Perinatal infection resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:  Rinky Agnes Botleroo, M.B.B.S.

Synonyms and keywords: Neonatal infection; TORCH infection

Perinatal infection Resident Survival Guide Microchapters

Overview
Causes
Diagnosis
Treatment
Dos
Don'ts

## Overview

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Most of the perinatal infections in the neonate are bacterial. These infections may be acquired from the mother prior to or at birth or from environmental sources. Premature babies are prone to perinatal infections. Neonates, especially those born prematurely have very limited ability to express symptoms, so, even minor deviations from normal behaviour should suggest bacterial disease. Chronic congenital and perinatal infections are usually asymptomatic in mother and neonate and may remain latent or sub-clinically active in host tissue for prolonged time.It may cause insidious injury to the central nervous and perceptual systems. When noticeable, these infections almost invariably cause mental or perceptual handicaps or both. Cytomegalovirus is the most common cause of congenital infections and the fetal effects of primary maternal infection during gestation can be devastating.Perinatal infection occurring in the 1st few days to 14 days occurs due to contact with the pathogens present in the cervico-vaginal canal during delivery. causes are Escherichia coli, Group B beta haemolytic Streptococci,Gonococci, Listeria monocytogenes ,Bacteroides species, Candida albicans, Cytomegalo virus,Herpes Simplex Virus Type-2.The mortality and morbidity associated with either acute or chronic infections is quite high. So, appropriate diagnosis and treatment is required and should be aggressive.

## Causes

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Perinatal infection occurring in the 1st few days to 14 days occurs due to contact with the pathogens present in the cervico-vaginal canal during delivery. causes are

* Escherichia coli
* Group B beta haemolytic Streptococci
* Gonococci
* Listeria monocytogenes
* Bacteroides species
* Candida albicans
* Cytomegalo virus
* Herpes Simplex Virus Type-2

Perinatal infections that occurs late, usually 3 to 6 weeks after birth are caused by environmental pathogens. Causes are

* Klebsiella
* Aerobacter
* Proteus species
* Staphylococcus aureus
* Haemophilus influenzae
* Pseudomonas aeruginosa
* Coxsackie B virus
* Candida albicans
* Echovirus
* Influenza virus
* Parainfluenzae virus
* Respiratory syncytial virus

Several vertically transmitted infections are included in the TORCH complex:[1]

1. T – toxoplasmosis from Toxoplasma gondii
2. O – other infections (see below)
3. R – rubella
4. C – cytomegalovirus
5. H – herpes simplex virus-2 or neonatal herpes simplex

Other infections include:

* Parvovirus B19
* Coxsackievirus
* Chickenpox (caused by varicella zoster virus)
* Chlamydia infection
* HIV
* Human T-lymphotropic virus
* Syphilis
* Zika fever, caused by Zika virus, can cause microcephaly and other brain defects in the child.
* Hepatitis B

## Diagnosis

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## Treatment

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Disease | Medical Therapy | Surgery | Prevention

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Toxoplasmosis | ❑ Mother:

Immediate administration of Spiramycin [2]

❑ Fetus and Newborn:

Pyrimethamine, Sulfadiazine, and folinic acid.[2]||

|  | ❑ Pregnant mother should avoid eating raw, undercooked, and cured meats.[3]

❑ Pregnant mother should avoid contact with cat litter.[3]

❑ Wash hands more frequently, especially after touching soil gardening.[3]

Rubella | ❑ Intrauterine rubella infection > 16 weeks:

Reassurance.

❑ Congenital rubella syndrome: Supportive care and surveillance.

❑ Live, attenuated rubella vaccine is contraindicated during pregnancy [4]

|  | ❑ Immunization of seronegative women before pregnancy.

❑ Nationally notifiable condition: Suspected congenital rubella syndrome must be reported to the local or state health department.[5]

Cytomegalovirus[6] | ❑ Fetus:

* Severe anemia: Intrauterine blood transfusions
* Thrombocytopenia: Platelet transfusions

❑ Newborn:

* Supportive therapy of symptoms,Ganciclovir[7], Valganciclovir, or Foscarnet

❑ Mother:

* Valacyclovir.

|  | ❑ Frequent hand washing.

❑ Pregnant women with risk factors for TORCH infection should avoid potentially contaminated workplaces such as schools, paediatric clinics. [8]

Herpesvirus[9] | ❑ Acyclovir 400 mg tablets 3 times daily

❑ Acyclovir 200 mg tablets 4 times a day from week 36 until delivery, and viral cultures on cervical-vaginal secretions from 36th week of gestation are required.

❑ Valacyclovir at a dose of 200 mg 2 times a day.[9]

|  | ❑ Antiviral therapy (Acyclovir) beginning at 36 weeks of gestation for individuals with a known history of HSV lesions.

❑ Cesarean section in women with active genital lesions or prodromal symptoms such as burning pain.

Parvovirus[10] | ❑ Intrauterine fetal blood transfusion in cases of severe fetal anemia.  |  | ❑ Hand hygiene (frequent hand washing).

❑ Pregnant women with risk factors for TORCH infection should avoid potentially contaminated workplaces such as schools, paediatric clinics.

Acquired immunodeficiency syndrome (AIDS) | ❑ Mother:

The US Public Health Service[11]published recommendations for the use of ZDV or AZT to reduce the risk of HIV transmission from infected women to their infants as a result of the AIDS Clinical Trials Group (ACTG) which includes:

* Antepartum: ZDV, 100 mg orally five times per day, starting at 14–34 weeks.[11]
* Intrapartum: ZDV, 2 mg/kg intravenously (IV), loading dose, given over 1 hour, followed by 1 mg/kg/hr IV until delivery.[11]
*   *

❑ Newborn:

ZDV syrup 2 mg/kg orally every 6 hours, beginning 8–12 hours after birth for the first 6 weeks of life

| ❑ A scheduled cesarean section can reduce vertical transmission to 2%. It is unclear if there is a significant benefit from cesarean delivery in patients who have viral loads of less than 1000 copies/ml who are on HAART.[12]❑ Maternal morbidity is greater with cesarean delivery, particularly in those women with low CD4 cell counts. Therefore, women who are HIV positive must be counseled about the maternal risks and potential benefits of both ZDV prophylaxis and cesarean delivery so that they can make informed choices.

❑ If cesarean delivery is chosen, it should be performed electively at 38 weeks of gestation. ZDV should begin 3 hours prior to delivery. It is important to use perioperative prophylactic antibiotics to reduce maternal infectious morbidity.

❑ The management of labor should include avoidance of scalp electrodes and scalp sampling.

| ❑ The newborn should be carefully cleaned off maternal blood and secretions.

❑ Breastfeeding is not recommended when there is a suitable alternative.

❑ Even if she is asymptomatic after delivery, she will require support and surveillance for disease progression.[13]

Varicella zoster virus | Pregnant women or newborns with (severe) infection: Acyclovir [14]

Administer postexposure prophylaxis in newborns if mother displays symptoms of varicella up to 7 days before delivery or up to 28 days after delivery: IgG antibodies (varicella-zoster immune globulin, VZIG)[15]

|  | Immunization of seronegative women of child breeding age before pregnancy.[16]

VZIG in pregnant women without immunity within 10 days of exposure.[17]

Hepatitis |  |  | Hepatitis A:

❑ Maintain hygienic practices such as hand washing with safe water, particularly before handling food, avoiding drinking water or using ice cubes of unknown purity, and avoiding eating unpeeled fruits and vegetables.

❑ The HAV vaccine is safe and develops protective levels of antibodies 2 weeks after the first dose of the vaccine and persists at least 10 to 29 years, if not lifelong after receiving the second dose. So, it should be administered before travelling to endemic areas.[18]

Hepatitis B:

❑ Testing for HBV surface antigen is recommended as a part of routine prenatal testing.

❑ Infants born to HBV-positive mothers should receive 0.5 mL of hepatitis B immune globulin within 12 hours of birth and simultaneously receive the first dose of HBV vaccine (half the adult dose). The remaining doses should follow the adult schedule. Complete immunization requires the initial dose with repeated doses at 1 and 6 months.

Hepatitis C:

❑ At present, no vaccine is available for HCV .

Influenza | ❑ Prompt antiviral therapy should be given where the medications reduce the risk of complications in pregnant women and reduce the teratogenic effects of the influenza infection.[19]

❑ Trans placental transfer of oseltamivir to fetus may occur. But there is no evidence of adverse fetal outcomes as of now.[19]

|  | Vaccination is the most effective strategy for preventing influenza infection during pregnancy whereby can protect both mother and the fetus.
Group B streptococci[20] | ❑ Intravenous penicillin G is the treatment of choice for intrapartum antibiotic prophylaxis against Group B Streptococci.

❑ Penicillin G 5 million units intravenous is administered as a loading dose, followed by 2.5 to 3 million units every 4 hours during labor until delivery.[21][20]

❑ Ampicillin is a reasonable alternative to penicillin G, which is administered as a 2 gm intravenous loading dose followed by 1 gm intravenous every 4 hours during labor until delivery.

❑ Antibiotic prophylaxis in patients with a history of anaphylaxis, angioedema, respiratory distress, or urticaria following penicillin or cephalosporin is guided by antibiotic susceptibility testing. If GBS is sensitive to both clindamycin and erythromycin, then clindamycin 900 mg intravenous every 8 hours is recommended for GBS prophylaxis during labor until delivery.[20][21]

❑ If the culture returns resistant to erythromycin, vancomycin 1 gm intravenously every 12 hours is recommended for GBS prophylaxis.

❑ If patient is penicillin allergic, vancomycin is the choice of treatment.

❑Cefazolin 2 gram intravenous loading dose followed by 1 gm every 8 hours may be used in patients without a history of anaphylaxis, angioedema, respiratory distress, or urticaria following penicillin or cephalosporin administration.[20]

|  | Initiating antibiotic prophylaxis greater than 4 hours before delivery is considered to be adequate antibiotic prophylaxis and is effective in the prevention of transmission of GBS to the fetus.[20]
Listeriosis | IV ampicillin and gentamicin (for both mother and newborn)  |  | *Avoidance of soft cheeses

* Avoidance of potentially contaminated water and food: See “Food and water safety” in food poisoning.
* Nationally notifiable condition: Listeriosis must be reported to the local or state health department.[22]

Syphilis | Therapy is indicated in the gravida with a positive FTA-ABS of recent onset, and the drug of choice is penicillin. [23] The regimen recommended is the same as in the nonpregnant woman. For early syphilis, a single dose of 2.4 million units of benzathine penicillin G is recommended. Some recommend a follow-up dose 1 week later, particularly in the third trimester. For late-stage syphilis (more than 1 year of duration), three doses are recommended. For the patient allergic to penicillin, treatment with penicillin after oral desensitization is recommended. This should be done in a facility that has appropriate provisions for resuscitation, if needed. [24] |  | *Maternal screening in early pregnancy

* Nationally notifiable condition: Congenital syphilis and syphilitic childbirth must be reported to local or state health department.[25]

Gonorrhea | current recommendations include one of the following regimens:

* Ceftriaxone, 125 mg IM, single dose
* Cefixime, 400 mg orally, single dose
* Spectinomycin, 2 g IM, single dose (for patients who cannot tolerate a cephalosporin).

In addition, treatment for Chlamydia should be administered because of the likelihood of coinfection. Disseminated infection in the newborn requires high-dose treatment, and ophthalmic infection should be treated both locally and systemically.

|  | Prevention of perinatal infection is best accomplished by careful maternal screening and treatment.
Chlamydia | ❑ Recommended treatment :

* Erythromycin base, 500 mg,or erythromycin ethylsuccinate, 800 mg orally four times daily for 7 days Amoxicillin, 500 mg orally three times daily for 7 days Azithromycin, 1 g orally as a single dose

|  | The question of maternal screening and prophylactic treatment to prevent neonatal infection is unsettled. As diagnostic studies have become more readily available, screening has become more practical. The decision to routinely screen a prenatal population should probably be based on a determination of the specific population prevalence.
Salmonella | ❑ chloramphenicol

❑ Alternate antibiotics are ampicillin or amoxicillin

❑ Combination of trimethoprim and sulfamethoxazole is useful for resistant strains but avoided in pregnancy if possible.

❑ Aspirin should be avoided because patients with typhoid are extremely sensitive and severe hypothermia may occur.

|  | ❑ Sanitation and hygienic processes and the control of faulty food processing.
Trichomonas vaginalis |  |  | Vaginal trichomoniasis has adverse pregnancy outcomes, so metronidazole, 2 g orally as a single dose, can be given after the first trimester.
Malaria |  |  | ❑ Pregnant woman who must travel to an endemic area should take Chloroquine phosphate, 500 mg once a week starting 1 week before the trip and continuing for 6 weeks. This is safe for pregnant women. [26]
Zika virus |  |  | ❑ Avoidance of travel to ZIKv endemic areas during pregnancy.

❑ The use of N,N-Diethyl-meta-toluamide, which has been recommended in pregnancy to prevent ZIKA infection.

❑ Long sleeves and pants or permethrin-treated clothing.

❑ Use of mosquito nets and window screens if living in or traveling to an endemic area.

❑ If the pregnant woman is living in an endemic area, areas of standing water such as tires, buckets, planters should be eliminated because they are a breeding area for mosquitoes.

❑ All pregnant women and their partners should receive counseling on prevention measures including avoidance of mosquito bites and sexual transmission.

❑ If a couple has a male partner and he travels to an area with ZIKA Virus, they should use condoms or abstain from sexual activity for 6 months (even if there is no symptoms).

❑ If a female travels to an area with risk of ZIKV, condoms or abstinence from sexual activity for 8 weeks (even in the absence of symptoms) is recommended.

❑ If a pregnant patient and her partner travel to or live in an area with Zika virus, condoms should be used each time the couple has sex for the remainder of pregnancy, or they should abstain from sexual activity. [27]

## Do's

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* The content in this section is in bullet points.

## Don'ts

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* The content in this section is in bullet points.

## References

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1. ↑ Neu N, Duchon J, Zachariah P (2015). "TORCH infections". Clin Perinatol. 42 (1): 77–103, viii. doi:10.1016/j.clp.2014.11.001. PMID 25677998.CS1 maint: Multiple names: authors list (link)
2. ↑ 2.0 2.1 Paquet C, Yudin MH (January 2013). "Toxoplasmosis in pregnancy: prevention, screening, and treatment". J Obstet Gynaecol Can. 35 (1): 78–81. doi:10.1016/s1701-2163(15)31053-7. PMID 23343802.
3. ↑ 3.0 3.1 3.2 Kravetz JD, Federman DG (September 2005). "Prevention of toxoplasmosis in pregnancy: knowledge of risk factors". Infect Dis Obstet Gynecol. 13 (3): 161–5. doi:10.1080/10647440500068305. PMC 1784564. PMID 16126501.
4. ↑ Freij BJ, South MA, Sever JL (June 1988). "Maternal rubella and the congenital rubella syndrome". Clin Perinatol. 15 (2): 247–57. PMID 3288422.
5. ↑ [Centers for Disease Control and Prevention. Three Cases of Congenital Rubella Syndrome in the Post elimination Era: Maryland, Alabama, and Illinois, 2012. MMWR Morb Mortal Wkly Rep. 2013; 62(12): pp. 226–229. url: https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6212a3.htm. ], additional text.
6. ↑ Pass RF, Arav-Boger R (2018). "Maternal and fetal cytomegalovirus infection: diagnosis, management, and prevention". F1000Res. 7: 255. doi:10.12688/f1000research.12517.1. PMC 5832908. PMID 29560263.
7. ↑ Kimberlin DW, Lin CY, Sánchez PJ, Demmler GJ, Dankner W, Shelton M, Jacobs RF, Vaudry W, Pass RF, Kiell JM, Soong SJ, Whitley RJ (July 2003). "Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial". J Pediatr. 143 (1): 16–25. doi:10.1016/s0022-3476(03)00192-6. PMID 12915819.
8. ↑ [Julie Johnson, MD, Brenna Anderson, MD, MSc, and Robert F. Pass, MD. Prevention of Maternal and Congenital Cytomegalovirus Infection. Clinical Obstetrics and Gynecology. 2013. url:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347968/], additional text.
9. ↑ 9.0 9.1 Straface G, Selmin A, Zanardo V, De Santis M, Ercoli A, Scambia G (2012). "Herpes simplex virus infection in pregnancy". Infect Dis Obstet Gynecol. 2012: 385697. doi:10.1155/2012/385697. PMC 3332182. PMID 22566740.
10. ↑ Giorgio E, De Oronzo MA, Iozza I, Di Natale A, Cianci S, Garofalo G, Giacobbe AM, Politi S (October 2010). "Parvovirus B19 during pregnancy: a review". J Prenat Med. 4 (4): 63–6. PMC 3279187. PMID 22439064.
11. ↑ 11.0 11.1 11.2 "Recommendations of the U.S. Public Health Service Task Force on the Use of Zidovudine to Reduce Perinatal Transmission of Human Immunodeficiency Virus".
12. ↑ Jamieson DJ, Read JS, Kourtis AP, Durant TM, Lampe MA, Dominguez KL (September 2007). "Cesarean delivery for HIV-infected women: recommendations and controversies". Am J Obstet Gynecol. 197 (3 Suppl): S96–100. doi:10.1016/j.ajog.2007.02.034. PMID 17825656.
13. ↑ Andiman W, Bryson Y, de Martino M, Fowler M, Harris D, Hutto C, Korber B, Kovacs A, Landesman S, Lindsay M, Lapointe N, Mandelbrot L, Newell M, Peavy H, Read J, Rudin C, Semprini A, Simonds R, Tuomala R (April 1999). "The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1--a meta-analysis of 15 prospective cohort studies". N Engl J Med. 340 (13): 977–87. doi:10.1056/NEJM199904013401301. PMID 10099139. Vancouver style error: initials (help)
14. ↑ Hayward K, Cline A, Stephens A, Street L (October 2018). "Management of herpes zoster (shingles) during pregnancy". J Obstet Gynaecol. 38 (7): 887–894. doi:10.1080/01443615.2018.1446419. PMID 29565203.
15. ↑ Heuchan AM, Isaacs D (March 2001). "The management of varicella-zoster virus exposure and infection in pregnancy and the newborn period. Australasian Subgroup in Paediatric Infectious Diseases of the Australasian Society for Infectious Diseases". Med J Aust. 174 (6): 288–92. PMID 11297117.
16. ↑ Daley AJ, Thorpe S, Garland SM (February 2008). "Varicella and the pregnant woman: prevention and management". Aust N Z J Obstet Gynaecol. 48 (1): 26–33. doi:10.1111/j.1479-828X.2007.00797.x. PMID 18275568.
17. ↑ [ Centers for Disease Control and Prevention. 2017 Nationally Notifiable Conditions. https://wwwn.cdc.gov/nndss/conditions/notifiable/2017/. Updated January 1, 2017. Accessed March 22, 2017], additional text.
18. ↑ Chaudhry SA, Koren G (November 2015). "Hepatitis A infection during pregnancy". Can Fam Physician. 61 (11): 963–4. PMC 4642904. PMID 26881283.
19. ↑ 19.0 19.1 Ghulmiyyah LM, Alame MM, Mirza FG, Zaraket H, Nassar AH (2015). "Influenza and its treatment during pregnancy: A review". J Neonatal Perinatal Med. 8 (4): 297–306. doi:10.3233/NPM-15814124. PMID 26836818.
20. ↑ 20.0 20.1 20.2 20.3 20.4 "Group B Streptococcus And Pregnancy - StatPearls - NCBI Bookshelf".
21. ↑ 21.0 21.1 "Committee Opinion No. 485: Prevention of Early-Onset Group B Streptococcal Disease in Newborns: Correction". Obstet Gynecol. 131 (2): 397. February 2018. doi:10.1097/AOG.0000000000002466. PMID 29370038.
22. ↑ [ Janakiraman V. Listeriosis in pregnancy: diagnosis, treatment, and prevention. Rev Obstet Gynecol. 2008; 1(4): pp. 179–85. pmid: 19173022. ], additional text.
23. ↑ [ Centers for Disease Control: Syphilis: CDC recommended treatment schedules. J Infect Dis 134: 97, 1976], additional text.
24. ↑ [ ACOG Educational Bulletin No 245, March 1998, American College of Obstetricians and Gynecologists ], additional text.
25. ↑ [Centers for Disease Control and Prevention. 2017 Nationally Notifiable Conditions. https://wwwn.cdc.gov/nndss/conditions/notifiable/2017/. Updated January 1, 2017. Accessed March 22, 2017. ], additional text.
26. ↑ [ Sever JL, Larsen JN, Grossman JH: Toxoplasmosis. In: Handbook of Perinatal Infections, pp 157–163. Boston, Little, Brown, 1979 ], additional text.
27. ↑ [ Centers for Disease Control and Prevention (CDC). Zika virus prevention. Available at: https://www.cdc.gov/zika/prevention/index.html. Accessed April 24,2017], additional text.

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