Neonatal conjunctivitis, also known as ophthalmia neonatal , is a disease of the ocular surface characterized by inflammation of the conjunctiva due to infectious or non-infectious causes before 30 days of life.1,2,3,4
Physical examination may demonstrate conjunctival chemosis (edema), injection (redness), lacrimation, and purulent or nonpurulent discharge.5 The margins of the eyelids and cornea may also be affected.6 Possible complications of neonatal conjunctivitis include endophthalmitis, keratitis , blindness (rare in developed countries) and, depending on the etiology, it may have associated systemic manifestations such as pneumonia, meningitis and sepsis.1
The etiology of neonatal conjunctivitis is generally chemical, bacterial and viral in nature.
Important bacterial causes include maternally sexually transmitted organisms such as Chlamydia trachomatis and Neisseria gonorrhoeae , those from the maternal gastrointestinal tract, and commensal organisms found on the skin.7 Specific bacterial causes that have been identified include Staphylococcus 1 and species of Streptococcus 3,8, Haemophilus influenzae ,9 Serratia marcescens ,10,11 Escherichia coli ,12 Moraxella catarrhalis ,1,3 and Neisseria meningitidis , among others.13
Newborns, especially those born prematurely , are at particular risk for conjunctivitis because they spend a lot of time with their eyes closed, allowing bacterial growth, and their immature lacrimal systems limit the distribution and drainage of tears.14 Newborns They also lack lymphoid tissue in the conjunctiva, and have decreased immunoglobulin A and lysozyme activity.15 These factors limit local immune function and contribute to the severity of the ophthalmic reaction.15
Additional risk factors for neonatal conjunctivitis include prenatal factors such as maternal vaginal infection (allowing transmission in the birth canal), maternal human immunodeficiency virus (HIV) infection, poor prenatal care, inadequate prophylaxis, premature rupture of membranes and prolonged labor. Postnatal risk factors include premature birth, low birth weight, birth trauma, poor hygiene during delivery, mechanical ventilation, and chemical exposure.5,7,14,16
The incidence of neonatal conjunctivitis varies from 1.6% to 12% of all newborns17; The incidence and specific etiology vary geographically and between different clinical settings. In a Finnish study of 9,600 births between 2010 and 2015, 173 newborns (1.8%) were found to have conjunctivitis.3 Of 163 of these neonates tested for C. trachomatis , none tested positive. In contrast, neonatal conjunctivitis causes significant ocular morbidity and blindness in developing countries.5,7,18 Studies from sub-Saharan Africa suggest that C. trachomatis may account for up to 33% of neonatal conjunctivitis cases.19 This variation has been attributed to differences in the prevalence of maternal infection and postnatal prophylaxis of the neonate.7
Although rare compared to its prevalence in other regions, chlamydia has been reported to be more common than N. gonorrhoeae in the developed world; In developing countries, chlamydial and gonococcal eye infections are common.7 Gonococcal ophthalmia is rare in the United States primarily due to prenatal screening and treatment for N. gonorrhoeae in pregnant women.20 In 1993, the Centers for The Disease Control and Prevention (CDC) began recommending routine prenatal screening and treatment of pregnant women for C. trachomatis.20 Prior to this, C trachomatis was the most common cause of neonatal conjunctivitis in the United States.20
The differential diagnosis of neonatal conjunctivitis includes congenital nasolacrimal duct obstruction, ocular foreign body, preseptal or orbital cellulitis, corneal abrasion or other traumatic injury to the eye after childbirth, dacryocystitis, keratitis, subconjunctival hemorrhage, and congenital glaucoma.21 These and others Causes should be considered in the evaluation of a neonate who presents with ocular findings concerning for conjunctivitis (Table).
| Prophylaxis |
Prophylaxis of neonatal conjunctivitis is credited to Dr. Carl Credé, who introduced the practice of using silver nitrate to prevent eye infection in the early 1880s.7,20 Other agents that have been used for prophylaxis include erythromycin ointment . 0.5%, 2.5% povidone-iodine, and 1% tetracycline ointment.22 Gentamicin ophthalmic ointment is not recommended as it has been associated with serious ocular reactions in neonates.23 In particular, some sources report that nitrate silver, erythromycin and tetracycline are only considered effective for gonococcal conjunctivitis and are ineffective as prophylaxis for chlamydial conjunctivitis.7,24
The US Task Force on Preventive Services (GTSP) recommends topical ocular medication for all newborns to prevent gonococcal conjunctivitis.25 This prophylaxis should be provided within the first hour after birth.17 The GTSP also recommends screening for gonorrhea in pregnant women, in all sexually active women 24 years of age and younger, and in older women at increased risk for infection.26 The CDC specifically recommends neonatal ocular prophylaxis with topical erythromycin.18,20
Currently, in the United States, erythromycin ophthalmic ointment is the only topical prophylactic option available for neonatal conjunctivitis; Tetracycline ointment is no longer manufactured, and silver nitrate for ophthalmic use has not been available for decades.20,26 Without ocular prophylaxis, the rate of transmission of gonococcal infection from mother to child varies from 30% to 50%. 26,27,28
Due to concerns about increasing antibiotic resistance, new drug candidates are being developed for prophylaxis, including fatty acid-based formulations that in early research have demonstrated efficacy against N. gonorrhoeae and have been shown to be safe for use. use in animal models.29 Monocaprine, a monoglyceride of capric acid, has shown promise as a potential treatment and prophylaxis agent in ocular models and in vitro studies against N. gonorrhoeae , N. meningitidis (whose consequences can be lethal), and C. .trachomatis .13
Some countries, such as the United Kingdom, Denmark, Norway, and Sweden do not use universal ocular prophylaxis, and the Canadian Pediatric Society published a policy statement in 2015 against routine topical ocular prophylaxis with erythromycin.24 There may be limited benefit from Universal topical prophylaxis in some parts of the world due to low prevalence and effective prenatal control. In a study of 27,556 live births at the National Maternity Hospital in Dublin, Ireland, from 2011 to 2013, no cases of neonatal gonorrhea were identified, and no topical prophylaxis was used.30
The incidence of neonatal conjunctivitis decreased in North America in the 1980s with the advent of routine prenatal screening and treatment of sexually transmitted infections,24 suggesting that addressing the causes of neonatal conjunctivitis in pregnant women may be in itself an effective form of prophylaxis. Protection of newborns against C. trachomatis , for example, relies primarily on prenatal screening and treatment. This practice has decreased both conjunctivitis and chlamydial pneumonia in neonates.20
A report from the American Academy of Pediatrics (AAP) examined the impact of parental refusal of topical prophylaxis or the potential for lack of topical ocular prophylaxis at the national level.31 The authors found that universal screening and treatment is expected during pregnancy reduce the burden of neonatal disease, but topical prophylaxis is recommended by the GTSP and required by law in most of the United States. Although prenatal care is the norm, 6.2% of births in the United States occur without prenatal care.
In cases without topical prophylaxis, the authors recommend evaluating parents for possible risk factors, documenting negative test results for gonorrhea in pregnancy in the baby’s medical record, and advising the family to seek immediate medical attention. against inflammation and conjunctival secretion. Testing can also be performed in the immediate peripartum and, if positive or pending but with concern for poor follow-up, treatment can be initiated.
| Laboratory diagnosis |
Diagnostic tests for neonatal conjunctivitis include cell culture (with Gram stain and sensitivity testing) along with non-culture-based tests.23
The American Academy of Ophthalmology recommends obtaining conjunctival culture specimens in all cases of suspected neonatal bacterial conjunctivitis.1 Nonculture-based tests include nucleic acid amplification tests ( NAATs ) and direct immunofluorescence tests (NAAT). IFD). (twenty-one)
IFD is the only culture-independent method approved by the US Food and Drug Administration (FDA) for the detection of chlamydia from a conjunctival swab specimen, but laboratories may offer NAATs for chlamydia after having verified the use of the sample in accordance with the Clinical Laboratory Improvement Amendments (CMLC) regulations.2
The diagnostic standard for suspected chlamydial conjunctivitis is to obtain a sample from an everted eyelid using a polyethylene terephthalate swab or the type of swab specified by the manufacturer’s kit.2 The sample should contain conjunctival cells, not secretion alone. 2.23
Similarly, although NAATs are not FDA approved for the evaluation of N. gonorrhoeae in a conjunctival swab specimen, they are more sensitive compared to culture. Many laboratories have met EMLC requirements and validated NAATs in extragenital samples.23
Culture is less sensitive because N. gonorrhoeae is labile and requires rapid transport from the bedside to the laboratory for successful growth of the organism.30 That said, culture can provide a definitive diagnosis of N. gonorrhoeae , and even the Gram stain of conjunctival exudates demonstrating increased leukocytes (polymorphonuclear) or intracellular gram-negative diplococci is sufficient for presumptive treatment.9
Polymerase chain reaction (PCR) testing is also useful in the diagnosis of viral infections.6 Neonates with systemic infection may be at risk for bacteremia, arthritis, sepsis, or meningitis; In these cases, additional investigations should be performed, including but not limited to blood cultures and cerebrospinal fluid analysis.18
| Chemical conjunctivitis |
Traditionally, chemical conjunctivitis in the newborn was associated with silver nitrate prophylaxis.7 Silver nitrate prophylaxis previously led to chemical conjunctivitis in approximately 50% of patients in whom it was administered.18,22
Conjunctivitis secondary to this noninfectious cause typically presents bilaterally within 1 to 2 days after exposure to a topical agent,22 distinguishing this diagnosis from infectious conjunctivitis, which generally presents later. Gram stain can reveal leukocytes but not organisms.22
Management is conservative and symptoms resolve in approximately 2 days.22 The replacement of silver nitrate administration with other means of prophylaxis has significantly reduced the incidence of neonatal chemical conjunctivitis. As noted above, povidone-iodine has been used for prophylaxis, but care should be taken to use a "prep solution and not a wash formula, as it causes significant chemical conjunctivitis and potentially corneal decompensation."22 Due to reactions severe eye infections in neonates associated with gentamicin ophthalmic ointment, it is no longer used for prophylaxis.23
| Chlamydial conjunctivitis |
Chlamydia is the most common infectious cause of neonatal conjunctivitis worldwide and is most commonly transmitted by passage through an infected birth canal.6
C. trachomatis is an obligate intracellular gram-negative bacterium with at least 15 serological variants (serotypes) known to cause various diseases.23 Serotypes A to C cause trachoma while serotypes B and D to K typically cause perinatal and genital infections.23
Trachoma causes up to 3% of blindness worldwide, making it the leading cause of infectious blindness worldwide.23 Trachoma presents with mucopurulent discharge that progresses to scarring and mechanical damage to the eyelids, conjunctiva, and cornea. .2,6 It is transmitted by the transfer of ocular discharge and is most common in resource-limited parts of the world.23 It is typically contracted outside of the neonatal period and is rarely seen in the United States.2,23
Symptoms of neonatal chlamydial conjunctivitis, in contrast, typically present 5 to 14 days after birth6,7 beginning with watery discharge that becomes more copious and purulent over time. Many cases are mild and self-limiting, but may progress to include chemosis, eyelid edema, conjunctival papillae, pseudomembrane formation, peripheral pannus, and corneal involvement.7
Chlamydia infection in pregnancy is a major cause of morbidity with potential complications including premature rupture of membranes, preterm labor and delivery, low birth weight, and fetal loss.19 Premature birth places the neonate at increased risk of morbidity. and mortality. After birth, C. trachomatis can cause pneumonia (typically occurring outside the neonatal period at 4–11 weeks of age)32 as well as conjunctivitis.19
It is estimated that in pregnant women with untreated active C. trachomatis , 30% to 50% of their newborns will develop conjunctivitis.19 Up to 20% of neonates exposed to C. trachomatis may develop pneumonia; Of these, approximately 50% have a history of conjunctivitis.6
The primary means of preventing neonatal chlamydia infection is screening and treatment of pregnant women, a practice that has been implemented in the United States and other countries.19
Neonatal chlamydial conjunctivitis can be treated with erythromycin 50 mg/kg/day orally in 4 divided doses for 14 days.23 The efficacy of erythromycin is approximately 80%, so a second course of treatment may be necessary. .23 Systemic use of erythromycin in neonates is associated with an increased risk of pyloric stenosis.33
Azithromycin is an alternative treatment option that is typically administered at 20 mg/kg as a single daily dose for 3 days,23 which may improve compliance due to less frequent dosing, but appears to be less effective than erythromycin.33 Neonates diagnosed with chlamydial conjunctivitis should be evaluated for gonococcal infection with appropriate management as indicated.
| Gonococcal conjunctivitis |
N. gonorrhoeae , a gram-negative diplococcus, is responsible for approximately 0.4 cases of neonatal conjunctivitis per 100,000 live births in the United States. Although it is a rare cause of conjunctivitis, it is associated with significant morbidity.25 Transmission generally occurs during childbirth with exposure to infectious vaginal secretions; The mother’s cervix and urethra can serve as bacterial reservoirs.9 Even with cesarean section, vertical transmission of
N. gonorrhoeae is possible. The CDC reported a rate of 179 gonorrhea cases per 100,000 population in 2019; this represents an 82.6% increase over the historic low in 2009.23 Pregnant women with N. gonorrhoeae infection are at increased risk of adverse birth outcomes including premature rupture of membranes, preterm birth, low birth weight, and mortality. perinatal.34
Gonococcal conjunctivitis typically presents as bilateral hyperacute conjunctivitis 2 to 5 days after birth.6,7 Even with prophylaxis (typically with erythromycin eye ointment in the United States), 10% of newborns exposed to gonorrhea during delivery can develop gonococcal conjunctivitis.35 N. gonorrhoeae has the potential to penetrate intact corneal epithelium, leading to corneal ulceration, which can progress to perforation and endophthalmitis.7
Systemic manifestations such as rhinitis, arthritis, sepsis and meningitis are also possible, highlighting the importance of detection and treatment of gonococcal infections.7
If confirmatory tests are not available and the physician has a high suspicion for gonorrhea and/or chlamydia, treatment against both should be initiated to avoid complications.18
The first-line treatment of gonococcal conjunctivitis consists of ceftriaxone. Non-disseminated infections can be treated with a single intramuscular or intravenous injection of ceftriaxone 25 to 50 mg/kg, not to exceed 125 mg, with contraindication if receiving simultaneous intravenous calcium.6,9,23 An alternative treatment is cefotaxime 100 mg/kg in a single intramuscular or intravenous dose.6,23 In any case, saline irrigation of the ocular surface should be performed.23 If disseminated infection is suspected, an infectious disease specialist should be consulted. In both cases, consultation with Ophthalmology and evaluation for concomitant infections such as HIV, syphilis and chlamydia is indicated.21
| viral conjunctivitis |
Several viruses have been implicated in neonatal conjunctivitis, including herpes simplex virus (HSV), adenovirus, rhinovirus, and coronavirus, among others.3 HSV conjunctivitis is typically associated with vesicular lesions on the skin of the eyelid.6,7 HSV can infect a newborn during vaginal delivery or even through ascending intrauterine infection if the pregnant woman has genital HSV.22
The risk of infection is significantly higher with primary maternal infection compared to reactivation (25%-60% vs. 2%, respectively).22 Neonatal infection can also occur through direct contact with caregivers affected by herpetic whitlow or herpes. lipstick.22
Clinically apparent illness usually appears 5 to 14 days after exposure; Systemic disease is also a possibility and may manifest up to 6 weeks after exposure.22 Although herpes simplex causes less than 1% of neonatal conjunctivitis, it should be included in the differential diagnosis in newborns presenting with unilateral chemosis. , serosanguinous discharge or vesicular lesions surrounding the eyelids.18
Complications are potentially life-threatening and may include disseminated and central nervous system disease.18
Laboratory testing should include HSV culture or PCR testing of the conjunctiva, corneal epithelium, or skin vesicle scrapings, PCR of cerebrospinal fluid and serum, and liver function tests.22 Infants with suspected ocular herpes simplex infection should be examined by an ophthalmologist since the infection can lead to corneal involvement, cataracts and/or chorioretinitis.21
Neonatal HSV infection is treated with intravenous acyclovir 60 mg/kg/day in 3 divided doses for 14 days, or 21 days in the setting of meningoencephalitis or disseminated disease.22,23 Adjuvant therapy with topical trifluridine may also be considered when 1% or 0.15% ganciclovir.22,23 Enteral suppression of acyclovir is continued for 6 months after completion of intravenous therapy in infants surviving neonatal HSV disease of any classification.23
Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), the cause of coronavirus disease 2019 (COVID-19), has been reported as a cause of conjunctivitis.15,36 One case report described a newborn who He presented with mucopurulent discharge, subconjunctival hemorrhage and eyelid injection.15 The laboratory diagnosis was negative for bacterial growth, C. trachomatis , N. gonorrhoeae and HSV. Nasopharyngeal and conjunctival PCR tests for SARS-CoV-2 were positive. These patients may also have other associated symptoms of COVID-19.
Adenovirus is a common cause of viral conjunctivitis that can also affect newborns. It is associated with petechial hemorrhage and occasionally large subconjunctival hemorrhages and lymphadenopathy.17 These neonates may have associated respiratory symptoms.
| Other causes |
Other bacterial causes of neonatal conjunctivitis include Staphylococcus aureus , Streptococcus pneumoniae , H. influenzae , E. coli , Klebsiella species , Pseudomonas aeruginosa , N. meningitidis and others.6,16,18,37 S. marcescens , an aerobic large negative bacillus , has been associated with nosocomial infections in NICUs and can present with conjunctivitis, urinary tract infection, pneumonia, sepsis, and/or meningitis.38,39
Hospital-acquired conjunctivitis usually occurs 48 hours or more after hospitalization; It is not always certain whether the infection was acquired during or after birth.10
Predictive factors include low birth weight, use of ventilation or nasal continuous positive airway pressure, and ophthalmological examination.14 A study of 1492 neonates admitted to a level III neonatal unit in Portugal showed a 4% incidence of cases. of nosocomial conjunctivitis, in which the most common pathogens were S. marcescens , E. coli and P. aeruginosa.10 Other studies have found coagulase-negative staphylococci, S. aureus and Klebsiella among the predominant pathogens.14
Empiric antibiotic therapy for bacterial conjunctivitis includes topical erythromycin, as well as fluoroquinolones such as ciprofloxacin, gatifloxacin, and moxifloxacin.16
Sanfilippo et al. (1) compared besifloxacin 0.6% and gatifloxacin 0.3% in a multicenter, randomized, double-blind, parallel group study of 33 newborns and found that clinical resolution and bacterial eradication were comparable between the groups, without any group showing any adverse effects related to the treatment. Moxifloxacin and ciprofloxacin have previously been shown to be effective.1
A pooled analysis of the use of topical fluoroquinolones to treat bacterial conjunctivitis revealed similar cure rates between newborns and older children, suggesting that these medications are reasonable for certain cases of neonatal bacterial conjunctivitis.16 In particular, fluoroquinolone resistance has been increasing among certain bacterial species. Consultation with a pediatric infectious disease specialist may be indicated, for example, in cases of pseudomonas conjunctivitis or methicillin-resistant S. aureus .
Linear immunoglobulin A bullous dermatosis is an autoimmune blistering disease that leads to skin and mucous membrane involvement, and includes conjunctivitis, as well as nasal erosions. Histopathology demonstrates linear deposit of immunoglobulin A in the area of the cutaneous basement membrane.40 The average age of onset is between 4 and 5 years, although presentations have been reported in neonates, even in a 3-day-old baby with vesicles and blisters. tightness in the area of the scrotum, face and neck along with bilateral mucopurulent conjunctivitis.40
A case report of neonatal Kawasaki disease described a 15-day-old infant who presented with poor feeding, irritability, fever, and rash.41 By the 6th day of illness, the infant presented with bilateral nonpurulent conjunctivitis. Antibiotic and antiviral therapies were ineffective. The patient met 3 of 5 criteria for Kawasaki disease and, with no other apparent diagnosis, was treated for incomplete Kawasaki disease with intravenous immunoglobulin with substantial improvement of symptoms within 48 hours. This disease should be considered in neonates who present systemic symptoms associated with conjunctivitis.
Summary
|
Board. Frequent causes of neonatal conjunctivitis and differential diagnosis (in each case a consultation with Ophthalmology should be made)
| Cause | Starting age | Characteristics | Diagnosis | Treatment |
| Chemical irritant | 1-2 days after exposure | Gram stain reveals leukocytes but no organisms | Recent exposure to silver nitrate, povidone-iodine wash formulation, or other irritants | Self-limited after stopping exposure |
| Neisseria gonorrhoeae | 2-5 days after birth | Bilateral hyperacute purulent conjunctivitis | Conjunctival swab sample nucleic acid amplification test, culture | Ceftriaxone or systemic cefotaxime |
| Chlamydia trachomatis | 5-14 days after birth | Watery discharge with increasing purulence | Conjunctival swab sample nucleic acid amplification test, culture | Systemic erythromycin or azithromycin |
| Herpes simplex | 5 to 14 days after birth; systemic disease may emerge as late as 6 weeks | Unilateral chemosis, serosanguinous discharge, vesicles around the eyelids | HSV culture or PCR test of conjunctiva, corneal epithelium, or scraping of skin vesicles | Systemic acyclovir +/- topical trifluridine or ganciclovir |
| corneal abrasion | After trauma to the corneal epithelium | Redness, pain, tearing | Fluorescein staining | Topical antibiotic ointment, typically erythromycin |
| Subconjunctival hemorrhage | After mild trauma to the conjunctiva | Redness without pain or discharge | Physical examination and rule out other causes | Self-limited |
| congenital glaucoma | It varies; possible neonatal onset | Sensitivity to light, watery discharge, spasm of the eyelids, enlargement of the affected eye(s), corneal striae | Measurement of intraocular pressure | Medical and surgical interventions to lower intraocular pressure |
| Comment |
Neonatal conjunctivitis is characterized by inflammation of the conjunctiva due to infectious or non-infectious causes before 30 days of life; Its etiology is generally chemical, bacterial or viral in nature.
The incidence and specific etiology vary geographically and between different clinical scenarios, a situation that must be considered to achieve an adequate diagnosis and treatment.
Possible ocular complications of neonatal conjunctivitis include keratitis, endophthalmitis, blindness, and sometimes systemic manifestations such as pneumonia, meningitis, and sepsis.
Prophylaxis of neonatal conjunctivitis varies worldwide, and is generally based on the most prevalent regional etiologies and the possibility of detecting and treating the causative diseases (mainly maternal sexually transmitted infections such as Chlamydia trachomatis and Neisseria gonorrhoeae ) in the period prenatal.
