Neonatal Infections

Pregnant people undergo prenatal testing for a variety of infections to assess the infant’s risk of infection and to limit transmission of certain infectious diseases. Infections commonly associated with congenital anomalies are often remembered with the mnemonic “TORCH." TORCH infections include toxoplasmosis, other (syphilis, varicella-zoster, parvovirus B19), rubella, cytomegalovirus (CMV), and herpes infections. Preterm infants are also at increased risk for certain other infections (particularly respiratory syncytial virus) while in the neonatal intensive care unit (NICU) and after discharge home.

This section covers the following topics:

• Prenatal Screening

• Neonatal Sepsis

• Respiratory Syncytial Virus

• Covid-19 in Neonates

Prenatal Screening

Pregnant people are screened for a variety of infectious diseases during pregnancy:

• Group B streptococcus (GBS): At 35 to 37 weeks’ gestation, a pregnant person is screened for GBS. Those who screen positive receive intrapartum antibiotic prophylaxis with penicillin, ampicillin, or cefazolin to reduce perinatal transmission and risk of early onset sepsis in the infant.

• Rubella: If rubella antibody titers indicate a pregnant person is rubella nonimmune, they will receive a vaccine after delivery. However, this does not protect the infant from rubella.

• Syphilis: If a pregnant person screens positive for syphilis, they will require confirmatory testing and prolonged treatment with penicillin if confirmed.

• Hepatitis B virus (HBV): The rate of maternal-to-neonatal transmission of hepatitis B is high. To limit infection, infants born to someone with hepatitis B should receive both the hepatitis B vaccination and hepatitis B immunoglobulin within the first 12 hours of life.

• Human immunodeficiency virus (HIV): Universal screening of pregnant people is recommended by ACOG as early as possible, with repeat testing for highrisk patients in the third trimester. Pregnant people should receive HIV-specific care prenatally and exposed infants require prophylaxis and follow up beyond the scope of this guide. Refer to the AAP Red Book for more information.

Other prenatal infectious disease risks include:

• Herpes simplex virus (HSV): Pregnant people with a history of HSV genital infection require valacyclovir prophylaxis for suppression starting at 36 weeks' gestation. If a pregnant person has active genital lesions at the time of labor, a cesarean section is recommended to reduce the risk of transmission to the infant.

• Zika virus: The CDC recommends Zika testing for pregnant people with symptoms of Zika and have traveled to an area with risk of Zika. Serum specimens should be collected as soon as possible after the onset of symptoms up to 12 weeks after symptom onset. If the pregnant person is asymptomatic, testing is not recommended unless ultrasound reveals findings consistent with congenital Zika virus syndrome. Please refer to the CDC for updated information.

• Varicella-zoster virus (VZV): Varicella immunity or lack thereof should be documented early in pregnant people. If the pregnant person is negative for prior infection or lack immunity from prior vaccination, they should not receive immunization during pregnancy due to the live nature of the vaccine. If a pregnant person is exposed to varicella and is nonimmune, varicella zoster immune globulin should be considered within 4 days of exposure.

See more on congenital infections in the Pediatric Infectious Diseases rotation guide.

Neonatal Sepsis

Neonatal sepsis is associated with high morbidity and mortality and can be either early-onset (first 72 hours of life) or late-onset (72 hours to 90 days of life). The etiology of early-onset sepsis is primarily considered an ascending infection (arising from vaginal flora). Late-onset sepsis occurs most often in newborns with central line access or who remain hospitalized.

Early-Onset Sepsis

Early-onset sepsis is most often caused by GBS, Escherichia coli, or Listeria monocytogenes. To reduce the incidence of perinatal GBS transmission, intrapartum antibiotic prophylaxis is administered to mothers who are GBS-positive at 35 to 37 weeks' gestation.

The rate of early-onset GBS is approximately 0.3-0.4/1000 live births. Risk factors for developing early-onset sepsis include maternal fever or chorioamnionitis diagnosis and a GBS-positive mother. Premature and low birth weight infants have a higher rate of early-onset sepsis.

Clinical manifestations include respiratory distress, tachycardia, and temperature instability. Lab abnormalities include hypoglycemia, abnormal white count or differential, positive blood culture, with or without abnormal cerebrospinal fluid (CSF) findings from lumbar puncture. Treatment with antibiotic therapy with either ampicillin and gentamicin or ampicillin and cefotaxime to cover possible gram-negative organisms is begun empirically and can be tailored to culture data later if needed.

The Neonatal Sepsis Calculator can be used to screen at-risk asymptomatic infants ≥34 weeks' gestation and calculate the probability of early onset sepsis per 1000 babies by entering values for specified maternal risk factors along with the infant’s clinical presentation. Risk stratification includes physical exam abnormalities (respiratory distress, temperature instability, hypoglycemia). Based on the risk of development of early onset sepsis, a blood culture and treatment may be indicated. Treatment usually includes empiric antibiotic therapy with either ampicillin and gentamicin or ampicillin and cefotaxime to cover possible gram-negative organisms.

Late-Onset Sepsis

Late-onset sepsis (from 72 hours to 90 days of life) occurs most often in hospitalized infants and premature infants, particularly those with low birth weight. The presence of a central venous catheter and mechanical ventilation are additional risk factors. Intrapartum antibiotic prophylaxis does not reduce the risk for late-onset sepsis. The most common pathogens in late-onset sepsis are Staphylococcus (coagulase negative) and Staphylococcus aureus, Streptococcus pneumoniae, GBS, E. coli, Listeria, or other gram-negative bacteria. The diagnosis of late-onset sepsis requires a complete blood count (CBC), blood culture, urine culture, and lumbar puncture for cerebrospinal fluid (CSF) studies and culture.

Respiratory Syncytial Virus (RSV)

Preterm infants are at increased risk for respiratory syncytial virus (RSV) infection, both during NICU hospitalization and after discharge. For more than two decades, the monoclonal antibody palivizumab (Synagis) was the only option to reduce the morbidity and mortality associated with RSV infection in preterm infants. However, a new monoclonal antibody, nirsevimab (Beyfortus), became available in 2023 for infants who were either born during RSV season or are entering their first RSV season. There is also an RSV vaccine (Abrysvo) available for pregnant persons between 32 and 36 weeks of gestation. The CDC has guidelines for administration of the RSV vaccine and monoclonal antibodies.

Covid-19 in Neonates

Covid-19, caused by SARS-CoV-2, emerged in late 2019 and led to a global pandemic by March of 2020. Although COVID-19 has primarily caused disease and mortality in the adult population, the neonatal world has been uniquely affected as well. This is because neonatal providers are present at deliveries of high-risk infants, which may include infants born to SARS-CoV-2-positive mothers. The AAP continues to revise recommendations to reflect new knowledge of the virus. These recommendations include delivery room management, maternal and newborn rooming, newborn admission to the neonatal intensive care unit versus rooming in, advice surrounding breastmilk, maternal visitation, and discharge.

Maternal vaccination against SARS-CoV-2 may provide passive protection against symptomatic infection for infants until they are eligible for vaccination.

In general, maternal SARS-CoV-2 infection is not an indication for delivery room presence by neonatal providers. However, if providers are present, full personal protective equipment (PPE) should be worn. T If infants need to be admitted to the NICU, the AAP recommends a single room with negative pressure potential, although proper precautions through cohorting can also be undertaken. If aerosol-generating procedures are performed, enhanced respiratory precautions should be used and providers should wear full PPE. Although the AAP provides recommendations, each institution has the ability to decide on the guidance to give parents based on resources available, local incidence, and local practices.