Chlamydia trachomatis infections in the newborn

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 usually presents as conjunctivitis and/or pneumonia [1].

The clinical features, diagnosis, and treatment of C. trachomatis conjunctivitis and pneumonia in the newborn and young infant are reviewed here.

Pneumonia in older children, other disorders caused by C. trachomatis or Chlamydia pneumoniae, and the possible role of infection in preterm delivery are discussed elsewhere. (See "Pneumonia caused by Chlamydia pneumoniae in children" and "Acute otitis media in children: Epidemiology, microbiology, and complications" and "Spontaneous preterm birth: Overview of risk factors and prognosis".)

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 [2]. The microbiology of C. trachomatis is discussed in greater detail separately. (See "Epidemiology of Chlamydia trachomatis infections", section on 'Microbiology'.)

EPIDEMIOLOGY AND TRANSMISSION — C. trachomatis is primarily transmitted to newborns via exposure to an infected mother's genital flora during vaginal birth [3]. The implementation of routine screening and treatment of pregnant women has dramatically reduced the incidence of perinatally acquired C. trachomatis infection in the United States.

Prevalence in pregnancy — The following is a brief review of the prevalence of C. trachomatis in pregnant women. The prevalence and risk factors for C. trachomatis infection in women in the general population are discussed elsewhere. (See "Epidemiology of Chlamydia trachomatis infections".)

The prevalence of C. trachomatis in pregnant women ranges from 2 to 20 percent depending on the population screened [2,4,5]. Similar to the increased prevalence of C. trachomatis in adolescent and young adult women in the general population, the highest prevalence rate in pregnancy occurs in adolescent and young adult women. This was illustrated in a British study that screened 1216 pregnant women for C. trachomatis infection by testing for the presence of the organism by ligase chain reaction from self-administered vaginal swab or first-pass urine specimens [6]. The overall prevalence of infection was 2.4 percent. In women less than 25 years of age and adolescents, the prevalence increased to 8.6 and 14.3 percent, respectively. In another study of 203 pregnant adolescents from the United States, 18 percent had C. trachomatis infection in the third trimester of pregnancy [7].

Although not specifically studied in pregnant women, other risk factors for C. trachomatis infection in sexually active women include multiple sex partners, non-use of barrier contraceptives, concurrent or prior sexually transmitted disease, and anatomic factors (eg, cervical friability or cervical ectopy). Presumably, these risk factors for C. trachomatis infection seen in the general population are also likely to be risk factors for infection in pregnant women. (See "Epidemiology of Chlamydia trachomatis infections".)

Risk of transmission — The risk of acquiring C. trachomatis in an infant born vaginally to a woman with chlamydial cervicitis is approximately 50 percent but has been reported to be as high as 60 to 70 percent [4,5,8-14]. However, this estimation includes newborns with asymptomatic infection of the nasopharynx or only serologic evidence of infection. The rate of symptomatic chlamydial infection in infants born to C. trachomatis-infected mothers is lower. Based upon positive cultures for C. trachomatis in symptomatic infants, the risk for neonatal-acquired conjunctivitis is between 20 and 50 percent and, for pneumonia, between 5 and 30 percent [2,8-10,13,14].

The discrepancy of transmission rate based upon detection methods and location of screening in at-risk infants is best illustrated by a prospective study of 5531 pregnant women [8]. Positive cervical cultures for C. trachomatis were detected in 262 women (4.7 percent), and 131 of their infants were followed prospectively. Sixty percent of these infants demonstrated positive serology for C. trachomatis, and, in 36 percent of infants, the organism was isolated from cultures of the nasopharynx, conjunctivae, rectum, and vagina. Culture-positive conjunctivitis was diagnosed in 23 of these 131 infants (18 percent) and pneumonia in 21 (16 percent). Rectal and vaginal colonization was demonstrated in 14 percent. However, the anti-C. trachomatis antibody was probably maternal in origin and did not represent infection [15].

While vaginal birth carries the highest risk of transmission, there is a small risk of acquiring infections in infants born by cesarean delivery both with premature rupture of membranes and intact membranes [3,16-19]. In one study of 141 exposed infants, for example, C. trachomatis was isolated from 58 of 125 infants delivered vaginally, 2 of 10 delivered by cesarean delivery with rupture of membranes, and 1 of 6 delivered by cesarean delivery without rupture of membranes [3]. The latter condition indicates either a transmembrane or a transplacental transmission of the infection.

CLINICAL MANIFESTATIONS

Conjunctivitis — The most frequent clinical manifestation of C. trachomatis infection in the newborn is conjunctivitis. The condition is sometimes referred to as inclusion conjunctivitis of the newborn or inclusion blennorrhea.

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 in infants born to mothers with premature rupture of the membranes [20].

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 Hong Kong with conjunctivitis, bloodstained eye discharge was found to have high specificity and positive predictive value for chlamydial conjunctivitis [21]. A membrane of granulation tissue (micropannus) may form, especially if the patient is untreated for more than two weeks [22].

Treatment of conjunctivitis usually results in healing without complications. However, untreated infection may persist for months and cause corneal and conjunctival scarring [23-25].

Pneumonia — Among infants born to mothers with cervical C. trachomatis infection, 5 to 30 percent develop pneumonia [8-10,13,14]. Approximately one-half of these infants have a history of conjunctivitis.

●Timing of presentation – Pneumonia due to C. trachomatis is recognized in most affected infants between 4 and 12 weeks of age, although essentially all are symptomatic before eight weeks [20]. Some infants may have upper respiratory tract symptoms as early as two weeks of age. C. trachomatis has been isolated from tracheal secretions of preterm infants with pneumonia diagnosed in the first week after birth [26,27]. Affected infants may have prolonged duration of symptoms. In one report, the mean duration of symptoms prior to admission was eight days [28].

●Signs and symptoms – Cough and nasal congestion without significant discharge are common, although occasional infants may have thick nasal secretions [29]. Patients usually are afebrile or have minimal fever. Characteristic features are a staccato cough that may occur in paroxysms, as well as tachypnea, although these are not universally present [2]. Preterm infants may have apneic spells associated with the infection. Rales are often present on auscultation of the lungs; wheezing is uncommon. The liver and spleen may be easily palpable because of the hyperinflated lungs [30]. Mild to moderate hypoxemia may be noted [20]. (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 [28,30].

The chest radiograph typically shows hyperinflation with bilateral, symmetrical interstitial infiltrates (image 1) [30].

DIAGNOSIS — Nucleic acid amplification tests (NAATs) are considered the gold standard for diagnosis of chlamydial infections. They have high sensitivity and specificity for detection of C. trachomatis in conjunctival or nasopharyngeal specimens [31,32], although they have not yet been cleared by the US Food and Drug Administration (FDA) for use in this setting. Several NAATs were approved by the FDA in 2019 for use in extragenital sites (pharynx and rectum) in adults. Laboratories do internal validation for use of NAATs for conjunctival and nasopharyngeal swabs.

Chlamydia culture previously was considered the gold standard for diagnosis; however, culture is more labor intensive and expensive and has largely been replaced by NAATs.

Indications for testing — C. trachomatis should be suspected in an infant less than one month of age with conjunctivitis if there is the possibility of exposure to the organism, specifically if the mother 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 examined with Gram stain and cultured using selective medium to detect 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 suspected of 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 — NAATs are considered the gold standard for diagnosing neonatal chlamydial infections. 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 [33-36]. There are six commercially available NAAT assays for detection of C. trachomatis that are approved by the FDA, though none is approved specifically for use in conjunctival or nasopharyngeal specimens from infants [34]. 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, it seems likely that NAATs will perform well in this setting and the available data support this [31,32].

Most NAATs are laboratory based, and results are typically not immediately available [35,36]. (See "Clinical manifestations and diagnosis of Chlamydia trachomatis infections", 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 has largely been replaced by NAATs.

Testing for Neisseria gonorrhoeae — A diagnosis of C. trachomatis in a neonate should prompt evaluation for possible N. gonorrhoeae infection [2]. 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 empiric until diagnostic test results are available [33]. A presumptive diagnosis is based upon characteristic clinical and radiographic findings, particularly in an infant born to a mother with a chlamydial infection that was not adequately treated prenatally. Other features that help distinguish chlamydial pneumonia from other respiratory infections in newborns 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 — Oral azithromycin is the preferred treatment for neonatal C. trachomatis infections, including both conjunctivitis and pneumonia [33]. The dosing regimen is the same for both indications: 20 mg/kg per day given orally once daily for three days [2]. Erythromycin base, 50 mg/kg/day in four divided doses for 14 days, is an alternative.

Data on the effectiveness of azithromycin in treating C. trachomatis infections in infants are limited [37,38]. 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 [38]. 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; topical therapy also does not eradicate nasopharyngeal infection [2,9,39]. This was illustrated in a randomized controlled study of infants with chlamydial conjunctivitis that reported eradication of the organism in 14 of 15 patients treated with oral erythromycin versus persistent conjunctival infection in eight infants and nasopharyngeal colonization in 3 of 14 infants treated with topical ointment [39]. These results demonstrate that oral compared with topical erythromycin provides better resolution of conjunctivitis and eradication of C. trachomatis from the nasopharynx.

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 [40]. Parents 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 mother — The infant's mother and her 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".)

PREVENTION

Maternal screening — Routine screening for chlamydial infection is recommended by the United States Preventive Services Task Force for all pregnant women <25 years of age and women ≥25 years of age with risk factors for sexually transmitted infection (table 1) [33,41]. Routine screening and treatment during pregnancy has resulted in a dramatic decrease in perinatal chlamydial infections in the United States. (See 'Epidemiology and transmission' above.)

In countries where prenatal screening is not routinely offered (eg, the Netherlands, China), perinatally transmitted C. trachomatis remains a common cause of neonatal conjunctivitis and respiratory illness in those regions [42-45]. In a study from Rotterdam, C. trachomatis was responsible for approximately 64 percent of the cases of neonatal conjunctivitis seen in a large university-affiliated hospital from 1999 through 2001 [42]. In another study from the same institution, respiratory C. trachomatis infection was confirmed in 7 percent of infants <6 months of age presenting with respiratory complaints [45].

Screening for chlamydial infections during pregnancy is discussed in greater detail separately. (See "Prenatal care: Initial assessment", section on 'Chlamydia'.)

Prophylaxis against conjunctivitis — In the United States, neonatal prophylaxis against gonococcal conjunctivitis is routinely performed at birth. However, neonatal ocular prophylaxis is not effective in preventing neonatal chlamydial conjunctivitis [46-51]. The diagnosis and treatment of chlamydial infections in pregnant women is the best method for preventing chlamydial disease. In Canada, the practice of routine neonatal ocular prophylaxis is no longer recommended and the emphasis has shifted to enhanced maternal screening [52]. (See "Prenatal care: Initial assessment", section on 'Chlamydia'.)

Prophylaxis for gonococcal conjunctivitis is discussed separately. (See "Overview of the routine management of the healthy newborn infant", section on 'Eye care' and "Gonococcal infection in the newborn", section on 'Ophthalmia neonatorum'.)

SUMMARY AND RECOMMENDATIONS

●Transmission – Infants who are born vaginally to mothers with untreated genital Chlamydia trachomatis infection are at risk for developing C. trachomatis conjunctivitis (15 to 50 percent) and/or pneumonia (5 to 20 percent). (See 'Epidemiology and transmission' 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 of life. 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 presents between 4 and 12 weeks of age, although most infants are symptomatic before eight weeks (image 1). Patients are usually afebrile or have minimal fever with a staccato cough. Many infants also have conjunctivitis. Apnea may be seen in infected preterm infants. (See 'Pneumonia' above.)

●Diagnosis – Nucleic acid amplification tests (NAATs) have high sensitivity and specificity for detection of C. trachomatis and are considered the gold standard for diagnosis. (See 'Diagnosis' above.)

●Treatment – Our 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. Initial therapy for chlamydial pneumonia is empiric until diagnostic test results are available. A presumptive diagnosis is based upon characteristic clinical and radiographic findings, particularly in an infant born to a mother with a chlamydial infection that was not adequately treated prenatally. (See 'When to initiate' above.)

•Choice of antibiotic – For neonates with C. trachomatis infections, including conjunctivitis or pneumonia, we suggest a course of oral azithromycin rather than other agents (Grade 2C). Azithromycin is given orally at a dose of 20 mg/kg once daily for three days. 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 women with genital C. trachomatis infection. The recommended topical therapies for preventing neonatal gonococcal conjunctivitis are 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.