. trachomatis remains a common cause of neonatal conjunctivitis and respiratory illness in those regions. (See 'Epidemiology' above.)
Screening for Chlamydia during pregnancy is discussed in greater detail separately. (See "Prenatal care: Initial assessment", section on 'Chlamydia'.)
Newborn ocular prophylaxis — In the United States, prophylaxis against gonococcal conjunctivitis with erythromycin ophthalmic ointment is routinely provided to all newborns at birth. However, newborn ocular prophylaxis is not effective in preventing neonatal chlamydial conjunctivitis [36,37]. In addition, ocular prophylaxis is not routinely provided to newborns in other countries. For example, in Canada, this practice was discontinued in 2015, in part due to ongoing shortages of erythromycin ophthalmic ointment [38]. The emphasis was shifted to enhanced screening for N. gonorrhoeae and C. trachomatis during pregnancy [35,38]. Prophylaxis for gonococcal conjunctivitis is discussed separately. (See "Gonococcal infection in the newborn", section on 'Newborn ocular prophylaxis'.)
SUMMARY AND RECOMMENDATIONS
●Transmission – Most perinatally-acquired Chlamydia trachomatis infections are transmitted from an infected birthing parent to the infant during vaginal birth. Approximately one-half of perinatally-acquired C. trachomatis infections are symptomatic and one-half are asymptomatic. (See 'Epidemiology' above.)
●Clinical manifestations – Neonatal C. trachomatis infection can present with (see 'Clinical manifestations' above):
•Conjunctivitis – The most common clinical manifestation of neonatal C. trachomatis infection is conjunctivitis, which usually presents between 5 and 14 days after birth. Symptoms range from mild swelling with a watery eye discharge, which becomes mucopurulent (picture 1), to marked swelling of the eyelids with red and thickened conjunctivae (chemosis). Untreated infants may have persistent conjunctivitis for months that may result in corneal and conjunctival scarring. (See 'Conjunctivitis' above.)
•Pneumonia – Neonatal C. trachomatis pneumonia usually presents between four to eight weeks of age, though it can present as early as two weeks or as late as three to four months of age. The most common presenting signs are nasal congestion, cough, and tachypnea. The cough characteristically has a staccato quality that may occur in paroxysms. Patients are usually afebrile or have minimal fever. Many infants also have conjunctivitis. Preterm infants may present with apnea. Peripheral eosinophilia is a characteristic laboratory finding. The chest radiograph typically shows hyperinflation with diffuse interstitial infiltrates (image 1). (See 'Pneumonia' above.)
●Diagnosis – Nucleic acid amplification tests (NAATs) are the standard method for diagnosis of chlamydial infections. They have high sensitivity and specificity for detection of C. trachomatis in conjunctival or nasopharyngeal specimens. (See 'Diagnosis' above.)
●Treatment – Our suggested approach to treating C. trachomatis infections in neonates is as follows (see 'Treatment' above):
•When to initiate therapy – For neonates with conjunctivitis, the decision to initiate treatment is based on a positive diagnostic test. For infants with pneumonia, initial treatment is presumptive until diagnostic test results are available. A presumptive diagnosis is based upon characteristic clinical and radiographic findings, particularly in an infant born to a birthing parent with untreated chlamydial infection. (See 'When to initiate' above.)
•Choice of antibiotic – For neonates with C. trachomatis infections, including conjunctivitis or pneumonia, we suggest a course of oral erythromycin base or ethylsuccinate rather than other agents (Grade 2C). Erythromycin is given orally at a dose of 50 mg/kg per day in four divided doses for 14 days. Oral azithromycin (20 mg/kg per day given once daily for three days) is a reasonable alternative. Topical therapy is not effective for C. trachomatis conjunctivitis and is unnecessary if the patient is treated systemically. (See 'Choice of antibiotic' above.)
●Prevention – The most effective way to prevent perinatal chlamydial infection is through a systematic program that identifies and treats all pregnant individuals with genital C. trachomatis infection. Neonatal ocular prophylaxis with erythromycin ophthalmic ointment is not effective for preventing chlamydial conjunctivitis. (See 'Prevention' above.)
ACKNOWLEDGMENT —
The UpToDate editorial staff acknowledges Mohan Pammi, MD, PhD, who contributed to an earlier version of this topic review.