MCARTOR SYMPOSIUM SUMMARY By Maria-Cristina Javier, MD Medical Director of Education
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1 MCARTOR SYMPOSIUM SUMMARY By Maria-Cristina Javier, MD Medical Director of Education LAURA E. RILEY, MD MATERNAL INFECTIONS AND THEIR LIFELONG CONSEQUENCES TO THE FETUS FEVER IN LABOR: WHAT DOES THAT MEAN FOR THE NEONATE? INTRA-AMNIOTIC INFECTION (IAI), chorioamnionitis 1-4% of all births Common organisms: Gardenella vaginalis GBS E.coli Bacteroides sp Maternal effect: Uterine wall dysfunctional labor = ineffective contractions, more likely to have c sections Endometritis Wound infection - surgical Pelvic abscesses, bacteremia 10%, hemorrhage (dysfunctional uterine contraction postpartum) Fetal side: Fetal inflammatory response syndrome (FIRS) Sepsis, asphyxia, pneumonia Maternal fever >38 C was associated with CP (infant temperature is 1F higher than mom: ex mom is 101F baby is 102F) Maternal infection present in 22% babies with CP vs 2.9% of controls (moms who are healthy) IV Antibiotics no difference in fetal mortality. Infant of moms who received antibiotics > risk for sepsis E. Coli resistance to ampicillin - because of antibiotic overuse NON INFECTIOUS FEVER Likely related to the epidural (15% of women) The longer the epidural is in the more likely to develop fever: 6-12 hour later fever Maternal fever associated with lower Apgar score, bag mask ventilation, More sepsis eval, more antibiotic treatment Epidural: maternal fever but no real infections just in inflammation What is an infection versus a chemochyme reaction? TFNa and IL1B increases in infected amniotic fluid
2 IL6 level higher in maternal fever not all of these women are infected Fever and neonatal encephalopathy: maternal Fever= inflammatory response may be toxic even without an infection INTRA-AMNIOTIC INFECTION (IAI) is still a diagnosis after the fact Unintended consequences of sepsis work-up on babies because of maternal fever: Antibiotic resistance from too much antibiotics use, separation of mom and baby Isolated maternal fever Suspected INTRA-AMNIOTIC INFECTION (IAI) if fever without clear source Amniocentesis to prove infection: fluid will have low glucose amniotic sac fluid and Gm stain Communication between OB and Peds to put the infant in context MOLLY STOUT, MD VAGINAL MICROBIOME IN PREGNANCY STATE OF THE UNION BUGS AND DRUGS PRINCIPAL UNRESOLVED PROBLEM IN PERINATAL MEDICINE: Preterm birth Treatment with antibiotics not effective Sometimes the treatment makes preterm labor more likely Too broad antibiotics, kill beneficial bacteria Ecological approach to vaginal MICROBIOME: clarify what is normal, understand abnormal, determine mechanism to smartly design therapy. PROBLEM: Normal is hard to define Lactobacillus - ph decrease so decrease pathogenic bacteria Bacterial vaginosis alteration in flora: increase STD, endometriosis Landmark studies: Human MICROBIOME project ; sequence the bacteria - a census of bacteria in each region Which species of lactobacillus is predominant? Healthy women : heterogeneous community of bacteria Black and Hispanic ; non lactobacillus predominant; so is it really bacterial vagionosis? MICROBIOME of pregnancy different?
3 2nd trimester women Unique vaginal MICROBIOME in pregnancy Is there a racial difference in preterm birth: Caucasian lower diversity of vaginal flora Pregnant women swabbed weekly : Changes in the the heterogeneity did not translate with preterm birth 16S V1V3 region sequence of the bacterial DNA (how they identified bacteria) Restoration of flora to C section infants: Vaginal gauze an hour in the vagina for microbial restoration procedure: swab baby mouth,face, body Timing and rate in development of flora to adult type= will eventually occur in infants born by c section even without microbial restoration procedure Large bacteria in the vagina are unassigned Operator Room bacterial flora: Skin, oral,vaginal bacteria 30% of sample were sequence failures (too little DNA) so OR relatively clean HUMAN MILK MICROBIOTA STAPH, ENTEROBACTERIACEAE, PSEUDOMONAS How gut MICROBIOME gets established in preterm infants Pattern of progression bacilli first,then clostridium,, then gammaproteo bacteria LOOK AT BOTH SIDES OF THE PLACENTA ; people who work on the OB and Peds side need to COMMUNICATE REESE CLARK, MD STAPHYLOCOCCUS AUREUS IN THE NICU WHAT DO WE KNOW? Antibiotics and similar drugs have been in use for the past 70 years Their frequent use is not without consequence: at least 2 million people/year are infected by bacteria that are resistant to antibiotics and 23,000 die each year. Bacteria have genetic strategies to protect itself making them antibiotic resistance. Bacterial resistance happens Livestock low dose antibiotics also affects humans (klebsiella resistance in China) MRSA IN PREGNANCY Community acquired infections 17% staph aureus and 2.85% of that is MRSA Decolonization in 2,294 infants will only prevent 1 infection (not cost effective) Need to know your own rate.
4 Chlorhexedine bath in newborns - not really necessary Staph aureus infections in the NICU: is from baby to baby transmission mostly coagulase negative staph (CONS) Infant with Serratia sepsis always assume meningitis GBS and E. Coli about 20% meningitis MRSA in the NICU MSSA infection is more common 30% S aureus infection in NICU are MRSA How do we reduce the burden of resistance in the NICU Antibiotics are not entirely safe = infant who received IV antibiotics are more likely to have asthma IV antibiotics in labor, infants likely to end up with CP Urgent need: Reduce Vancomycin use GINA BERTHOLD, MD VERTICAL TRANSMISSION OF HIV: PREVENTION, CHALLENGES AND BREAKTHROUGHS RETROVIRUS. Within 24 hours of infection become intracellular (the virus become part of the genomic sequence) Perinatal transmission without intervention 12-40% Most transmission occur intrapartum (during labor) but also occur in utero and through breastfeeding also. Rupture of membranes (ROM ) <4 hours = 15% vertical transmission Every hour of ROM = 2% increase in transmission Can be asymptomatic for up to 5 years HIV DNA PCR 2 is positive in 93% at birth 1 month of age 95% False negative PCR can happen on infant on prophylaxis Subsaharan Africa 53% HIV positive before age 2 75% by age 3 Viral load rises peaking to 10 million Intrapartum AZT: drops Perinatal transmission <2% Crosses placenta readily AZT is metabolized to active form in the placenta
5 AZT has Higher CNS penetration than other nucleoside reverse transcriptase inhibitors (NRTIs) The standard treatment consists of a combination of at least three drugs (often called highly active antiretroviral therapy or HAART) that suppress HIV replication. Three drugs are used in order to reduce the likelihood of the virus developing resistance. ART has the potential both to reduce mortality and morbidity rates among HIV-infected people, and to improve their quality of life Suppression therapy during pregnancy: suppression = virus undetectable (not cured just suppressed) ¾ of pregnant moms who receive therapy achieve viral suppression by the time they delivery (by 36 weeks) The higher the viral load the more urgent starting suppression treatment is Starting at 17weeks = suppressed by 36 weeks If Started at 22 weeks onward = not suppressed by 36 weeks so risk of transmission is higher In utero transmission. If Preconception suppression therapy on HIV (+) women - vertical transmission is zero Do baseline genotype testing on mom s virus (to see if her virus is resistant or not) but begin suppression treatment prior to results. Anti retro viral treatment fetal side effects: Efavirenz- potential risk for neural tube defect Protease inhibitor- preterm labor Tenofovir- potential effect on bone growth Rate of birth defects not significantly different in infants exposed to HAART = same as general population (2% ) Check Viral load 2-4 weeks after starting therapy then monthly till undetectable Once suppressed (viral load undetectable) : do viral load testing Q 3 months till weeks GA If Amniocentesis is needed, should be performed after HAART and ideally after suppressed If viral load (VL) <1000 no episode of transmission even without intrapartum AZT If HIV VL >1000 copies schedule C section at 38 weeks catch her before she has rupture of membranes Zidovudine (AZT) IV VL>1000 copies begin 3 hours prior to delivery Avoid artificial ROM, fetal scalp electrodes, forceps or vacuum assistance If ROM csection no longer protective. Recommendation in the USA: avoid breastfeeding even if viral load is zero
6 Baby: PCR test at birth, 2 weeks 1-2 months 4-6 months Mixed HIV population in the blood stream - the wild type virus is the one transmitted to the infant. Wild type is more is likely to cross the placenta Even if mom s virus is AZT resistant: Still give it during labor : the wild type virus is still susceptible Resistant strains are less firm, less likely to cross the placenta and this may lead to decrease transmission. PERINATAL INFECTION: PCR testing: If positive confirm by repeat testing Presumptive negative PCR if negative at 2 weeks and 1 month or older NEGATIVE if PCR negative 1 month and 4 month or older Confirm negative with HIV antibody test at months (maternal HIV antibiotics would be gone from the baby s system by then) - if baby is antibody positive get PCR Preconception counseling Discuss potential of pregnancy with all HIV positive women of childbearing age Discuss contraception Begin HAART and reach an undetectable VL in women who are contemplating pregnancy When able, counsel sexual partners re HIV transmission and testing Getting tested every 3 month for HIV negative partner Discordant couple (one partner is HIV negative and one HIV positive) Treat HIV positive partner with viral suppression Limiting conception attempts (unprotected sex) to peri ovulation period only HIV positive woman artificial insemination HIV negative woman with HIV positive man : sperm donor or sperm preparation (washing sperm) In 6 states it is illegal to use HIV positive sperm to an HIV negative woman NC not one of those states
7 5-10% in vitro clinics will refuse HIV positive parents Pre-conception prophylaxis for discordant couples Start Family tenofovir/emtricitabine 95% prevention Do HIV and pregnancy testing every 3 months PER CDC begin one month prior to attempting conception and unit one month after may need to continue throughout pregnancy Acute HIV while pregnant higher incidence of transmission HIV negative women All should be screen during pregnancy In discordant relationship repeat testing during 3rd trimester In discordant relationship counsel re condom use HIV viral load in placental, genital fluids and breast milk during acute infection : over 3,000 exposed infant in NY Acute infection during pregnancy 22% transmission versus 1.8% Transmission in women Preexisting infection prior to pregnancy Barriers perinatal transmission prevention : Only 44% of pregnant Women received HIV testing in 2013 Option b+ Infant born to HIV positive mother: Begin prophylaxis >6 weeks with AZT if mom did not achieve viral suppression (virus was still detected in maternal blood stream at birth) add Nevirapine RICHARD POLIN, MD RECENT ADVANCES IN DIAGNOSIS AND PREVENTION OF NEONATAL SEPSIS GBS is still the leading pathogen of sepsis and E. Coli is second ⅔ of E. Coli isolates are resistant to ampicillin Always draw a minimum of 1 ml of blood for blood culture Draw your first CBC and CRP at least 6-12 hours (these test are negative predictors= if CBC and CRP are reassuring then infant is NOT septic) In a vigorous infant, can do a physical exam and strict observation (Q 2-4 hours : checking for vitals: respirations, temperature, activity) and not start antibiotics. If CBC (I:T ratio or immature to total neutrophil of <0.2 ) and CRP are within normal limits infant is not septic, can d/c home in 48 hours (48 hours minimum observation, NO EARLY DISCHARGE!). Remember: NOTHING REPLACES CAREFUL OBSERVATION AND A GOOD PHYSICAL EXAM! MATERNAL HEPATITIS B AND C INFECTION: Dr. Laura Riley
8 Hepatitis B infection: (+) anti e = chronic active infection Hepatitis BsAg positive mom = give HBIg and Hep B vaccine For moms that are high risk (IV drug users) re screen for HepBsAg at 28 weeks gestation: might miss a mom who got recently infected. Infant is asymptomatic but will present with acute hepatitis later. Check Viral load Hepatitis B is safe for pregnant women Complete the whole series because incomplete vaccination develops resistance to the WHOLE CLASS of medications Ideally, universal screening for Hepatitis C because no treatment yet for this. Check infant Hepatitis C PCR at 2 months of age.
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