Neonatal sepsis is a frequent cause of neonatal mortality; unfortunately, the symptoms of sepsis are not specific and may be attributed to other, noninfectious, causes. It is, therefore, crucial to pay attention to the risk factors for neonatal sepsis.

For early-onset infections, the maternal status of colonization by microorganisms and associated factors are the most important predictors of sepsis in neonates. Infection by group B streptococcus (GBS) species is the most frequent cause of neonatal sepsis, although the prophylactic antibiotic administration has decreased its incidence. Escherichia coli is another common cause of early-onset infections, followed in frequency by other organisms, such as haemophilus influenzae. Organisms such as GBS can invade the amniotic fluid during labor or through occult tears, and cause chorioamnionitis. Women with premature rupture of membranes are also at high risk for colonization of the amniotic fluid, as are those who have preterm labor. All of the above factors can suggest risk for sepsis in the newborn [1] [2]. In one study, women in preterm labor and with premature rupture of membranes were found to have a 75% incidence of microbial invasion of the amniotic cavity [3].

The most important risk factor for late-onset sepsis is the gestational age at delivery: premature newborns are at increased risk because of a weak immune system, or procedures utilizing invasive devices. The most common agent of late-onset sepsis is the group of coagulase-negative staphylococci, major nosocomial pathogens.

Initial signs of neonatal sepsis include decreased activity, feeding and breathing difficulties, abnormal temperature (too high or too low), and diarrhea or vomiting. Hypoglycemia, hyperglycemia, and metabolic acidosis often accompany sepsis, but also occur in purely metabolic conditions. Pneumonia, whether of intrauterine or intrapartum origin, may not be easy to differentiate from respiratory distress syndrome. Coughing, irregular respiration, decreased breath sounds and other symptoms characterize both diseases. Neurological signs (changes in consciousness, seizures, and others) are characteristic of meningitis, which is the common form of central nervous system infection in neonatal sepsis.

• Fever

  To prevent infection in the baby, expectant women can be treated with IV antibiotics for several hours before delivery, if indicated by prenatal screens or clinical signs such as maternal fever or uterine tenderness. [my.clevelandclinic.org]

  Older babies who have normal lab results and have only a fever may not be given antibiotics. Instead, the child may be able to leave the hospital and come back for checkups. [medlineplus.gov]

  Abnormalities of fetal heart rate, maternal fever, premature separation of the placenta from the uterine wall, or foul smelling/cloudy amniotic fluid all indicate a high-risk labor and delivery. [medicinenet.com]

  In term neonates, incidence is lower than in preterm, with 1–2 cases/1000 live births.4 Risk factors for neonatal sepsis include chorioamnionitis, intrapartum maternal fever (temperature ≥ 38°C [100.4°F]); rupture of membranes for 18 hours or longer5; [accesspediatrics.mhmedical.com]

  Risk Factors: Early onset Sepsis Major Maternal prolonged Rupture of Membranes >18-24 hours Intrapartum maternal fever >38 C (>100.4 F) Chorioamnionitis Sustained Fetal Tachycardia >160 beats per minute Minor Intrapartum maternal fever >37.5 C (>99.5 [fpnotebook.com]

• Cerebral Palsy

  Brain damage Cognitive impairments Cerebral palsy Edema (fluid buildup in the brain) Brain abscesses (pus-filled pockets) Cerebral palsy Developmental delays Seizure disorders Learning disabilities What Are the Signs and Symptoms of Neonatal Sepsis and [michigancerebralpalsyattorneys.com]

  Cerebral white matter and neurodevelopment of preterm infants after coagulase-negative staphylococcal sepsis. Pediatr Crit Care Med. 2012;13:678-84., 2222. Wu YW, Colford Jr JM. Chorioamnionitis as a risk factor for cerebral palsy: A meta-analysis. [scielo.br]

  Antenatal, Intra Partum, and Neonatal Risk Factor for Cerebral Palsy in Children in Podlaskie Province. Journal of Polish Society of Child Neurology. 2009; 18: 19-24. Schlapbach LJ, Aebischer M, Adams M, et al. [jkb.ub.ac.id]

  Neonatal risk factors for cerebral palsy in very preterm babies: case-control study. BMJ 1997 ;314: 404 - 408 3. Stoll BJ, Hansen NI, Adams-Chapman I, et al. [nejm.org]

• Pallor

  One study, 56 which included all neonates, could not find a significant association between pallor and sepsis. Another multicenter study, 45 which also included all neonates, clustered pallor and/or mottling under impaired peripheral perfusion. [pediatrics.aappublications.org]

  […] signs with poor feeding Splenomegaly Neurologic Activity decreased or lethargy Irritability Tremor, jitteriness or Seizure Hyporeflexia or hypotonia High pitched cry Swelling of Fontanel Cardiovascular Hypotension Metabolic Acidosis Tachycardia Skin Pallor [fpnotebook.com]

  General features of neonatal sepsis Pallor, lethargy, jaundice Fever, hypothermia, temperature instability. Note: One-third of confirmed sepsis cases are normothermic. [www2.health.vic.gov.au]

• Pneumonia

  Among positive cases, the bacteriological profile was found highest for Staphylococcus aureus (35.6%) followed by Klebsiella pneumoniae (15.3%). [bmcresnotes.biomedcentral.com]

  Full Text Dear Editor, Streptococcus pneumoniae (pneumococcus) is a microorganism with high morbidity in children, especially when related with the respiratory tract (in the form of pneumonia) and as a focus of infection in the otorhinolaryngological [archbronconeumol.org]

  Also, S. pneumoniae Pneumococcal Infections Streptococcus pneumoniae (pneumococci) are gram-positive, alpha-hemolytic, aerobic, encapsulated diplococci. [msdmanuals.com]

  Abstract Infections (including sepsis, meningitis, pneumonia and tetanus) stand as a major contributor to neonatal mortality in Haiti (22%). [tropej.oxfordjournals.org]

  Both organisms produce diseases with many features in common, especially fulminant courses with respiratory distress and pneumonia, and often have a fatal outcome. ( AJDC 1986;140:117-121) [jamanetwork.com]

• Abdominal Distension

  The patient had no history of hematemesis, jaundice, abdominal distension or abdominal pain. There was no family history for coagulation disorders. At admission the complete blood count was normal and the inflammatory markers were negative. [termedia.pl]

  Hepatomegaly, splenomegaly, abdominal distension. Hypothermia, hyperthermia. Exclusion criteria Babies with the following signs and symptoms: Congenital infection. Early neonatal sepsis. Perinatal asphyxia. Congenital anomalies. [mmj.eg.net]

  distension Splenomegaly Neurologic Convulsions Hypotonia and Hypodynamia Lethargy [ 12 ] Symptoms of Cardiovascular and Skin Disorders: Cardiovascular: Hypotension Metabolic Acidosis Tachycardia Skin: Pale or marble with petechia or purple Mottling Cold [intechopen.com]

  Gastrointestinal (GIT) symptoms poor feeding vomiting abdominal distension feed intolerance bilious aspirates/vomits loose stools. Central nervous system (CNS) symptoms lethargy irritability seizures. [www2.health.vic.gov.au]

  Commonly used clinical and laboratory criteria of sepsis Clinical criteria Laboratory criteria Abdominal distension Skin and subcutaneous lesions such as petechial rash, abscesses, sclerema Cardiovascular signs (tachycardia/bradycardia, hypotension, poor [cochranelibrary.com]

• Tachycardia

  Risk Factors: Early onset Sepsis Major Maternal prolonged Rupture of Membranes >18-24 hours Intrapartum maternal fever >38 C (>100.4 F) Chorioamnionitis Sustained Fetal Tachycardia >160 beats per minute Minor Intrapartum maternal fever >37.5 C (>99.5 [fpnotebook.com]

  Assessment Patient may manifest Irritability Weakness Temperature above normal level (36 oC) Skin warm to touch Presence of tachycardia (above 160 bpm) Presence of tachypnea (above 60 bpm) WBC elevated Nursing Diagnosis Hyperthermia related to inflammatory [rnpedia.com]

  The child showed extreme hemodynamic instability (with bursts of his paroxysmal supraventricular tachycardia (heart rate >250beats/min) alternate to bradycardia (heart rate He rapidly developed oligoanuria and was not responsive to furosemide. [karger.com]

• Hypotension

  […] sepsis is suspected; Instability of body temperature; Gastro-intestinal symptoms (vomiting, abdominal distension, blood in stool, increase in quantity of residual mass in stomach); Neurological symptoms; Cardiorespiratory dysfunction (100 180, 30 60, hypotension [intechopen.com]

  Treating Hypotension in Preterm Neonates With Vasoactive Medications. NCBI. Retrieved September 12, 2022. Wynn, J. L., & Wong, H. R. (2011, June 01). Pathophysiology and Treatment of Septic Shock in Neonates. Clinical Perinatology, 37(2), 439-479. [nurseslabs.com]

  Diarrhea Abdominal Distention Ileus Dehydration signs with poor feeding Splenomegaly Neurologic Activity decreased or lethargy Irritability Tremor, jitteriness or Seizure Hyporeflexia or hypotonia High pitched cry Swelling of Fontanel Cardiovascular Hypotension [fpnotebook.com]

• Neonatal Jaundice

  The distribution of 70 respondents obtained as much 15 neonates have history neonatal sepsis of which 12 neonatal jaundice and 3 not became neonatal jaundice. [eprints.ums.ac.id]

  Jaundice in the newborn breastfed babies. Pathological neonatal jaundice can be caused by a number of factors, including: blood group incompatibility;... [evidence.nhs.uk]

  In the current study we did not find UTI among jaundiced neonates aged 5 days and younger. UTI was detected among 24 neonates who presented with jaundice between 5–7 days of age. [ijp.mums.ac.ir]

  However, there are concerns about high resistance rates, and side effects such as neonatal jaundice have been reported [71]. [journals.plos.org]

• Genital Lesions

  Guidelines for prevention of perinatal transmission of HSV recommend cesarean delivery for women with active genital lesions or prodromal symptoms. [link.springer.com]

  Prevention of Viral Infection Prevention of neonatal HSV has been successful with the implementation of cesarean sections for women with active genital lesions who have first-episode disease, and viral suppression during pregnancy is also helpful. [cmr.asm.org]

• Vaginal Bleeding

  Thurnau et al., “Perinatal outcomes in women with preterm rupture of membranes between 24 and 32 weeks of gestation and a history of vaginal bleeding,” American Journal of Obstetrics & Gynecology, vol. 193, no. 1, pp. 164–168, 2005. [hindawi.com]

• Febrile Seizures

  677 Slipped Capital Femoral Epiphysis 679 Femoral Anteversion 680 Patellofemoral Problems 682 OsgoodSchlatter Disease 683 Blounts Disease 684 Genu Valgum 685 Metatarsus Adductus 686 Clubfoot 687 Scoliosis 689 Kyphosis 692 Cervical Spine Problems 693 Febrile [books.google.de]

Early diagnosis is critical for starting therapy. The pathogen should be identified as soon as possible, so that the treatment with broad-spectrum antibiotics, which carries potential risks if continued too long, can be replaced by a regimen using more specific agents. Analysis of the complete blood cell count with differentials, together with cultures of blood, cerebrospinal fluid and urine (the latter only for late-onset sepsis) are performed in suspected cases.

Thrombocytopenia [4] and neutropenia [5] are frequently observed but are not specific signs. The immature to total neutrophil ratio is a more sensitive indicator of sepsis [5]. Sepsis screening panels use a variety of indicators, including leukocyte counts, neutrophil counts and immature to total neutrophil ratios [6]; their positive predictive value is highly diagnostic.

Blood cultures should test for both aerobic and anaerobic bacteria; growth usually occurs within two days. Results from tests using the polymerase chain reaction (PCR) are available in five hours [7]. Testing for herpes simplex virus is also done by PCR in cases where there is a strong indication of infection by the virus.

Of the acute phase proteins, C-reactive protein and procalcitonin have been used most extensively [8] [9]. A raised procalcitonin level 24 hours after birth is a good indicator of sepsis [10].

Analysis of the cerebrospinal fluid shows increased protein concentration and white blood cell count and decreased glucose concentration in case of meningitis. Cerebrospinal fluid culture should be obtained in cases of suspected sepsis if lumbar puncture can be performed. If the culture shows bacterial growth, further samples should be taken to follow the course of the disease and the effectiveness of treatment.

Chest radiography and imaging of the head by computed tomographic scan, magnetic resonance imaging, or ultrasonography are performed as needed.

• Nephrolithiasis

  It has also been rarely associated with biliary pseudolithiasis, nephrolithiasis, and pulmonary impairment due to precipitation with calcium ions in neonates with both elevated and normal serum calcium levels ( 226 – 230 ). [cmr.asm.org]

• Salmonella Typhi

  The most commonly implicated bacteria include Staphylococcus aureus, coagulase negative staphylococci (CONS), Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, and Group [link.springer.com]

Treatment / Management Empiric treatment with antibiotics should be started as soon as sepsis is clinically suspected, even without confirmatory lab data. [ncbi.nlm.nih.gov]

These tests will be done to look for signs of infection: Blood tests Urine tests Lumbar puncture to check the fluid around the brain and spinal cord Respiratory secretion testing Treatment Treatment depends on how severe the problem is. [cancercarewny.com]

[…] of drug-resistance to the current WHO recommended treatment regimen (ampicillin and gentamicin). [gardp.org]

[…] for neonatal sepsis but not to prolong treatment unnecessarily. [journals.lww.com]

Prognosis and Treatment Sepsis in a newborn is treated with antibiotics given intravenously. Antibiotics are often started even before laboratory and culture results are available. [rchsd.org]

The prognosis for babies with bacterial infections is quite good. Most newborns will recover quickly from the infection as soon as proper medication begins. [news-medical.net]

Expectations (prognosis) With prompt treatment, many babies with these bacterial infections will recover completely with no remaining problems. Nevertheless, neonatal sepsis is a leading cause of infant death. [coordinatedhealth.com]

Prognosis and Treatment Sepsis in a newborn is treated with antibiotics given intravenously. Treatment is started even before laboratory results are available; a different antibiotic may later be chosen based on the results of laboratory tests. [hon.ch]

Outlook (Prognosis) Many babies with bacterial infections will recover completely and have no other problems. However, neonatal sepsis is a leading cause of infant death. The more quickly an infant gets treatment, the better the outcome. [ufhealth.org]

IGBS is associated with both early and late onset sepsis and the most common etiologic agent of neonatal meningitis. [atlases.muni.cz]

There is a clear need for investment in expanded surveillance activities and in more research on diagnosis, etiology, and treatment of neonatal sepsis at all levels of the health system, and especially at the community level. [who.int]

Early-Onset Infection Prior to the 1970s, staphylococci and gram-negative rod species were the predominant etiologic agents of neonatal sepsis. [obgynkey.com]

Neonatal septicemia: incidence, etiology, and outcome: a 6-year analysis. Acta Paediatr Scand Suppl 1989;360:113-9. Tessin I, Trollfors B, Thiringer K. Incidence and aetiology of neonatal septicemia and meningitis in western Sweden, 1975–1986. [saripediatri.org]

Bernhard Resch, MD Division of Neonatology Department of Pediatrics Research Unit for Neonatal Infectious Diseases and Epidemiology Silvia Edlinger, MD Research Unit for Neonatal Infectious Diseases and Epidemiology Wilhelm Müller, MD Division of Neonatology [journals.lww.com]

Centers for Disease Control and Prevention investigators have studied the changing epidemiology of invasive EOS for several decades. [pediatrics.aappublications.org]

EPIDEMIOLOGY Neonatal sepsis incidence is 1–5 cases/1000 live births. [accesspediatrics.mhmedical.com]

Baker, Changing epidemiology of group B Streptococcal colonization, 1999 8. Noormanto, Antibiotika profilaktik pada neonatus dengan ketuban pecah dini, uji klinis terkendali acak, 1995 9. R.A. Watase, K.Y. Hirata, T.S. [i-lib.ugm.ac.id]

Society for Healthcare Epidemiology of America/Association for Professionals in Infection Control/Infectious Diseases Society of America. MMWR Recomm Rep. 2002;51(RR–16):1–45, quiz CE1–4. 30. [dovepress.com]

[…] use of instrumentation, such as forceps, or placement of electrodes for intrauterine monitoring during labor and delivery.6 Black race is a risk factor for both early- and late-onset GBS sepsis, and the reasons behind this are not fully understood.7 PATHOPHYSIOLOGY [accesspediatrics.mhmedical.com]

[…] organisms like Coagulase-negative Staphylococcus, Staphylococcus aureus, E.coli and GBS, risk factors for late-onset neonatal sepsis include: Extended use of catheter during pregnancy [7] Extended hospital stay after the baby is born [8] Neonatal Sepsis Pathophysiology [pregmed.org]

Pathophysiology and Treatment of Septic Shock in Neonates. Clinical Perinatology, 37(2), 439-479. [nurseslabs.com]

Centers for Disease Control and Prevention. Prevention of perinatal group B streptococcal disease: a public health perspective. Centers for Disease Control and Prevention. MMWR Recomm Rep. 1996 May 31. 45 (RR-7):1-24. [QxMD MEDLINE Link]. [emedicine.medscape.com]

Contemporary cases demonstrate the limits of current prevention strategies. We continue to identify missed opportunities for GBS prevention. [jamanetwork.com]

Maternal immunization against invasive pathogens could prevent disease in the triad of mother, fetus, and newborn, a worthy goal. 14 GBS immunization would prevent both early- and late-onset neonatal disease and might have an impact on other adverse outcomes [pediatrics.aappublications.org]

Pregnant women may need preventive antibiotics if they have: Chorioamnionitis Group B strep colonization Given birth in the past to a baby with sepsis caused by bacteria Other things that can help prevent sepsis include: Preventing and treating infections [medlineplus.gov]

prevention of infections in very premature babies (LACUNA), ISRCTN66482337; oral lactoferrin supplementation for prevention of sepsis in preterm neonate, NCT01821989; Enteral Lactoferrin In Neonates (ELFIN), ISRCTN88261002 [ 4 ]. [omicsgroup.org]

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3. Romero R, Quintero R, Oyarzun E, et al. Intraamniotic infection and the onset of labor in preterm premature rupture of the membranes. Am J Obstet Gynecol. 1988 Sep;159(3):661-666.
4. Khashu M, Osiovich H, Henry D. Persistent bacteremia and severe thrombocytopenia caused by coagulase-negative Staphylococcus in a neonatal intensive care unit. Pediatrics. 2006 Feb. 117(2):340-348.
5. Engle WD, Rosenfeld CR. Neutropenia in high-risk neonates. J Pediatr. 1984;105(6):982–986.
6. Rodwell RL, Leslie AL, Tudehope DI. Early diagnosis of neonatal sepsis using a hematologic scoring system. J Pediatr. 1988;112(5):761–767.
7. Chan KY, Lam HS, Cheung HM, et al. Rapid identification and differentiation of Gram-negative and Gram-positive bacterial bloodstream infections by quantitative polymerase chain reaction in preterm infants. Crit Care Med. 2009 Aug. 37(8):2441-2447.
8. Vouloumanou EK, Plessa E, Karageorgopoulos DE, Mantadakis E, Falagas ME. Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and meta-analysis. Intensive Care Med. 2011;37(5):747–762.
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10. Altunhan H, Annagür A, Örs R, Mehmetoglu I. Procalcitonin measurement at 24 hours of age may be helpful in the prompt diagnosis of early-onset neonatal sepsis. Int J Infect Dis. 2011 Dec. 15(12):e854-458.