Theodore R. Thompson, M.D.

NEONATAL CASE STUDY
(courtesy of CM Bendel MD)

Prenatal Course:

• 17-year old, G1, P0-0-0-0, single, Caucasian female.
• LMP 9/15/94 and EDC 6/22/95.
• A positive, rubella immune, HBsAg negative, VDRL non-reactive.
• Level II ultrasound at 28 weeks gestation without anomalies.
• Screening cervical culture at 28 weeks gestation positive for group B streptococci (GBS); followed by 14 days of Amoxicillin.
• Urine culture negative, urine toxicology screen positive for THC.
• Preterm labor with 2cm cervical dilatation at 31 3/7 weeks gestation requiring hospitalization for IV magnesium sulfate (5 days total) and bedrest (15 days total).
• Upon presentation, she received a course of IM betamethasone which was repeated weekly until delivery.
• Cervical and urine cultures on admission were negative for GBS.
• Level II ultrasound at 33 3/7 weeks gestation showed very poor interval fetal growth and the decision was made to induce labor secondary to the concern for intrauterine growth retardation.
• The mother reported declined an amniocentesis for fetal lung maturity studies.

Perinatal Course:

• Pitocin augmentation of labor at 33 4/7 weeks gestation after AROM producing clear amniotic fluid at 0945 hours.
• Labor progressed with multiple late decelerations throughout the latter course.
• The only medications given to the mother were narcotics for pain.
• A male infant was delivered vaginally from a vertex presentation at 2046 hours (11 hours of ruptured membranes).
• Apgar scores were 5 and 8, at one and five minutes.
• He required blow-by oxygen and one dose of Narcan in the delivery room.
• Because of his prematurity, and continued grunting and retractions, he was transferred to the NICU for further evaluation and therapy.

Postnatal Course:

• PE: Gestational age by exam = 34 weeks
• Weight = 1960 gm OFC = 30 cm Length = 45 cm
  (< 1 SD) (< 1 SD) (< 1 SD)
• Vital signs: T=98.2oF, RR=70, HR=176, BP=56/34
• Exam significant only for slightly poor perfusion with weak, but symmetric pulses in all extremities. No cardiac murmur was heard and breath sounds were clear bilaterally, but shallow. He still demonstrated minimal intercostal retractions and intermittent grunting. No anomalies were noted.
• After a brief trial of nasal CPAP he was intubated secondary to increasing respiratory distress and given exogenous surfactant.
• Initial ventilator settings were PIP=20, PEEP=4, R=20 and 60% FIO2 with an ABG=7.36/38/66/21.
• CXR revealed diffuse bilateral infiltrates with fluid in the fissure.
• Umbilical arterial and venous lines were placed.
• Blood and urine cultures were obtained, followed by intravenous ampicillin and gentamicin.
• CBC revealed Hgb = 12.2, plt = 329K, WBC = 4,500 with 5% neutrophils (ANC = 225) and 89% lymphocytes.
• Serum electrolytes normal with the exception of a glucose of 34. (IV dextrose given)
• CSF glucose 45 (serum 60), protein 129, WBC 23 lymphocytes.
• At two hours of age this infant had a major respiratory and systemic decompensation with decreased oxygen saturations despite increased supplemental oxygen concentrations (100% FIO2), poor perfusion and hypotension (BP=34/16) that was minimally responsive to maximal therapy over the next ten hours.
• The severe hypotension persisted (mBP < 25) and he developed an intractable metabolic acidosis (measured bicarb < 12), both unresponsive to the administration of sodium bicarbonate; multiple rounds of colloid (PRBC, FFP, cryoprecipitate, plasminate), calcium and the addition of inotropic agents (Dobutamine 20 mcg/kg/min, Dopamine 20 mcg/kg/min and epinephrine 0.1 mcg/kg/min).
• He showed evidence of persistent pulmonary hypertension with severe post-ductal hypoxemia unresponsive to conventional ventilatory hyperventilation. He was switched to high frequency oscillatory ventilation with a transient improvement in oxygenation. Nitric oxide therapy was attempted without a positive response. At 9 hours of age ABG = 7.21/31/34/12.
• He developed a consumptive coagulopathy PT = 30, PTT = 92, Fib = 0.08.
• Repeat CBC at 6 hours of age showed Hgb = 13.1, plt = 88K, WBC = 2,300 with 10% neutrophils (ANC = 230).
• The severe acidosis, hypotension and hypoxemia persisted and the infant began to have multiple episodes of bradycardia.
• His parents decided to discontinue support in light of his grave prognosis and he was extubated and died in his mothers arms at the age of 11 hours.
• One hour after his death the initial blood culture was reported as positive for gram positive cocci, later identified as group B beta hemolytic streptococcus.
• Autopsy obtained confirmed these findings.
  

Predisposing Factors to Neonatal Early-Onset GBS Infection

1. Prematurity
   Risk of sepsis and mortality increase with decreasing gestational age
   About 70% of patients are near- or full-term infants
2. Maternal fever - chorioamnionitis
3. Rupture of membranes > 18 hours (? 12 hours)
4. Bacteriuria (GBS)
5. Heavy colonization (multiple sites)
6. Lack of specific maternal antibody to GBS capsular polysaccharide
7. Perinatal distress
8. Age below 20 years
9. Black race
10. Male sex
11. Multiple births
12. Diabetes mellitus

Clinical Manifestations of Maternal Group B Streptococcal Infections

1. Anorectal / lower vaginal colonization (15-40%)
2. Urinary tract infection
3. Postpartum febrile morbidity
   Endometritis (20%)
   Post C-section bacteremia (20%)
4. Chorioamnionitis; amniotic infection
5. Premature ROM?

Clinical Presentation of Neonatal Group B Streptococcal infections

Characteristic	Early Onset	Late Onset
Onset	birth to 7d	>7d - 3m
Transmission	vertical	vertical, horizontal
obstetrical complications (e.g. PROM)	frequent	rare
Presenting signs & symptoms	respiratory distress apnea shock pulmonary hypertension metabolic acidosis meningitis (30%) asymptomatic bacteremia	meningitis osteomyelitis septic arthritis
Mortality	Preterm: 24-30% Term: 2-8% Overall: 15%	Overall: 10%

Overall Mechanisms for Prevention of Neonatal Group B Streptococcal Infections

• Maternal active immunization (studies in progress)
• Maternal, neonatal passive immunization (immunoglobulin)

• Large amounts of immunoglobulin
• In utero GBS acquisition

• Intrapartum maternal chemoprophylaxis

• 50-75% of infants born to GBS-positive mothers are colonized
• » 1-2% of colonized infants develop invasive disease
• Reduces early-onset neonatal GBS infection by 30-fold
• Effective if > 2 doses (> 4 hours) of antibiotics (penicillin, ampicillin) given to mother
• About 70% of GBS patients are near- or full-term infants; premature infants have higher mortality

• Neonatal chemoprophylaxis

• Penicillin at birth
• Effective if GBS acquired at birth (about 33% of patients)
• Not effective if in utero acquisition (>60-70% of patients have onset within 4-6 hours of birth)

Identification of Maternal Colonization with Group B Streptococci

• Rapid identification techniques (must be easy, timely, reliable, inexpensive)

• Gram stain (cervical, vaginal) - 90% sensitivity, 70% specificity
• Starch serum media, coagglutination test
• Latex particle agglutination - enzyme immunoassay

• Most sensitive of tests for heavy colonization
• Rapid, easy

• DNA gene probe?

• Culture - rectal, vaginal

Management of Neonatal GBS Sepsis/Pneumonia/Meningitis

• Antibiotics

• Aqueous penicillin G, 250,000-300,000 U/kg/day, or
• Ampicillin, 200-300 mg/kg/day

• 2-3 equally divided doses
• 10-14 days (sepsis, pneumonia), 21 days (meningitis - minimum.
  plus

• Gentamicin, 5 mg/kg/day

• 2 equally divided doses
• Monitor peak (6-10 µg/ml), trough (< 2 µg/ml levels)
  

• Maintain ventilation, oxygenation, acid-base balance (alkalosis with pulmonary hypertension)

• Monitor arterial blood gases, SaO2
• Conventional ventilation ---> high-frequency oscillatory ventilation
• Nitric oxide inhalation (improve oxygenation)
• ECMO: oxygenation index = (MAP x FIO2 x 100)/ postductal PaO2 > 40-45
  

• Surfactant administration
  
• Maintain blood pressure, perfusion

• Colloid: fresh-frozen plasma
• Inotropic agents

• Dobutamine: 10-20 µg/kg/min
• Dopamine: 2.5-10 µg/kg/min
• Epinephrine: 0.05-0.5 µg/kg/min
  

• Sedation, pain relief (e.g., fentanyl)
• Monitor vital signs, input and output, and labs closely

Ongoing Issues Regarding Screening and Intrapartum Maternal Antibiotic Therapy for Group B Streptococci

• Screening: None or third trimester?
• Intrapartum maternal therapy:

• All women with high-risk factors (e.g., preterm labor, ROM > 12-18 hours, fever) (CDC)
• All colonized (light, heavy) women with GBS (CDC)
• Only GBS-colonized women with high-risk factors (AAP)
• Paternal?

• Length of maternal treatment? Repeat courses?
• Neonatal therapy - length, amount

• Maternal colonization
• Maternal therapy

• Resistant organisms

Prevention Strategy For Early-Onset Group B Streptococci (GBS) Disease
Using Prenatal Screening At 34-37 Weeks

Prevention Strategy For Early-Onset Group B Streptococci (GBS) Disease
Using Risk Factors

Centers for Disease Control and Prevention. Prevention of perinatal group B streptococcal disease: a public health perspective. MMWR 1996;45[RR-7:1-24

RECOMMENDED REGIMENS FOR INTRAPARTUM ANTIMICROBIAL PROPHYLAXIS FOR PERINATAL GROUP B STREPTOCOCCAL DISEASE

Recommended	Penicillin G, 5mU IV load, then 2.5mUs IV q4h until delivery
Alternative	Ampicillin, 2gm IV load, then 1gm IV q4h until delivery
If PCN allergic
Recommended	Clindamycin, 900mg IV q8h until delivery
Alternative	Erythromycin, 500mg IV q6h until delivery

Note: If patient is receiving treatment for amnionitis with an antimicrobial agent active against group B streptococci (e.g., ampicillin, penicillin, clindamycin or erythromycin), additional prophylactic antibiotics are not needed.

EMPIRIC MANAGEMENT OF THE NEONATE BORN TO A MOTHER WHO RECEIVED INTRAPARTUM ANTIMICROBIAL PROPHYLAXIS FOR PREVENTION OF EARLY-ONSET GBS DISEASE

• Full diagnostic evaluation: CBC and differential, blood culture, and chest radiograph if respiratory symptoms. A lumbar puncture is performed at the discretion of the physician.
• Duration of therapy will vary depending on results of blood culture and CSF findings (if obtained), as well as on the clinical course of the infant. If laboratory results and clinical course are unremarkable, duration may be as short as 48-72h.
• Limited Evaluation: CBC and differential and blood culture.

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REFERENCES

General

Alkalay AL, et al. Management of neonates born to mothers with group B streptococcus colonization. J Perinatol 16:470, 1996.

Allen UD, et al. Effectiveness of intrapartum penicillin prophylaxis in preventing early-onset group B streptococcal infection: results of a meta-analysis. Can Med Assoc J 149:1659, 1993.

Baker C. Maternal chemoprophylaxis for group B streptococcal (GBS) sepsis. Report on Pediatric Infectious Diseases 3:1, 1991.

Baker CJ. Group B streptococcal infection in newborns. Prevention at last? N Engl J Med 314:1702, 1986.

Baker CJ. Group B streptococcal infections. Clin Perinatol 24:59, 1997.

Baker CJ. Maternal chemoprophylaxis for group B streptococcal (GBS) sepsis. Rep Pediatr Infect Dis 3:1, 1991.

Boyer KM, Gotoff SP. Prevention of early-onset neonatal group B streptococcal disease with selected intrapartum chemoprophylaxis. N Engl J Med 314:1665, 1986.

Committee on Infectious Diseases and Committee on Fetus and Newborn. Guidelines for prevention of group B streptococcal (GBS) infection by chemoprophylaxis. Pediatr 90:775, 1992.

Committee on Infectious Diseases and Committee on Fetus and Newborn, American Academy of Pediatrics. Revised guidelines for early-onset group B streptococcal (GSB) infection. Pediatrics 99:489, 1997.

Dashefski B, et al. Prevention of early-onset group B streptococcal sepsis. J Pediatr 112:1039, 1988.

Dillon HC, Jr., et al. Group B streptococcal carriage and disease: A six-year prospective study. J Pediatr 110:31, 1987.

Dinsmoor MJ. Group B streptococcus still poses a challenge. Contemp Ob/Gyn May 1990, p. 95.

Edwards MS, et al. Long-term sequelae of group B streptococcal meningitis in infants. J Pediatr 196:717, 1985.

Ferrieri P. Prevention of group B streptococcus infections. Sem Pediatr Infect Dis 8:117, 1997.

Givner LB. Management of newborn infants whose mothers received intrapartum antimicrobial chemoprophylaxis. Rep Pediatr Infect Dis 6:?, 1996

Gotoff SP, Boyer KM. Prevention of early-onset neonatal group B streptococcal disease. Pediatrics 99:866, 1997.

Greenberg DN, Yoder BA. Changes in the differential white blood cell count in screening for group B streptococcal sepsis. Pediatr Infect Dis J 9:886, 1990.

Heimier R, et al. Identification of sepsis in neonates following maternal antibiotic therapy. Clin Pediatr March 1995, page 133.

Hertz DE, et al. Sepsis in asymptomatic term newborns delivered of antibiotic-treated mothers. J Perinatol XIV:446, 1994.

Larsen JW, Dooley SL. Group B streptococcal infections: An obstetrical viewpoint. Pediatrics 91:148, 1993.

Maxwell GL, Watson WJ. Preterm premature rupture of membranes: Results of expectant management in patients with cervical cultures positive for group B streptococcus or Neisseria gonorrhoeae. Am J Ob Gyn 166:945, 1992.

Mead PB, Moderator. Group B strep in pregnancy: Can screening mothers safeguard babies? Contemp Ob/Gyn May 1991, p. 100.

Minkoff H, Mead P. An obstetric approach to the prevention of early-onset group B ß-hemolytic streptococci sepsis. Am J Obstet Gynecol 154:973, 1986.

Morales WJ, et al. Use of ampicillin and corticosteroids in premature rupture of membranes: A randomized study. Obstet Gynecol 73:721, 1989.

Payne NR, et al. Correlation of clinical and pathologic findings in early-onset neonatal group B streptococcal infection with disease severity and prediction of outcome. Pediatr Infect Dis J 7:836, 1988.

Pylipow M, et al. Selective intrapartum prophylaxis for group B streptococcus colonization: Management and outcome of newborns. Pediatrics 93:631, 1994.

Rouse DJ, et al. Strategies for the prevention of early-onset neonatal group B streptococcal sepsis: A decision analysis. Obstet Gynecol 83:483, 1994.

Society of Obstetricians and Gynecologists of Canada and Canadian Pediatric Society. National consensus statement on the prevention of early-onset group B streptococcal infections in the newborn. J Soc Obstet Gynecol Canada Can Pediatric Soc 16:2271, 1994.

Rapid Screening Test

Baker CJ, et al. Immunization of pregnant women with a polysaccharide vaccine of group B streptococcus. N Engl J Med 319:1180, 1988.

Brady K, et al. Reliability of a rapid latex fixation test for detecting group B streptococci in the genital tract of parturients at term. Obstet Gynecol 73:678, 1989.

Clark P, et al. Assessment of a rapid latex agglutination test for group B streptococcal colonization of the genital tract. Obstet Gynecol 79:358, 1992.

Feld SM, Harrigan JT. Vaginal gram stain as an immediate detector of group B streptococci in selected obstetric patients. Am J Obstet Gynecol 156:446, 1987.

Holls WM, et al. Cervical gram stain for rapid detection of colonization with ß streptococcus. Obstet Gynecol 69:354, 1987.

Isada MB, Grossman JH, III. A rapid screening test for the diagnosis of endocervical group B streptococci in pregnancy: Microbiologic results and clinical outcome. Obstet Gynecol 70:139, 1987.

Morales WJ, Lim D. Reduction of group B streptococcal maternal and neonatal infections in preterm pregnancies with premature rupture of membranes for a rapid identification test. Am J Obstet Gynecol 157:13, 1987.

Sandy EA, II, et al. Gram stain and the rapid determination of maternal colonization with group B streptococcus. Obstet Gynecol 71:796, 1988.

Skoll MA, et al. Evaluation of two rapid group B streptococcal antigen tests in labor and delivery patients. Obstet Gynecol 77:322, 1991.

Tuppurainen N, Hallman M. Prevention of neonatal group B streptococcal disease: Intrapartum detection and chemoprophylaxis of heavily colonized parturients. Obstet Gynecol 73:583, 1989.

Yancey MK, et al. Assessment of rapid identification tests for genital carriage of group B streptococci. Obstet Gynecol 80:1038, 1992.

Immunology

American College of Obstetricians and Gynecologists. Group B streptococcal infections in pregnancy. Washington, DC: American College of Obstetricians and Gynecologists. July 1992. ACOG technical bulletin No. 170.

Baker CJ, et al. Response to type III polysaccharide in women whose infants have had invasive group B streptococcal infection. N Engl J Med 322:1857, 1990.

Boyer KM, Gotoff SP. Antimicrobial prophylaxis of neonatal group B streptococcal sepsis. Clin Perinatol 15:831, 1988.

Coleman RT, et al. Prevention of neonatal group B streptococcal infections: Advances in maternal vaccine development. Obstet Gynecol 80:301, 1992.

Erickson NC, Blanco JD. Group B streptococcal infection in pregnancy. Sem Perinatol 17:432, 1993.

Insel RA. Maternal immunization to prevent neonatal infections. N Engl J Med 319:1219, 1988.

Mohle-Boetani JC, et al. Comparison of prevention strategies for neonatal group B streptococcal infection. JAMA 270:1442, 1993.

Van Oppen C, Feldman R. Antibiotic prophylaxis of neonatal group B streptococcal infection. BMJ 306:411, 1993.

Latex Agglutination - Neonatal

Ascher DP, et al. Group B streptococcal latex agglutination testing in neonates. J Pediatr 119:458, 1991.

Sanchez PJ, et al. Significance of a positive urine group B streptococcal latex agglutination test in neonates. J Pediatr 116:601, 1990.

Revised 8/22/97